Conducting research on the stem cell lines might bring some worthy good to public. Human Stem Cells (hSCs) research has provided opportunities for scientific progresses and new therapies, but some complex ethical matters should be noticed to ensure that stem cell research is carried out in an ethically appropriate manner. The aim of this review article is to discuss the importance of stem cell research, code of ethics for stem cell research in Iran and ethical recommendation. Generation of stem cells for research from human embryo or adult stem cells, saving, maintenance and using of them are the main ethical, legal and jurisprudence concerns in Iran. Concerns regarding human reproduction or human cloning, breach of human dignity, genetic manipulation and probability of tumorogenisity are observed in adult/somatic stem cells. Destruction of embryo to generate stem cell is an important matter in Iran. In this regards, obtaining stem cell from donated frozen embryos through infertility treatment that would be discarded is an acceptable solution in Iran for generation of embryo for research. Ethical, legal, and jurisprudence strategies for using adult/somatic stem cells are determination of ownership of stem cells, trade prohibition of human body, supervision on bio banks and information of Oversight Committee on Stem Cell Research. Recommendations to handle ethical issues for conducting stem cell research are well-designed studies, compliance codes of ethics in biomedical research , appropriate collaboration with ethics committees and respecting of rights of participants  in research. In addition, there is a necessity for extending global networks of bioethics for strengthening communications within organizations at both the regional and international level, strengthening legislation systems, designing and establishing convenient collaborative educational courses at different levels. The word ‘stem cell’ by itself has been association with complexity (1). Patients, scientists, and the public, on hearing the term ‘stem cell’, may be confused for reason that they cannot separate experimental stem cell interventions from proven stem cell therapies -8. Stem Several highly multipotent stem cells for example mesenchymal stem/stromal cells and stem cells obtained from amniotic fluid, umbilical cord blood, adipose tissue, or urine providing the occasion for widespread bio banking and increasing availability . PluripoReports concerning carry out of studies on the use of animal embryonic stem cells have been published since the early 1980s. Cell differentiation research and therapeutic use of embryonic stem cells in order to renew tissues in a wide range of serious, but common, diseases have been reported . In 1998Over the last 20 years a revolution has been happened in researchers’ ability to produce stem cells from several sources . A commiStem cell research is considered as a surprising but complex and controversial science. Stem cell-based researchers have considerable attention in this filed, since stem cell publications overall are cited 50% more than all other publications in related fields . This reThe United States is considered as leader in stem cell research since that they publish the highest articles focus on stem cell research with high field-weighted citation impact. Recently, stem cell research has risen extraordinarily, showing a growing rate more than double the rate of world research publications from 2008-2012. Nevertheless, this growth is not equal across all stem cell research fields, for instance citation of induced pluripotent stem (iPS) cell publications is approximately three times the global rate in compare with ES cell publications. Nearly half of all stem cell publications are related to regenerative medicine or drug development using iPS cell research . The main purposes of hSCs research are genetic disorders modeling and stem cell-based human therapies and tissue or organ transplantation , 14. HumExploration pharmacogenomics and development of organoids and other products for use in regenerative medicine are other usages of stem cells research , 21-30. The ethical implications of sources of stem cells are complex and controversial . DiscoveAll the contemporary ethical principles and SRH rights are highlighted in Islamic Shariaa. SRH care services should be provided for Muslim families or communities. Islam always encouraged scientific research, especially research on finding cures for human disease. Therefore human embryonic stem cell research is supported and permitted for the reason of potential benefits . In IranIt should be noticed that bioethics researches in Islamic countries have been joined to religious jurisprudence. Ethical issues concerning stem cell research are debated among medical physicians and religious scholars . In the According to Islamic view ensoulment is happened at 120 days after fertilization (whereas a minority of Muslims believe that it is occurred 40 days after conception) . Based oIn the recent years, considerable advances have been happened in biomedical ethics, particularly in the field of education, research and legislation in Iran. The establishment of the National and Regional Committees for Medical Research Ethics, the development of national codes of ethics in biomedical research in the 1990s, then the first, the second and the third revision of them in 2002, 2005 and 2014 respectively and also the introduction of a comprehensive strategic plan for medical ethics at the national level in 2002 were valuable activities by the Ministry of Health and Medical Education (MOHME) , 53-56.An over view on the responsibility of ethics committees in research shows research ethics committees in general play an important role in evaluating the ethical aspects of medical research. A ‘Research Ethics Committee' (REC) is defined as a multidisciplinary, independent, body charged with reviewing research involving human participants to guarantee that their dignity, rights and welfare are protected, through reviewing research proposals, monitoring the conduct of research and dealing with problematic issues that may arise from research. They should be familiar with biomedical research principles including status and duties of research ethics committees and consequently strengthen the RECs in Iran . RECs activate in universities of medical sciences at the national, regional and local level. Although in Iran, Council of Policy Making in Medical Ethics and National Committee of Medical Ethics work on biomedical ethics issues but stem cell research centers and institutes have selected and formed their REC members and work under supervision of research deputy by selves. Lack of specific REC for stem cell research and oversight committee on stem cell research in Iran are obviously challenge that need to be resolved.Human dignity and health related issues, moral status of embryo and participants safety have especial value in Iranian culture -58, 59. Article 1: Authorized sources for producing pluripotent stem cells are 1) supernumerary embryos from IVF treatment programs (only with the purpose of infertility treatment), 2) aborted embryos, 3) induced embryos from research-therapeutic simulation, 4) IPs, 5) cord blood or placenta of delivered newborn.Article 2: Researchers should use only the surplus embryos that they produce in order to treat infertility at the beginning. Article 3: Donated embryos for research must not be implanted into uterus of another women or another species of animals.Article 4: Oocyte, sperm, embryo, fetus or any human biological material should not be obtained from commercial means.Article 5: Freely informed consent should be gotten from both parents of embryo or fetus and third party who have donated the gamete in the time of donation for use of final embryo in research. Article 6: Infertility therapists should not be as a member of researchers group who investigate on stem cells. Article 7: Use of fetus for obtaining of stem cells should not have any impact on decision concerning abortion. In the case, physicians who decide to terminate the pregnancy should not be as one of research team members.Article 8: Producing of oocyte is forbidden in order to generate stem cells, but use of supernumerary oocytes after infertility treatments are acceptable. Article 9: IPs should not be donated through research process: 1) Even though in autologous donation, 2) They should not be combined with human or non-human embryo and 3) They should not be added to human or non-human embryo. Article 10: Freely informed consent should be obtained from all participants in research. Article 11: Specific freely informed consent is mandatory from all participants in research based on type of research. Article 12: All needed information should be given for decision making to participate in the research in order to get freely informed consent, including: 1) explanations regarding type of using from donated human biological materials, 2) destruction probability of donated human biological materials across producing stem cells, 3) possibility of long-term saving of donated human biological materials in order to use of them in the future, 4) probability of economic interests resulted from research in present or in the future, 6) medical and therapeutic benefit resulted from research are not limited to donor and the public may use these benefits, 7) rejection of donors to participate in the research has not any impact on their treatment process, 8) donors can exclude from the research any time they would like to withdraw from participation in the research without any influence on their treatment, 9) donated embryo is not used in order to treat another couples with infertility, 10) necessity of conducting genetic and infection diseases screening tests by donor, 11) possibility of genetic changes in donated biological materials, 12) commercialization probability of donated biological materials without any right of donor for use it.Article 13: In order to respect participants’ right of confidentiality all individual information should be kept in confidence.Article 14: Research centers and treatments should provide necessary considerations to respect participants’ right of confidentiality (coding their records), even if/ though if they cannot provide them they should trash these information.Article 15: Avoiding obtaining and saving of unnecessary information of participants.Article 16: Research institutes should conduct enough pre-clinical research on animal models. Article 17: Small animal models should be used in order to 1) examination of wild type stem cells bond or ill or genetic modification, 2) assessment of healing after cell therapy, 3) investigation of tissue recovery mechanism, 4) assessment of diseases mechanism for effectiveness, age and degree, 5) assessment of rate and pathway of cell therapy. Article 18: Big animals models should be used in research that small animal models are not enough and research on structural tissues such as bone, tendon or cartilage.Article 19: Research on primates should be conducted in the condition of necessity for providing the information that is not available from other ways. These researches should be directly supervised by an expert zoologist .StrengthnessesThe main principles of global bioethics  are acceptable in Islamic opinion , 58-60, In addition, Iranian investigators can use the holy Quran recommendations, principles of Islamic ethics; the religious perspectives (Fatwa) of Islamic experts on special problems; the national laws or ethics codes; international guidelines; and the norms of the society. Dynamic nature of Islamic bioethics helps investigators to conduct their research based on the modern innovations in scientific fields, such as the principles of “the public interest” (Maslaha) and “do no harm” (La Dararwa la Derar) , 64. In Iran, several laws related to bioethics were approved by the parliament legislation system in order to be used and compliance in the clinical practice by bioethics researchers . In Iran, developing codes of bioethics in research including stem cell research have been provided by specialists’ expert in different related fields of philosophy, law, jurisprudence, medicine and other related sciences. Therefore Islamic values and cultural norms including goods of public and individuals have been anticipated in development of the aforementioned codes . It seemFor instance articles 1, 2, 3, 4, 8, 9, 15, 16 aforementioned codes have been written based on “Do no Harm” or “La Darar” principle. In articles 5, 7, 10, 11, 12, 13, 14 principle of autonomy has been considered. Principle of justice has been taken into account in article 6 and principle of beneficence has been noticed in articles 17, 18, 19. In addition, in developing of the codes major issues on participants, rights in research such as informed consent, confidentiality, decreasing the risks and harms to the possible minimal level during research process, reducing of conflict of interest and patenting issue and even animals’ rights in research have been anticipated and respected.Although the establishment of the national codes of ethics in biomedical research including stem cell research in Iran has been an appreciable effort but it seems that these codes have not enough clarity, comprehensiveness and precise , 65, 66.In addition, protection of confidentiality right of participant’s information has been mentioned generally and necessary details has not been considered such as duration, type of protecting system, level of confidentiality protection and accessibility, education of research team members and staffs. Risks management should be discussed more. Although compensation payments has been considered in the clinical trials codes of ethics but the role of health insurance system, length of compensation payments, approval process regarding types of risks and harms that induced by research itself should be mentioned with more clarity. Increasing interrelation of medicine, religion, ethics and law requires greater understanding and analysis of medical ethics issues and the provision of culturally-adapted solutions .Ethical recommendations for stem cell researchers are well-designed studies, appropriate collaboration with ethics committees and respecting of human rights in research , 65, 67.Advancement in medical knowledge and practice is linked to stem cell research especially in reproductive medicine. Stem cells research is an inevitable necessity and the usefulness of stem cell technology for combating many diseases as well as to improve fertility treatment has been proved. In Iran, Islamic perspective supports scientists to conduct well-designed and ethically accepted research on finding cures for human diseases. Though human embryonic stem cell research has been permitted for the reason of potential benefits but human cloning has been forbidden. Recommendations to handle ethical issues for conducting stem cell research are well-designed studies, appropriate collaboration with ethics committees and respecting of rights of participants  in research. In addition, appropriate collaboration is needed at national and international level to extend global networks of bioethics for strengthening communications within related organizations. This article has focused on main ethical, legal and jurisprudence concerns regarding stem cell research in Iran and has provided applicable suggestions based on Iranian Islamic norms and values. In addition the strengthnesses and weaknesses analysis of national codes of ethics for stem cell research may encourage bioethics codes developers attempt for better modification, adjusting and revision of national valuable codes of ethics for stem cell research in Iran. Resolving of ethical, legal and jurisprudence concerns and challenges help Iranian stem cell researcher and scientists to produce and publish valuable and credible findings and introducing new products and drugs for marketing and treatment of serious diseases.


Although the effectiveness of community mobilisation and promotive care delivered by community health workers in reducing perinatal and neonatal mortality is well established, evidence in support of home-based neonatal resuscitation and infection management is mixed. We assessed the effectiveness of adding training in neonatal bag and mask resuscitation and oral antibiotic therapy for suspected neonatal infections to a basic preventive and promotive interventions package delivered by public sector community-based lady health workers (LHWs) in rural Pakistan.We did a cluster-randomised controlled trial in two subdistricts of Naushahro Feroze in rural Sindh, Pakistan, between April 15, 2009, and Dec 10, 2012. LHWs, trained in basic newborn resuscitation and in recognition and treatment  of suspected neonatal respiratory infections, were linked with traditional birth attendants and encouraged to attend home births. Control clusters received routine care through the existing national programme. The primary outcome was all-cause neonatal mortality. Independent data collection teams recorded data for all pregnancies and their outcomes, morbidity, mortality, and household practices related to maternal and newborn care.Of the 27 randomised clusters with functional LHW programmes, 13 were allocated to the intervention group (n=242 749) and 14 to the control group (n=256 985). In the intervention group, LHWs did 80% of the planned community mobilisation sessions, but were able to attend only 1184 (14%) of 8425 deliveries and 4318 (25%) of 17 288 neonatal visits within 72 h of birth (p<0·0001 for both variables compared with the control group). The neonatal mortality rate was 42 deaths per 1000 livebirths in intervention clusters compared with 55 per 1000 in the control group .The reduction in neonatal mortality in intervention clusters occurred against a background of improvements in domiciliary practices for maternal and newborn care. However, the poor reach of LHWs in accessing newborn infants at birth and in the early postnatal period underscores the limitations of tasking community health workers in public sector programmes working in similar circumstances with such complex interventions. Such community-based interventions in health systems should be accompanied by concerted efforts to improve quality of care in facilities and referral systems.Saving Newborn Lives, Save the Children USA. Globally, 5·9 million children still die yearly before reaching their fifth birthday.About two-thirds of the global burden of maternal deaths, neonatal deaths, and stillbirths is concentrated in ten large countries in sub-Saharan Africa and south Asia, of which Pakistan is one.Evidence before this studyThe role of community-based approaches and community health workers in promotion of care and delivery of health-care messages to improve perinatal and newborn care is well established. We did a systematic review of available information about community-based strategies for improving newborn care with community health workers in Pakistan, and also consulted the global literature. We searched PubMed, the Cochrane library, and regional databases of WHO and UNICEF with the terms “community health workers” or “community platforms” and “newborn”, and linked these medical subject heading terms to “Pakistan” to identify articles published in English on or before March 31, 2017. A Cochrane review included data from 26 cluster-randomised or quasi-randomised trials of a wide range of interventional packages, including two subsets from three trials. The data showed major reductions in neonatal mortality , stillbirths, and perinatal mortality as a result of implementation of community-based interventional care packages. Although we identified strong evidence of improved household behaviours and improved care seeking in facilities, results for home-based neonatal resuscitation by either community health workers or traditional birth attendants were mixed, and results for antibiotic administration by community health workers were limited to a few efficacy trials, none of which were done in large public sector programmes. After completing a feasibility assessment, we worked with the National Program for Family Planning and Primary Care in Pakistan to assess the effect of training lady health workers (LHWs) in rural Pakistan to attend births, provide home-based bag and mask resuscitation as required, and provide oral amoxicillin to neonates with suspected pneumonia or serious infections before referral.Added value of this studyOur cluster-randomised trial showed that community intervention by the LHW programme led to a 20% reduction in neonatal mortality and was associated with significant improvements in household practices and newborn care practices. However, overall effective coverage by functional LHWs was only 48%, and they were able to perform resuscitation in only 4% of potentially eligible neonates with birth asphyxia. The intervention had no effect on cause-specific neonatal mortality due to asphyxia or suspected serious infections. We also identified no effects on care seeking for facility births and stillbirths in the intervention clusters.Implications of all the available evidenceOur trial supports the use of community health workers in large programmes for community mobilisation and support strategies for preventive and promotive maternal and newborn care. However, in view of the reality of large-scale public sector programmes, tasking such health workers with complex additional domiciliary care responsibilities might not be advisable. Improvement of maternal and newborn care in facilities and promotion of care seeking and transportation could prove more effective.vs 60% in rural areas) and neonatal mortality .In Pakistan, despite some improvements in coverage of antenatal care and skilled attendance, a high proportion of neonatal deaths occur at home, particularly in rural areas, where few trained professionals and skilled birth attendants are available.Several community-based trials have been done in rural Pakistan to assess the potential effects of training community health workers on neonatal mortality. These trials included both public sector LHWs and community health workers supported by non-governmental organisations to deliver community mobilisation, health education through home visits,In collaboration with Pakistan's national programme for family planning and primary care, we did a cluster-randomised effectiveness trial of training LHWs to deliver a preventive and promotive community mobilisation and education packagetalukas (subdistricts) and an official population of around 1·3 million. The trial was done in a subpopulation of 0·56 million in two talukas of Naushahro Feroze  and three talukas of Moro and Kandiaro (combined population 0·07 million). The study site is typical of most rural districts in Sindh and southern Punjab. The trial was approved by the ethics review committee of the Aga Khan University (1212-Ped/ERC). All households in the selected districts were included in the study. Community assent was obtained from village representatives for participation in the study; participating women gave verbal consent.We did a prospective cluster-randomised trial between April 15, 2009, and Dec 10, 2012, in the district Naushahro Feroze in rural Sindh. The district is located 450 km north of Karachi and has five To develop the intervention and define the clusters, we did a baseline cross-sectional household survey of the catchment population of 35 health facilities  between April 15 and Aug 30, 2009. We collected information about knowledge and practices relating to neonatal care from a random sample of newly delivered mothers identified in the baseline survey. We then did a formative qualitative study to develop and adapt the proposed intervention package to the local context and assess acceptability in close consultation with the federal and provincial LHW programmes and health departments. The preventive component of the package was adapted from one used in a previous trial.We did a planned pilot trial of improved practices between July 1 and Dec 31, 2009, in the catchment population of one health facility, which was subsequently excluded from the main trial. The study tested the package, refined implementation, and assessed the feasibility of linking LHWs with traditional birth attendants so that LHWs could attend home births, and the ability of LHWs to use a bag and mask for neonatal resuscitation. On the basis of this pilot trial, the intervention package was finalised before rollout in the main trial .Table 1DWe defined a cluster as the catchment population of an individual functional primary care facility  and their affiliated LHWs. Basic health units typically serve a population of 10 000–20 000 and have 10–20 affiliated LHWs. Rural health centres cater to a population of 25 000–50 000 and have 25–50 affiliated LHWs. Most LHWs have a catchment population of about 1000 individuals (120–200 households), are mostly resident in the same area, and are not transferred to other facilities or areas. In the original trial proposal, we anticipated the potential inclusion of 34 clusters representing the entire district.Clusters were assigned (1:1) to either the intervention or control groups. To ensure reasonable balance between the two arms, we used stratified, restricted randomisation to allocate clusters. Two strata were defined on the basis of level of health facilities: hospital or rural health centre (nine clusters) or basic health units (18 clusters). 1 million random allocation schemes were generated by the study statistician (SC), who used a computer algorithm. Acceptable schemes were those in which the total populations of each arm was restricted to within 15 000 of each other, total livebirths per year per arm to within 1000 of each other, overall neonatal mortality rates to within five per 1000 livebirths of each other, the ratio of LHWs to population to be within one per 10 000 population of each other, and overall female literacy rates to be within 5% of each other. In all, 28 476 distinct allocation schemes satisfying these restriction criteria were available, of which one was randomly chosen by the algorithm, with random allocation of one of the arms to the intervention.The trial was fully integrated and implemented within a programmatic setting. Senior faculty members of the Division of Women and Child Health of Aga Khan University  held 5 days' training for LHW programme master trainers, who subsequently trained LHWs from the intervention clusters at the health facilities to which they were affiliated . Study supervisors along with LHW programme managers monitored the refresher sessions. Each intervention LHW was provided with a bag and mask for neonatal resuscitation  and oral amoxicillin . LHWs were also given pictorial guides describing the management of asphyxia, thermal care, co-bedding, breastfeeding of low-birthweight babies, and recognition of suspected pneumonia and administration of oral amoxicillin before referral.As already included in the LHW programme guidance, we reinforced the importance of linkages of LHWs with traditional birth attendants in their areas. LHWs were encouraged to maintain close links with traditional birth attendants, keep records of expected births, and attend home deliveries. Clean delivery kits were provided to pregnant women in the intervention clusters during health education sessions delivered by LHWs, and the importance of provision of urgent neonatal care at birth, if needed, was emphasised. LHWs were trained as per national and project guidelines to do additional postnatal visits on days 3, 7, 14, and 28 after birth. LHWs were reimbursed additional travel costs, if any, to attend deliveries or postnatal visits, but no additional salary or other financial incentives were provided. A 3-day orientation programme in basic immediate maternal and newborn care was also organised for traditional birth attendants in the intervention arm, who were trained in the use of clean delivery kits, and strongly encouraged to inform LHWs in a timely manner to attend the home birth. No remuneration, commodities, or resuscitation training was provided to traditional birth attendants.Separate training sessions on health education and community mobilisation were held for male community mobilisers—volunteers from the villages, who were tasked with monthly mobilisation and review meetings with male elders and members of the community. These meetings aimed to promote antenatal care, postnatal care, and facility births. For people choosing to deliver at home, the importance of informing the LHW so that she could attend the childbirth was also reinforced, and volunteers were identified to escorts LHWs to attend deliveries, especially after dark.In the control clusters, the LHW programme continued to function as usual. LHWs continued to have regular monthly debriefing and refresher trainings according to the standard national LHW programme curriculum in the health facilities to which they were affiliated. However, as in the intervention arm, health-care providers from public sector facilities in the entire district received a one-time refresher training on essential neonatal care and management of sick newborn infants according to WHO guidelinesLHW programme supervisors monitored the delivery of the intervention package and related components and maintained their own records. An independent surveillance system was implemented, with 13 data collection teams visiting each household in the trial area quarterly. Verbal consent from heads of households and respondents was obtained for data collection. These data collectors were managed and deployed independently of the LHW programme and shuffled periodically as per previous surveillance protocols.In addition to their official logbooks, LHWs in the intervention clusters were encouraged to record and maintain information about home visits, neonatal illnesses, management of babies with breathing difficulties, low birthweight, and suspected serious infections, referrals, and outcomes on separate forms provided by the research team. The research team monitored the monthly LHWs refresher training meetings and reviewed the forms provided by LHWs. Verbal autopsies of all stillbirths and neonatal deaths were done by a separate team of trained anthropologists within 2–16 weeks of the event with standard WHO-recommended instruments.31The primary outcome of the trial was all-cause neonatal mortality. The initial proposal included perinatal mortality as a primary outcome, but on the basis of feedback from the LHW programme and the range of outcomes captured therein, we principally focused on neonatal mortality instead. Secondary outcomes included cause-specific neonatal mortality due to intrapartum events, prematurity, and sepsis, and the stillbirth rate.In the Hala trial,ClinicalTrials.gov (NCT01350765).We compared baseline characteristics of intervention and control areas by visual inspection. During the intervention period, frequency of birthing practices, LHW contacts, and neonatal morbidity rates in both groups were compared with logistic regression, with robust SEs to account for between-cluster variation, and adjusted for surveillance round and randomisation stratum. Analysis of mortality outcomes was done with generalised estimating equations, with robust SEs to account for the cluster randomisation. To obtain estimates of the risk ratio for intervention versus control clusters, binomial regression models with a log link were fitted, controlling for cluster-level log, randomisation stratum, and surveillance round. The trial is registered with Although SW was involved in periodic review of the study progress, the funder of the study had no role in study design; data collection, analysis, or interpretation; or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.The trial was planned to span 36 months, but ended in Dec 10, 2012 (after quarterly surveillance round 11), because of the conclusion of activities in Pakistan by the Saving Newborn Lives programme of Save the Children, USA. Seven of the 34 clusters in the study area could not be included because no LHWs were posted therein. Thus 27 clusters, including 35 health-care facilities and their affiliated LHWs, were included . The entvs 44·5 per 1000 livebirths, and 39·4 vs 42·7 per 1000 total births, respectively; At baseline, the study groups were balanced in terms of population and number of households . 73% of Of the 63 457 households in the study area, 35 155 (55%) were included in the LHW programme registers and hence covered. Of the 272 officially appointed LHWs in the intervention clusters, only 228 (84%) were fully functional and working  and deliveries facilitated by skilled birth attendants  of whom were resuscitated by LHWs attending births  than from control clusters (2%) reported visits by LHWs during the antenatal period  at catchment facilities, and monitoring of intervention delivery by programme supervisors and district health officials. The regular refresher sessions were based on the LHW programme's standard protocols and well documented.Second, we used a detailed, independent data-collection system. We gathered data for outcomes and exposures through a quarterly active surveillance system via independent teams of data collectors. As part of the quality-assurance process, around 5% of the households were revisited by independent monitors within 3 days of the surveillance visits to corroborate findings. Trained programme managers also monitored LHW performance and activities with standard checklists and generated monthly summaries. Despite a few transfers of LHWs and some choosing not to participate, randomisation through the reporting facilities ensured no contamination between intervention and control clusters, although some sharing of messages between families and residents was inevitable.Our trial also had several limitations in view of its scale and the fact that implementation was largely dependent upon LHW functionality and availability. There was a substantial loss of working days and suspension of routine and project-specific mother and child health-care intervention activities as a result of LHWs' deployment in periodic mass polio immunisation campaigns. LHWs were frequently tasked with additional duties for immunisation activities such as measles campaigns and child health days. During the massive seasonal floods of 2010 and 2011,Information obtained by data collectors on household practices was based on maternal recall and not validated through direct observations, and the possibility of some respondent bias and over-reporting of recommended health-care activities cannot be ruled out. Owing to low maternal literacy and social taboos, a large proportion of mothers did not remember or report the exact date of their last menstrual period, and the possibility of differential misclassification of miscarriages and stillbirths cannot be excluded either.Our effectiveness trial included fewer newborn infants in the early neonatal period than did other efficacy trialsA significant difference from previous findings in SindhWe firmly believe that if packages of community-based maternal and newborn care are delivered through community health workers, appropriate measures to strengthen health systems, transport systems, and quality of care therein are also needed. In addition to community mobilisation and support, urgent attention is needed for the provision of adequate basic and emergency newborn care facilities in health facilities, accompanied by strengthening of quality care for preterm infants and infants with presumed serious bacterial infections.


Racism is an important health determinant that contributes to ethnic health inequities. This study sought to describe New Zealand adults’ reported recent experiences of racism over a 10 year period. It also sought to examine the association between recent experience of racism and a range of negative health and wellbeing measures.The study utilised previously collected data from multiple cross-sectional national surveys  to provide prevalence estimates of reported experience of racism (in the last 12 months) by major ethnic groupings in New Zealand. Meta-analytical techniques were used to provide improved estimates of the association between recent experience of racism and negative health from multivariable models, for the total cohorts and stratified by ethnicity.Reported recent experience of racism was highest among Asian participants followed by Māori and Pacific peoples, with Europeans reporting the lowest experience of racism. Among Asian participants, reported experience of racism was higher for those born overseas compared to those born in New Zealand. Recent experience of racism appeared to be declining for most groups over the time period examined. Experience of racism in the last 12 months was consistently associated with negative measures of health and wellbeing . While exposure to racism was more common in the non-European ethnic groups, the impact of recent exposure to racism on health was similar across ethnic groups, with the exception of SF-12 physical health.The higher experience of racism among non-European groups remains an issue in New Zealand and its potential effects on health may contribute to ethnic health inequities. Ongoing focus and monitoring of racism as a determinant of health is required to inform and improve interventions. Racism has been established as an important determinant of health and a root cause of racial/ethnic health inequities . Racism There has been considerable growth over the last two decades in research on the negative impacts of racism on health, particularly with regards to the impact of experience of interpersonal racism . There iIn New Zealand (NZ), there are long-standing and systematic ethnic inequities in health outcomes, risk factors  and health care, particularly between Māori (the indigenous peoples) and European ethnic groups –14. PopuLongitudinal evidence for these links is also available from New Zealand. The NZ Attitudes and Values study has shown that experience of racism was negatively linked to subsequent wellbeing among Māori . The GroThese studies provide an important local evidence base to build upon in order to better understand and address racism as a determinant of health in New Zealand. To date, local studies have tended to focus on a relatively small pool of exposed individuals  or limited study time periods. These studies can consequently be limited in their power to examine relationships between recent experience of racism (last 12 months) and health, particularly for specific ethnic groups. In addition, there is limited international evidence of the relationship between racism and health for individual ethnic groups, although existing research suggests that the strength of association may differ by race/ethnicity and by time from exposure to outcome .The routine monitoring of experience of racism as a determinant of health and wellbeing has now been implemented in multiple time periods for two of our national surveys, the New Zealand Health Survey  and the General Social Survey . This monitoring allows us greater scope to examine recent experiences of racism by ethnicity over time, alongside links between racism and health, with improved precision for specific ethnic groupings. Specifically this study aimed to: examine the prevalence of reported experience of racial discrimination (in the last 12 months), including changes over time, using multiple data sources  and New Zealand Health Surveys (NZHS)); and examine the relationship between self-reported experience of racial discrimination (in the last 12 months) and measures of health and wellbeing, for both the overall adult population and stratified by major ethnic groupings.This study undertakes a comprehensive analysis of secondary data from multiple national surveys of New Zealand adults, including the New Zealand Health Survey  and the General Social Survey . Both survey types allow for the calculation of nationally representative data through appropriate analysis incorporating the complex survey design (see details below). The surveys are repeated cross-sectional surveys.The study followed Statistics New Zealand processes for accessing microdata . Data weThe New Zealand Health Survey (NZHS) provides information on self-reported health status and chronic conditions, health risk and protective factors, experience and utilisation of health care and sociodemographic factors . The NZHThe NZHS used multistage, probability-proportional-to-size (PPS) sampling methods to select participants from people who usually reside in New Zealand  and were aged 15+ years (for the adult survey) . In 2002The GSS collects data biennially on adults aged 15 years and over who usually reside in New Zealand in private dwellings and do not reside in insitutions . It provThe GSS has a three-stage sampling process. Primary sampling units (PSU) are selected from the Statistics New Zealand Household Survey Frame (HSF) based on NZ Census data. Individual dwellings are selected randomly within these PSUs, followed by random selection of eligible individuals within these dwellings . The GSSThe first GSS was conducted in 2008. To enable comparisons across time periods and combination of results across survey instances, we prioritised selection of consistent variables (and categorisation of variables) across all surveys.Both surveys  provide data on participant experiences of racial discrimination, asked in either a one-step or two-step questioning process .because of your ethnicity in New Zealand?”, with response options: Yes, within the past 12 months; Yes, more than 12 months ago; No; Don’t know; Refused [The NZHS uses a one-step process and asks directly about experience of racial/ethnic discrimination in New Zealand in five situations: physical and verbal attack, and unfair treatment because of ethnicity in health, housing and work situations. For example, “Have you ever been treated unfairly at work or been refused a job  Refused . Items wThe GSS uses a two-step process whereby participants are initially asked about any experience of discrimination in the last 12 months , with a follow-up question on the attribution of discrimination e.g. due to skin colour, nationality, age, gender etc. Experience of racial discrimination for this study was categorised based on discrimination reported as being due to ‘skin colour’, and/or ‘nationality, race or ethnic group’ in any setting. This is in line with NZ legislative and policy definitions of racism and racial discrimination whereby ‘colour’, ‘race’ and ‘ethnic or national origins’ are prohibited grounds for discrimination (Human Rights Act 1993). For analysis over time, and in examining associations between racism and health, any experience of racism in the last 12 months was used in analyses compared with no experience of racism in the last 12 months. The number of times participants experienced discrimination overall was also asked but could not be analysed for racial discrimination specifically .The GSS also asks about the settings where discrimination occurred. In this study, settings where people experienced racial discrimination were examined. Some settings options were grouped where they were examining similar areas. These groups were ‘in public’ , in work , in justice . Other settings were: at home (single response option); school ; joining an association or club of any kind (single response option); housing (applying for or keeping a flat or housing of any kind); dealing with other government officials (single response option); health ; and Other (with no further detail available in the source data).The two approaches for how the discrimination questions were asked across the NZHS and GSS can be found in The NZHS and GSS use the standard NZ Population Census ethnicity question that allows people to self-identify their ethnic group or groups. The question provides a number of ethnic group response options, along with an “Other” category accompanied by a free-text field where people can write in their ethnicity if it is not captured by the response options. NZ uses a hierarchical classification system to classify responses to the ethnicity question from Level 1 (broad aggregate groupings) to Level 4 (detailed ethnic groups). For prevalences of experience of racial discrimination, ethnicity was categorised as total Māori, total Pacific, total Asian compared to a mutually exclusive European/Other group , and SF-12 mental and physical health component summary scores  . AnalysiOther variables considered in multivariable models include: age ; gender ; and nativity (born in NZ vs. born overseas). Socioeconomic variables included an area-based measure : quintiles from 1 (least deprived) to 5 (most deprived) , and an All analyses accounted for the complex survey nature of the dataset, and adjusted for both inverse sample weighting, stratification of the sampling frame, and clustering by PSU (see survey sampling method above.) Analyses of the individual survey instances were conducted in SAS 9.4  using the SURVEYFREQ, SURVEYLOGISTIC, and SURVEYREG procedures. Random effects meta-analysis to combine regression estimates across the six NZHS/GSS survey instances were conducted in R 3.2  using the meta package .Reported experience of any racial discrimination (in the last 12 months) by major ethnic grouping was analysed for each survey. Prevalences of racial discrimination by setting were analysed for the GSS 2008, 2010, and 2012 in the Statistics New Zealand data lab and are subject to data lab confidentiality rules related to outputs . Trends Multiple regression analysis was undertaken in each individual survey instance to examine the sociodemographic patterning of reported experience of racial discrimination in the last 12 months , across all surveys. Standard random-effects meta-analysis methods , 56, 57 Multiple regression analyses were used to examine associations between experience of racial discrimination in the last 12 months  and health and wellbeing measures for each survey. These analyses were conducted for the total adult samples, and also stratified by ethnicity (to determine the impact of racism within each ethnic grouping). Logistic regression was used for binary health variables  and linear regression for contiuous measures . Logistic regression analyses present the odds ratios (ORs) for poor health outcomes comparing those reporting experience of racism in the last 12 months to those not i.e. a positive OR indicates a relationship between experience of racism and poor health or dissatisfaction. Linear regression models present the mean difference in SF-12 scores for those reporting experience of racism in the last 12 months and those not i.e. a negative results indicates an association between experience of racism and negative health.Meta-analysis techniques using random effects models were used to combine effect sizes. Models presented in the main text of this manuscript were adjusted for age, gender, ethnicity, nativity, NZDep and education qualification; and adjusted for age, gender, nativity, NZDep and education qualification in ethnicity-stratified models. Estimates from the unadjusted models are presented in The GSS enabled examination of the settings in which participants reported experiencing racism. The two most common such settings were public settings  and work settings  .The final analyses further examined the relationship between racism and health/wellbeing measures stratified by respondent ethnicity. This study focuses on New Zealand adults’ reporting of recent experience of racism (in the last 12 months) utilising data from multiple repeated cross-sectional national surveys over a ten-year period (NZHS 2002/03 to GSS 2012). Recent experience of racism was most commonly reported by Asian participants followed by Māori and Pacific peoples, with the largely European group (European/Other) reporting the lowest experience of racism. Among Asian participants, reported experience of racism was higher for those born overseas compared to those born in New Zealand. Encouragingly, reported recent experience of racism appears to be declining for most of these groups over the time period examined.The results also demonstrated a consistent association of recent experience of racism with negative measures of health and wellbeing, including indicators of mental health , physical health  and overall life satisfaction. While the impact of experience of racism appeared similar when analyses were stratified by ethnicity , it is important to note that the burden of higher prevalence of racism for Māori, Pacific, and Asian groups means that the population-level impact of racism disproportionately affects these groups.As expected the prevalence of reported racism in the last 12 months was lower than experience ‘ever’, as can be seen by comparing data from the NZHS in this study with previously published data from 2002/03 and 2006/07 , 17. TheA major strength of this study is the documentation of recent experience of racism from multiple national studies at six time points to examine trends in self-reported experience of racism over time. Previous analyses of NZHS and GSS data have documented prevalence estimates of experience of racism and relationships with health for individual studies , 58, 59.Another strength of this study is the examination of how nativity influences experience of racial discrimination in New Zealand. The majority of participants in the Asian and Pacific ethnic groupings were born outside of New Zealand. Our findings showed that experience of racial discrimination for Asian and European/Other people born outside of New Zealand was higher than those born in New Zealand. In the US, where the majority of literature on racism and health is situated, most studies that examine the effect of nativity have found that reporting of racism among people from minoritised racial/ethnic groups born outside of the US is lower than their US-born counterparts  . HoweverThis study was also able to present the most common settings that people experience racism from the GSS data. These were at work and in public, which is in line with the settings for experiences of discrimination more broadly . It is iAnother study strength is the use of meta-analysis to combine data over multiple survey instances for improved precision of estimates. We used meta-analysis methods , 64 to pAs per any meta-analysis, there is no particular requirement that outcomes and exposures be measured in the exact same manner across studies : an addiThe relationship between reported racism and health has previously been examined using data from the NZHS for 2002/03 and 2006/07 data separately, although again this has largely used experience of racism ‘ever’ in a person’s life-time –18, 22, A number of limitations should be considered in the interpretation of findings. Our study is cross-sectional and therefore limited in terms of attributing causality. However, experience of racism has been linked to negative health and well-being outcomes in prospective studies, both in New Zealand , 24 and In addition, our prevalence estimates for experience of racism may be underestimates, particularly for non-European groups. Firstly, questions asked about a limited number of settings and forms of racism . Previous research has shown that Māori, Asian and Pacific groups are more likely to experience multiple forms of racial discrimination , 17. WidWhile the racism questions are consistent within repeats of each of the two surveys (i.e. NZHS and GSS), the questions are not identical in these two data sources. The major distinction is that they ask about experience of racism in two commonly used but distinct approaches , 48, 69:Our study focuses on experience of racism measured at the interpersonal level. As such it does not capture racism at the institutional or structural level well. Associations between individual experience of racism and our outcomes were adjusted for a number of covariates, including socioeconomic measures. Socioeconomic position (SEP) is highly patterned by ethnicity in New Zealand with large inequities between European and non-European ethnic groups , 70, 71.While the use of meta-analysis techniques allowed for improved precision of effect sizes for the impact of racism when stratified by ethnicity, compared to considering a single survey analysis in isolation, these stratified estimates were still limited by smaller numbers and hence poorer precision of estimates. This also limited our ability to undertake more in-depth analysis of the patterning of racism within ethnic groups by other variables. This has implications for survey design, where it is important to sample populations with higher needs adequately. In New Zealand, this means adequately sampling smaller ethnic groups in order to provide robust evidence by ethnicity.This study provides a comprehensive overview of the experience of racism using nationally collected survey data from the NZHS and GSS over a ten-year period. It extends previous analyses of these studies to focus on recent experience of racism and its link to several distinct negative health and wellbeing measures. It also utilises meta-analysis techniques to improve precision for estimates, which is of particular use for analytical questions that were previously limited by small respondent numbers. Racism is a broad system and requires multiple methods to measure and intervene to not only improve health and reduce ethnic health inequities but also to improve social wellbeing and reduce inequities more broadly. While further research and different study designs are necessary to understand specific mechanisms, causal health effects, and the effectiveness of specific interventions, the on-going monitoring of racism as a determinant of health at a population level remains a key component of understanding, prioritising and addressing racism as not only a health, but also a human rights issue.S1 FigFigure note: Data is from the Statistics New Zealand data lab.(TIFF)Click here for additional data file.S2 Fig(DOCX)Click here for additional data file.S3 Fig(TIFF)Click here for additional data file.S4 Fig(TIFF)Click here for additional data file.S5 Fig(TIFF)Click here for additional data file.S6 Fig(TIFF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 TableA. Unweighted frequency gives total number of respondents answering yes to recent experience of racism. B. Unweighted frequency gives total number of respondents for total Māori, Pacific, Asian ethnic groups and residual European/Other group. C. Weighted prevalence gives estimated prevalence of recent experience of racism for NZ adult population (95% CI further accounts for stratification and clustering of responses).Table notes: (DOCX)Click here for additional data file.S3 TableaMāori overseas born are included in the model but data is not shown because of small numbers.Table note: Ethnicity is prioritised in the following order: Māori, Pacific, Asian, European/Other. (DOCX)Click here for additional data file.S4 TableTable note: Percentages are weighted to give population prevalences. Total ethnicity is used for Māori, Pacific and Asian groups, with a mutually exclusive European/Other comparator group. Data is from the Statistics New Zealand data lab and conforms to Statistics New Zealand data lab rules with rounding to 3 of raw freqencies and suppression of cells with small numbers . Microdata output guide (Third edition). Wellington, Statistics New Zealand).(DOCX)Click here for additional data file.S5 Tableadata only available for GSSs; bNZHS 2002/03 not analysed because used an earlier version of SF-12; prioritised ethnicity.Notes: OR = Odds ratio; MD = mean difference; (DOCX)Click here for additional data file.


Background: Healthcare personnel often use incorrect technique for donning and doffing of personal protective equipment (PPE).Objective: We tested the hypothesis that medical students receive insufficient training on correct methods for donning and doffing PPE.Methods: We conducted a cross-sectional survey of medical students on clinical rotations at two teaching hospitals to determine the type of training they received in PPE technique. The students performed simulations of contaminated PPE removal with fluorescent lotion on gloves and were assessed for correct PPE technique and skin and/or clothing contamination. To obtain additional information on PPE training during medical education, residents, fellows, and attending physicians completed written questionnaires on PPE training received during medical school and on knowledge of PPE protocols recommended by the Centers for Disease Control and Prevention.Results: Of 27 medical students surveyed, only 11 (41%) reported receiving PPE training, and none had received training requiring demonstration of proficiency. During simulations, 25 of 27 (92.5%) students had one or more lapses in technique and 12 (44%) contaminated their skin with fluorescent lotion. For 100 residents, fellows and attending physicians representing 67 different medical schools, only 53% reported receiving training in use of PPE and only 39% selected correct donning and doffing sequence.Conclusions: Our findings suggest that there is a need for development of effective strategies to train medical students in correct use of PPE.Abbreviations: PPE: Personal protective equipment; MRSA: Methicillin-resistant Staphylococcus aureus; SARS: Severe acute respiratory syndrome; MERS: Middle East respiratory syndrome; WHO: World Health Organization; CDC: Centers for Disease Control and Prevention; OSCE: Objective structured clinical examination Clostridium difficile [Staphylococcus aureus (MRSA) [Effective use of personal protective equipment (PPE) is essential to protect personnel and patients in healthcare settings . Howeverifficile  and meths (MRSA) , and plas (MRSA) ,7.One strategy to reduce the risk for contamination during donning and doffing of PPE is to educate personnel on proper technique based on Centers for Disease Control and Prevention (CDC) protocols . HoweverThe goal of our study was to test the hypothesis that medical students receive insufficient training on correct methods for donning and doffing PPE. We employed both qualitative  and quantitative  methods. Medical students from three Northeast Ohio medical schools were interviewed regarding PPE training, and simulations were conducted to assess PPE technique and risk for skin and/or clothing contamination. To further investigate PPE training across a wide range of medical schools, residents, fellows, and attending physicians were surveyed regarding PPE training they received during medical school and on knowledge of PPE protocols recommended by the Centers for Disease Control and Prevention.The study was conducted at two acute-care teaching hospitals in Cleveland between October 2015 and May 2016. The hospitals provided training for medical students from three different medical schools, residents in internal medicine and surgery, and fellows from multiple subspecialties. The institutional review boards of both institutions approved the study protocol.Medical students were interviewed to obtain information on year of training, number of clinical rotations, and prior training in use of PPE. Students donned and doffed contact isolation gowns and nitrile gloves using their usual technique. After donning gloves, fluorescent lotion was applied to gloved hands. After PPE removal, a black light was used to assess for contamination of the skin of the hands and wrists. Simulations were observed and deviations in technique from CDC recommendations were recorded using a standardized checklist .Figure 1A convenience sample of medical residents, fellows, and attending physicians at the two study hospitals was asked to complete a questionnaire that included questions on years of experience in healthcare, name and location of medical school, training in use of PPE during medical school, and questions on the sequence for donning and doffing recommended by the CDC. Questionnaire data was analyzed using R 3.2.2 statistical software. Pearson’s Chi-square test with Yates’ continuity correction was used to compare responses between groups of physicians .For 27 medical students participating in the study, the average number of weeks of clinical experience was 24 (range 0–52 weeks). Of the 27 students, 16 (59%) did not recall prior training in the use of PPE, six (22%) completed an online computer-based training module at the start of their clinical rotations, three (11%) received a lecture that included PPE training, and two (7%) reported having a demonstration on how to use PPE. For those completing computer modules, it was noted that the training focused primarily on the type of PPE to be employed in different situations rather than on how to use PPE. None of the students recalled having to demonstrate their proficiency in use of PPE. Several students commented that they did not receive instruction on how to use PPE, but learned by observing other personnel.During simulations of contaminated glove removal, five students (19%) exhibited correct donning technique and six (22%) exhibited correct doffing technique; only two students (7%) exhibited correct donning and doffing technique. Of the 27 students, 12 (44%) contaminated their hands and/or wrist with fluorescent lotion during glove removal.Training in correct use of PPE and other basic infection control practices should ideally be an integral part of medical education. However, our findings suggest that training in correct use of PPE is suboptimal or nonexistent in many medical schools. Only 41% of medical students from three schools in Northeast Ohio reported receiving training in PPE use, and none reported a requirement for demonstration of proficiency. In simulations of contaminated glove removal, 7% of students exhibited correct donning or doffing technique and 44% contaminated their hands and/or wrist with fluorescent lotion. The survey of residents, fellows and attendings representing 67 medical schools in 18 countries revealed that training in correct use of PPE was uncommon during medical education with less than 40% of participants choosing the correct donning and/or doffing sequences based on CDC recommendations.Previous studies have identified deficiencies in knowledge of medical students regarding standard precautions and hand hygiene –15. We aIn addition to protecting healthcare personnel, correct use of PPE is essential for patient safety. A significant proportion of healthcare delivery has moved from healthcare facilities to outpatient and homecare settings ,20, and Our study has some limitations. The medical students were from only three medical schools. However, the surveys of residents, fellows, and attendings from 67 different medical schools clearly suggest that suboptimal PPE training is commonplace in medical education. In addition, there is a possibility of recall bias on the part of the current practicing physicians regarding PPE training during their medical school education. Further studies are needed to evaluate the curriculum of medical schools with regard to training in basic infection control practices such as effective use of PPE.Our findings suggest that training in correct use of PPE is insufficient in medical school education. Incorrect use of PPE puts students at risk for acquisition of infection and contribute to transmission of pathogens. Future studies are needed to develop effective strategies to train medical students in correct use of PPE.


Here, we collected the papers that presented and discussed at this meeting by specialists that currently researched about the overlaps of the fields of reproductive biology and stem cells and their applications in regenerative medicine.This paper summarizes the proceedings of a 1 day national symposium entitled “Reproductive biology, stem cells biotechnology and regenerative medicine” held at Shahid Sadoughi University of Medical Sciences, Yazd, Iran on 3 The well-organized and on time reconstitution capability of the cells and tissues of the reproductive tract as an organ system confirm the existence of a relatively high ratio of stem cells. The main locations in female and male reproductive system which stem cells reside and can be either generated or isolated are the ovary, endometrium, decidua, and the testis. The cells derived from these tissues include oocytes, embryos, embryonic stem cells (ESCs), oogonial stem cells, endometrial mesenchymal stem cells (EnMSCs), trophoblast cells, and spermatogonial stem cells (SSCs) . Growingrd March 2016. A recent 1-day national symposium entitled “Reproductive biology, stem cells biotechnology and regenerative medicine”, sponsored by the Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Yazd Province Organization of Academic Center for Education, Culture and Research (ACECR), Council for Development of Stem Cell Sciences and Technologies (CSCT), Presidency of the Islamic Republic of Iran Vice-Presidency for Science and Technology, and hosted by the Shahid Sadoughi University of Medical Sciences, brought together specialists that researched about the overlaps of the fields of reproductive biology and stem cells and their applications in regenerative medicine on 3Here, we collected the papers that presented and discussed at this meeting. This symposium was divided into three sessions: The first session was about the generation and isolation of stem cells from reproductive system sources. The second session was about the differentiation of stem cells to reproductive cells. In the third session, specialists discussed about the ethics and tissue engineering and the future regenerative medicine applications in reproductive tract.At the beginning of the scientific sessions, Shoae-Hassani on behalf of Hamidieh discussed about the stem cells and reproductive medicine and mentioned that “investigation in stem cells and regenerative medicine is greatening more and more, and its translation to the clinic is going fast by the recent massive volume of clinical trials. Over the past decade, scientists have advanced the field of reproductive tissue engineering to restore normal sexual function and preserve fertility in both female and male patients”. Moreover, they previously reported that many of reproductive derived stem cells could find clinical application in the future . Another paper by Baharvand described the derivation of ESCs and embryonic germ cells (EGCs) and their use in germ cell differentiation -5. In continues, Movahedin talked about the importance of SSCs in male reproduction and spermatogenesis. She demonstrated that only 0.03% of all germ cells include SSCs. SSCs transplantation can be used in cancer patients who had chemo/radiotherapy. Irreversible azoospermia is one of the side effects in these patients that can affect their quality of life seriously. Therefore, optimizing of culture’s conditions and enrichment of cryopreserved SSCs are main goals of male reproductive medicine . One of the populations of stem cells in female reproductive system resides in endometrium. Another paper by Salehnia described about isolation and characterization of EnMSCs, and their capability for self-renewal, colony-forming units (CFU), differentiation into mesoderm-derived lineages including adipogenic, myogenic, chondrogenic, osteogenic and expression of CD146, CD90, CD73, CD105, SOX2 markers and the lack of CD34 and CD14 marker expression . in vitro  cells can be differentiated into the male germ cell in vitro .in vitro differentiate into ectodermal and mesodermal cell types, which show their inherent plasticity. Also, other groups confirmed in their studies that amniocytes have stem cells characteristics  as a model for early human trophoblast invasion studies. In addition, trophoblast bodies closely mimicked early invasive stages of implantation when incubated with human endometrial stroma  therapy . Shahverdi discussed about “genetic causes of infertility among men, most commonly due to the de novo deletion of one or more Azoospermia Factor (AZF) regions of the human Y chromosome. Pure sterile phenotypes in men with deletions vary from the complete absence of germ cells and sperm  to production of germ cells that arrest in development  to very low sperm counts (oligospermia). Of new therapies, stem cells have opened new window for infertility treatments". In this regard, others reported that hESCs as pluripotent cells could differentiate into post meiotic male germ cells . in vitro ESCs derived gametes provides powerful model for understanding of epigenetic modifications during gametes development, causes of infertility and other molecular base of reproductive disorders. Bahmanpour presented about mouse ESCs (mESCs) differentiation into oocyte- like cells with ovarian somatic cell co-culturing in combination by bone morphogenic protein 4 (BMP4) and retinoic acid (RA) supplementation . Bahmanpin vitro maturation (IVM) of immature (GV and MI) oocytes. In this regards, Khalili described about IVM of immature oocytes as one of the choices for fertility preservation. He suggested that future studies focused on improvement of the oocyte maturation procedure, like co-culture system for infertile patients with PCOs or young cases with life circumstances (cancer). These oocytes represent pool of germ cells that can be matured and used in assisted reproductive program  is  program . In the last session, Haghirosadat discussed about the general ethical issues in the field of reproductive biology and stem cells according to the Islamic rules and international laws . Arjmand discussed about stem cells translational medicine and mentioned that stem cell therapy has introduced promising hopes for the treatment of various diseases. But, during this translation, quality level should be performed based on good manufacturing practice (GMP) standards and rules . Niknejad described that the amniotic membrane (AM), with unique characteristics and natural biomaterial components in extra cellular matrix (ECM) of basement membrane including collagen, fibronectin, laminin and other proteoglycans could be used as a natural scaffold in tissue engineering . In continuous, Kajbafzadeh discussed about tissue engineering and regenerative medicine of reproductive tissues and organs. Furthermore, he mentioned the natural history of reproductive system decellularization, preserved ECM and in situ scaffold recellularization/cell seeding, differentiation of umbilical cord stem cells into germ cells, vagina and urethral reconstruction by ECM . In the field of female reproductive tissue engineering, Nikukar mentioned malfunctioned of main organs are the causes of transient or constant infertility and artificial or organic scaffolds as basement membranes can carry and affect the selected pluripotent stem cells. It is not so far unpredictable that you could creative an organ or a tissue by prescription of your physician. But the gap between laboratory tests and clinical applications is deep enough to use the regeneration as a treatment technique for the patients . As an example of the future possible application of tissue engineering in male reproductive regenerative medicine, Borzouie presented the data of her Ph.D. thesis which was about the development of an artificial human testis using a novel 3D culture device applying a home-made scaffold. However, the research was in preliminary stages but it could lend itself into the future cell therapy applications in the field of male infertility . Finally, Aflatoonian discussed about the derivation of Yazd hESCs  and mentioned about the future applications of hESCs in regenerative medicine. hESCs with pluripotency capacity could differentiate into every cell types derived from three embryonic germ layers such as, neurons, cardiomyocytes, hepatocytes, hair cells, retinal pigmented epithelial (RPE) cells, and even post meiotic germ cells. Moreover, in vivo animal model studies are performing to modify the capacity of the hESCs-derived cells in regenerative medicine . Efforts


Under rapid urban sprawl in Northeast China, land conversions are not only encroaching on the quantity of cultivated lands, but also posing a great threat to black soil conservation and food security. This study’s aim is to explore the spatial relationship between comprehensive cultivated soil heavy metal pollution and peri-urban land use patterns in the black soil region. We applied spatial lag regression to analyze the relationship between PLI (pollution load index) and influencing factors of land use by taking suburban cultivated land of Changchun Kuancheng District as an empirical case. The results indicate the following: (1) Similar spatial distribution characteristics are detected between Pb, Cu, and Zn, between Cr and Ni, and between Hg and Cd. The Yitong River catchment in the central region, and the residential community of Lanjia County in the west, are the main hotspots for eight heavy metals and PLI. Beihu Wetland Park, with a larger-area distribution of ecological land in the southeast, has low level for both heavy metal concentrations and PLI values. Spatial distribution characteristics of cultivated heavy metals are related to types of surrounding land use and industry; (2) Spatial lag regression has a better fit for PLI than the ordinary least squares regression. The regression results indicate the inverse relationship between heavy metal pollution degree and distance from long-standing residential land and surface water. Following rapid urban land expansion and a longer accumulation period, residential land sprawl is going to threaten cultivated land with heavy metal pollution in the suburban black soil region, and cultivated land irrigated with urban river water in the suburbs will have a higher tendency for heavy metal pollution. Suburbs are the conjunction between urban and rural settlements and are characterized by integration of agricultural production in miniature, disordered industrial manufacturing, and flowing residential settlements ,2. As thTraditional studies on heavy metal pollution of cultivated soils combined with land use includes investigating and evaluating heavy metal concentrations, analyzing potential sources by principal component analysis, and isotopic tracing of heavy metal outputs from potential sources ,12,13,14Black soil is named according to the standard classification and codes for Chinese soil and is analogous to Mollisol. The black soil region of Northeast China is one of few black soil resources in the world that provides high soil fertility and massive grain production . HoweverThe study was carried out in a suburb of Changchun Kuancheng District , one of A total of 137 soil samples  were col3, HCl, HF, and HClO4). Total concentrations of As and Hg were analyzed via the atomic fluorescence spectrometry (AFS) method; soil was digested with chloroazotic acid and reduced by KBH4 solution prior to analysis. Thirteen certified reference material samples were processed and measured to assess analysis quality. Soil chemical analysis methods were conducted according to the specifications for national multi-purpose regional geochemical survey (NMPRGS) by the China Geological Survey, and analysis results are consistent with the analytical requirements developed in the NMPRGS  after soil samples were pressed into pellets. The total concentration of Cd was analyzed via inductively-coupled plasma mass spectrometry (ICP-MS) method after a four-acid digestion  for As, Hg, Cd, Pb, Cr, Ni, Cu, and Zn were applied to determine the pollution status of cultivated soil:In Equation (1), where nd value  applied To map the spatial distribution of soil heavy metal concentration and PLI, an ordinary Kriging interpolation was applied in this paper. Kriging interpolation is one of the best linear unbiased estimator methods for mapping soil properties . It is aThe spatial distribution of land use types in the study area was interpreted from high-resolution remote sensing images (IKONOS) in 2014 using ArcGIS  along with a field survey. Land uses were classified into seven types: cultivated land , industrial land , residential land , transportation land (highway and railway), ecological land , unutilized land (bare land surface without covering of vegetation or constructions), and surface water (river and irrigation reservoirs). In consideration of the accumulative characteristics of soil heavy metals, two potential pollution sources and unstable land use types, industrial land and residential land, were both divided into two groups: land developed before 2009 and land developed after 2009 .With the aim of gathering land use information for ecological land and providing spatial analysis, Thiessen polygons were constructed according to locations of sampling points. Spatial autocorrelation analysis and spatial auto-regression were performed on the basis of Thiessen polygons.Soil heavy metal pollution degree has certain spatial dependencies, including spatial autocorrelation. Therefore, simulation deviations will be created owing to spatial data autocorrelation for traditional regression analysis. To simulate the relationship between PLI and land use influencing factors preferentially, a spatial auto-regression model was adopted (Equation (2)). Among the four variant forms of spatial auto-regression models, spatial lag model and spatial error model are the most widely used, and they are the models discussed here in this paper:In Equation (2), The spatial lag model shows that the dependent variable is under the influence of explanatory variables, locally, along with dependent variables in the neighborhood. The spatial error model shows that the dependent variable is under the common influence of local explanatory variables, dependent variables, and explanatory variables in the neighborhood ,16.p-value > 0.05), the results of OLS regression are retained. If only one of them is significant , the model applied will correspond to the significant Lagrange multiplier, lag or error. If they are both significant, the one with lower p-value between the robust Lagrange multiplier (lag) and robust Lagrange multiplier (error) will determine the application of the spatial lag model or spatial error model [Spatial model selection depends on the significance test results of the Lagrange multiplier for ordinary least squares (OLS) regression. There are four indicators of Lagrange multiplier statistics, Lagrange multiplier (lag), robust Lagrange multiplier (lag), Lagrange multiplier (error), and robust Lagrange multiplier (error). If the Lagrange multiplier (lag) and Lagrange multiplier (error) are both non-significant  indicate the logical fitting for heavy metals and the fitted semi-variogram models reflect their spatial structures  for As, Cr, Ni, Cu are all below 25%, which indicates strong spatial correlation and structural factors are the dominant influence on spatial variation. C0/(C + C0) for Hg and PLI are between 25% and 75%, which indicates moderate spatial correlation and the influence on spatial variation by structural factors and random factors are similar.As shown in To increase the spatial differentiation for heavy metal concentrations, quantiles were used to classify each concentration range. Spatial interpolation maps for concentrations of As, Hg, Cd, Pb, Cr, Ni, Cu, and Zn are presented in To quantify the effects of land use pattern on heavy metal pollution of cultivated land, a spatial regression model was applied to analyze the relationship between heavy metal pollution and influencing land use factors.p-value < 0.05), and coefficients show negative relationships. With the spatial autocorrelation analysis of all variables for spatial regression and residuals of OLS regression for PLI . In addition, the robust Lagrange multiplier (lag) is of relatively higher significance than the robust Lagrange multiplier (error), thus, the spatial lag model should be applied for the PLI spatial regression.To decide which spatial regression model should be applied, a Lagrange multiplier test was carried out for the OLS regression results . As show2 and log likelihood values . This relationship indicates that long-standing residential land and agricultural irrigation pollution by surface water are the major influencing factors driving soil heavy metal pollution of suburban cultivated land. The regression coefficients (−4.08 × 10−5 and −9.30 × 10−5) represent the inverse relationship between heavy metal pollution degree and distance from long standing residential land and sources of surface irrigation water, respectively. To model a better fitting regression relationship, all non-significant redundant variables were removed; this model is hereafter known as spatial lag model B. All explanatory variables of spatial lag model B are significant, which indicates that it has a better fit for the regression than spatial lag model A.According to the significance test , among aTypes and density of anthropogenic activities carried by different land use types are diverse; soil heavy metal concentrations vary with the land use type on account of the discrepant output of heavy metals ,26. SubuAs shown in According to spatial regression results , residenIn addition, according to the spatial distribution characteristics of heavy metal pollution, we conclude that the heavy metal pollution of cultivated land in the Yitong River catchment and its branches are more severe than other areas. The Changchun section of the Yitong River has been reported on several times for poor water quality and potential heavy metal pollution . There aThis study analyzed the relationship between spatial distribution characteristics of heavy metal pollution and land use patterns of suburbs in a black soil region using spatial lag regression. The empirical case study area was cultivated land of suburban Kuancheng District, north of Changchun, China. Heavy metal pollution shows spatial characteristics in a rural-urban fringe. Similar spatial distribution characteristics are detected between Pb, Cu, and Zn, between Cr and Ni, and between Hg and Cd. In a comparison with the map of land use types, the Yitong River catchment in the central region and Lanjia County residential community in the west are the main hotspots for eight heavy metals and PLI. Beihu Wetland Park, with a larger area distribution of ecological land in the southeast, has the lowest concentrations of heavy metals. Spatial distribution characteristics of cultivated heavy metals are related to types of surrounding land use and industry. Moreover, spatial lag model regression provides better fitting for PLI than the ordinary least squares regression, and removes the spatial autocorrelation impact of residuals. Regression results indicate an inverse relationship between heavy metal pollution and the distance from long-standing residential land and surface water. Following rapid urban land expansion and longer accumulation periods, residential land sprawl is going to threaten cultivated land with heavy metal pollution in the suburban black soil region; suburban cultivated land irrigated with urban river water is more likely to be polluted by heavy metals.


The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the successful prevention of chronic renal disease in captive cheetahs. Acinonyx jubatus) are considered endangered primarily by habitat loss, habitat fragmentation and conflict with livestock and game farmers. Road traffic accidents, hunting and illegal trade also contribute to the decline in the free-ranging cheetah population[Lynx canadensis), clouded leopards (Neofelis nebulosa), cougars (Puma concolor), jaguars (Panthera onca), ocelots , leopards (Panthera pardus), lions (Panthera leo), snow leopards (Uncia uncia) and tigers (Panthera tigris)[Populations of free-ranging cheetahs ,8. Renala tigris),9,10. Mia tigris). Glomerua tigris) and a sta tigris),10 and na tigris). Excessia tigris). Despitea tigris)–17. In aa tigris),19 and ga tigris)–22. The a tigris)Deposited amyloid fibrils disrupt tissue architecture and result in progressive renal dysfunction in humans, domestiHelicobacter spp. infection[Gastritis is associated with infection. Howeverinfection–33. Stroinfection. Gastritinfection, which iinfection. Diet ininfection,37. Cheeinfection.Given the susceptibility to CRD of captive cheetahs, the suspected role of alimentary tract inflammation in the pathogenesis of CRD and the effect of CRD on the sustainability of captive cheetah populations, we conducted a retrospective necropsy study to investigate the relationships between alimentary tract and renal lesions; the association between individual renal lesions and death due to CRD; and comparisons of lesion prevalence between captive bred and wild born and between normal coated and king coated cheetahs in 243 captive cheetahs from one institution.Acquisition, breeding, disease and mortality records as well as pathological descriptions were examined for 243 cheetahs from a single cheetah breeding centre (1967–2014). All cases included were animals submitted for necropsy examination to investigate the cause of death. All cases included were animals submitted for necropsy examination to investigate the cause of death so an ethical statement is not relevant. The project was approved by the University of Pretoria Animal Ethics Committee (Project number VO63-14) and the National Zoological Gardens of South Africa Research Ethics and Scientific Committee (Project number P13/27). One author (E.P. Mitchell) conducted full necropsies and histological examinations of all tissues apart from the eye and spinal cord on 231 of the cheetahs between 1996 and 2014 and scrutinized the necropsy reports and, where available, histological slides from the remaining 12 cheetahs .The following data were recorded: sex; date of birth  and estimated date of birth ; whether or not the cheetahs had normal coats or were king coat variants; and age at death. Based on published life history information, five agHistological examination was done on sections of formalin fixed paraffin embedded tissues stained with hematoxylin and eosin, von Kossa and Masson’s trichrome stains, and a mhttps://www.r-project.org/) using the library MASS for generalized linear models. In each case, models were compared using Akaike’s Information Criterion adjusted for small sample sizes (AICc)[Statistical analyses were based on a set of ordinal variables. Hypotheses were tested using generalized linear models and included variables with binomial distributions ; variables with Poisson distributions ; or a continuous (Gaussian) variable (age in days). All analyses were carried out in R 3.13 . In eaches (AICc). For eacEffects and covariates included in the generalized linear models varied according to the nature of the question being examined. Four analyses were performed. Firstly, a hypothesis that alimentary tract and renal lesions result in reduced survival was tested by comparing the age at death (in days) of cheetahs with differing lesion scores. However, in all lesions, a higher score was seen in older animals, indicating a direct relationship between pathology and age at death. Therefore, lesions were treated as dependent variables on age at death for further analysis and the continuous variable age at death (in days) was used in all statistical hypotheses tested. This was necessary not only to detect an influence of age on the data, but also to account for any effects of age when testing influence/s of other variables. Secondly, generalized linear models with and without age at death as a covariate and its interaction with various lesions, were compared to examine the relationships between focal palatine erosions, gastritis, enterocolitis, medullary fibrosis and amyloidosis, glomerulosclerosis, cortical fibrosis and chronic renal infarcts. Due to autolysis obscuring details in various organs, comparisons had different sample sizes so models were run using data subsets of equal size, including only those cheetahs for which all factors present in a particular model had available data. Thirdly, to investigate the association between renal lesions and death due to CRD, the effect of each lesion (with and without age at death as a covariate) on death due to CRD was evaluated using generalized linear models for subsets of equal sample size. Lastly, two discrete variables were used as effects in generalized linear models for each lesion to indirectly assess the effect of stress and genetic factors respectively: whether cheetahs were wild or captive born; and whether cheetahs had the double recessive gene for the king coat variant or had normal coats. Age at death (Effect 1) and its interactions with the main effect (Effects 2 and 3) were included in the stepwise modeling procedure and models including both wild born and king coated cheetahs were also incorporated to test for interactive effects in these two factors.Affected kidneys were small, with multifocally pitted and indented cortical surfaces , with ilThe number and age of cheetahs with and without alimentary tract and renal lesions and death due to CRD are shown in The significant influence of age at death on the prevalence of all lesions documented in our study complicated the assessment of the associations between focal palatine erosions, enterocolitis, medullary amyloidosis, glomerulosclerosis and chronic renal infarcts with gastritis, cortical and medullary fibrosis. After age was taken into account, significant associations were found only between enterocolitis and gastritis, medullary amyloidosis and medullary fibrosis and between chronic renal infarcts and cortical fibrosis . Of the Of the cheetahs with CRD, medullary fibrosis was present in 53.4%, cortical fibrosis in 49.3%, medullary amyloidosis in 43.8%, chronic renal infarcts in 40.1% and glomerulosclerosis in 19.2% of animals. Chronic renal disease caused death in 56 animals. Renal medullary fibrosis was the only factor significantly associated with death due to CRD  and no cThe number and percentage of wild born, captive bred, king coated or normal coated cheetahs with each lesion and the significance of CRD are shown in Lesion prevalence in the cheetahs described here was generally similar to that described in other cheetah populations, with some differences that may have been due to different selection criteria for animals surveyed, health management regimens and other management or environmental differences,26,29,36Nonetheless, medullary fibrosis was the only renal lesion statistically associated with death due to CRD in this population of captive cheetahs. It was more diffuse than medullary amyloidosis, occurred in more cheetahs with CRD than any other renal lesion and no cheetah died of CRD without medullary fibrosis. In contrast, some cheetahs that died of CRD did not have medullary amyloidosis, glomerulosclerosis, cortical fibrosis or chronic renal infarcts. This effect of medullary fibrosis is consistent with studies showing that renal fibrosis is the renal lesion that most closely positively correlates with azotemia and, therefore, function of the residual renal mass in humans and domeApart from medullary amyloidosis, which is rare in domestic cats, the macroscopic and histological findings in cheetahs in this and other,5,6 studStress is thought to play a key role in mediating tubular hypoxia in CRD in domestic cats which suffer from stress-related cystitis associated with stimulation of the sympathetic nervous system without increased adrenal steroid production. In humaGlobal glomerulosclerosis is thought to be an ischemic change in humans and is tChronic renal disease is a common age-related disease in many species including domestic cats,49,64, d6 deficient diet developed tubular lesions, oxalate crystals and periglomerular and peritubular fibrosis that extended radially from the corticomedullary junction[Dietary factors have been postulated to play a role in the initiation and progression of CRD in cats,49. Inte junction. Captive junction,37,74,75Prior episodes of alimentary tract disease may influence the initiation and progression of CRD in humans and catsThe predominant effect of age at death, differing ages between groups, and unequal group sizes limited robust statistical comparison of lesion prevalence in wild born and captive bred, and king and normal coated cheetahs. Further research to determine whether these apparent differences are related to age, differing genetic diversity, or to stress levels will be hampered by the relatively small numbers of wild born and king coated cheetahs available for research.Our results suggest that CRD in our population of captive cheetahs was primarily due to medullary fibrosis. We found no evidence to support a link between alimentary tract lesions and medullary amyloidosis. Medullary fibrosis and glomerulosclerosis in cheetah may be associated with age and or stress related tubular and glomerular hypoxia. The presence of CRD in subadult cheetahs suggests that prevention, early identification and mitigation of stress may be critical to the successful prevention of CRD in this species in captivity.S1 Table(XLSX)Click here for additional data file.


This article includes data from three prospective longitudinal human cohorts of prenatal marijuana exposure (PME) and offspring outcomes from the fetal period through young adulthood. The table herein contains an overview of the major adverse effects associated with PME from the following human cohorts: (1) The Ottawa Prenatal Prospective Study (OPPS); (2) The Maternal Health Practices and Child Development Study (MHPCD); and (3) The Generation R Study (Gen R). In the OPPS, fetal gestational age was measured and age-appropriate standardized neuropsychological instruments were used to assess neonatal responses, and infant–child and adolescent–young adult cognitive and behavioral skills. In the MHPCD, birth length and weight, neonatal body length, and infant–child sleep, cognition, and behavioral parameters were measured. In the Gen R, birth weight and growth were measured, as were infant–child attention and aggression. The data in this article are in support of our report entitled “Prenatal Cannabis Exposure - The "First Hit" to the Endocannabinoid System”   Specifications TableValue of the data•This dataset is of value to the scientific community because it can serve as a reference for other researchers interested in the adverse effects of prenatal marijuana use on offspring outcomes from the fetal period through young adulthood.•These data are of value to the scientific community because they can open doors for new collaborative research efforts between physician-scientists (neonatologists), psychiatrists, drug addiction counselors, and/or basic drug abuse and addiction research scientists.•These data highlight the need for more extensive basic, clinical, and translational research on the impact of prenatal marijuana exposure on the development of cognitive and psychological processes in exposed offspring.•These data highlight the need for researchers to develop novel strategies for improving the health of and healthcare for pregnant women and their children.1The data described herein are adapted from three articles 2The OPPS assessed the effects of prenatal tobacco, alcohol, and marijuana exposure in a low-risk, middle-class, mostly Caucasian, and predominantly Canadian cohort of women. The offspring of participants were followed until the age of 18–22 years The MHPCD assessed the effects of prenatal alcohol and marijuana exposure in a cohort of Caucasian (43%) and African American (57%) women of low socioeconomic status who were predominantly single (71%) in Pittsburgh, Pennsylvania, USA. Follow-up assessment data of offspring have been reported up to age 14 The Gen R is an ongoing, population-based, large-scaled, multi-ethnic prospective cohort investigation of prenatal marijuana exposed offspring from the fetal period to early childhood in Rotterdam, The Netherlands.