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It is important to emphasize that these subserosal cytokeratin-expressing reactive cells, if not correctly identified, may be a source of diagnostic error, particularly in the distinction between desmoplastic malignant mesothelioma and fibrous pleurisy.
Acute pleuritis is typically either suppurative or fibrinous. Suppurative disease is typically infectious in nature, occurring with extension of a pulmonary bacterial infection. Abundant acute inflammation is present, extending throughout the pleural and subpleural tissues. Nonbacterial causes of acute pleuritis are associated with more fibrin and granulation tissue (fibrinous pleuritis) although acute inflammation is often still present. Within the edematous and fibrinous material, a proliferation of fibroblasts or submesothelial connective tissue and/or vascular tissue is often seen that may raise concern for malignancy. Although there may be some cytologic atypia with areas of increased cellularity with benign and reactive disease, the atypia usually resolves as one moves away from the pleural space toward the underlying lung or soft tissue (zonation).
Chronic pleuritis is typically only sampled if there is some degree of fibrosis (fibrosing pleuritis). The disease is often associated with chronic inflammation (lymphocytes and plasma cells) but it can be virtually acellular, with dense, parallel sheets of fibrosis (thus, at one end of the spectrum, it is histologically identical to an asbestos-related pleural plaque (see following discussion). Occasionally, the fibrosis can extend into the subpleural adipose tissue and one should be careful not to interpret this as desmoplastic mesothelioma (see following texts) (5). Adjacent to the pleural space, mesothelial hyperplasia may be present. Here, a vascular proliferation can also be seen with the reactive vessels coursing parallel to one another and perpendicular to the pleural space. Chronic pleuritis can be associated with collagen vascular disease or chronic irritation by another cause. Rarely, familial cases have been reported (6).
Granulomatous pleuritis refers simply to pleuritis associated with necrotizing or nonnecrotizing granulomatous inflammation. Foreign body type granulomas, replete with polarizable foreign bodies, are typically associated with talc. Infectious causes include tuberculosis, fungal disease, and other infectious agents. Rarely, the granulomas may be associated with rheumatic or autoimmune disease. Other variants of pleuritis include eosinophilic pleuritis (often associated with a history of pneumothorax) (7) and xanthomatous pleuritis (8).
NONNEOPLASTIC MESOTHELIAL PROLIFERATIONS
Unambiguous distinction between malignant epithelioid mesothelioma and adenocarcinoma is now relatively easy as a result of recent advances in immunohistochemistry. However, the distinction between mesothelial hyperplasia and mesothelioma continues to be a difficult diagnostic challenge for which immunohistochemistry is still of limited value (9).
Any chronic irritation may cause hyperplasia of the epithelioid mesothelial cells of the serous mesothelial surface as well as the submesothelial cytokeratin-expressing spindle cells. Because it may be very difficult to distinguish the epithelioid component of such hyperplasias from incipient, well-differentiated epithelioid mesothelioma, it is very important to base the diagnosis in such cases on a careful histologic evaluation with consideration of the total clinical and radiologic picture (9,10).
True invasion of the underlying tissue, particularly adipose tissue and skeletal muscle of the parietal pleura, remains the most reliable criterion of malignancy in epithelioid mesothelial proliferations. Here, it is important not to confuse entrapped mesothelial cells with invasion. Entrapped mesothelial cells are usually close to the pleural surface and are well delimited from the underlying adipose tissue, which they do not invade. Reactive fibrosis and inflammatory infiltrates are often present around and near the entrapped mesothelial cells (Fig. 27.3). Clearly, generous and nonfragmented biopsy specimens are essential to avoid error.
The appearance of the pleural surface, particularly at the time of thoracoscopy or thoracotomy, plays an important role in this differential diagnosis. The presence of confluent tumor nodules over large areas of the pleural surface favors malignancy. Absence of such nodules favors a reactive process. Additionally, malignant mesothelioma may be made up of monotonous tumor cells with little or moderate atypia, whereas reactive mesothelial cells may show similar atypical features. Thus, cytologic atypia, unless severe, may not be a reliable criterion for malignancy. Of note, the presence of tubular and papillary patterns of growth favors mesothelioma because these patterns are rarely seen in mesothelial hyperplasia.
In the distinction between fibrous pleuritis and desmoplastic malignant mesothelioma, particular attention should be placed to the presence of zonation because it strongly favors a reactive process (9). The term zonation means a higher cellularity (and at times atypia) of spindle-shaped, cytokeratin-positive mesothelial cells toward the pleural surface, with less cellular and more collagenous layers beneath. Often, fibrinous deposits and capillaries growing perpendicular to the surface are noted in these reactive processes. However, it is important to emphasize that a reactive and fibrous pleuritis may be caused by the presence of an underlying malignancy, including mesothelioma. Ample and deep sampling, as well as partial decortication of the parietal pleural lesions, is thus very helpful. It cannot be overemphasized that a diagnosis of desmoplastic malignant mesothelioma must rest on the clear evidence of invasion.
ANCILLARY STUDIES FOR DISTINGUISHING HYPERPLASIA AND NEOPLASIA
Immunohistochemistry, as will be discussed later in greater detail, helps to identify the mesothelial lineage of the proliferating cells but is of limited value to distinguish between mesothelial hyperplasia and mesothelioma. However, pancytokeratin stains may be useful to identify invasion (Fig. 27.4).
Although some have reported that p53 protein is frequently overexpressed by mesothelioma and not by reactive mesothelial proliferations (11–13), others have found otherwise (14–16). Moreover, studies using molecular biologic methods have revealed a low rate of p53 mutations in mesothelioma (16). Nonetheless, in an isolated case, strong nuclear immunostaining for p53 by the majority of the mesothelial cells supports mesothelioma over hyperplasia.
Some (17) have reported that GLUT-1, a member of the family of glucose transporter isoforms, may be a potential marker for distinguishing benign reactive mesothelium from malignant epithelial mesothelioma. They reported GLUT-1 expression in 100% of 40 mesotheliomas and in none of 40 cases of reactive mesothelium. Others (18,19) have not shown as robust results, and staining should be interpreted with caution.
Chiosea et al. (20) have reported that fluorescence in situ hybridization (FISH) analysis on paraffin-embedded tissue demonstrated the homozygous deletion of the 9p21 locus in 35 (67%) of 52 pleural mesotheliomas and in none of 40 cases of reactive pleural mesothelial proliferations. These results have been validated by others, and loss does seem to be specific for mesothelioma when compared to benign mesothelial proliferations (18). Immunohistochemical staining for loss of the p16 does not achieve the same specificity (20).
Other markers have also been suggested for distinguishing benign and malignant mesothelial proliferations, especially with cytology specimens that, by their nature, cannot demonstrate actual invasion. These include immunohistochemical staining for IMP3, desmin, XIAP, and EMA, among others (21).
Determination of DNA aneuploidy on serous effusions may serve as a marker for malignant cells. However, its usefulness to distinguish mesothelioma from carcinoma is controversial. El-Naggar et al. (22) compared the DNA flow cytometric characteristics of 23 epithelioid mesotheliomas and 41 pulmonary adenocarcinomas from paraffin-embedded blocks. They reported that 78% of the mesotheliomas were diploid versus a statistically significant 88% aneuploidy rate for the adenocarcinomas. Additionally, these authors found a significantly higher proliferative rate in adenocarcinoma than in mesothelioma. Similar findings were reported by Esteban and Sheibani (23). Thus, it would appear that the finding of a diploid tumor by flow cytometry favors a diagnosis of mesothelioma over adenocarcinoma. Pyrhönen et al. (24), by using fresh-frozen tumor samples, reported 16 (52%) of 31 mesotheliomas as diploid and found that the ploidy status was of no prognostic value in mesothelioma. Similar lack of prognostic value was reported by Dazzi et al. (25). Frierson et al. (26) studied effusion fluids and compared them with paraffin-embedded samples. They found a 53% rate of aneuploidy in mesothelioma and concluded that aneuploidy in an effusion specimen containing atypical mesothelial cells would strongly support a diagnosis of mesothelioma.
FIBROSIS AND PLEURAL PLAQUE
Chronic injury to the pleural surface may result in the formation of dense layers of scarlike tissue involving visceral as well as parietal pleura (see earlier discussion). Among causes of pleural fibrosis are asbestosis and other pneumoconiosis, inflammatory pleurisy including rheumatoid pleuritis, and, most commonly, bacterial pneumonias. Pleural fibrosis also may result from the intentional introduction of irritants (such as talcum powder) into the pleural cavity to promote therapeutic pleural fusion (pleurodesis).
A frequent area of diagnostic difficulty is the distinction between fibrous pleuritis and desmoplastic malignant mesothelioma, and this is now one of the most common requests to the United States–Canadian Mesothelioma Reference Panel (9). This difficult differential diagnosis will be discussed in some detail later.
These forms of pleural fibrosis should not be confused with pleural plaques, which are, in the vast majority of cases, caused by asbestos exposure (27,28). Pleural plaques arise over the parietal pleura particularly at the lower chest and the diaphragmatic pleura. Usually, they develop at least two to three decades after asbestos exposure. Grossly, they consist of well-delimited, irregularly shaped, raised, grayish-white to ivory plaques ranging to several centimeters in size. They have a cartilaginous consistency and often calcify. Microscopically, they consist of dense strands of virtually acellular, intensely hyalinized collagen fibers that feature a reticulated, meshlike appearance, a pattern that has been referred to as “basket weave” (Fig. 27.5). Pleural plaques are clinically silent but serve as a reliable marker of asbestos exposure. It has been shown that pleural plaques contain asbestos fibers (29–31).
ADENOMATOID TUMOR (BENIGN LOCALIZED EPITHELIAL MESOTHELIOMA)
Adenomatoid tumors of the pleura are exceedingly rare. The few that have been reported were found incidentally at lung resection for other conditions. Histologically, they were similar to the more common pelvic and peritoneal adenomatoid tumors (32–34).
Etiology, Incidence, and Pathogenesis
Since 1960, after pioneering studies on the incidence of mesothelioma in South African asbestos miners by Wagner et al. (35), the mesothelial carcinogenesis of inhaled asbestos fibers has been firmly established (36–42). Moreover, a correlation between the intensity and duration of exposure to asbestos fibers and the risk of developing mesothelioma is well documented (43,44). It also is evident, however, that some mesotheliomas, especially many of those occurring in young people, those in women, and those of the peritoneum, may not be related to asbestos exposure (45). The incidence of asbestos-related mesothelioma cases has ranged in different series from 10% to 99% (46). Although non–asbestos-related pleural malignant mesotheliomas undoubtedly exist, it remains difficult to determine their true incidence for two main reasons: (a) there is no defined threshold of exposure to asbestos fibers in relation to the development of mesothelioma (additionally, the issue of threshold is complicated by the possible effect of individual susceptibility ); and (b) there is a decades-long period of latency between the exposure to asbestos and development of the neoplasm (43,48). It was suggested (49) that even smaller exposures, such as that which may occur in the household, may be sufficient to induce mesothelioma. In a review of 668 cases of malignant mesothelioma, McDonald and McDonald (50) found that only 50% of the cases in men and 5% of the cases in women were associated with occupational exposure to asbestos. However, Vianna et al. (49) proposed that the wide variation in estimates of asbestos exposure in patients with malignant mesothelioma was a result of history taking.
Experimental and epidemiologic evidence suggests that other etiologic agents may be associated with mesothelioma as well (39,50–56). Such agents include radiation; minerals such as erionite, silica, and beryllium; and synthetic fibers, although evidence for the latter is far from conclusive (43). The finding of Simian virus 40–like DNA sequences (SV40) in some cases of human malignant mesothelioma suggested that the SV40 virus, which was a contaminant of some polio vaccines, may be implicated as a co-carcinogen or as directly causing mesothelioma (57,58). However, more recent studies report a low prevalence of SV40 in mesothelioma patients and suggest that earlier reports were a result of laboratory contamination (59). Of additional significance is the fact that several epidemiologic studies have failed to support an etiologic role of SV40 in mesothelioma (60–65). Finally, our understanding of genetic predisposition in the development of mesothelioma continues to evolve. Epidemiologic studies and reports of a number of kindreds have suggested that genetics plays some role in the development of some mesotheliomas (66–68). Recently, a familial cancer syndrome associated with germline mutations of BAP1 and the development of mesothelioma, uveal melanoma, and other cancers has been described (69–71).
Malignant mesothelioma is a rare tumor. McDonald and McDonald (50) estimated the combined United States–Canadian incidence to be 2.8 per million male and 0.7 per million female persons but then noted a steady increase in cases in men, which they attributed to occupational exposure to asbestos. A significant increase in the incidence of pleural mesothelioma among white men older than 55 years during the years of 1973 to 1980 was reported by Spirtas et al. (72) after a study of incidence rates based on data from population-based cancer registries in New York State (exclusive of New York City) and Los Angeles County (California) and the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute. In this study, even after histopathologic review, a notable upward trend remained. The tide has recently begun to change, however, and the incidence of pleural mesothelioma has started to decline in the United States (73).
The pathogenesis of malignant mesothelioma remains unclear. The presence of asbestos fibers in the vicinity of the serosal surfaces appears to be a crucial pathogenic factor. In both epidemiologic and experimental studies, differences in the tumorigenicity of asbestos fibers have been found, depending of the composition and physical characteristics of the fibers. Contributions of other factors (including heredity and exposure to other carcinogens such as tobacco smoke) to the pathogenesis of mesothelioma are not clear in most cases. Nonetheless, there is no compelling evidence that smoking increases the risk for the development of mesothelioma in asbestos workers (74).
Malignant mesothelioma of the pleura is at least three times more common in men than in women (50,75). Most cases occur in patients between ages 50 and 70 years. Chest pain and shortness of breath are the most frequent initial symptoms; these are followed by weakness, fatigue, and weight loss. Clinical signs of pleural effusion are by far the most common finding at the initial physical examination and, in some cases, may precede the development of clinically detectable mesothelioma by several years (76). Chest roentgenograms or computerized tomography will reveal irregular pleural thickening that is most apparent after evacuation of the pleural fluid. Irregular thickening of the interlobar fissures is another characteristic radiographic feature of pleural mesothelioma. In patients who have had significant exposure to asbestos fibers, the presence of pleural plaque will frequently be discovered by these examinations. The effusions, which often are bloody, tend to recur rapidly after evacuation, but with progressive obliteration of the chest cavity by the growing tumor, they may subside. There may be involvement of pericardium and mediastinum as well as invasion of the soft tissues of the chest wall, particularly at biopsy sites or at the location of chest tubes after surgery. Metastases are uncommon in the early stages of the disease, but they may be seen in later stages and are a frequent finding at autopsy. Rarely, cases of metastatic mesothelioma with initial presentation as lymph node metastases have been reported, although many of these have been peritoneal mesotheliomas (77).
Historically, the average survival time from the onset of symptoms is approximately 15 months, but much longer survivals have been reported (78,79). Patients with pure epithelioid mesotheliomas tend to survive longer than those with sarcomatoid mesotheliomas (75,80). The treatment of mesothelioma is generally ineffective. Surgery is of limited benefit for pleural mesothelioma, although extrapleural pneumonectomy and extended pleurectomy and decortication are advocated by some. Radiation therapy and intracavitary instillation of radioactive substances have not been shown to be effective other than for palliation (38,81,82). However, combinations of surgical resection, radiation, and chemotherapy have been found to prolong life in selected cases (83). Overall, the literature regarding treatment for pleural mesothelioma is hampered by the fact that true randomized controlled studies have not been performed in spite of the fact that therapies are often extremely morbid. It can be said that healthier patients with lower stage tumors tend to survive longer and tend to undergo more aggressive therapies.
Gross Findings. The gross appearance of mesothelioma depends on its stage at diagnosis. When diagnosed early, it appears as numerous small nodules or plaques extending over the visceral and parietal pleural surfaces. Later, confluence of the nodules results in a rindlike mass encasing and compressing the lungs. Usually, the tumor is thickest in the lower portions of the lung and over the diaphragm. At autopsy, invasion of the chest wall, lung, and mediastinum and distant metastases are common. The tumor may be firm, yellowish, and leathery, particularly in the desmoplastic variant, or it may be soft and gelatinous, especially in the poorly differentiated epithelioid types. In the latter, abundant foci of degeneration and necrosis are commonly seen at autopsy. The gross appearance of mesothelioma may be complicated by its intermingling with asbestos-related fibrous plaque.
Classification. Three major histologic types of diffuse malignant mesothelioma are described: epithelioid, sarcomatoid (fibrous), and biphasic (mixed); in each of these, cellular differentiation varies over a wide range. Diagnostic difficulties are presented by cases at all levels of differentiation. For example, well-differentiated epithelioid mesothelioma must be distinguished from reactive mesothelial hyperplasia, poorly differentiated epithelioid mesothelioma must be distinguished from metastatic undifferentiated carcinoma and other poorly differentiated malignancies, and epithelioid mesothelioma of intermediate degree of differentiation must be distinguished from pleural involvement by an adenocarcinoma of lung origin or from a distant metastasis from an adenocarcinoma arising elsewhere in the body. The distribution of the various histologic types varies from series to series, but usually epithelioid mesothelioma predominates. Because virtually all series are composed of consultation cases, they tend to underestimate the percentage of biphasic cases because these are easier to diagnose and less likely to require consultation.
Unusual Variants of Mesothelioma. Unusual variants include clear cell mesothelioma, a form of epithelioid mesothelioma that resembles metastatic renal cell carcinoma (84,85), and lymphohistiocytoid malignant mesothelioma, which mimics malignant lymphoma or other lymphoproliferative disorders (86,87). In these cases, immunohistochemistry is very helpful because the neoplastic cells express a mesothelial lineage immunophenotype. Another rare mesothelioma variant is the so-called deciduoid malignant mesothelioma, which is a large cell type of mesothelioma resembling exuberant ectopic decidual reaction. Although deciduoid mesothelioma is more commonly seen in the peritoneal cavity, cases have also been reported involving the pleura (88,89).
Localized malignant mesothelioma that is histologically and immunophenotypically indistinguishable from diffuse malignant mesothelioma has also been reported. These mesotheliomas exhibit a different biologic behavior than their diffuse counterparts, with many patients having a long survival after surgical resection (90,91).
Well-differentiated papillary mesothelioma (WDPM) is most commonly seen in the peritoneal cavity of women. It is characterized by papillary formations lined by bland epithelioid mesothelial cells with no or only superficial invasiveness. Like its peritoneal counterpart, WDPM of the pleura has an indolent clinical course (92,93).
Unusual Mimics of Mesothelioma. Infrequently, epithelioid vascular malignancies (hemangioendothelioma and angiosarcoma) involving the pleura may also enter the differential diagnosis with mesothelioma (see following discussion) (94–97). Thymomas arising from ectopic thymic tissues may rarely present as pleural-based tumors, occasionally with total encasement of the lung and clinically and macroscopically mimicking malignant mesothelioma. Histologically, they are indistinguishable from classical mediastinal thymomas (98,99). However, distinction from mesothelioma, particularly its lymphohistiocytoid variant, may be difficult on morphologic grounds alone, particularly with scant or fragmented biopsies. In these circumstances, immunohistochemistry can be very helpful because the epithelial cells express p63 and the lymphocytes show immunophenotypic features of T lymphocytes and express terminal deoxynucleotidyl transferase (TdT) (100,101). Synovial sarcomas, hematolymphoid malignancy, and other small blue cell tumors may also involve the pleura and can simulate mesothelioma clinically and histologically (see following discussion).
Histologic Features and Differential Diagnosis. The epithelioid type, if sufficiently differentiated, is characterized by predominantly papillary and tubular patterns of growth (Figs. 27.5 and 27.6). A variable proportion of solid growth, sometimes with a marked discohesiveness of the tumor cells, may be present in the less differentiated types and is the prevailing histologic pattern in poorly differentiated epithelioid mesothelioma (Fig. 27.7). The tumor cells are usually cuboidal, with a bulging, domelike apical portion, but may be flattened and rarely columnar. A common finding in well-differentiated epithelioid mesothelioma is the presence of single or multiple, sharply delimited, clear, round cytoplasmic vacuoles. These resemble those commonly seen in adenomatoid tumors and, under electron microscopy (EM), are identifiable as intracytoplasmic lumina. Because adenocarcinomas, epithelioid hemangioendotheliomas, and other neoplasms may contain intracytoplasmic lumina, this finding is of limited diagnostic value.
A brush border–like rim—corresponding to the abundant long microvilli seen by EM—may be seen on the free portions of the cell surfaces in thin sections of well to moderately differentiated epithelioid mesothelioma (Figs. 27.8 and 27.9). This is useful in distinguishing epithelioid mesothelioma from adenocarcinoma because the latter seldom has thick brush borders. Several immunostains to membrane-based marker molecules help to highlight this feature (Figs. 27.8, 27.10, and 27.11). Microcalcifications (psammoma bodies) may be seen, particularly in the tubulopapillary forms of epithelioid mesothelioma. They are of no diagnostic value.
Diffuse sarcomatoid mesothelioma (sarcomatoid or fibrous mesothelioma) is made up predominantly of malignant-appearing spindle cells growing in short fascicles within a variable amount of fibrous stroma (Fig. 27.12). A storiform pattern of growth and focal hemangiopericytoma-like patterns are not uncommon (Fig. 27.13). Although not frequent, multinucleated atypical cells may be present and may give the neoplasm an appearance resembling malignant fibrous histiocytoma. However, sarcomatoid mesothelioma may also be well differentiated, with the neoplastic cells having a bland cytologic appearance resembling reactive fibroblasts. Considerable amounts of collagenous stroma may separate the neoplastic cells (Fig. 27.14). Such well-differentiated sarcomatoid mesotheliomas may resemble fibromatoses and are often designated as the desmoplastic variant of malignant sarcomatoid mesothelioma (102). They differ from the fibromatoses in that their neoplastic cells consistently express cytokeratins. However, their distinction from reactive pleural fibrosis is often difficult, as discussed earlier. Sarcomatoid mesothelioma also may imitate solitary fibrous tumor, schwannoma, and other sarcomas (103).
The mixed type, also called biphasic malignant mesothelioma, is the most easily diagnosed. As the name implies, it consists of a mixture of epithelioid and sarcomatoid cellular components (Fig. 27.15). For this reason, it has often been compared with synovial sarcoma, to which, however, it has only a superficial resemblance. Nonetheless, synovial sarcoma may present as a pleural-based lesion and mimic mesothelioma clinically and morphologically (104,105). The epithelial component of synovial sarcoma is often mucicarmine positive and expresses several epithelial markers by immunohistochemistry (106). Additionally, the translocation t(X;18) (SYT-SSX) characteristic of synovial sarcoma is not found in sarcomatoid mesothelioma (107). Sarcomatoid carcinoma of the lung with pleural involvement, a rare occurrence, may also simulate biphasic mesothelioma. Such cases can be identified by appropriate use of immunohistochemical procedures (see following texts) (108).
Clearly, malignant mesothelioma exhibits a wide range of differential diagnoses, from metastatic carcinoma of various origins to several types of sarcomas, as well as benign reactive processes. Although some cases of mesothelioma are sufficiently typical to permit a relatively firm diagnosis based on routine morphologic examination, in a large proportion of cases, its diagnosis is often imprecise and prone to be controversial. It had once been correctly stated that interobserver variability was greater for the diagnosis of malignant mesothelioma than for most other human neoplasms (109). Thus, numerous ancillary procedures, in particular histochemistry, EM, and immunohistochemistry, have been used in an attempt to improve the accuracy of mesothelioma diagnosis. Certainly, the widespread access to specific and sensitive immunohistochemical markers has done much to improve this problem over the years.
Adequacy of Biopsy Material. Decades ago, many believed that autopsy was the only way to ascertain a diagnosis of mesothelioma. Currently, with adequate biopsy, a firm diagnosis is nearly always possible. In many instances of differential diagnosis between malignant epithelioid mesothelioma versus adenocarcinoma, a needle biopsy, if representative of tumor tissue, may suffice. Indeed, with the help of immunohistochemistry, it is now possible, in many instances, to diagnose malignant epithelioid mesothelioma based solely on small samples. However, distinguishing between reactive hyperplasia and epithelioid mesothelioma or between fibrous pleuritis and desmoplastic malignant mesothelioma often requires more extensive sampling, preferably using thoracoscopy or thoracotomy. This is so because demonstration of invasiveness can be of foremost importance in the differential diagnosis in these cases.
Ancillary Diagnostic Procedures. Because no single test is currently capable of providing an unambiguous confirmation of the histologic diagnosis of mesothelioma, such diagnosis must be based on the accumulation of evidence. Nonetheless, recent advances in immunohistochemistry have markedly improved the accuracy of mesothelioma diagnosis to the point of rendering many older tests obsolete.
Histochemistry. Histochemical stains, such as mucicarmine, periodic acid-Schiff (PAS), and Alcian blue, once considered useful for the distinction between epithelioid mesothelioma and adenocarcinoma, have been largely superseded by the more specific and sensitive immunohistochemical stains.
Electron Microscopy. Before recent progress in immunohistochemistry, EM was often used to distinguish between epithelioid mesothelioma and adenocarcinoma. The ultrastructural hallmark of epithelioid mesotheliomas consists of the presence of long, thin, branching “bushy” microvilli, devoid of a glycocalyx coating, over much of their free cell surface (Figs. 27.8 and 27.9).
Warhol et al. (110) attempted to establish objective criteria for the ultrastructural diagnosis of mesothelioma and concluded that only the length-to-diameter ratio of the microvilli and the abundance of tonofilaments were of diagnostic value. Adenocarcinomas have fewer and shorter microvilli than do mesotheliomas. Additionally, microvilli in adenocarcinomas are usually present only on the apical portion of the cell surface, whereas in mesothelioma, they tend to involve all free cell surfaces (Fig. 27.8). Burns et al. (111) found a median length-to-diameter ratio of 11.9 in mesothelioma and 5.28 in adenocarcinoma. However, overlapping cases create a relatively wide “gray zone.” Dardick et al. (112) emphasized that poorly differentiated epithelioid mesothelioma and sarcomatoid mesothelioma may show no evidence at all of such long microvilli. Moreover, practically all mesotheliomas exhibiting long, sinuous microvilli also have a typical mesothelioma immunophenotype and often reveal thick brush border staining with membrane-based markers.
Distinction of sarcomatoid mesothelioma from true sarcomas is also simpler and more accurate by immunohistochemical means than by EM. Thus, EM is no longer needed for the diagnosis of mesothelioma, although it remains an essential tool for the identification and quantification of asbestos fibers in lung and pleural tissue (29,113).
Immunohistochemistry. Immunohistochemistry has evolved into the most important ancillary procedure in the distinction of epithelioid malignant mesothelioma from its mimics. However, there is yet no consensus about which is the ideal antibody panel, and there still remain some discrepancies on how best to interpret some of these immunostains.
Not too long ago, most relied chiefly on the use of antibodies binding to molecules expressed predominantly by carcinoma cells such as carcinoembryonic antigen (CEA), B72.3, CD15, and others. Thus, the diagnosis of mesothelioma was based on negative results, an unsatisfactory situation. This dramatically changed with the introduction of antibodies of relative specificity for mesothelial cells (Table 27.1). As a result, rarely are cases left undiagnosed when a well-chosen immunohistochemical panel is used. Because none of these new markers is by itself sufficiently specific or sensitive, they need to be used within a diagnostic panel. Clearly, as the number of available markers—particularly those of mesothelial lineage—continues to grow, pathologists need to periodically reevaluate their antibody panels to keep them reasonably sized with no loss of accuracy.
It is important to remember that specificity in immunohistochemistry is a relative concept because it depends in great part on the differential diagnosis in any particular case. For example, a partially mesothelial-restricted marker, such as Wilms tumor gene product (WT-1), has a very high specificity when the differential diagnosis is between mesothelioma and adenocarcinoma of the lung in a male patient. However, when ovarian carcinoma enters the differential diagnosis, this marker’s specificity dramatically decreases as it is expressed by a large proportion of serous carcinomas. Thus, awareness of each marker’s limitations is fundamental to select the antibody panel most suitable to the differential diagnosis at hand.
CYTOKERATINS (KERATINS). Keratins comprise a family of at least 20 individually gene-coded filamentous proteins that are the dominant cytoskeletal filament of epithelial cells. Which member(s) of the keratin family is expressed depends on the type of epithelial cell. Neoplasms derived from different epithelia tend to express the same combination of cytokeratins as their cell of origin. Thus, the cytokeratin immunophenotype of tumors is sometimes used as an indicator of cell lineage.
The cytoskeletal phenotype of mesotheliomas closely resembles that of reactive and resting mesothelium. When broad-spectrum antibodies (pancytokeratin antibodies)—recognizing epitopes shared by multiple members of the keratin family—are correctly used, almost all mesotheliomas and adenocarcinomas immunostain strongly and diffusely. Therefore, the use of pancytokeratin antibodies is not helpful for distinguishing mesotheliomas and carcinomas. However, pancytokeratin antibodies are valuable in the diagnosis of sarcomatoid mesothelioma and to identify invasiveness, particularly in the desmoplastic type.
Many monoclonal antibodies (MoAbs) recognizing epitopes restricted to certain members of the keratin family are currently available. Among these, one binds to an epitope shared by cytokeratins 5 and 6 and is of diagnostic value for epithelioid mesothelioma in paraffin-embedded tissues. Although MoAbs to cytokeratins 7 and 20 may help to pinpoint the site of origin of metastatic adenocarcinoma, they are of little value in the differential diagnosis between adenocarcinoma and epithelioid mesothelioma.
VIMENTIN. Vimentin, the chief intermediate filament of mesenchymal cells, is now known to be expressed by a large proportion of epithelium-derived neoplasms (114). Thus, earlier publications claiming usefulness of the demonstration of vimentin for the differential diagnosis between adenocarcinoma and mesothelioma are now less valid. In fact, some have found that a majority of epithelioid mesotheliomas do not express vimentin or do so minimally (115). However, vimentin, using clone V9 without antigen retrieval, is a useful universal control to detect overfixation and other types of antigen damage (116).
Mesothelial Markers (Positive Markers). This group consists of antibodies that bind to epitopes of molecules expressed mainly by normal mesothelial cells and their tumors. These antibodies should thus be regarded as markers of mesothelial lineage rather than as mesothelioma markers. As already stated, none of these is sufficiently specific or sensitive; thus, they need to be used within a diagnostic panel.
CALRETININ. Calretinin, a calcium-binding protein in the family of S-100 protein, was initially found to be present in central and peripheral neural tissues. Later, it was also found in adipocytes, renal tubular cells, Leydig and Sertoli cells, eccrine glands, and mesothelial cells (117,118). As is the case with S-100 protein, it is localized in both cytoplasm and nuclei (Figs. 27.6 and 27.16). Doglioni et al. (117) reported calretinin to be expressed by normal mesothelial cells and mesothelioma and rarely by adenocarcinoma. Several studies have confirmed a high sensitivity of this marker for epithelioid mesothelioma, while uncovering its expression by a small fraction of adenocarcinomas (119–121). However, although mesotheliomas usually immunostain strongly and diffusely, in the few positive adenocarcinomas, the staining tends to be weak and focal.


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Local and international bodies are mounting pressure on President Goodluck Jonathan to urgently look inwards and fashion out solutions to the challenges posed by the activities of the Boko Haram sect in the North-east of the country.
The Nigerian Labour Congress (NLC) described the recent massacre of defenseless students in Yobe state and the routine decimation of communities in Borno and Adamawa states as “un-acceptable”.
International rights group, Human Rights Watch (HRW), and the Nigerian Bar Association (NBA) have also condemned the recent attacks in the region.
While warning that the NLC will not be an indifferent by-stander while Nigeria’s territory is being ceded away and scores of innocent lives and priceless property are being wasted on a daily basis, the body’s leadership disclosed that it is planning a mass protest against insecurity in the country.
The NLC, in a press statement signed by its President, Abdulwaheed Omar, said the massacre and routine decimation of communities in the states brought to the fore the gory reality of the new phase of war on terror.
“The attacks on Buni Yadi, Michika, Madagali and Shuwa, in Yobe, Adamawa and Borno States respectively were more audacious as the terror elements were said to have moved in murderous convoys of Hilux, chanting war songs in broad day light, killing, pillaging and daring any one to challenge them. Distress calls to our security forces were said to have elicited no reaction”, the statement pointed out.
“We at the Nigeria Labour Congress are shocked by this brazen and ferocious savagery and saddened by the seeming helplessness of our security forces. The earlier successes of the declaration of emergency seem to have petered away, giving room to despair”, the statement said.
“What could have been responsible for these painful reversals? Are the insurgents getting better organised, armed or funded? Have inter-agency and service rivalries worsened? Are security votes drying up or are they being mis-applied? Are our forces sufficiently and adequately armed and motivated?”, the NLC asked.
The labour union continued: “Where is our Air Force? What has happened to our satellites? What is the role of Cameroun in all this? Is 2015 part of this war? Who ordered the withdrawal of security forces before the attack on helpless students? Who and what prevented our troops from responding to distress calIs? Is this a prelude to the removal of opposition civilian governors?
“Accordingly, and consistent with our peace initiative last year christened Peace Summit, we shall mobilise our members to the streets to protest these massacres and the questionable responses of our security forces,” Omar declared.
Similarly, Ms Mausi Segun, Nigeria Researcher, HRW, in an electronic mail sent to newsmen yesterday urged the federal government to bring the perpetrators to justice.
“Human Rights Watch calls on the Nigerian Government to urgently take steps to protect the lives of citizens in vulnerable communities in the North-east and to rescue the scores of girls taken captive by the insurgents in the past few weeks.
“These measures must be carried out in ways that do not further jeopardize the rights and safety of members of those communities.
Furthermore, all those most responsible for these horrific crimes must be brought to justice as soon as possible,” Segun said.
In another development, Mr. Onyekachi Ubani, Chairman of the Ikeja branch of the NBA, has urged the government to change its strategies in tackling the insurrection.
But, Minister of Information and supervising Minister of Defence, Mr. Labaran Maku, has called for more cooperation from the public in the fight against terrorism.
Maku made the call in Lagos at the 30th Memorial of the founder of The Punch newspapers, Chief James Aboderin, Saturday night at the Intercontinental Hotel, Victoria Island, Lagos.
“To defeat insurgency is for every citizen to cooperate. For example, you ought to know the movement of people in your village and if you see suspicious movement you should communicate immediately to security agents.
“If you are in urban area and a stranger comes into your compound, maybe it’s a tenant, you need to find out what time he goes out and what time he comes in, who are those visiting him what he does for a living.
“All those questions have become very important today because if you keep quiet and do not cooperate, you will find out that everybody is the enemy of terrorists; nobody is immune. So, it is important for state governments particularly to coordinate public information gathering”, he said.
Meanwhile, Senate President David Mark, in a statement issued by his Chief Press Secretary, Paul Mumeh, while reacting to the latest attacks on Michika in Adamawa and Maiduguri in Borno at the weekend, said the dimensions of the renewed attacks have gone beyond human comprehension.
“With cooperation and support of the citizenry, we can salvage the situation”, he assured.
In a related development, Mark has reiterated the call for death penalty against kidnappers, insisting that this is the only way to discourage the ugly trend in the country.
Speaking at St Mark’s Catholic Church, Abagana, in Anambra state, during the funeral church service of late James Emeka Iloenyosi, who died in the hands of kidnappers, Mark submitted that the perpetrators of the evil act do not deserve to live among normal human beings.
“It is a big challenge to all of us. Government is there to take responsibilities, but the community cannot absolve herself of basic responsibilities. These kidnappers live among us. It is therefore incumbent on community leaders to fish them out. Today, it is Chief Iloenyosi, who knows the next victim tomorrow”, he asked rhetorically.
“If a traditional ruler like Chief Iloenyosi is kidnapped and died in the hands of his abductors, then who is safe in this community? That is why everybody must vow to say enough is enough and no more to kidnapping in Anambra state”, he said.
However, the Northern States Governors’ Forum (NSGF) has assured Nigerians, especially those living in the troubled North-east states, that a lot was being done to guarantee peace in the area.
Chairman of the forum and governor of Niger state, Dr. Mu’azu Babangida Aliyu, in a statement, urged all stakeholders to continue to pray to God to end the scourge of the senseless killing of defenceless citizens.
The statement, signed by his spokesman, Danladi Ndayebo, in Minna, yesterday, urged the perpetrators of the dastardly acts to lay down their arms and embrace dialogue.
“The Forum deeply regrets this utterly heinous descent to new depths of terror by the perpetrators at a time when security agencies are doing their best to put an end to it,” the statement said.
The NSGF chairman urged members of Boko Haram to embrace dialogue, assuring them that “the surest way to resolve grievances is through dialogue and not violence”.

domain: sociology


Cabinet Office Minister Michael Gove confirms that the government's "stay at home message" has been scrapped.
He said: "We want to see more people back at work on the shop floor, in the office, wherever they can be."
Gove also added: "I think we should do everything we can to encourage people and support people to wear face masks in enclosed places."
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ERIC Number: EJ1065242
Record Type: Journal
Publication Date: 2014
Abstractor: As Provided
A Behavior Analytic Approach to Exploratory Motor Behavior: How Can Caregivers Teach EM Behavior to Infants with Down Syndrome?
Bauer, Sara M.; Jones, Emily A.
Infants and Young Children, v27 n2 p162-173 Apr-Jun 2014
Impairment in exploratory motor (EM) behavior is part of the Down syndrome behavioral phenotype. Exploratory motor behavior may be a pivotal skill for early intervention with infants with Down syndrome. Exploratory motor impairments are often attributed to general delays in motor development in infants with Down syndrome. A behavior analytic perspective suggests a model that integrates environmental and biological variables in explaining EM development. We propose that Down syndrome is a setting event that changes the value of consequences associated with EM behavior and the likelihood that an infant with Down syndrome will engage in EM behavior. On the basis of this approach, we then outline intervention strategies that caregivers can use to improve EM behavior in infants with Down syndrome.
Descriptors: Behavior Modification, Psychomotor Skills, Caregivers, Down Syndrome, Physical Disabilities, Early Intervention, Infants, Environmental Influences, Genetic Disorders, Child Development, Infant Behavior
Lippincott Williams & Wilkins. Available from: Wolters Kluwer. 351 West Camden Street, Baltimore, MD 21201. Tel: 800-638-3030; e-mail: MR-WKCustomerSupport@wolterskluwer.com; Web site: http://www.lww.com
Publication Type: Journal Articles; Reports - Descriptive
Education Level: N/A
Authoring Institution: N/A

domain: medical


NOTE: Valley Metro is finalizing details on a new service model that will provide Dial-a-Ride passengers valley-wide with standardized regional fares and more service options. The new service model will go into effect on July 1, 2017. The city will share information about changes to the program as they become available.
Dial-A-Ride is available to each and every resident of Surprise and has the capability of transporting wheelchair clients. This service is provided by Valley Metro, through a contract with Discount Cab. For more information, see the Dial-A-Ride website or call 602-266-8723
The City’s Park & Ride facility is located on Bell Road, just east of Grand Avenue at 13327 W Bell Rd. It features 230 car spaces (216 covered) and 3 bike racks. Park free and take a Valley Metro bus to your final destination!
Bus, ride share and light rail service provided by Valley Metro. Visit the Valley Metro web site for bus fare information, schedules, transit maps, transit center locations, park and ride locations and more...
Title VI Info
The City of Surprise is committed to ensuring that no person is excluded from participation in, or denied the benefits of its transit services on the basis of race, color, or national origin, as protected by Title VI in Federal Transit Administration (FTA) Circular 4702.1.A. Click here for more info...


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This gorgeous blanket is just for me! It’s my lounge blanket. I am loving it! It
These past few months, with a group of friends, I have been making blankets that are
Hello! Wow, just a few days until Christmas, how exciting! I love Christmas ☺ I didn’t
October was a really busy month for me. I had several orders to make, plus I
Good evening! It’s been a busy day so I am writing this as I crochet in
September was a very busy month for me; I had a lot of orders to complete.

domain: artistic


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Total Credits: 1 including 1 Personnel/Human Resources - Non-technical
Discover a new way of thinking regarding diversity and inclusion in the workplace that helps to position D&I as part of a company or organization’s culture. Strategies and approaches will be shared that put the focus on promoting a culture of inclusion, empathy and compassion to ensure company-wide, long-term integration and sustainability of diversity and inclusion practices.
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With more than 25 years of progressive experience in communications, community relations, corporate giving, and diversity and inclusion, Bridget Hurd has worked in the health care industry helping to facilitate stronger linkages among the community and health care institutions and fostering a culture of inclusion in the health care community and among employees.
Ms. Hurd is the Chief Diversity Officer and vice president, Diversity and Inclusion, at Blue Cross Blue Shield of Michigan where she is responsible for leading and executing the corporate diversity and inclusion strategy and shaping a BCBSM culture of inclusion that emphasizes the recognition, understanding, and acceptance of the differences and similarities in people and that is culturally competent in providing services to its members and customers. She facilitates the Diversity Leadership Council and oversees diversity and cultural competency learning opportunities for employees and 10 employee resource networks. Ms. Hurd is also responsible for leading the Health Disparities Action Team focusing on systemic approaches to addressing health and health care disparities. She also cultivates strong stakeholder relationships and partnerships in diverse and ethnic communities. Ms. Hurd currently represents Blue Cross on the Michigan Coronavirus Task Force on Racial Disparities, appointed by Governor Gretchen Whitmer in April 2020. She is a recipient of the DentaQuest 2020 Health Equity Heroes award which recognizes the work of individuals working to achieve equity during this time of coronavirus.
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New low on Goat Simulator today in GamersGate's 2nd PC Gaming Summer sale. Previous low was $6 back in early July, but since has been a $10 game.
The extremely realistic physics game Goat Simulator dropped 40% today at GameFly in their Indie-Pendence day sale - a new low for the game by $2.
For some reason GameFly's 25% off coupon is now working on titles under $10. Notably, this slashes the price on the popular/zainy Goat Simulator down to $7.49 - the lowest price ever.
Yesterday's release Goat Simulator is still 20% off w/ coupon at GMG. Surprising that the coupon works on titles under $10.
Your LOL deal of the day is Goat Simulator at GMG. The game released just today and GMG's April Fools random discount coupon is currently taking 22% off. Surprising that the coupon works on titles under $10.
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domain: game


You shouldn't need much convincing to watch a film from Gattaca's Andrew Niccol. The trailer for In Time debuted at Comic-Con last week and shows Justin Timberlake in what could be a true breakout role for him. The Friends with Benefits actor stars alongside Amanda Seyfried in the dystopian sci-fi thriller that finds the masses dying at age 25 – unless they can buy more time to save their lives. Access Hollywood has provided a new trailer, which features additional footage surrounding Olivia Wilde as Will Salas' (Timberlake) mother. Check out both clips below.
Some low-res images from Ridley Scott's one-time Alien prequel, Prometheus, have showed up online courtesy of Dread Central. The images come from Comic-Con and an anonymous reader who took some snaps off the screen in San Diego. You can catch a glimpse of stars Charlize Theron, Noomi Rapace, Idris Elba, Logan Marshall-Green, Ben Foster, and Michael Fassbender in what appears to be a teaser trailer that we'll be likely to see closer to the June 8, 2012 release date.
Prometheus will follow a team of scientists and explorers on a journey that will " … test their physical and mental limits and strand them on a distant world, where they will discover the answers to our most profound questions and to life’s ultimate mystery." The 3D movie – which isn't sure if it wants to be PG-13 or R-rated just yet – stars Theron as the head of the Weyland-Yutani corporation, while Rapace will play Dr. Elizabeth Shaw (being compared to Ellen Ripley's character). Marshall-Green is Shaw's love interest, Elba stars as Captain Janek, and Fassbender plays an android (where can I buy one?).
[Images removed by request]


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Several molecules, including growth factors and cytokines, produced by endothelial cells and by other cells within the vicinity of the capillary network, regulate apoptosis and angiogenesis. Impact of IL28B and PNPLA3 polymorphisms on treatment outcomes in patients infected with genotype 6 hepatitis C virus. A law of mutation: power decay of small insertions and small deletions associated with human diseases. From lysosomes to cells, from cells to Leishmania: amino acid esters as potential chemotherapeutic agents. Progeny of hens that had been vaccinated at 1 and 3 or 2 and 4 weeks of age with chi3985 were used to determine the effect of maternal immunity on vaccine efficacy.
Optimization for Service Routes of Pallet Service Center Based on the Pallet Pool Mode. Validation and application of a rapid in vitro assay for assessing the estrogenic potency of halogenated phenolic chemicals. Capillary electrophoresis (CE) is one of the suitable separation techniques used to analyze drugs or metabolites in complicated sample matrices such as plasma, serum and urine. A 42-year-old man with a rare huge primary cardiac hemangioendothelioma that arose from the right atrium is reported.
The formation of uric acid is accompanied by an enhanced synthesis of reactive oxygen species which play a significant role in tissue damage. Comparison of the proliferation and differentiation ability between adult rat retinal stem cells and cerebral cortex-derived neural stem cells. It was performed in Isfahan and Najafabad counties (intervention area) and Arak county (reference area), all in central Iran. Between the GPA levels of 3.0 and 3.8, the chance of acceptance increased by a factor of buy viagra online about two for each increment of .2 in the GPA. Differential cytokine expression in skin graft healing in inducible nitric oxide synthase knockout mice.
Here we report on studies investigating the molecular basis of the inherent propensity of the milk protein, kappa-casein, to form amyloid fibrils. elegans and plays a crucial role in the control of buy viagra online molting through LRP-1 internalization and cholesterol traffic. Oxidized low-density lipoproteins (oxLDLs) play an important role in the progress of atherosclerosis. A series of alkyl/aryl/heteroaryl piperazine derivatives (37-54) were designed and synthesized as potential anticonvulsant agents. Fc epsilon RI is a tetrameric receptor, composed of a ligand recognition subunit, alpha, a beta chain, and dimeric gamma chains. Cardiac vagal activity following three intensities of exercise in humans.
The te st was quick, simple and available, which is suitable for early and specific clinical diagnosis, and will be greatly significant to clinical treatment. A time/code division multiple access protocol is adopted for conflict-free communications, where packets are transmitted in repetition of fixed-length time-slots with specific codes. Effects of three different training modalities on the cross sectional area generic cialis cost of the lumbar multifidus muscle in patients with chronic low back pain. Moreover, in the less favourable environment of the southern regions, selection is still sex-specific. The afferent volley effectiveness was estimated by the firing index of a motoneuron.
sobria should be considered as the pathogen of peritonitis in PD patients who have history of wounds from contaminated water. The histological findings were generic cialis cost characteristic of hemangiopericytoma. Human GDNF cDNA with Kozak sequence was cloned by RT-PCR, and then was transfected into SH-SY5Y cell line of human neuroblastoma. To this end, preclinical simian immunodeficiency virus (SIV)-based nonhuman primate immunization regimens have been designed to evaluate and enhance antibody-mediated protection.
Compound 12 is proposed as the reactive intermediate generated by the reaction of 2 with stannic chloride. We report two cases of pancreatic cancer with both biliary and duodenal obstructions treated successfully with simultaneous duodenal metal stent placement and EUS-CDS. Basic features of the national policy–and the core program and administrative infrastructure of the OAA–may serve as a model to meet the special challenges of child and family services. Extinction of conditioned fear requires consolidation of new memories that compete with fearful associations. The prevalence of depression in the elderly is high and remains high into old age, perhaps due to increased functional disability. The findings suggest that direct contact with patients and generic cialis cost handling of blood and other body fluids are risk factors related to occupational infection with HBV.
It has been proposed that these cellular effects could be linked to its ability to cause hyperacetylation of histone through the inhibition of histone deacetylase. Surgical treatment is the front line therapy for IE and IIE1 stages of primary gastric lymphoma. Two pigeons were trained with positive reinforcement on a multiple FR VI 2 schedule. Changes were compared with the clinical and biochemical features of buy viagra online the patients studied.
Although the need for counseling is as constant as any need facing the supervisor, a number of commonly encountered barriers often prevent effective counseling. Recurrence, pain, infection, return to full function and associated complications were assessed at 24 h, 1 and 6 weeks, and 1 year. We could not find any morphological feature on baseline MRI that predicted later onset of ICB. Therefore, hormone therapy should be avoided in patients who became symptomatic. Serum estradiol 17-sulphate and lipid peroxides in late pregnancy.
Roots of maize (Zea mays L.) seedlings continue to grow at low water potentials that cause complete inhibition of buy viagra online shoot growth. In the present study, FVB/N mice were exquisitely sensitive to injection of KA at all doses, while susceptibility in C57BL/6 mice was dose dependent. Audit is essential to monitor and improve performance in clinical practice. Osteoblasts on the films are observed to attach, proliferate, and grow in good state, and have good alkaline phosphatase activity. We show that Grp78 is present on the surface of endothelium and monocyte/macrophage-like cells in atherosclerotic lesions. Physical activity, quality of life, weight status and diet in adolescents.

domain: literature


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Although spanning motion graphics, identities, web design, animation, art direction and everything in-between, design studio Golgotha’s work is some of the most visually succinct (and striking) we’ve seen in a long time. Based in Paris, the studio was started in 2013 by Guillaume Hugon, Marvin De Deus Ganhitas and Antoine Aillot and has built up a portfolio that is loud and buoyant, not to mention impressive.
Guillaume, Marvin and Antoine studied graphic design together at École Nationale Supérieure des Arts Décoratifs in Paris and, initially, Golgotha was the trio’s band name. “We played around with ‘veejaying’ by using basic 3D tools for parties and shows. This mainly brought us into the video world and we had fun mixing 3D and motion with the usual 2D design tools,” they recall. “With the 3D tools, we felt like there was an infinite creative world of possibilities opening just in front of us. It was very exciting!”
From here, the studio – whose name is inspired by “extreme death metal band names” and is also the place that Jesus was crucified – was born. Years later, Golgotha has developed a strong and distinctive visual language, largely characterised by its busy aesthetic and attention to detail.
This meticulous approach can be seen in one of Golgotha’s projects for the release of Nike’s VaporMax. Tasked with creating a video around the theme of the city, the trio explains how “of course, we imagined a rollercoaster style looping video with lots of details and small elements you can not even see on the screen because of the speed.” With the shoe at the centre, the video whizzes through multiple worlds packed full of flying objects. “We even 3D scanned ourselves, rigged and animated our virtual bodies to run inside the scene,” Guillaume, Marvin and Antoine reveal.
Although clearly proficient in new technologies, Golgotha got to flex their muscles with more traditional animation and character design when creating the video for Ground Zero’s spring/summer 2017 collection. With a cast of virtual heroes, the video is a refreshingly different take on a fashion film, feeling straight out of a Saturday morning cartoon.
Whether creating highly fabricated visuals inspired Pokémon and Dragon Ball Z or working with live action footage, Golgotha’s daring and almost gaudy designs are impossible to ignore. Despite having such a characteristic visual language, the studio explains how, “we don’t think about how to fit into a style or specific signature, everything comes very naturally,” concluding that, “Golgotha is permanently the result of our three minds.”
- Stefanie Gutheil uses oil paintings to explore the masks we wear to fit in
- “I have to print or photograph something ‘real’”: Kai Udema on his approach to design
- Haein Kim reimagines fleece as a symbol of maternal love in her latest animation
- How Netflix's Klaus is bringing hand drawn 2D animation back to the big screen this Christmas
- Sophie Williams shares intimate behind-the-scenes footage from Mura Masa's latest music videos
- Wide-eyed and scratchy-haired, read the twisted diaries of Irene Montemurro
- Pentagram rebrands Warner Bros. with a “sleek and clean” update to its shield logo
- Manchester Girls, the new series from Dean Davies, is a visual homage to the women of the north
- Relive the lazy, hazy, crazy days of summer through Summer of Something Special
- Viktor Hübner photographs American anxieties amongst a shifting political environment
- Jiří Makovec’s photographs meander between the personal and the universal
- Berlin Wall graffiti is made into a typeface to warn how "division is freedom's biggest threat"

domain: design


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113 Museums to explore in Italy
Located in Southern Europe consisting of a peninsula delimited by the Alps and surrounded by several islands.
The Accademia Gallery is Florence’s most visited museum right after the Uffizi Gallery. The original statue of Michelangelo’s famous David actually has made the Accademia the most popular museum in Florence. It also has other sculptures by Michelangelo and a large collection of paintings by Florentine artists, mostly from the period 1300–1600, the Trecento to the Late Renaissance. In 2016, it had 1.46 million visitors, making it the second most visited art museum in Italy, after the Uffizi.
The archaeological park of Urbs Salvia is a state archaeological area located in the municipality of Urbisaglia. It is the largest archaeological park in the Marche. The excavation area owned by the Italian State, since 1998 has been granted under management to the Municipality of Urbisaglia, which is also the site of museum, musical and artistic events. In 2015 it registered 8 239 visitors.
The term " Grotte di Catullo " identifies a Roman villa built between the end of the 1st century BC and the 1st century AD in Sirmione, in the province of Brescia, on the southern shore of Lake Garda. The archaeological complex, part of which, especially in the northern sector, which has always remained insight, has been the subject of scholarly visits and speculations since the 15th century, is today the most important testimony of the Roman period in the territory of Sirmione and is the exampl
The Bagatti Valsecchi Museum is a historic residence located in the Montenapoleone district, in the center of Milan. "Palazzo Bagatti Valsecchi", which houses the museum, was purchased by the Lombardy Region in 1975 and is one of the most important and best-preserved museum houses in Europe. Since October 2008 it has been part of the " Case Museo di Milano " circuit.
The Bargello Museum is located in the impressive Palazzo del Bargello, a fortress with powerful embattlements which surround the austere facade. Begun in 1255, the building was the headquarters of the Capitano del Popolo and later of the Podestà and Council of Justice. In 1574, it became the living quarters for the Captain of Justice (chief of police) and was used as a prison.
The renowned state museum in Rome distinguished for its collection of Italian Baroque paintings and ancient sculptures. It is located in the Borghese Gardens on the Pincian Hill and is housed in the Villa Borghese, a building designed by the Dutch architect Jan van Santen (Giovanni Vasanzio) and built between 1613 and 1616. It houses a substantial part of the Borghese collection of paintings, sculpture, and antiquities, begun by Cardinal Scipione Borghese, the nephew of Pope Paul.
Ca' Rezzonico is a palazzo on the Grand Canal in the Dorsoduro sestiere of Venice, Italy. It is a particularly notable example of the 18th century Venetian baroque and rococo architecture and interior decoration, and displays paintings by the leading Venetian painters of the period, including Francesco Guardi and Giambattista Tiepolo. It is a public museum dedicated to 18th-century Venice and one of the 11 venues managed by the Fondazione Musei Civici di Venezia.
The Capitoline Museums are the main civic museum of the city of Rome. The historical seat is constituted by the Palazzo dei Conservatori and the Palazzo Nuovo. The two buildings are located on the Campidoglio Square remodeled following the design of Michelangelo and are linked by the Galleria Lapidaria, an underground passage that crosses the Campidoglio Square without having to go outside the museums.
Casa Santi or Rafael's Birthplace is a museum in the city of Urbino. It belongs to the Historic Center of Urbino, declared a World Heritage Site by Unesco in 1998. The house where Raphael was born in 1483 was built in the 14th century and, since 1460, Giovanni Santi, father of the famous painter, who was himself a painter and poet, lived there. In 1637 the building was acquired by Muzio Oddi, a local architect; and in 1837 it became the headquarters of the Rafael Academy.
Castel Nuovo, also called Maschio Angioino or Mastio Angioino, is a historic medieval and Renaissance castle, as well as one of the symbols of the city of Naples. The castle dominates the scenic Piazza Municipio and is the seat of the Neapolitan Society of Homeland History and of the Naples Committee of the Institute for the history of the Italian Risorgimento, housed in the premises of the SNSP. The civic museum is also located in the complex.
The castle of Gradara is the complex that stands on the top of a hill in the municipality of Gradara, in the province of Pesaro and Urbino, in the Marche region, consisting of a medieval castle - fortress and the adjacent historic village, protected by a outer wall that extends for almost 800 meters, making the entire structure imposing. Over time, the castle has progressively become one of the most visited monuments in the region and is the scene of museum, musical and artistic events.
The Castello di Rivoli Museum of Contemporary Art is home to the Museum of Contemporary Art housed in a building of historical interest located, a Unesco World Heritage Site in Rivoli, about 15 km west of Turin, in Piedmont. It was the former Residence of the Royal House of Savoy in Rivoli. which was built in the 9th–10th centuries.
The Fantiscritti quarries are white marble quarries located in the municipality of Carrara . The whole, now a museum, was created forty years ago by Walter Danesi. There is a railway station built for the line of the Carrara Private Marble Railway . It houses a "Museum of the quarries" and is often a stage and scenery for artists' exhibitions.
The house of Christopher Columbus in Genoa is the reconstruction of the building in which Christopher Columbus lived in his youth. Today used as a historic museum of the Municipality, the house is located a short distance from the Porta Soprana, just outside the ancient medieval walls. Historical documents have made it possible to ascertain that the navigator lived there in the lapse of time included - indicatively - between 1455 and 1470.
This tall structure halfway down Via dei Calzaiuoli looks more like a Gothic warehouse than a church—which is exactly what it was, built as a granary/grain market in 1337. On the ground floor of the square building are the 13th-century arches that originally formed the loggia of the grain market. The second floor was devoted to offices, while the third housed one of the city's municipal grain storehouses, maintained to withstand famine or siege.
One of the oldest museums in Italy, and it is devoted to art produced in the last two centuries. It was opened to the public in 1863, and it keeps over 40.000 pieces, among paintings, sculptures, installations, drawings, and engravings. Particularly important is the film and artistic videos collection, one of the most famous in Europe.
The Civic Museums have been housed since 1936 in the headquarters of Palazzo Mosca, former residence of one of the most important families of the Pesaro nobility. The displays occupy five halls in the first floor, and include works from diverse centuries. Among the Renaissance works is the large altarpiece, called the Pesaro Altarpiece or Pala di Pesaro, depicting the Coronation of the Virgin (1475) by Giovanni Bellini. It was originally located in the church of San Francesco, Pesaro.
The Correale Museum of Terranova is an archaeological museum, art gallery, and art gallery in Sorrento: in its interior furniture of the XVII century, paintings ranging from the fifteenth to the nineteenth century, archaeological and porcelain, especially of the Capodimonte school. The museum exhibits collections of Neapolitan painters dating from the 17th and 18th century. It contains valuable Capodimonte and Sèvres ceramics, Murano glassware, Bohemia crystals, and a collection of watches.
D'Albertis Castle is a historical residence in Genoa, north-western Italy. It was the home of sea captain Enrico Alberto d'Albertis and was donated to the city of Genoa on his death in 1932. It currently houses the Museo Delle Culture del Mondo. IT was built in the gothic revival style and The Museum displays furniture, décor, ethnographic, and archaeological finds collected by Enrico and Luigi Maria d'albertis during their trips to Africa, America, New Guinea, and Oceania.
A dazzling pink and white marble design and has been described - fairly accurately - as an oversized wedding cake. Much of the present building dates from the 15th century – although an earlier building on the spot may date back to the 9th century - and has been rebuilt and added on to several times. The palace was the residence of the Doge of Venice, the supreme authority of the former Republic. It was built in 1340, and extended and modified in the following centuries. It became a museum in 19

domain: geography


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Charming coffee table book published by our Historic Preservation Committee to tell the stories about the historic homes and heritage oaks in our community. (hardcover)
A comprehensive coffee table-worthy book on the history of the Diablo Country Club. Written by resident historian David Mackesey. (hardcover)
Jim Stone, Diablo's original historian, tells the history of Diablo from 1912-1990s through reflections and recollections of past residents. (hardcover)
A 1980s tell all by the late Arnold Blackmur that tells the social history of Diablo. (paperback)
Diablo residents chip in annually toward beautification, community connection and historic preservation
Double your $150 annual contribution and receive a flag you can keep to raise on patriotic holidays as a thank you gift.
Purchase your own flag to hang and celebrate our amazing community!
A PDF of our directory is distributed annually via email to all residents. Printed copies available upon request.
PROCEEDS BENEFIT THE DIABLO PROPERTY OWNERS' ASSOCIATION


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This article is free to access.
Background: Sudden death in the young is a tragic complication of a number of medical diseases. There is limited data regarding the utility of post-mortem Magnetic Resonance (MR) imaging and Computer Tomography (CT) scanning in determining the cause of sudden death. This study sought to compare the accuracy of post-mortem cross-sectional imaging (MR and CT) with the conventional autopsy in determining the cause of sudden death in the young. Methods. Consecutive patients from 2010 to 2012 (aged 1-35 years) who had sudden death were included. Patients were scanned by CT and 1.5 T MR imaging prior to the conventional autopsy being performed. The primary outcome was diagnostic congruence between imaging and conventional autopsy. Results: In 17 patients studied, the mean age at death was 23 ± 11 years, with a male predominance (n = 12; 71%). The most common cause of death was a primary cardiac pathology (n = 8; 47%), including ARVC (24%) and ischemic heart disease (12%). Non-cardiac causes identified included pulmonary embolism (6%), and aortic dissection (6%). MR imaging correctly identified the diagnosis in 12 patients who subsequently had positive findings at conventional autopsy, while the diagnosis in the remaining 5 cases remained unexplained. MR imaging was found to be highly sensitive (100%) with a high negative (100%) and positive (80%) predictive value. Conclusions: Dedicated post-mortem MR imaging of the heart and brain is a useful modality in determining the cause of sudden death in children and young adults, particularly in situations where a conventional autopsy cannot be performed for logistic, cultural or personal reasons. © 2014 Puranik et al.; licensee BioMed Central Ltd.
Puranik, R., Gray, B., Lackey, H., Yeates, L., Parker, G., Duflou, J., & Semsarian, C. (2014). Comparison of conventional autopsy and magnetic resonance imaging in determining the cause of sudden death in the young. Journal of Cardiovascular Magnetic Resonance, 16(1). https://doi.org/10.1186/1532-429X-16-44


Our kid is back with his third solo record. Wow! Where did the time go?
C'mon You Know showcases much more diversity of style than I would have expected. I mean, we all know what Liam does and he does it well. But check out this track.
Sure, it sounds like Liam when he sings (no one else sounds like him) but the music has a definite hip-hop vibe.
This track sounds like it could have been on Standing On The Shoulder of Giants.
And, of course, we have vintage Liam (aka my favorite track on the record)
This album is his strongest yet. Go buy it!
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Examples of physiology in a Sentence
She took a course in anatomy and physiology.
the physiology of diseased plants
Recent Examples of physiology from the Web
One of three Americans who share the 2017 Nobel Prize in physiology or medicine is a Kansas City native.
Reach Bryant Stamford, a professor of kinesiology and integrative physiology at Hanover College, at firstname.lastname@example.org.
Frykholm’s team analyzed physiology and gastric emptying rates and found that a half-hour safety margin after drinking clear fluids was enough to circumvent rates of aspiration.
Even stranger, this fall in relative humidity may be mediated by plants, which have already changed their physiology in response to our newly high-CO2 world.
The 1952 medicine and physiology prize went to Selman Waksman for the discovery of the antibiotic streptomycin, and ignored Waksman’s graduate student Albert Schatz, who actually found the chemical.
This was also true of Monday’s medicine/physiology Nobel for the discovery of the circadian clock.
Whatever the reality, the preeminent concern here is not one of physiology.
Kraus is a professor of neurobiology, physiology; otolaryngology in the department of Communication Sciences and Disorders at Northwestern University and is the principal investigator for the Auditory Neuroscience Lab.
These example sentences are selected automatically from various online news sources to reflect current usage of the word 'physiology.' Views expressed in the examples do not represent the opinion of Merriam-Webster or its editors. Send us feedback.
physiology Has Latin Roots
The Latin root physio- generally means "physical", so human physiology deals with just about everything that keeps us alive and working, and other physiology specialties do the same for other animals and for plants. To do anything serious in the field of health, you've obviously got to know how the body's organs and cells function normally. Physiology used to be considered separately from anatomy, which focuses on the body's structures; however, it's now known that structure and function can't easily be separated in a scientific way, so "anatomy and physiology" are often spoken of in the same breath.
Origin and Etymology of physiology
First Known Use: 1615See Words from the same year
PHYSIOLOGY Defined for English Language Learners
PHYSIOLOGY Defined for Kids
medical Definition of physiology
- the physiology of the thyroid gland
Seen and Heard
What made you want to look up physiology? Please tell us where you read or heard it (including the quote, if possible).


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Free Sewing Pattern – 5 Minute Lip Balm CarrierDecember 12, 2016 / byFree Designs Admin / Categories : Free Printables, Free Project, Free Sewing Patterns
Presenting a new take on an old project! Make a little lip balm holder carrying case to clip to your key ring or bag using scraps of ribbon, vinyl, real or faux leather, ripstop nylon or laminated fabric. The non-fraying properties of these materials enable you to sew this up in a flash. Make 16 of them out of a dollar store placemat. Pair that up with inexpensive hardware (split key rings and small swivel lobster clasps) and you have a project that’s both cheap and fast! What’s not to like??
RECOMMENDED WITH THIS PATTERN
- 8″ x 1.5″ Non-fraying material
- Split key ring
- Small swivel lobster clasp


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Sunday, 3 August 2008
Cats (b. India, 1974), are animals. Cats walk around and go under cars. Sometimes they come out of alleyways and have a look at you. One time I owned one and it would do things like go into the garden, and look at birds, and sometimes go underneath my dad's car. My cat was called 'Frisky'. Other cats have other names, things like: 'Gentleman Jim' and 'Fuckwand' and 'Marmeduke.' I don't know if those are real cat names. I just made them up. My cousin has a cat called 'Linford'. Other people I know have cats called things like 'Pixie' and 'Elvis'. I once saw something on the internet about a cat circus. There were cats wearing clown costumes, balancing on balls, etc. Cats can be trained. Cats also live in the wild.
Other Types of Cat
Lion (like a normal cat but larger and more dangerous)
Tiger (see Lion above)
Wild Cat (like a 'house cat' but stays outside)
Homeward Bound the Incredible Journey 1&2
A Fistful of Dollars or For A Few Dollars More (briefly -- gets scared by a gunshot and runs offscreen about an hour and a bit in)

domain: pet


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Recently, I presented at a conference for educators. As I welcomed attendees, I heard someone in the hallway declare, “I actually might come because I need this desperately.” Most of the day’s presenters offered innovative approaches to teaching students but few offered self-care tools for the educators charged with doing the actual teaching. As we began our journey, I reminded them of the gentle flight attendant instruction “secure your own mask first.”
The room filled, I smiled, and began my talk. Someone interrupted, “Can everyone come all the way into the room so we can close the door? Its really loud out there.”
“If you can sit quietly after difficult news; if in financial downturns you remain perfectly calm; if you can see your neighbors travel to fantastic places without a twinge of jealousy; if you can happily eat whatever is put on your plate; if you can fall asleep after a day of running around without a drink or a pill; if you can always find contentment just where you are: you are probably a dog.” – Jack Kornfield
Alas, we can’t close out the world. We can’t close the door on life because life is about being vulnerable. Being with and amidst our experience.
This is contrary to the image of mindfulness in popular culture. An image of tranquility on the face of someone meditating in the lotus pose on a secluded, sunny beach is not the true image of mindfulness. Instead, mindfulness is about navigating the sometimes chaotic, sometimes overflowing, always changing experience of being human. Sure, we may practice alone in a quiet room, but the real work of mindfulness takes place in our interactions, our relationships and our everyday environment.
My teacher Jonathan Foust describes a “life of overflow”. Sure, overflow is messy. But it is also a sign of authentic living. Another way to think of this is as being at the edge of your comfort zone. Or perhaps, could it be thought of as a method to share your experience, your passion, your wisdom, with others? The overflow is not us, its our circumstances.
So what can we do? Several years ago, I was struggling with challenges of work and family illnesses. My initial response was “How can I fix this?” But everything I did to try to figure it out only made it worse. I became caught up in old routines that didn’t serve to change my circumstances and certainly cause stress and frustration.
In Man’s Search for Meaning, Holocaust Survivor Victor Frankl wrote, “When we are no longer able to change a situation, we are challenged to change ourselves.” The practice of mindfulness allowed me to create a space to gently and thoughtfully respond to my circumstances without trying to change them. When I found myself caught, the practice of mindfulness returned me to the anchor of my breath, my body, my senses and my intention. I learned to surf.
My conference talk went well. We left the door open and allowed the noise of the hallway to be part of our experience. Using the anchor of our body, we practiced mindfulness and used this distraction as the trigger to return to ourselves in the present moment.
I welcome your comments and encourage you to check out the resources available on www.yourmindfulcoach.com. Check out the full youtube video of my presentation to educators at https://youtu.be/v3hVeCkXjcU or download a handy resource guide.

domain: psychology


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Manos del Uruguay Fino
Elegant and refined, Fino combines the softness of merino wool with the luster of silk in a lightweight yarn that’s perfect for heirloom accessories or luxurious garments. Fino features a new dye process that yields complex, subtle, tonal colors.
Fino Mini-Skein Sets: At last -- a chance to play with a handful of gorgeous Fino colors all at once. Perfect for a favorite gradient shawl pattern! The five 20g mini-skeins in each kit add up to one 100g skein of Fino.
Fiber Content: 70% extrafine merino wool, 30% silk
Yardage: approx. 490 yds / 450 mts per 3.5 oz / 100 g
Gauge: 1.4em;">24-28 sts = 4” / 10cm
Needle Size: US 3-5
Care Instructions: Hand wash in cold water. Dry flat.

domain: hobby


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The 21-Day Shake Diet regimen, created by health and wellness train Drew Sgoutas, claims that replacing several of your meals with smoothie mixes will certainly result in quick as well as simple weight management. Similar to numerous weight-loss strategies, consisting of restrictive diet regimens like this one, the information are essential 21 day smoothie diet Broken Arrow Oklahoma.
As part of a well balanced diet, shakes can aid you lose weight. But ingredients, section dimension, and your general consuming strategy will make all the distinction. A diet regimen containing primarily smoothies, nonetheless, may not work for every person as a solution for long-lasting fat burning success.
Sgoutas (that is not a signed up dietitian), produced the 21 Day Shake Diet regimen to help his customers drop weight. His electronic book, “The Healthy smoothie Diet,” includes 36 shake dishes, shopping lists, and a three-week timetable that information which healthy smoothies to prepare every day. The electronic book also offers a “detox” strategy with recipes and also directions for changing 3 meals a day with healthy smoothies for a total of 3 days.
The 21 Day Smoothie Diet plan encourages eating normally (however still “healthy and balanced”) eventually weekly as well as consists of a recommended food listing for that day. Sgoutas recommends duplicating the 21 day cycle whenever you would love to lose weight, yet there is minimal study to suggest that a smoothie diet is an effective approach for fat burning.
In the short term, fans of this diet regimen might lose weight. However to keep it off, they may need to remain on the diet plan past the 21 day duration, which is not a healthy and balanced long-term solution considering that it suggests that crucial food groups including crucial nutrients are continuing to be restricted.
For the majority of people, 2 homemade meal-replacement drinks daily, plus a “routine” dish, might not give the right balance of calories, protein, carbohydrates, and also healthy and balanced fats the body needs. Any kind of meal-replacement diet plan is difficult to stick to for the long haul since these replacements commonly aren’t as pleasing as strong food.
What Can You Eat?
On the 21-Day Smoothie mix Diet, followers prepare and also consume 2 shakes a day as meal replacements. The smoothie ingredients differ, focusing on great deals of vegetables and fruits with some protein and healthy fats.
The diet plan’s e-book supplies some support on the one solid-food dish followers are encouraged to eat each day (consisting of suggestions for what to consume and also some “entire food” dishes), along with pointers for low-sugar, high-fiber snacks. You are also enabled to eat generally someday per week, as long as the dishes follow the suggestions in the electronic book.
What You Need to Know.
The strict “detox” plan changes all 3 day-to-day meals with smoothie mixes for 3 days. On the 21-day strategy, you’ll consume two meal-replacement smoothies (morning meal and also lunch), one solid-food dish, and a couple of snacks. Though not a part of Sgoutas’ “authorities” smoothie diet, some plan for a “flex day” to make the diet more sustainable.
Nevertheless, Sgoutas explains that if the routine meals are too expensive in calories, the diet plan most likely won’t be effective for fat burning. Also of note: The electronic book suggests that this diet regimen is except individuals with food allergic reactions.
What to Eat.
- Great deals of fruits and vegetables.
- Nutritious meal when per day.
What Not to Consume.
- No solid food for two dishes a day.
The recipes consisted of in the 21-Day Smoothie mix Diet plan consist of lots of fruits as well as veggies, have a tendency to be reduced in calories, and also give vital phytonutrients. While fruit offers healthy nutrients, it likewise includes naturally taking place sugar, which might not help you if you’re attempting to lower your sugar consumption. Some smoothies additionally ask for honey, which only includes more sugar.
In addition, a lot of the diet’s smoothies are very reduced in healthy protein, as well as a few fall short in healthy and balanced fats. Sgoutas does emphasize obtaining sufficient protein throughout the day and recommends at the very least 50 grams daily by consuming a little with each meal as well as treat. However, some individuals may discover it challenging to satisfy their day-to-day protein needs on this strategy, especially those that don’t invest a great deal of time meal preparation.
If you are utilizing a shake as a meal substitute, ensure it includes each important macronutrient: protein, fat, and carbs. You might take into consideration talking to a nutritionist or signed up diet professional for even more assistance– though they would likely recommend that you avoid a smoothie-based diet plan as well as try other, much healthier strategies instead.
Benefits and drawbacks Of The Smoothie Diet regimen.
- Emphasis on fruits and vegetables.
- Less calorie-counting and also food tracking.
- Shopping lists included.
- High in sugar.
- Preparation could be lengthy.
- Not lasting.
- Does not have clinical support.
Is the Smoothie Diet Regimen a Healthy Choice for You?
As a whole, fruit shakes often tend to include calories from carbohydrates and also a percentage of fat. Yet to give a well-shaped meal, they likewise require a good source of lean healthy protein.
Healthy protein assists build muscle, which you need to keep a healthy and balanced metabolic rate. A diet containing mostly healthy smoothies would likely fall short of satisfying your daily consumption of protein.
Shake diets like the 21-Day Shake Diet regimen are popular, yet you’ll also discover resemblances between this diet plan and also other short-term, low-calorie, meal-replacement diet regimens such as SlimFast. Realize that these diet plans do not satisfy professional recommendations on healthy eating plans.
The USDA 2020– 2025 Dietary Guidelines for Americans advises consuming a range of nutrient-dense foods as well as beverages while staying within the advised restriction of 2,000 calories a day for weight administration.
The 21-Day Smoothie Diet plan does not adhere to federal standards since it excludes numerous healthy and balanced foods that compose a balanced diet regimen.
For weight-loss, the USDA suggests a daily calorie intake of concerning 1,500 calories. While Sgoutas suggests roughly 1,500 calories daily in the electronic book, the smoothie mix recipes in “The Smoothie Diet regimen” clock in at a lot less than that, making it tough to reach the 1,500-calorie target without overindulging in the one daily solid-food dish.
Developing a calorie deficiency is commonly the best way to slim down efficiently and also sustainably. However a healthy everyday calorie goal is various for everyone, due to elements such as age, sex, weight, and task degree. Utilize this calculator to determine the calorie objective that may help you.
It is likely that individuals will certainly slim down quickly when they start the 21-Day Smoothie Diet Regimen due to the fact that they are reducing calories (while also potentially reducing nutrients like protein and healthy and balanced fats). Yet changing meals with liquids, as well as surviving on so few calories, isn’t something that the majority of people can securely remain to do for the long term.
Health and wellness Risks.
There is no strong scientific evidence to sustain the idea of detoxification diets– partially due to the fact that there is no clear interpretation of what a “detox diet” does. The body naturally “detoxes” itself via digestion and excretion (such as bowel movements and also sweat). Cleansing is a primary function of body organs like the liver and also kidneys. No person food or food combination can do this on its own.
The high sugar from the Smoothie mix Diet regimen could be a concern for individuals with certain medical problems (which is why it’s not suggested for individuals with diabetic issues). Additionally, it is feasible to shed muscle mass if you drop weight as well quickly. And also if somebody adhering to the weight-loss diet regimen returns to their regular eating behaviors as well as raises their calorie consumption, they are not likely to maintain their weight management long-lasting. This could be why the electronic book suggests repeating the 21-day diet as frequently as essential.
Keep in mind that “detoxification” diet regimens are not indicated for some individuals, including youngsters, expectant and also nursing people, and people with particular health and wellness problems. Before starting any diet regimen be sure to discuss it with your doctor first.

domain: food


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Regional integration seen fending off uncertainty
Increasing regional integration and cooperation in trade and investment in the Asia-Pacific region has helped the region improve its economic resilience to uncertainty in the global economic and trade policy environment, said a report released on Wednesday.
The Asian Economic Integration Report 2017, released by the multilateral Asian Development Bank (ADB), pointed to strong intraregional trade and investment in 2016 as a sign of increased integration and cooperation among countries in the region.
"Strong intraregional trade and investment are acting as a buffer for the region against uncertainties in global trade and economic growth," the ADB said in a statement accompanying the release of the report.
The value of intraregional trade among countries in the Asia-Pacific region accounted for 57.3 percent of the total trade for the region in 2016, which is a record high and up from an average of 55.9 percent from 2010 to 2015, the report noted. Asia's trade grew 1.7 percent in 2016, faster than 1.4 percent in the previous year, while world trade growth slowed to 1.3 percent in the year from 2.6 percent in 2015, the report said.
In terms of investment, the total amount of foreign direct investment (FDI) within the Asia-Pacific region rose to 2 billion in 2016, on a backdrop of a 6 percent decline in global FDI flows into the region, according to the report. The share of intraregional FDI accounted for 55 percent of the region's total in 2016, up from 48 percent in 2015, it said.
Moreover, the report noted that Asian economies have continued to expand their global presence, with Asia-originated FDI rising 11 percent year-on-year to 2 billion in 2016.
"Asia and the Pacific is leading a recovery in world trade that is helping the region to maintain strong growth momentum amid global economic and trade policy uncertainty," Yasuyuki Sawada, the ADB's chief economist, was quoted as saying in the statement. "Asia's continued integration and cooperation will underpin regional economic growth and financial resilience."
With the report, the ADB also introduced a new composite index, the Asia-Pacific Regional Cooperation and Integration Index (ARCII), which measures regional integration in six areas: trade and investment, money and finance, regional value chains, infrastructure and connectivity, movement of people, as well as institutional and social integration.
The ARCII is at 0.448, which is below a reading of 0.617 for the EU but above the level in Africa and Latin America, according to the report.

domain: news