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This was a qualitative study using grounded theory method.
To explain the process of family-centered empowerment in a population of individuals with SCI living in Iran.
Brain and SCI Research Center, Social Welfare Center, and SCI Association of Tehran; Iran.
Participants were 19 persons with traumatic SCI, 13 family member caregivers, and 11 health care providers selected through purposeful sampling. Data were collected using face-to-face, semi-structured interviews, which were continued until data saturation. The interview data were methodically collected and analyzed using Strauss and Corbin’s (1998) recommended method for grounded theory. Constant comparative analysis was simultaneously conducted through reviews of the interview statements, observations of behavior, interviewer field notes, and interviewer memos. The analysis was managed in MAXQDA software version 10.
The process of family-centered empowerment following SCI included five categories: (1) disruption in the existential integrity of the individual; (2) constructive life recovery; (3) inhibitors of family-centered empowerment; (4) facilitators of family-centered empowerment, and (5) back on track. Constructive life recovery was selected as the core variable using the grounded theory method. This core variable identified the strategies most frequently used by the participants to cope with the challenges of SCI-related impairment, disability, and overall life management.
Family-centered empowerment process in individuals with SCI living in Iran emerged from the data. The model includes early disruptions in the bio-psycho-social and vocational lives of individuals with SCI and their families, strategies for recovery post injury, inhibitors and facilitators of family-centered empowerment, the gradual return to work and daily activities, and the expected social roles for individuals with SCI.
Spinal cord injury (SCI) is among the most devastating problems of the central nervous system , afflicting patients not only with sensory-motor problems, but often with numerous physical complications for the remainder of their lives. Autonomic dysreflexia, urinary tract stones, urinary infections, anal sphincter dysfunction, decubiti ulcers, heterotopic ossification, osteoporosis, stiff joints, and sexual problems are some of the complications that may add to the impairment [2, 3].
The World Health Organization reported that worldwide, 250,000–500,000 people suffer from SCI, which is associated with considerable costs for individuals and societies . In Iran, the prevalence of traumatic spinal injury in Tehran was reported as 1.2–11.4 injuries for every 10,000 people from 2008 to 2009 .
Costs of care for SCI and its secondary conditions may impose a heavy financial burden on all involved [6, 7]. Persons with SCI often face multiple challenges that extend beyond physical impairment and disability, including the absence of financial, emotional, psychological, and social support. Moreover, their families often are the primary source of care .
Families are the most valuable, yet most vulnerable, source of care, and support for their family member with chronic healthcare needs . If they accept the responsibility of providing care, they often are exposed to numerous psychological and social issues, themselves . In fact, the management of a chronic condition at home can be a very complex and time consuming activity that far surpass mere medical treatment . Many of the social and psychological complexities associated with having SCI are often ignored by professional healthcare providers making family support even more challenging. Yet, management for these devastating injuries are next to impossible without the involvement of families . Strategies for helping both individuals and families play an active healthcare role must emphasize empowerment that extends beyond the provision of traditional medical services .
In this way financial, social, and emotional dimensions of the lives of patients, their families, and societies can better be addressed. For example, caregivers can assist patients in enhancing their quality of life and can play a role in decreasing social and psychological impairment that often comes with chronic illness . Moreover, to be most effective, healthcare providers need to leverage family caregivers and engage both patients and families in the process of empowerment to promote everyone’s long term health and well-being .
Family-centered care for persons with SCI may be more challenging than care for other chronic health problems. The management of SCI is a multidimensional (physical, psychological, social, cognitive, cultural, and economic) process, which is influenced by various underlying factors . Understanding this process—which starts from the moment of hospital admission and goes through discharge to home and return to society-depends on socio-cultural factors, multidisciplinary interactions in dynamic contexts that occur between healthcare providers, individuals with SCI and their family caregivers.
Grounded theory method (GTM) is a systematic research methodology used in the social sciences that involves the construction of theory through methodical gathering and analysis of data . GTM works inductively, often beginning with a question or with the collection of qualitative data to study social interactions, structures, and processes. GTM was employed in the current study to examine persons with SCI, their families, and their healthcare providers in their respective lives and roles. Thus, for the first time in Iran, we aim to explain the process of family-centered empowerment for individuals with SCI using GTM.
Methods and participants
This study was a qualitative study using GTM, to investigate the process of family-centered empowerment in individuals with SCI in Iran .
Family-centered empowerment is a complex and multidimensional phenomenon, and there is little information about it available in scientific literature. GTM was useful to gather information to improve our understanding of social processes and human interactions by collecting free expression of emotions, reported behaviors, and the participants’ life experiences .
This study was approved by Institutional review Board at Tehran University of Medical Sciences (No. IR.TUMS.REC.1394.1493). Participants voluntarily participated in this study and could refuse to participate or withdraw at any time for any reason. Furthermore, participants were informed that all identifying information and responses would be kept confidential. The participants who agreed to join in the study were asked to sign an informed consent document.
Sampling and data collection
Participants were recruited from three centers in Tehran: Brain and SCI Research Center, Social Welfare Center, and SCI Association of Tehran using a purposeful sampling technique with a maximum variation sampling strategy to ensure maximum variation among those selected to participate . For example, we collected information on gender, marital status, socio-economic level, cultural background, clinical context, and healthcare profession to ensure the sample included a wide breath of participants. Forty-three people agreed to participate: 11 were healthcare providers, 19 were persons with traumatic SCI, and 13 were family caregivers. Recruitment was from November 2015 to October 2017.
The inclusion/exclusion criteria were as follows:
Healthcare providers: willing to participate in the study and share information and experiences; at least 3 years of clinical experience with SCI; and Iranian and Farsi/Persian speaking. Persons with SCI: over 18 years of age; traumatic SCI at least 1-year post; diagnosed paraplegia or tetraplegia; without cognitive impairment or head injury; without extremity fractures; not pregnant; and literate.
Family caregivers: any member of a family (sibling, parent, spouse, or child) of a person with SCI for at least 1 year; literate; physically and mentally healthy; responsible for the care of an individual with SCI (caregiver approved by the individual with SCI), and not a member of the healthcare treatment team.
Data were collected by using semi-structured, face-to-face interviews until data saturation (i.e., to the state when data review creates no new codes and the extracted categories are considered coherent and logical) . The interviews were performed at a convenient time and place for the participants, which included participants’ homes, private interview rooms in the research center, or in private areas of the hospital. Interviews were 30–90 min in length. Interview questions are presented in Table 1.
The first author (MS), experienced in qualitative research, employed the analysis strategy recommended by Strauss and Corbin (1998) in which constant comparative analysis is used simultaneously with data collection. In this method, interviews are continuously reviewed, along with observations during the interviews, field notes (written records produced by fieldwork) and memos (records of the researcher’s developing ideas about codes and their interconnections). Furthermore, this method has three basic steps: open coding, axial coding, and selective coding .
All interviews were transcribed and the responses were reviewed and read several times to get a sense of the general concepts and themes that could be identified and coded (i.e., open coding). Next, these codes were compared with each other and overlapping concepts were combined into specified categories and assigned proper descriptive titles (i.e., axial coding) . Field notes were collected in participants’ homes and during occupational therapy sessions in which were the families of individuals with SCI or healthcare providers in order to understand the actions, interactions, verbal, and nonverbal behaviors. These notes were also entered into the software for analysis. The number of initial codes was 2300. Eventually, these codes were organized into five main categories and seventeen axial categories. This analysis was managed in MAXQDA software version 10.
The researchers worked to establish trusting relationships and credibility with the participants with the goal of data enrichment and optimal understanding of the experiences being described. Most participants were interviewed once; three were interviewed multiple times to get enough information. Furthermore, a number of participants (7%) reviewed summary themes and interpretations of the data being collected to validate that researcher’s coding/interpretations accurately represented their experiences (member checking). Maximum variation also increased the study’s credibility. In order to enhance the reliability of the coding of the participant’s statements (confirmability), the interviews and extracted categories were reviewed and verified by two impartial faculty members to confirm agreement on the codes and themes identified. Their perspectives were included. All steps of the study process were described to these two external reviewers and captured for future auditing of the research. Direct quotes, specific examples, and precise descriptions gathered from the participants are provided to assist potential generalization (i.e., transferability) to other situations and patients with SCI .
Demographic characteristics of the participants are presented in Table 2. Five main categories emerged from the data analysis: (1) disruption in existential integrity of the individual; (2) constructive life recovery; (3) inhibitors of family-centered empowerment; (4) facilitators of family-centered empowerment and; (5) back on track. Constructive life recovery was selected as the core variable and was a set of strategies participants most frequently used to deal with the injury and its consequences. The categories and subcategories are fully described below:
Disruption in existential integrity of the individual
Participants reported that several dimensions of their lives are affected following SCI. Subcategories that emerged from the analysis are described below:
Potentially harmful emotional reactions
Negative emotions, such as, denial, anger, and depression are themes included in this subcategory.
Poor social interactions and isolation
Most of the families and individuals with SCI prefer to stay at home and isolated from others. They cite their reasons as shame over physical impairments, pain and/or muscle spasm, and fear of frustration. Social isolation was somewhat more common than “fear of frustration”, which included two themes: “restrictive concerns about employment or an educational situation” and “concerns about the impossibility of marriage”.
Family structure transformation
This subcategory included themes, such as “changes in interpersonal relationships,” “changes in the role of family members,” and “dealing with family deprivations.” Changes in interpersonal relationships included such concepts as harmony of relationships, distressed relationships, and total relationship breakdown. Some of the identified causes of interpersonal relationship disruption were lack of sexual activity with the spouse, blaming a family member for the accident that caused the SCI, and poor financial situations as a result of increased healthcare expenses.
Changes in the role of family members included additional subcategories of “increased workload” followed by “increase in the responsibilities” and “long-term involvement in the role of caregiver.” We found that in most cases, one family member assumes the burden of care for the injured person.
Dealing with loss is another problem area for families. This includes loss of work and educational opportunities, loss of comfort, loss of emotional support for spouse and children, financial damage, physical and psychological damage, and loss of dignity in the family.
Difficulties caused by physical problems
Restricted mobility (e.g., paraplegia and tetraplegia), bowel disorders, sexual disorders, pain and/or muscle spasms, immobilization caused by problems, such as decubitus ulcers, osteoporosis, and heterotopic ossification were frequently mentioned themes.
Constructive life recovery
This concept was revealed in the data as the core variable and described the strategies most frequently used to deal with participants’ greatest concerns about SCI-related impairment, disability, and life management post injury. This core category emerged from three big subcategories, including the following:
Active coping with disability
This subcategory was comprised of several themes including positive emotions, such as exploration, recovery of hope and motivation, establishing social communications, reaffirming spirituality, correcting faulty thinking, and reforming attitude.
Most individuals with SCI and their families, especially in the first year post injury, did not have sufficient information about SCI. They obtained knowledge through the Internet, healthcare providers, peers, relatives, workshops presented by SCI associations, and occasionally through TV programming. Health information, governmental and nongovernmental support networks were part of this theme.
Recovery of hope and motivation
Within this theme, some participants reported hope and motivation by comparing their own situations to those of other patients and families dealing with more complicated physical impairments (e.g., the loss of a hand or complete quadriplegia), noticing the return of physical sensation and mobility, and a sense of responsibility for the family.
Establishing social relationships
Individuals with SCI and their families were trying to reconnect with their social communities, as they may have become isolated post injury. These communications included reestablishing relationships with noninjured peers (i.e., friends and relatives), and building relationships with peers in the patient associations, health centers, research centers, and/or through the Internet (e.g., responding to others with SCI through social media such as Telegram or WhatsApp). Most of those who were in contact with others using social media were young and those with paraplegia.
This concept emerged from themes, such as trust in God, pilgrimage, prayer, and vows. Most of the individuals with SCI and their families used the term “trust in God” in their interviews. In the Iranian culture, people become closer to God and pray more when they are in trouble. Also, most individuals with SCI consider their disability as the will of God. In the Islamic–Iranian culture, the belief in the “divine test” makes facing challenges easier.
Participants reported using their faith and spirituality to reduce stress and anxiety, and to cope. The religious practice of the pilgrimage of Imams was another coping strategy.
The other themes in this category were resorting to prayer and vows. Some individuals with SCI and their families vow to do good deeds for the sake of God, if they can overcome current difficulties or improve circumstances. These vows typically include charitable acts, such as giving food or money to those who are in need.
Correcting faulty thinking
Cognitive reframing was another theme that emerged from the data. When attitudes and cognitions change, behavior change often follows. Interview data suggested that positive attitudes helped the participants to more effectively cope with daily struggles. This theme included “correcting thinking” and “optimism.”
A number of participants also tried to be more positive about those around them. Interview data suggested that an attitudinal shift makes them less anxious.
Efforts to achieve and promote physical function
Many persons with SCI, with the support of family caregivers and the rehabilitation team, make efforts to reach physical and functional independence. This subcategory included physical rehabilitation and assistive devices, complementary medicine methods, and achieving self-reliance.
Using physical rehabilitation and assistive devices
Strengthening exercises, and the use of assistive devices, such as canes, walkers, AFO’s and KFO’s, and wheelchairs are included in this category. Rehabilitation services (i.e., occupational therapy and physiotherapy) and home modifications to ensure accessibility also were described. A small number of individuals with SCI with greater financial resources purchased elevators and electric wheelchairs.
Using complementary medicine
Some study participants used complementary medicine and expressed an open attitude toward energy therapy (e.g., using physical touch for stress reduction and health), homeopathy, traditional medicine (e.g., treatment based on the body’s temperament and individual characteristics, and beliefs related to herbal, animal and mineral medicines), acupuncture, water therapy, and cell therapy.
Most of the participants described significant attempts to become independent. There were two themes: “innovation in building rehabilitation assistance tools by the family” and “efforts for becoming independent in personal affairs.” A small number of participants and their families had invented creative devices to assist rehabilitation; some of the participants also tried to do more to take care of their personal affairs. Some families were described as playing an important role in helping the individual with SCI to become more independent.
Efforts for life management
This subcategory includes concepts of self-awareness, self-control, and life balance.
Thinking and self-awareness
Some individuals with SCI and their families have thought about the ramifications of ongoing physical impairment and have become aware that SCI is a lifelong condition that may require alterations in life plans.
A number of participants explained taking control over themselves and their behavior.
A number of participants worked to restore a sense of balance to their lives.
Inhibitors of family-centered empowerment
Several variables that inhibit empowerment of individuals with SCI and their families were identified. The main category of inhibitors of empowerment consists of five sub categories which are described below:
Lack of family and patient education
One of the most frequently mentioned needs of persons with SCI, their families, and healthcare providers was training and education in the comprehensive management of SCI. Themes included the following:
Lack of proper training programs
Participants described a failure to educate patients and families about basic primary health issues associated with SCI.
Independence vs. dependence on others
During the interviews, many families expressed the desire to help their injured member as much as possible and seemed unaware of the potential of encouraging greater dependence and furthering unnecessary disability.
Being in problem-oriented healthcare system
Some participants believed that a portion of the barriers to family-centered empowerment are associated with the healthcare system, itself, and its acute care emphasis. These were identified in themes of:
Lack of professional competence
A number of participants cited negative interactions, lack of communication skills, and lack of SCI knowledge in healthcare providers.
Teamwork among providers was described as weak.
Lack of patient follow-up system
Participants noted a lack of follow-up services or systems to ensure ongoing care.
Lack of government-sponsored home care services
Most participants noted the high costs of care without insurance benefits, travel difficulties for rehabilitation therapists, and a lack of SCI awareness in the community.
Lack of shared decision making
Most participants and many of the healthcare providers described the need for more shared decisions about SCI care.
Failure to support transition back into the community
The themes that created this subcategory included the following:
Lack of social facilities
The primary codes such as “lack of accessible entertainment places in the community,” inaccessible streets and sidewalks,” and “inadequate insurance coverage” (which was noted most frequently) created this category.
Lack of financial resources
One of the most concerning issues described by the majority of participants was the lack of state funding and the low economic status of many patients.
Some participants said that inadequate financial allocation of resources in our country has significantly affected urban planning, legislation, adaptation, and disability focused services.
Lack of employment opportunities
Participants noted the shortage of jobs and a failure to comply with employment laws for disabled people.
Hurtful reactions from others
Many participants expressed distress with the responses of people in their communities. They described reactions to their physical impairment made them feel socially isolated. Two themes were identified:
Many individuals with SCI and some of their families mentioned that the reactions of others felt demeaning and discouraged them from being out in the world.
Many participants perceived that others felt sorry for, or stared at them inappropriately.
Some participants described increasing dependence on others, post injury, due to the development of secondary physical impairments. Physical complications, such as carpal tunnel syndrome and pressure ulcers, were specifically identified as playing a role in limiting independence in patients with SCI.
Nonadherence to recommendations for independence
Nonadherence to recommendations was another subcategory that described barriers to becoming independent in activities of daily living and activities outside the home. The following themes emerged:
Lack of cooperation with family and the healthcare team
Family members described the lack of willingness for the injured person to do anything to take care of themselves or work toward independence.
Discounting the experiences of peers with SCI
Some individuals with SCI did not care to learn about or use the experiences of injured peers.
Facilitators of family-centered empowerment
A number of factors facilitated the family-centered empowerment process. The subcategories described below were identified as enhancing empowerment:
The subcategory of personal characteristics included themes around “religious beliefs,” “supportive family,” and “disability benefits.” Religious beliefs were described as extremely helpful for individuals with SCI and their families. In addition, a family psychological support seemed to facilitate empowerment. Finally, a small number of individuals with SCI received disability income post injury, which partly helped them to pay for costs of care.
High quality rehabilitation services
The quality of healthcare and the available rehabilitation services were a source of empowerment for patients and their families.
Benefiting from NGOs and charities
Participants spoke positively about organizations that provide rehabilitation services at low prices and offer free transportation.
Back on track
A number of participants reported their lives returned to some sense of normalcy post injury. Some returned to work; some married and had children. This category consisted of two subcategories:
Gradual return to society
Some individuals with SCI were able to return to their previous jobs or find new jobs with support of their families. Others were able to continue their education.
Recovery of normal life
Marriage and having children were included in this category.
This qualitative study was an exploration of the process of family-centered empowerment in individuals with traumatic SCI living in Iran. GTM was used to develop our model. The analysis for the present study was based on five main categories, entitled, “disruption in existential integrity of the individual,” “constructive life recovery,” “inhibitors of family-centered empowerment,” “facilitators of family-centered empowerment,” and “back on track”
The process of family-centered empowerment in individuals with SCI starts with a disruption in the existential integrity of the injured person. This main category included changes in physical and psychological function, along with alterations in family and social interactions. Egnew stated that the absence of health threatens the existential integrity of the individual as comprehended within a whole related to physical (i.e., body function), mental (i.e., psychological well-being), and social (i.e., interpersonal and family relationship) . The analysis of the interviews conducted with this study population identified content reflective of Egnew’s concepts.
Constructive Life Recovery was identified as the core variable in this study. This core variable identified the strategies most frequently used by the participants to cope with the challenges of SCI-related impairment, disability, and overall life management. The findings were that SCI affected the injured person and his/her family, alike. As a result, families and individuals with SCI struggled to cope with issues of a devastating injury and the subsequent physical impairment, while they simultaneously worked toward functional recovery, independence, and successful management of a lifelong condition.
The first subcategory under Constructive Life Recovery was active coping with disability, which included themes of coping with injury, such as exploration, recovery of hope and motivation, reestablishing social relationships, reaffirming spirituality, and a reforming attitude. The existing literature on persons with SCI supports similar findings. Matter et al. reported that people with SCI typically seek information from a variety of resources to learn more about their condition or related issues . Dorsett reported that increasing sensations and movement in paralyzed limbs after a period of time boosted hope in individuals with SCI . Kennedy et al. reported that most individual with SCI eventually reintegrate with their family, friends, and expanded social networks similar to the participants in the current study . Furthermore, reaffirming spirituality in the present findings was similar to Marini et al.’s results. They noted that the majority of persons with SCI used spirituality to cope with their injury and that some patients believed that SCI made them more spiritual, in general . In addition, Kennedy et al. found a correlation between optimism and functional independence in the SCI population .
The second subcategory under Constructive Life Recovery included efforts to achieve and promote physical function. Three themes were identified: physical rehabilitation and use of assistive devices, complementary medicine, and achieving self-reliance.
Kehn and Kroll, in a qualitative study, found that individuals with SCI desire to participate in activities, but face a number of obstacles, such as the lack of financial means for rehabilitation equipment . Van Buyten et al. reported that people with SCI used various complementary therapies including massage, acupuncture, and percutaneous electrical therapies to reduce the pain often associated with injury . Lam et al. found that individuals with SCI try to walk with the aid of assistive devices (such as prostheses, orthoses, canes, or walkers) . The theme of achieving self-reliance found in the current analysis included leveraging rehabilitation assistance and working toward independence in personal affairs. Gowan and Roth reported that strong family functioning was related to independence in persons with SCI, which was similarly noted in our findings .
Efforts for life management was the third subcategory in the core category of Constructive Life Recovery, which included themes of thinking and self-awareness, self-control, and life balance. Boschen et al. evaluated coping strategies in persons with SCI and indicated that individuals sometimes modified their life goals and altered their expectations toward goals they perceived as more achievable. They noted that family members, friends, or rehabilitation professionals could help in this regard, and conversely, that negative attitudes of others could lead to limited choices and a reduced sense of self-control, thus compromising the independence of the individual with SCI .
The third main category was entitled, Inhibitors of family-centered empowerment, and addressed barriers to the care and management of persons with SCI. Inhibitors to empowerment were lack of family and patient education, a problem-oriented healthcare system, lack of social facilities, poor financial support, hurtful reactions from others, and unintended dependence. Lack of family and patient education was a broad subcategory including lack of proper patient and family training programs, misconceptions about disability, and lack of family participation and patient in care-related decision-making. Juguera et al. noted that both the patient and family need information, training throughout the process of suffering, and the creation of informal groups of mutual aid . Shields et al. investigated children with physical disabilities and found that barriers for activity included parental behavior, negative attitudes about disability, lack of disability knowledge, and inadequate community facilities . These barriers were similar to those identified by adults with SCI in the present study.
Problem-oriented healthcare systems that focus on acute problems at the expense of chronic care management were seen as inhibitors to empowerment. Some of the issues identified were lack of comprehensive services, lack of professional expertize, poor healthcare teamwork, lack of a patient follow-up system, and lack of government-sponsored home care services. The lack of professional competence and expertize was similar to the concerns raised by Chang who was working to develop a successful rehabilitation model. Chang described the importance of specialized training for the members of the rehabilitation team, which included not only technical skills, but also communication competencies to provide appropriate care to the SCI population . Furthermore, home care in Iran is not government supported. Nikbakht-Nasrabadi and Shabany-Hamedan have called for the establishment of a home healthcare system for helping this population .
Lack of social facilities, low socio-economic status, hurtful reactions from others, unintended dependence, and nonadherence to recommendations for independence were subcategories and viewed as barriers to family-centered empowerment. Physical and financial dependence on one or more family members is an obstacle; moreover, inadequate social facilities, restricted access to healthcare services, and limited social support networks can impair the empowerment of people with physical impairment and disability . Hurtful reactions from others was a subcategory of the inhibitors. Hosseinigolafshani et al. found that individuals with SCI believed people that do not have any experience with or exposure to SCI, and often expressed hurtful, negative, and misinformed attitudes toward injured persons. These reactions were described by persons with SCI as extremely painful, undermining, and in some cases were described as being more difficult to cope with than the actual SCI event. Importantly, the negative attitudes of others were reported to worsen the injured persons’ sense of hope and confidence . Nonadherence to recommendations for independence was another subcategory of barriers to empowerment. This subcategory captured persons with SCI who were unwilling to engage in their care and develop independence in functioning. It seemed that some participants struggled to come to terms with the fact that they have sustained a life changing injury that requires them to modify almost everything in their lives. Olney et al. found that one of the consequences of such denial is poor psychosocial adjustment, which makes the follow-up and treatment of patients difficult .
The fourth main category of family-centered empowerment was called facilitators of family-centered empowerment. Personal characteristics and benefiting from quality services were subcategories. Personal characteristics included religious beliefs, a supportive family, and a professional position before injury. Löfvenmark et al. conducted a qualitative study on individuals with SCI and reported findings, which emphasized strong family support, adequate source of income, and faith as strong empowerment facilitators . High quality rehabilitation services were another subcategory in the fourth main category. According to a World Health Organization report, deficient rehabilitation care for people with physical impairments and disabilities is an obstacle to full societal integration and that this is a problem not just in acute care, but across one’s lifespan. Therefore, quality services may be a facilitator in the family empowerment path . Benefiting from NGOs and charities was another subcategory. Khan et al. stated that NGOs and charities have been essential in funding rehabilitation services to help empower affected people .
Back on track was the final main category in the present study. It had two subcategories including gradual return to society and recovery of normal life. Lidal et al. found that return to work rates following SCI ranged from 11.5 to 74% . In a qualitative study conducted by Pashaei Sabet et al., findings included that people with disability seek return to normal conditions and gradually adapt to their problems over time . The themes of marriage and having children were included in the subcategory of return to normal life. Zahra Khazaeipour et al.’s study noted that childbearing after SCI makes individuals feel that they have returned to the life they expected prior to injury  and this finding was similar to the sentiments expressed in the present study.
One of the limitations of the current study was the variability in the study population of level of SCI. Because different types of SCI might be associated with different challenges and experiences, some of the findings might not be generalizable to a larger SCI population. Furthermore, the cause of injury was a result of trauma for all of the participants and their families. As a result, the findings in this study population might not generalize to the broader population of persons with SCI. Finally, there are geographic constraints. Because participants were recruited from care centers in Tehran province, results might not be generalizable to other countries.
Our investigation of family-centered empowerment in individuals with traumatic SCI found the process to be dynamic, complex, multifaceted, and ongoing. We generated a conceptual model of these processes through the methodical gathering and analysis of interview data from individuals with SCI, their family caregivers, and their healthcare providers. Numerous changes across several dimensions in the lives of patients with SCI and their families were identified, including the significant challenges of coping with impairment and disability, while simultaneously working toward functional independence and management of life following injury. Factors inhibiting empowerment were categorized as deficiencies in patient education and specialized rehabilitation services, acute focused healthcare, and negative reactions from others about SCI-associated impairment. Factors determined to facilitate empowerment were categorized as psycho-social-vocational characteristics of the patient, high quality rehabilitation care, and support through NGOs and charities. According to the barriers mentioned, further research is needed to provide a prescriptive model that can improve the overall health and independence of the SCI population.
Education and communication need to be improved in healthcare systems and in providers’ work practices to achieve integrated rehabilitation and family-centered empowerment for persons with SCI.
Self-care education is needed for individuals with SCI and their families.
SCI awareness is necessary in Iranian society for both individuals with SCI as well as the larger population.
The datasets generated and/or analyzed during the current study are not publicly available due to confidentiality and privacy of the participants but are available from the corresponding author on reasonable request.
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Marini I, Glover-Graf NM. Religiosity and spirituality among persons with spinal cord injury: attitudes, beliefs, and practices. Rehabil Couns Bull. 2011;54:82–92.
Kennedy P, Evans M, Sandhu N. Psychological adjustment to spinal cord injury: the contribution of coping, hope and cognitive appraisals. Psychol Health Med. 2009;14:17–33.
Kehn M, Kroll T. Staying physically active after spinal cord injury: a qualitative exploration of barriers and facilitators to exercise participation. BMC Public Health. 2009;9:168 https://doi.org/10.1186/1471-2458-9-168.Pmc2694784.
Van Buyten JP, Van Zundert J, Vueghs P, Vanduffel L. Efficacy of spinal cord stimulation: 10 years of experience in a pain centre in Belgium. Eur J Pain. 2001;5:299–307. https://doi.org/10.1053/eujp.2001.0249.
Lam T. A systematic review of functional ambulation outcome measures in spinal cord injury. Spinal Cord. 2008;46:246–54. https://doi.org/10.1038/sj.sc.3102134.Pmc3095631.
McGowan MB, Roth S. Family functioning and functional independence in spinal cord injury adjustment. Paraplegia. 1987;25:357–65. https://doi.org/10.1038/sc.1987.64.
Boschen KA, Tonack M, Gargaro J. Long-term adjustment and community reintegration following spinal cord injury. Int J Rehabil Res. 2003;26:157–64.
Juguera Rodriguez L, Pardo Rios M, Leal Costa C. Relatives of people with spinal cord injury: a qualitative study of caregivers’ metamorphosis. Spinal Cord. 2018;56:548–59. https://doi.org/10.1038/s41393-018-0092-0
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Khazaeipour Z, Nikbakht-Nasrabadi A, Mohammadi N, Salehi-Nejad A, Shabany M The childbearing experience of women with spinal cord injury in Iran: a phenomenological study. Spinal Cord 2018. https://doi.org/10.1038/s41393-018-0162-3.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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The authors declare that they have no conflict of interest.
We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research.
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Shabany, M., NikbakhtNasrabadi, A., Mohammadi, N. et al. Family-centered empowerment process in individuals with spinal cord injury living in Iran: a grounded theory study. Spinal Cord 58, 174–184 (2020). https://doi.org/10.1038/s41393-019-0348-3


Help finding ERV flat roof vent
Much like the title says, I am having trouble finding appropriate flat roof vents for two spot ERV units I am installing. I don’t think I have an issue with the exhaust, as I would think that any roof vent would work. I am having more trouble trying to find a roof vent for a flat roof for the intake side, which as I understand it, would need to not have a gravity damper on it.
Any recommendations would be appreciated. Placement of bathrooms means that there is really only one way to go… Up. Panasonic seems to have an interesting wall vent that both intake and exhaust use, but I haven’t seen something similar for roof.
GBA Detail Library
A collection of one thousand construction details organized by climate and house part


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A special concert featuring Hessle Ceilidh Band’s Quentin Budworth on hurdy gurdy and occasional guest caller Amanda Lowe premiered the other night featuring ongs telling folk tales of a journey to a new land, of love and loss, and a new beginning. Inspired by the small Alpine Primula Auricula and its 16th century journey to England with the Huguenot refugees. Here is the review.
Google Swanland Village Hall and some links would send you to Willerby, and while that’s hardly the other side of the world the hassle of unexpectedly having to get from one place to the other might put you ever so slightly in the right mindset to hear the story related by The Auricula Suite.
It’s a tale, told with music and a bit of spoken word, of how the Huguenots fled religious persecution in mainland Europe and came to the UK. Granted, some of them travelled thousands of miles, over land and sea, in the days when it was even less comfortable to get around than on Northern Rail today.
The Theatre, the Stage and Lou But at least they were able to take their time, whereas anyone making the mistake of going to Willerby would have been up against the clock to get across the bypass in time for the start of the show..
Especially as the show started early; a sign of its success.
Appropriately enough for a “bring-your-own-picnic” gig there were more than 120 people squeezed in like the sausage rolls in supermarket packaging being enjoyed by the folk on a table near me, but thankfully not like sardines in a tin, because it was far too warm and intimate for that sort of cuisine.
“Unusual” would be one word, but it’s probably not strong enough to describe the variety of sights and sounds in and around the lovingly-restored venue.
The black duck-goose-swan-like creations that hopped out of the adjacent pond and patrolled the car park are unusual. The hurdy gurdy and hammer dulcimer on the makeshift stage are seldom seen and heard. And you don’t often witness women of a certain seniority sporting tattoos and knocking back Stella in a bottle. Not in Swanland anyway.
So “bizarre” is the word we’re looking for to capture the whole combination, as admitted by Lou Duffy-Howard as she introduced the show which she created with flower-fancying husband Rich.
And when Rich spoke about sitting at home with friends, smelling the Primula auricula flowers and discussing the scent, he did so with the passion of Oz Clarke sticking his nose into a decent red wine or of Michael Jackson (no, not that one) sniffing a selection of finest malt whisky.
Songs about flowers then, and there have been a few. Tulips From Amsterdam, Where Have All The Flowers Gone, English Rose, Ramblin’ Rose, Build Me Up Buttercup.
We could go on, but what Rich did was research the history of his flowers to make the connection to the Huguenots and to the history of their journey to provide the inspiration for Lou’s compositions. So these songs are about love and loss; the experiences of companions and lovers separated forever by the exodus which followed religious persecution.
Thoughtfully, the lyrics and stories behind each song were posted on display boards at one side of the stage. At the other were Robin and Annabel Graham of Drointon Nurseries, internationally-renowned Primula auricula specialists based near Ripon, with a display of their blooms in traditional auricula theatre style.
Amanda Lowe and Quentin Budworth, Auricula Première, Swanland Village Hall In the middle of the set was an interlude, during which Amanda Lowe and Quentin Budworth lifted some of the mystery surrounding their instruments, a sort of medieval masterclass. .
Amanda admitted she didn’t know what a hammer dulcimer was when she first came across one in the United States about 30 years ago. Which is comforting because I didn’t know what one was either. Lou and Rich mentioned the instrument when we started promoting the gig a couple of months ago and, after nodding unconvincingly I went home, Googled hammer dulcimer and found out it’s a hall at Willerby. But really it’s a board with a load of strings that Amanda taps expertly with small hammers to create some very pleasant sounds.
The physical commitment required to get the right noises out of a hurdy gurdy would appear to be on a par with the effort exerted by some drummers. And sure enough Quentin confirmed afterwards that his right shoulder has just about had it from years of turning the handle on the instrument. It’s not the sort of thing you can easily even-out by alternating between left and right -handed.
As instruments which date back to the Middle Ages the hammer dulcimer and hurdy gurdy are in the right era for Lou’s stories. As Loudhailer, Lou and Rich often perform the songs using only their guitars, but Amanda and Quentin add real depth and the result is an often enthralling balance of sounds from the various instruments.
The style takes a bit of getting used to, and there would have been very few connoisseurs in an audience that ranged from probable JLS fans sitting on parents’ knees right up to a few folk who are a bit more Vera Lynn.
But the strength of the songs is such that it’s easy to imagine them being performed by other bands with more modern instruments. Amanda and Quentin both demonstrated that the hammer dulcimer and hurdy gurdy can rock, and there will be plenty of 1970s-influenced combos who would fancy incorporating these tales of epic voyages, lost loved ones and sweet-smelling blooms into a medievally-fuelled set if they haven’t done so already.
In my favourite, My Ancestors Were French, the spoken word of Lou Duffy-Howard sounded at times uncannily like Lou Reed.
The initial bemused looks across the fold-away tables and picnic plates made way for smiles and nods of appreciation and even a bit of foot-tapping and knee-slapping. By the time of the grand finale any barriers were long gone and Amanda and Quentin had the audience eating out of their hands. And doing bear impressions.
Apparently it was the first complete sell-out at Swanland Village Hall, and that was great news for the Matthew Good Foundation which was set up in memory of the former joint managing director of Hull-based John Good & Sons, specialists in international freight management and logistics. Matthew, who was 32, died last summer while running the Humber Half Marathon for charity. The charity helps to fund research and education surrounding sport-induced heat stroke and you can find it here: http://www.matthewgoodfoundation.org
6 May 2012
Phil Ascough is a writer and media/PR consultant who specialises in general business, sport and music. He has worked in the media for more than 30 years and has recently published two books with Bloomsbury, Kissing The Badge – about 20 years of the Premier League – and The Armchair Olympian
– about the Olympic Games.

domain: artistic


Ferguson-Florissant school board will keep at-large voting for April election
Updated at 4:43 p.m. on Dec. 22 to include ACLU's follow-up motion
School board elections in the Ferguson-Florissant School District will continue unchanged, at least until an appeal to a court ruling is heard.
A district judge previously had ordered the school system to use cumulative voting after the NAACP and others sued the board because they believed its election process is stacked against black voters. On Wednesday, Judge Rodney Sippel granted a stay requested by the district to hold off on his judgment, pending the school board's appeal to the Eighth Circuit Court of Appeals.
On Thursday, the ACLU of Missouri filed an emergency motion urging the court to either vacate the stay or speed up the process so that cumulative voting can be used for the April election.
The school district currently holds its elections in a manner widely common in other districts: at-large voting. A judge had ordered the district to instead adopt cumulative voting, which allows voters to submit as many votes as there are candidates and distribute votes among the candidates how they choose.


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On April 4, 2017, David Siders writes in The Sacramento Bee:
Gov. Jerry Brown, casting a living wage as a moral imperative while questioning its economic rationale, signed legislation Monday raising California’s mandatory minimum to $15 an hour by 2022, acting within hours of a similar bill signing in New York.
The bill’s enactment comes one week after Brown, Democratic lawmakers and labor leaders announced an agreement on the wage increase, averting a brawl on the November ballot.
In adopting the measure, California joined New York as the first states in the nation to enact a plan to raise their statewide minimums to $15. New York Gov. Andrew Cuomo signed his state’s legislation and was cheered by labor unions at a rally moments before Brown spoke in California.
Brown, a fiscal moderate, had previously expressed reservations about a wage increase. But amid growing concern about income inequality in California and the national thrust of the labor-backed “Fight for 15” campaign, his hand was forced. Public opinion polls showed strong support for increasing the state’s mandatory minimum beyond its current $10.
The compromise Brown offered lawmakers – then celebrated with a bill-signing in Los Angeles – includes a provision allowing the governor to postpone a wage increase in the event of an economic downturn. It replaces a ballot measure that, if passed, would have raised the minimum wage to $15 by 2021, a year faster.
Brown, traveling to the state’s largest media market to sign the landmark bill, remained hesitant about the economic effect of raising the minimum wage, saying, “Economically, minimum wages may not make sense.”
But he said work is “not just an economic equation,” calling labor “part of living in a moral community.”
“Morally and socially and politically, they (minimum wages) make every sense because it binds the community together and makes sure that parents can take care of their kids in a much more satisfactory way,” Brown said.
The wage measures in California and New York reverberated nationally. Democratic presidential candidate Hillary Clinton appeared with Cuomo at a rally in his state, while her rival Bernie Sanders, said in a prepared statement that he was “proud that today two of our largest states will be increasing the minimum wage to a living wage of $15 an hour.”
The California legislation will raise the statewide minimum to $10.50 on Jan. 1 for businesses with 26 or more workers, the first of several incremental increases to $15, with future raises tied to inflation. Smaller businesses will have an additional year to phase in each increase.
The law follows measures in Los Angeles and San Francisco, among other cities, to gradually raise their own minimum wages to $15. It is expected to affect millions of low-wage workers and businesses that employ them, especially in the state’s agriculture, restaurant and retail industries. Some 6 million Californians currently earn the minimum wage.
By 2022, a full-time minimum-wage worker would see annual earnings increase to $30,000 from $20,000 today.
Senate President Pro Tem Kevin de León cast the legislation Monday as a recognition of “the contributions of hard-working men and women” throughout the state.
“No one who works full time should live in poverty,” he said.
In a concession to the state’s influential labor unions, the bill will also provide in-home health aides three annual sick days.
The Democratic-controlled Legislature passed the measure quickly last week, and on partisan lines. While labor unions and their Democratic allies celebrated the bill’s passage, no Republican supported it in either house.
Republicans and business groups said rising wages will force employers to increase prices or to cut costs by laying off workers or reducing their hours.
Research on the economic effect of a minimum wage increase is mixed, with findings ranging from little or no impact on employment rates, on one hand, to rising unemployment, on the other.
The measure will not come without a cost. According to the state Department of Finance, a $15 minimum would cost California about $4 billion a year.
Using common sense, if raising the minimum wage will not kill jobs then why not raise the minimum wage to $25.00 or $50.00 or $100.00 per hour? Of course there are consequences that either are reflected in job elimination or increased prices. Virtually never are the OWNERS of corporations willing reduce profits. If wage levels were not a factor there would be no reason for ANY company to exit production in the United States and move production to foreign lands with significantly less labor costs. Also, there is the impact on pricing levels, as any increases in the cost of production or service always results in pricing increases.
If this were not the case, then no companies would be compelled to seek other more cost-efficient means of production or to move production to foreign countries whose workers are paid far less than Americans. Increasingly, companies are seeking more efficient and less long term costs that non-human technology can deliver to reduce their operating costs, provide higher build quality, automate service, and maximize profits for their OWNERS. As is virtually always the case, the OWNERS of companies do not want to reduce profits.
What the proponents of raising the minimum wage fundamentally are addressing is that low-paid American workers need to earn more income.
We need to begin focusing on the means for people to earn more income, not dependent on earnings from jobs, which are being destroyed with tectonic shifts in the technologies of production. We need to implement financial mechanisms to finance future economic growth and simultaneously create new capital asset owners. This can be accomplished with monetary reform and using insured, interest-free capital credit (without the requirement of past savings), repayable out of the future earnings in the investments in our economy’s growth.
But how, you ask, can such an OWNERSHIP CREATION solution be implemented?
We can and should do more to create universal capital ownership not only for workers of corporations but ALL citizens. What I believe is crucial to solving economic inequality and building a future economy that can support general affluence for EVERY citizen is to address concentrated capital ownership, the fundamental cause of economic inequality. The obvious solution is to de-concentrate capital ownership by ensuring that all future wealth-creating, income-producing capital asset formation will be financed using insured, interest-free capital credit, repayable out of the future earnings of the investments, creating ownership participation by EVERY child, woman, man. This should be about investment in real productive capital growth, not speculation as with the stock exchanges. But the problem is, whether with his call for tax credits and health savings accounts, that the vast majority of Americans have no savings, or at best extremely limited savings, insufficient to be meaningful as increasingly Americans are living week to week, month to month, and deeply in consumer debt. So there is no feasible way that past savings can continue to be a requirement for investment if we are to simultaneously create new capital owners with the productive growth of the economy. The current economic investment system is structured based on the requirement of past savings used directly or as security for capital credit loans. But past savings are not necessary as viable capital formation projects pay for themselves. This is the logic of corporate finance.
Capital acquisition takes place on the logic of self-financing and asset-backed credit for productive uses. People invest in capital ownership on the basis that the investment will pay for itself. The basis for the commitment of loan guarantees is the fact that nobody who knows what he or she is doing buys a physical capital asset or an interest in one unless he or she is first assured, on the basis of the best advice one can get, that the asset in operation will pay for itself within a reasonable period of time––5 to 7 or, in a worst case scenario, 10 years (given the current depressive state of the economy). And after it pays for itself within a reasonable capital cost recovery period, it is expected to go on producing income indefinitely with proper maintenance and with restoration in the technical sense through research and development.
Still, there is at least a theoretical chance, and sometimes a very real chance, that the investment might not pay for itself, or it might not pay for itself in the projected time period. So, there is a business risk. This can be solved using private capital credit insurance or a government reinsurance agency (ala the Federal Housing Administration concept). On a larger scale, the path to solve the security issue, that is, the risk can be absorbed by capital credit insurance or commercial risk insurance. Thus, in order to achieve national economic democracy, we need a way to handle risk management in finance by broadly insuring the risks. Such capital credit insurance would substitute for the security demanded by lenders to cover the risk of non-payment, thus enabling the poor and others with no or few assets (the 99 percenters) to overcome the collateralization barrier that excludes the non-halves from access to productive capital.
One feasible way is to lift ownership-concentrating Federal Reserve System credit barriers and other institutional barriers that have historically separated owners from non-owners and link tax and monetary reforms to the goal of expanded capital ownership. This can be done under the existing legal powers of each of the 12 Federal Reserve regional banks, and will not add to the already unsustainable debt of the Federal Government or raise taxes on ordinary taxpayers. We need to free the system of dependency on Wall Street and the accumulated savings and money power of the rich and super-rich who control Wall Street. The Federal Reserve System has stifled the growth of America’s productive capacity through its monetary policy by monetizing public-sector growth and mounting Federal deficits and “Wall Street” bailouts; by favoring speculation over investment; by shortchanging the capital credit needs of entrepreneurs, inventors, farmers, and workers; by increasing the dependency of with usurious consumer credit; and by perpetuating unjust capital credit and ownership barriers between rich Americans and those without savings. The Federal Reserve Bank should be used to provide interest-free capital credit (including only transaction and risk premiums) and monetize each capital formation transaction, determined by the same expertise that determines it today––management and banks––that each transaction is viably feasible so that there is virtually no risk in the Federal Reserve. The first layer of risk would be taken by the commercial credit insurers, backed by a new government corporation, the Capital Diffusion Reinsurance Corporation, through which the loans could be guaranteed. This entity would fulfill the government’s responsibility for the health and prosperity of the American economy.
The Federal Reserve Board is already empowered under Section 13 of the Federal Reserve Act to reform monetary policy to discourage non-productive uses of credit, to encourage accelerated rates of private sector growth, and to promote widespread individual access to productive credit as a fundamental right of citizenship. The Federal Reserve Board needs to re-activate its discount mechanism to encourage private sector growth linked to expanded capital ownership opportunities for all Americans.
Until we address concentrated capital ownership and implement solutions to simultaneously broaden capital ownership by creating new capital owners with the growth of the productive economy, money power will reside in the hands of politicians and bankers, not in the hands of the citizens. That is why to reform the system leaders and advocates for economic justice must focus on money, how it should be created and measured, how it should be controlled and why a more realistic and just money system is the key to universal and equal citizen access to future ownership opportunities as a fundamental human right. Then prosperity and economic democracy can serve as the basis for effective and non-corruptible political democracy, an ecologically sustainable environment, and global peace through justice.

domain: news


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Affectionate, gentle breed that loves to be held. Very docile temperaments perfect for cuddles.
An easygoing breed content to relax quietly on a cozy lap or sunny window perch.
Large, adaptable breed that tends to be very mellow and gentle. Peacefully accepts new people/pets.
Norwegian Forest Cat
One of the gentlest cat giants, the Maine Coon remains playful yet mild-mannered into adulthood.
Sweet-natured cats that form deep bonds with their families while maintaining laidback attitudes.
Though playful at times, Persians also love lounging around the house and relaxing with their loved ones.
Descended from Persians, Exotics inherit a similarly easygoing and gentle way about them.

domain: pet


text:
Cyclophosphamide (CP) is prescribed in treating different types of neoplasms as well as an immunosuppressive drug in autoimmune diseases and organ transplantation [1
]. Despite its chemotherapeutic efficacy and cost effectiveness, CP has a narrow therapeutic index and may be responsible for severe toxicity of vital organs [3
]. Toxicity to liver and kidney are considered the two major ones, being the key organs responsible for CP metabolism and excretion, respectively [5
]. CP is a prodrug that is metabolized within hepatocytes to generate two reactive metabolites, phosphoramide mustard and acrolein [7
]. Phosphoramide mustard possesses antineoplastic activity, while acrolein is reported to be responsible for the CP-induced cytotoxic effects [8
]. Acrolein initiates oxidative stress via the production of reactive oxygen species (ROS) causing the depletion of cellular defense mechanisms, induction of lipid peroxidation [10
], nucleic acid damage and mutation [11
]. The overproduction of ROS also induces several signaling molecules including nuclear factor kappa-B (NF-kB), which regulates the activation of different pro-inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α [12
]. Moreover, CP is reported to down- regulate the stress sensor transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2); one of the main defensive mechanisms against stress induced injuries [13
CP is commonly administered with 2-mercaptoethane sulphonic acid (mesna); an adjuvant chemotherapeutic treatment regimen to counteract the prevalence of hemorrhagic cystitis and hematuria caused by the toxic metabolite acrolein [15
]. However, the recurrence of hemorrhagic cystitis was reported with mesna [16
] along with ineffectiveness in prevention of other reported CP-induced adverse drug reactions [15
Because no adjuvant regimen is reported to offer protection to the healthy organs and tissues against CP toxicities without compromising its chemotherapeutic efficacy, enhancement of the antioxidant defense system to avert and/or reduce the adverse effects of CP and its reactive metabolites has been suggested [17
]. Plant derived antioxidants preparations showed promising synergistic efficiency when co-administered with chemotherapeutic drugs mainly through their free radical scavenging and anti-inflammatory activities [18
]. Natural antioxidants can enhance the current chemotherapeutic strategies not only by guarding against the adverse effects of chemotherapy but stimulating the host immune status as well [20
Labill. (Myrtaceae) (EG) is an evergreen tree that is cultivated worldwide [21
]. The leaf extract of EG exerts antimicrobial, antibacterial, anti-inflammatory, antioxidant, antihelmintic, and antiviral activities [22
]. Moreover, previous studies reported that Eucalyptus
extracts exhibited potent cytotoxic effects in various cell lines [23
] and promising antitumor activity against Ehrlich ascites carcinoma in mice [25
]. These properties could be related to the abundance of phenolic compounds in the extract such as caffeic acids, quinic, luteolin, dihydroxyphenylacetic, and hydrolysable tannins [27
To the best of our knowledge, no previous study has investigated the hepatic and renal protective roles of EG against CP-intoxication. This study aims to identify and characterize the chemical profile of E. globulus (EG) and also investigate its protective role against CP-induced hepatic and renal toxicities in comparison to the adjuvant drug "mesna" by investigating the related mechanisms of action.
2. Material and Methods
2.1. Drugs, Reagents and Instrumentations
CP (Endoxan®) and mesna (Urometixan®) were purchased from Baxter Oncology GMBH, Halle, Germany. Dimethyl sulfoxide (DMSO) and phosphate buffered saline solution (PBS) were purchased from Sigma-Aldrich Chemical Co., MO, USA and Lonza Bio-products, Verviers, Belgium, respectively. All other solvents and reagents were of the highest grade commercially available. The 1H and 13C-NMR experiments were carried out using a BRUKER 400 MHz NMR spectrometer and samples were dissolved in deuterated DMSO-d6.
2.2. Preparation, Extraction and Fractionation of EG Leaf Extract as well as Chromatographic Isolation
Fresh leaves of EG were collected from Giza Governorate in June 2016. The identification and authentication of the collected plant was established by Dr. Tearse Labib, Botany Specialist, Department of Flora and Taxonomy, El-Orman Botanical Garden, Giza, Egypt.
Air dried leaves (1.5 kg) were extracted three times with methanol (4 L) at room temperature (25 ± 2 °C), the extract was concentrated via a rotatory evaporator to afford 220 g methanol extract. It was then defatted with 1.5 L petroleum ether (60–80 °C) to afford petroleum ether extract (25 g) and defatted methanol extract DME (175 g). DME (40 g) was subjected to polyamide (S6) column chromatography (CC) using polyamide column eluted with H2O/EtOH mixtures up to pure EtOH. By using PC, UV light and spray reagents, similar fractions were collected together to obtain three main fractions. Fraction (I) was purified via Sephadex LH-20/ EtOH & BIW (ethanol & butanol: isopropanol: water) to obtained compounds 1 and 2. Fraction II was subjected to successive CC on Sephadex LH-20/ EtOH & BIW to obtained compound 3. Fraction III was subjected to Sephadex LH-20 column and eluted via EtOH & BIW to yield compound 4.
2.3. HPLC-DAD-ESI-MS/MS Conditions
HPLC-DAD-ESI-MS/MS was employed to investigate the chemical constituents of the extract. The LC system was Thermo Finnigan (Thermo electron Corporation, OK, USA), coupled with an LCQ Duo ion trap mass spectrometer with an ESI source (ThermoQuest). A Silica gel C18 reversed-phase column (Zorbax Eclipse XDB-C18, Rapid resolution, 4.6 × 150 mm, 3.5 µm (Agilent, CA, USA) was used for the separation process. Water with a gradient increase from 5% to 50% of acetonitrile (ACN) (with 1% formic acid each in the positive mode) was applied in 60 min, with a flow rate 1 mL/min, and then increased to 90% ACN in the next 30 min. The samples were injected automatically using auto sampler surveyor ThermoQuest. The instrument was controlled by Xcalibur software (Thermo Fisher Scientific Inc., OK, USA). The MS operating conditions were applied in the negative ion mode, as previously described by us [29
]. The ions were detected in a full scan mode and mass range of 50–2000 m/z
Adult male Swiss albino mice weighing between 25 ± 5 g (purchased from the Schistosome Biology Supply Center, Theodor Bilharz Research Institute, Giza, Egypt) were used. Mice were kept in the animal house facility of the institute in standard polypropylene cages at 25 ± 2 °C temperature with 50–60% relative humidity, 12 h light–dark cycles with free access to ad libitum food and water. The study protocol was approved by the Research Ethics Committee of Theodor Bilharz Research Institute (PT: 19/2/467). All procedures were conducted in accordance with the guidelines of the National Institutes of Health (NIH, 1996) and its amendments for the care and use of laboratory animals.
2.5. Experimental Design
Mice were randomly allocated into five groups each of six animals. Group 1 (control): Received vehicle for EG (0.5% DMSO in PBS solution) for 15 consecutive days; Group 2 (CP): Received CP in PBS (200 mg/kg, [30
] on day 12 and 13 of the experiment, Groups 3 (CP + mesna): Received the positive control mesna (40 mg/kg, [31
] 1 h before and 4 h after each CP application, Groups 4 and 5 (CP + EG): Received EG in doses of 50 and 100 mg/kg [25
], respectively once daily for 15 days along with CP (on day 12 and 13). All treatments were administered intraperitoneally (i.p.).
After the end of treatments mice were killed under anesthesia. Blood, kidney, and liver samples were collected. Sera were separated by centrifugation and stored at −80 °C until analysis. The livers and kidneys were washed in cold PBS; sections of livers and kidneys were fixed in 10% neutral buffered formalin for histopathological and immunohistochemical examinations. The remaining tissue samples were homogenized (10% w/v) in cold PBS for biochemical analyses.
2.6. Determination of Liver and Kidney Toxicity Indices
Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were spectrophotometrically determined using commercially available kits (Biodiagnostics, Cairo, Egypt).
2.7. Determination of Oxidative/Nitrosative Stress Markers and Protein Carbonyl in Liver and Kidney Tissues
The supernatants of homogenized liver and kidney samples were used for determination of reduced glutathione (GSH) and lipid peroxidation (MDA) levels according to Ellman, 1957 [32
] and Ohkawa et al., 1979 [33
], respectively. The protein carbonyl (PC) (OxiSelect Cell Biolabs, CA, USA) and nitric oxide (NO) levels (Biodiagnostics, Cairo, Egypt) were measured using commercially available kits and the amount of total protein was determined by BCA protein assay kit (Thermo Fischer Scientific, IL, USA).
2.8. Determination of Nrf2/HO-1 Pathway Activation in Liver and Kidney Tissues
Gene expression levels of Nrf2 were determined using quantitative reverse transcriptase real time polymerase chain reaction (qRT-PCR). Briefly, total RNA was isolated from hepatic and kidney samples using TRIzol (Invitrogen, CA, USA), and quantified using a nanodrop. RNA samples were used for DNA synthesis using cDNA Synthesis Kit. Amplification of the cDNA was carried out by SYBR Green master mix (Applied biosystems, CA, USA). All values were normalized to the housekeeping β-actin gene. Relative expression of studied genes was calculated using the comparative threshold cycle method (2−ΔΔCt method).
The sequences of PCR primer pairs used were:
|Nrf2 F: TTGTAGATGACCATGAGTCGC|
|Β-actin F: AGGAGTACGATGAGTCCGGC|
Next, the hepatic and renal levels of heme oxygenase-1 (HO-1) were measured using the commercial ELISA kit according to the manufacturer’s instructions (OxiSelect Cell Biolabs, CA, USA).
2.9. Determination of Pro-inflammatory Markers and Caspase-3 in Liver and Kidney Tissues
The liver and kidney pro-inflammatory markers, TNF-α and IL-6, were measured using the commercially available ELISA kits according to the manufacturer’s instructions (OxiSelect Cell Biolabs, CA, USA) and the amount of total protein was determined by a BCA protein assay kit.
Moreover, sections on charged slides (Superfrost charged slides, Thermo Scientific, Braunschweig, Germany) from liver and kidney tissues were immunohistochemically stained with anti-NF-κB and anti-caspase-3 (Santa Cruz Biotechnology, CA, USA, respectively) using an Ultra Benchmark machine (Roche, Tucson, USA) and an Optiview Detection kit with haematoxlin as the counterstain. The percent of positively stained brown nuclei and cytoplasm for NF-κB and caspase-3, respectively, were examined in five microscopic fields (at x400 under Zeiss light microscopy, Jena, Germany).
2.10. Histopathological Examination
Liver and kidney tissues embedded in paraffin blocks were sectioned at 4 µm thickness. Sections were stained with hematoxylin/eosin (H&E) and blindly examined for the extent of liver and kidney damage under bright field microscope (Olympus BX53F).
2.11. Statistical Analysis
Data are expressed as mean ± SEM. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey–Kramer as post hoc test for multiple comparisons (GraphPad Software, San Diego, CA, USA, version 5.03). p < 0.05 was considered statistically significant.
3.1. HPLC-DAD-ESI-MS-MS Annotation and Chromatographic Isolation of Polyphenolic Compounds
In the current study, HPLC-DAD-ESI-MS/MS was used to identify the polyphenolic secondary metabolites in the methanol extract of E. globulus
leaves. Based on the retention time and fragmentation pattern in the negative ion mode, 26 compounds were tentatively identified in the extract and were categorized as phenolic acids, flavonoids, and hydrolyzable tannins. The major identified compounds were gallic acid pentoside (1), gallic acid rhamnoside (2), gallic acid (3), methyl gallate (4), isorhamnetin 3-O
-glucuronoside (12), galloyl cypellocarpin B (13), galloyl ester of a methylellagic acid glucoside (17), quercetin-3,4’-dimethyl ether (18), cypellocarpin C (20), dihydroquercetin (22), valoneoyl-digalloyl-glucopyranose (24), eicosanoic acid (25), and valoneic acid dilactone (26) (Supplementary data S1
). The results are documented in Table 1
and Figure 1
. Out of the annotated compounds, 4 compounds were isolated and characterized based on their NMR data as (1) 4-(O
-xylopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (2) 4-(O
-rhamnopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (3) 3,4,5-trihydroxybenzoic acid (gallic acid), and (4) methyl 3,4,5-trihydroxybenzoate (methyl gallate) (Figure 2
) (Supplementary data S2
3.2. EG Pretreatment Alleviated CP Induced Liver and Kidney Damage
CP caused a substantial increase in serum levels of ALT, AST, creatinine, and BUN (3, 3.6, 1.9, and 3.4 fold, respectively) when compared to normal controls. Mesna modestly reduced their levels when compared to CP treated animals. Pretreatment with EG at doses of 50 and 100 mg /kg resulted in a significant dose dependent reduction in these parameters when compared to corresponding CP or mesna treated mice. EG when given in a dose of 100 mg/kg normalized the levels of ALT, AST, and creatinine (Table 2
Hepatic tissues of CP treated mice revealed hydropic degeneration of hepatocytes, hyperemia, congestion, dilatation of sinusoids. Minor to moderate improvement in hepatic damage was recorded in mesna and EG (50 mg/kg) treated mice, respectively, whereas normal hepatic architecture was recorded upon pretreatment with 100 mg/kg EG (Figure 3
A). Renal tissues of CP treated mice showed degenerated renal tubules with hyaline casts, atrophy in the glomeruli with mesangeal proliferation, tubular degeneration and dilatation in bowman capsules. Pretreatment with EG in doses of 50 and 100 mg/kg revealed a dose dependent improvement in the histological changes of the glomeruli and renal tubules (Figure 3
3.3. EG Pretreatment Mitigated CP-induced Oxidative/Nitosative Stress and Protein Carbonylation in Liver and Kidney Tissues
CP caused a considerable increase in the liver and kidney MDA levels (2.3- and 2.4-fold, respectively) with depletion in their GSH contents (71.7 and 67.6%, respectively) as compared to normal controls. Mesna revealed insignificant changes in hepatic GSH content, trivial decrement in the increased MDA levels, but resulted in significant improvement in renal GSH contents (50.6%) in comparison to CP treated mice. Compared to CP or mesna treated mice, pretreatment with 50 mg/kg EG resulted in significant drop in the hepatic and renal MDA levels with marked increase in their GSH contents. Pretreatment with 100 mg/kg EG restored their normal levels in both the hepatic and renal tissues (Figure 4
Compared to normal mice, CP induced a marked increase in NO and PC levels of both hepatic (3.5- and 1.9-fold, respectively) and renal (3.5- and 2-fold, respectively) tissues. Mesna showed a significant decrease in their levels in hepatic (23.8 and 26.80%, respectively) and renal (18.7 and 31.2%, respectively) tissues when compared to CP treated animals. Pretreatment with either 50 or 100 mg/kg EG notably alleviated the increased levels of PC and NO in the liver and kidney in a dose dependent way when compared to CP and mesna treated mice. Pretreatment with 100 mg/kg EG neutralized the increased PC and NO levels in the liver and kidney of CP treated mice (Figure 4
Data are represented as mean ± SEM (n = 6). * p < 0.05 vs. normal control, # p < 0.05 vs. CP, † p < 0.05 vs. CP + mesna, ‡ p < 0.05 vs CP + EG (50 mg/kg). Statistical analysis was done using one-way ANOVA followed by Tukey’s multiple comparisons test. MDA: malondialdehyde, GSH: reduced glutathione, NO: nitric oxide, PC: Protein carbonyl, Nrf2: nuclear factor erythroid 2-related factor 2, HO-1: heme oxygenase-1, NC: normal control, CP: cyclophosphamide, EG: E. globulus.
3.4. EG Pretreatment Activated Nrf2/HO-1/Antioxidant Signaling in The Livers and Kidneys of CP Treated Mice
CP treated mice showed a substantial drop in hepatic and renal gene expression of Nrf2 (54 and 59.1%, respectively) in comparison to normal controls. Mesna demonstrated a moderate decline in hepatic (28.9%) and renal (29.8%) expression of Nrf2 as compared to CP treated mice. Mice treated with either 50 or 100 mg/kg EG exhibited a considerable rise in the hepatic (62.2 and 91.1%, respectively) and renal (72.3 and 110.6%, respectively) Nrf2 mRNA expression when compared with CP treated animals. Moreover, the enhancement in the hepatic (25.86 and 48.28%, respectively) and renal (32.79 and 62.30%, respectively) Nrf2 expression was more prominent when compared to mesna treated groups (Figure 4
The cytoprotective isoenzyme HO-1 levels were significantly reduced in hepatic (68.7%) and renal (74.5%) tissues of CP treated mice when compared to normal controls. Mesna did not reveal any significant changes in hepatic HO-1 levels whereas a significant rise of renal HO-1 levels (40.8%) was recorded in comparison with CP treated groups. Mice pretreated with EG in a dose of 50 and 100 mg/kg showed a dose dependent increase in hepatic HO-1 levels when compared to either CP (2.4- and 3-fold) or mesna (1.9- and 2.3-fold) treated groups, respectively. Similarly, a dose dependent elevation in renal HO-1 levels was detected in pretreated groups with EG (50 and 100 mg/kg) when compared to either CP (3.2- and 3.7-fold) or mesna (2.3- and 2.6-fold) treated groups. Moreover, pretreatment with 100 mg/kg EG normalized the reduced HO-1 levels in livers and kidneys of CP-treated mice (Figure 4
3.5. EG Pretreatment Down-regulated CP-induced Inflammation in Liver and Kidney Tissues
The levels of the pro-inflammatory cytokines, TNF-α and IL-6, were increased in the livers (92.1% and 129.9%) and kidneys (80.8% and 97.8%) of CP treated mice when compared to normal controls. Mesna caused a partial reduction in both hepatic and renal levels of TNF-α (23.6% and 17%) and IL-6 (17.7% and 28.5%) when compared to CP treated groups. Pretreatment with EG resulted in a dose dependent reduction in their hepatic and renal levels in comparison to either CP or mesna treated groups. Additionally, EG pretreatment in a dose of 100 mg/kg neutralized the elevated hepatic and renal levels of both cytokines (Figure 5
IHC expression of NF-κB revealed minimal basal levels in normal hepatic and renal tissues. However, a prominent up-regulation in its expression was detected in CP-treated liver (mainly in hepatocytes around the central vein) and kidney (identified in the renal tubules and glomeruli) tissues by 52.2- and 60-fold, respectively, as compared to normal controls. Mesna showed a significant reduction by 16.7% and 25%, respectively, when compared to the CP-treated group. EG pretreatment in doses of 50 and 100 mg/kg exhibited a dose dependent decline in hepatic expression of NF-κB in comparison to CP (54.8% and 83.4%, respectively) and mesna (45.7% and 80%, respectively) treated groups. A similar dose dependent down-regulation was observed in NF-κB renal expression in comparison to CP (55.6% and 77.8%, respectively) and mesna (40.7% and 70.4%, respectively) treated groups (Figure 5
Data are represented as mean ± SEM (n = 6). * p < 0.05 vs. normal control, # p < 0.05 vs. CP, † p < 0.05 vs. CP + mesna, ‡ p < 0.05 vs. CP + EG (50 mg/kg). Statistical analysis was done using one-way ANOVA followed by Tukey’s multiple comparisons test. TNF-α: tumor necrosis-α, IL-6: interleukin-6, NF-κB: nuclear factor-kappa B, NC: normal control, CP: cyclophosphamide, EG: E. globulus.
3.6. EG Blocked CP-induced Apoptosis in the Liver and Kidney of Mice
IHC expression of caspase-3 was markedly up-regulated in CP treated hepatic (34.2-fold) and renal tissues (43.2-fold) when compared to untreated tissues. Caspase-3 positively stained cells were observed mainly in hepatocytes around the central vein and in the renal tubules and glomeruli. Administration of mesna did not show significant changes in hepatic and renal caspase-3 expression when compared to CP-treated groups. EG pretreatment in doses of 50 and 100 mg/kg showed dose dependent reduction in hepatic expression of caspase-3 in comparison to CP (53.7% and 80.5%, respectively) and mesna (48.7% and 78.4%, respectively) treated groups. Also, a dose dependent down-regulation in caspase-3 renal expression was observed in comparison to CP (46.5% and 69.8%, respectively) and mesna (37.8% and 64.9%, respectively) treated groups (Figure 6
Data are represented as mean ± SEM (n = 6). * p < 0.05 vs. normal control, # p < 0.05 vs. CP, † p < 0.05 vs. CP + mesna, ‡ p < 0.05 vs. CP + EG (50 mg/kg). Statistical analysis was done using one-way ANOVA followed by Tukey’s multiple comparisons test. NC: normal control, CP: cyclophosphamide, EG: E. globulus.
In this study, the hepato–renal protective activities of EG were examined in CP treated mice. Results were compared to the uroprotective thiol “mesna”, which is routinely prescribed as an adjuvant treatment regimen to reduce the risk of hemorrhagic cystitis [15
In this study, CP treated mice revealed a prominent increase in serum levels of hepatoxicity biomarkers (ALT and AST) by approximately 3-fold, as previously described [17
]. Hepatotoxicity is reported to be one of the major side effects of CP induced hepatic damage with increased permeability of cell membrane and leakage of liver enzymes, specifically ALT and AST [50
]. EG did not only normalize the elevated levels of ALT and AST but also restored the normal hepatic architecture. In CP treated mice, impairment in kidney functions was expressed as increased leakage of creatinine and urea into the systemic circulation, glomerular degenerative changes, and atrophy in kidney tissues. The recorded steep reduction in the levels of creatinine and BUN accompanied with amelioration of the kidney degenerative changes in EG pretreated groups may point to a possible nephro-protective activity.
In the current study, the oxidative/antioxidative mechanisms were examined, since oxidative stress is well known to play a pivotal role in the pathogenesis of CP induced toxicity, which mainly results from its toxic metabolite acrolein [51
]. Acrolein induces the generation of ROS leading to enhanced lipid peroxidation and reduction in the antioxidant defense system in liver and kidney tissues [14
]. In agreement with previous studies [17
], our data showed an exacerbation in ROS production as denoted by the significant increase in the final product of lipid peroxidation, MDA, in liver and kidney of CP treated mice. Moreover, a substantial depletion in hepatic and renal GSH contents (by 72% and 68%, respectively) was observed. This could be attributed to the direct conjugation of CP and its metabolites (acrolein and phosphoramide mustard) to the free or protein-bound –SH groups of GSH [53
], denoting declined cellular defenses [54
]. Pretreatment with EG restored the deficient thiol store in hepatic and renal cells by promoting the de novo synthesis of GSH. Previous studies documented the free radical scavenging activities of EG in alloxan-induced oxidative stress [55
] and acetaminophen-induced kidney damages in rats [56
]. In this study HPLC-DAD-ESI-MS/MS analysis of EG leaf extract revealed the presence of polyphenols with flavonoids (luteolin, kampferol and iridin) and tannins (gallotannins and ellagitannins) as major constituents. Flavonoids [29
] and tannins [58
] are reported to exhibit powerful antioxidant and free radical scavenging effects.
NO is known to play an essential role in regulating cellular stress [59
]. NO directly result from the up-regulated expression of inducible NO synthase (iNOS) indicating impaired cellular viability [60
]. NO is apparently involved in CP induced toxicity [59
], this is in coherence with our findings where NO was significantly increased in both the hepatic and renal tissues of CP treated mice by almost 3-fold. Moreover, the detected increase in NO was accompanied with elevated liver and kidney PC contents in CP treated mice by almost 2-fold. PC content is a marker expressing the extent of protein damage [62
], and its enhanced levels is indicative of DNA damage and mutation resulting from excessive production of ROS in liver [64
] and kidney [65
] tissues. EG pretreatment led to normalization of NO levels indicating hepato- and nephro-protection against CP induced oxidative stress. In addition, the reduced hepatic and renal PC contents may indicate significant recovery of DNA damage suggesting possible assistant role for EG in tissue regeneration.
In addition, we investigated the impact of EG pretreatment on the up-regulation of the Nrf2/HO-1/antioxidant signaling pathway, which is considered one of the key defense mechanisms against stress-associated injuries [66
]. Under stress conditions, various stimuli as ROS and pro-inflammatory cytokines [67
] adversely result in the down-regulation of Nrf2 expression in liver and kidney cells, thereby moderating the transcription of the cytoprotective isoenzyme heme oxygenase-1 (HO-1) [14
]. In the current work, CP resulted in a significant down-regulation of the hepatic and renal Nrf2 gene expressions along with marked reduction in their HO-1 levels, which could be linked to the excessive production of ROS, as previously reported [68
]. Notably, pretreatment with EG demonstrated an activation of Nrf2 gene expression complemented with subsequent elevation in HO-levels in both hepatic and renal tissues implying that the recorded EG antioxidant effects can be partly attributed to the up-regulation of the Nrf2/HO-1 antioxidant signaling pathway.
Additionally, the oxidative/nitrosative stress generated by CP is known to be associated with the subsequent activation of inflammatory cascades [19
]. NF-κB is a redox-sensitive transcription factor that regulates the expression and activation of pro-inflammatory cytokines and other mediators of inflammation including IL-6, TNF-α, and iNOS [70
]. In the current study, CP-treatment elicited an increase in NF-κB IHC expression with marked elevation in levels of TNF-α and IL-6 in hepatic and renal tissues [14
]. The increased NF-kB expression is known to trigger the expression of iNOS, which in turn causes the overproduction of NO [73
], as reported herein. The recorded decrease in the hepatic and renal levels of the pro-inflammatory cytokines (TNF-α and IL-6), NO along with subsequent down-regulation in NF-κB expression in EG pretreated mice could be related to EG compensatory mechanism against the inflammatory milieu generated in CP treated mice. The anti-inflammatory activities of EG was previously demonstrated in inflammatory-mediated disorders [74
CP induced oxidative/nitrosative stress and inflammatory responses are also known to trigger apoptotic cell death via both mitochondria-dependent and mitochondria-independent apoptotic pathways [75
], leading to activation of the executioner apoptotic marker caspase-3 [76
]. The IHC expression of caspase-3 was up-regulated in both hepatic and renal tissues of CP treated mice. Pretreatment with EG extract counteracted the CP-induced apoptotic changes as evidenced by the marked regression in caspase-3 positively stained cells. This observed anti-apoptotic effect of EG could be directly linked to its antioxidant and anti-inflammatory properties.
In this study, mesna demonstrated minor to moderate hepatoprotective and nephroprotective activities. EG showed better results in terms of dose dependent improvement in the assessed biochemical and imunohistopathological parameters upon the use of EG, especially when the dose of 100 mg/kg was applied. These findings are in agreement with US FDA report (2009) [15
] stating the ineffectiveness of mesna in preventing or ameliorating other reported multi-organ toxicity elicited by CP. Our findings may be explained in the view of the pharmacokinetic profile of mesna, which is known to be distributed in the body in its biologically inactive disulfite form. It passes through the hepatic vasculature in an unchanged form [77
] and undergoes reduction in the renal epithelial cells to the pharmacologically active thiol form, mesna, which is then excreted in urine and combines with acrolein to form the stable uro-nontoxic compounds via its sulfhydryl group [78

domain: medical


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I have never seen over past summer camp years such chaos and irresponsibilty. They have way too many children then they can handle. Not to mention they have teenagers in charge of groups of children. There should be an adult for every young helper. Not to mention the rude staff greeting parents and the unexperienced person who is in charge now! This is a safety issue and for the money they get parents need to feel their child is safe. Their parking is rediculous and original teachers are Not happy with changes.

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Badger hockey teams both winners Friday
Published 02/25/2012, Pierce County Herald
-- The University of Wisconsin men's hockey team won only its second road game of the season in their very first trip to Bemidji State Friday while the women easily won their first playoff game.
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