Adolescents have special sexual and reproductive health needs . This review assesses the impact of interventions to improve adolescent sexual and reproductive health  and to prevent intimate violence. Our review findings suggest that sexual and reproductive health education, counseling, and contraceptive provision are effective in increasing sexual knowledge, contraceptive use, and decreasing adolescent pregnancy. Among interventions to prevent FGM/C, community mobilization and female empowerment strategies have the potential to raise awareness of the adverse health consequences of FGM/C and reduce its prevalence; however, there is a need to conduct methodologically rigorous intervention evaluations. There was limited and inconclusive evidence for the effectiveness of interventions to prevent intimate partner violence. Further studies with rigorous designs, longer term follow-up, and standardized and validated measurement instruments are required to maximize comparability of results. Future efforts should be directed toward scaling-up evidence-based interventions to improve adolescent sexual and reproductive health in low- and middle-income countries, sustain the impacts over time, and ensure equitable outcomes. A significant number of adolescents around the globe are sexually active, and this proportion increases steadily from mid- to late adolescence Nearly a quarter of girls aged 15–19 years are married with an estimated 16 million adolescents giving birth each year globally, of whom, 95% are from low- and middle-income countries (LMICs) Female genital mutilation/cutting (FGM/C) is a hazardous traditional practice on prepubescent girls that involves partial or total removal of the external female genitalia or other injury to the female genital organs for nonmedical reasons In 2011, the World Health Organization (WHO) issued guidelines on preventing early pregnancy and poor reproductive outcomes in adolescents from LMICs focusing on four major pregnancy prevention outcomes: (1) increasing access to and use of contraception; (2) preventing marriage before 18 years; (3) increasing knowledge and understanding of the importance of early pregnancy prevention; and (4) preventing coerced sex Adolescents have special sexual and reproductive health needs that remain unmet, mainly due to lack of knowledge, social stigma, laws and policies preventing provision of contraception and abortion to unmarried (or any) adolescents, and judgmental attitudes among service providers 1.Overview of systematic reviews: We conducted an overview of systematic reviews for interventions where recent systematic reviews existed;2.Updating existing reviews: We updated the existing systematic reviews if the existing review only included evidence prior to 2011; and3.De novo review: For interventions where no reviews existed, we conducted a de novo review.We systematically reviewed all published literature up to December 2014 on interventions to improve sexual health in adolescent population focusing on sex education, preventing unintended adolescent pregnancy, intimate partner violence, and FGM/C. We took a systematic approach to consolidate the existing evidence through the following three methodologies in order to include all the recent evidence:For the purpose of this review, the adolescent population was defined as aged 11–19 years; however, since many studies targeted youth (aged 15–24 years) along with adolescents, exceptions were made to include studies targeting adolescents and youth. Studies were excluded if they targeted age groups other than adolescents and youth or did not report segregated data for the age group of interest. The search was conducted till December 2014, and we did not apply any limitations on the start search date or geographical settings and have attempted to carry out subgroup analysis for various interventions and settings, where data permitted.For de novo reviews, our priority was to select existing randomized, quasi-randomized, and before/after studies, in which the intervention was directed toward adolescents and related to sexual and reproductive health outcomes. A separate search strategy was developed for each aspect using appropriate keywords, medical subject heading, and free text terms. The following principal sources of electronic reference libraries were searched to access the available data: The Cochrane Library, Medline, PubMed, Popline, LILACS, CINAHL, EMBASE, World Bank's JOLIS search engine, CAB Abstracts, British Library for Development Studies BLDS at Institute of Development Studies, the WHO regional databases, Google, and Google Scholar. The titles and abstracts of all studies identified were screened independently by two reviewers for relevance and matched. Any disagreements on selection of studies between these two primary abstractors were resolved by the third reviewer. After retrieval of the full texts of all the studies that met the inclusion/exclusion criteria, data from each review or study were abstracted independently and in duplicate into a standardized form. Quality assessment of the included randomized controlled trials (RCTs) was done according to the Cochrane risk of bias assessment tool. We conducted a meta-analysis for individual studies using the software Review Manager, version 5.3 . Pooled statistics were reported as the relative risk (RR) for categorical variables and standard mean difference (SMD) for continuous variables between the experimental and control groups with 95% confidence intervals (CIs). A grade of “high,” “moderate,” “low,” and “very low” was used for grading the overall evidence indicating the strength of an effect on specific health outcome according to the Grading of Recommendations Assessment, Development and Evaluation criteria We considered all available published systematic reviews on the interventions to improve adolescent sexual health. Our priority was to select existing Cochrane and non-Cochrane systematic reviews of randomized or non-RCTs, which fully or partly addressed the interventions. A broad search strategy was used that included a combination of appropriate keywords, medical subject heading, and free text terms, and search was conducted in The Cochrane Library, Medline, and PubMed. The abstracts (and the full sources where abstracts are not available) were screened by two abstractors to identify systematic reviews adhering to our objectives. Any disagreements on selection of reviews between these two primary abstractors were resolved by the third reviewer. After retrieval of the full texts of all the reviews that met the inclusion/exclusion criteria, data from each review were abstracted independently and in duplicate into a standardized form. Information was extracted on (1) the characteristics of included studies; (2) description of methods, participants, interventions, and outcomes; (3) measurement of treatment effects; (4) methodological issues; and (5) risk of bias tool. We extracted pooled effect size for the outcomes of interest with 95% CIs. We assessed and reported the quality of included reviews using the 11-point assessment of the methodological quality of systematic reviews (AMSTAR) criteria We updated the existing systematic reviews only if the most recent review on a specific intervention was conducted before December 2011. For updating the existing reviews, we adopted the same methodology and search strategy mentioned in the existing review to update the search and find all the relevant studies after the last search date of the existing review. After retrieval of the full texts of all the articles that met the inclusion/exclusion criteria, data from each study were abstracted independently and in duplicate into a standardized form. Information was extracted on study design, geographical setting, intervention type and description, mode of delivery, and outcomes assessed. We then updated the estimates of reported outcomes by pooling the evidence from the new studies identified in the updated search and reported new effect size for the outcomes of interest with 95% CIs. We then assessed and reported the quality of included reviews using the 11-point AMSTAR criteria We found existing systematic reviews on interventions for improving adolescent sexual and reproductive health; however, they were limited in their scope to a particular strategy such as school-based interventions Studies were included if any form of sexual and reproductive health education, counseling, and access to contraception was delivered to adolescents compared to no intervention or general health education. We identified 1,123 titles from the search conducted in all databases. After screening the titles and abstracts, 84 studies were identified that met the inclusion criteria Moderate quality data suggest that sexual and reproductive health education, counseling, and contraceptive availability increased “mean knowledge score about sexual health and contraception” , “mean condom use self-efficacy score” , use of any contraception , and condom use , and HIV prevention education were effective in improving contraceptive use but did not impact mean knowledge scores. Subgroup analysis for HICs and LMICs could not be conducted due to limited number of studies in LMIC settings . Data quA search was conducted for literature published after March 2011 following the same methodology as Berg et al. A total of 11 studies We report the findings from a Cochrane review by Fellmeth et al. Our review suggests that sexual and reproductive health education, counseling, and contraceptive availability are effective in increasing adolescent knowledge related to sexual health, contraceptive use, and decreasing adolescent pregnancy. We could not conduct subgroup analysis for the effectiveness of these interventions in HICs and LMICs since there were limited studies from LMIC settings. Among interventions to prevent FGM/C, community mobilization and female empowerment have the potential to raise awareness of the adverse health consequences of FGM/C and decrease its prevalence; however, there is a need to conduct methodologically rigorous intervention evaluations. Overall, there was limited and inconclusive evidence for the effectiveness of interventions to prevent intimate partner violence.Our findings are in concordance with existing reviews evaluating the effectiveness of various interventions for improving adolescent sexual and reproductive health and also collate various interventions under a broader umbrella to evaluate the combined effectiveness of these interventions. An existing Cochrane review on primary prevention interventions  on unintended pregnancies among adolescents also suggests that combination of educational and contraceptive interventions can lower the rate of unintended pregnancy among adolescents with nonconclusive evidence on secondary outcomes, including initiation of sexual intercourse, use of birth control methods, abortion, childbirth, and STIs The United Nations Fund for Population Activities (UNFPA) and United Nations International Children's Emergency Fund (UNICEF) joint program, developed in 2007 to protect girls and women by accelerating abandonment of FGM/C and providing care for its consequences, has accelerated existing changes toward FGM/C abandonment by legal frameworks, coordination mechanisms, and access to services at both community and national level. But, further efforts are needed, especially at the national and community levels, to bring changes in behaviors and practices This existing evidence on adolescent sexual reproductive health has several limitations. Most trials failed to utilize allocation concealment, blinding, and randomization to optimize their outcomes. Hence, most of the outcomes were rated as low or moderate in methodological quality. There was a lack of rigorous study design for the interventions to prevent FGM/C with most studies utilizing before and after designs without comparable controls, although individual or cluster RCTs to address FGM/C would pose huge ethical challenges. Nevertheless, many of the trials focused on nonstandardized and self-reported outcomes with short follow-up periods that might have been insufficient to detect any meaningful behavioral changes to establish or to wash out the effect of intervention. Most studies on intimate partner violence analyzed outcomes such as attitude and knowledge rather than episodes of violence and behavioral change. Furthermore, we found a dearth of evidence on interventions for improving sexual health of adolescents living in LMICs where the majority of the adolescent population of the world resides. This might lead to limited external validity for many of these interventions. Most of the studies did not report data segregated by gender which is essential since males and females might respond differently to behavioral interventions. The wide variability in study constructs, nonuniformity in subgroup population, lack of subgroup analysis of gender, socioeconomic status, and nonstandardized outcomes all preclude the external validity and effectiveness of the present interventions in LMICs.Our review suggests that a range of comprehensive interventions targeting sexual health education, counseling, consistent birth control methods promotion, and provision have the potential to prevent and control the adverse outcomes related to risky sexual behavior. However, much more is needed to increase awareness and prevent FGM and intimate partner violence.


Neglected tropical diseases (NTDs) prevail among poor people in developing countries who that largely remain out of reach of national health care delivery systems. Since 2005, the WHO has moved away from a disease-centred to an integrated, intervention-based approach to counter these diseases, providing marginalised communities with better access to health care .In 2007, a meeting of the WHO’s global partners marked a turning point in efforts to overcome NTDs, resulting in an increased commitment and engagement from endemic WHO Member States and the pharmaceutical industry and expanded collaboration among partners [In 2012, inspired by the WHO Roadmap on NTDs, multiple stakeholders, including chief executive officers from the world’s major pharmaceutical companies, donors, and government representatives, met in London and pledged to work together to accelerate the control, prevention, elimination, and eradication of ten NTDs  by signiIn 2015, increased donations of essential medicines have enabled access to treatment for almost a billion people, mainly through preventive chemotherapy for at least one NTD (billion here is defined as a thousand million) . TargeteIn 2015, all Latin American countries achieved universal blood screening for Chagas disease among blood donors. Dracunculiasis is poised for eradication, with a total of only 25 human cases  from only three countries still reporting transmission. Mali reported zero cases for the first time in 2016.Elimination of human African trypanosomiasis (sleeping sickness) as a public health problem is in sight, with fewer than 3,000 cases reported worldwide in 2015 .In 2016, the WHO certified six countries—Cambodia, Cook Islands, Maldives, Niue, Sri Lanka, and Vanuatu—as having eliminated lymphatic filariasis as a public health problem . A furthIn the region of the Americas, onchocerciasis has been almost eliminated; Guatemala (2016), Mexico (2015), Ecuador (2014), and Colombia (2013) have recently been declared free of the disease .While tackling NTDs prioritises the public health needs of poor people, it may be time to revisit the fundamentals of preventive interventions for vector control, veterinary public health, and measures associated with safe water, sanitation, and hygiene.Clearly, the strategies and responses developed more than a decade ago to control or eliminate NTDs are now woven into the fabric of the 2030 agenda for achieving the Sustainable Development Goals (SDGs). Not only are there many areas of alignment, but many of the same NTD programmes and interventions have implications for multiple goals.Preventive chemotherapy, for example, has a bearing on poverty, nutrition, education, employment, and gender equality. Combating vector-borne diseases through the provision of safe water or safe water storage has an impact on making cities safer, whereas strengthening linkages between veterinary, environmental, and medical communities can better focus attention on emerging diseases and tackle antimicrobial resistant pathogens .Many of the challenges presented by NTDs require the kind of multisectoral responses encouraged by the 2030 agenda as demonstrated by the numerous alliances working in partnership “to end the epidemic of NTDs.” Nowhere is the issue of integration more pertinent than in relation to goal three of the SDGs—the health goal—which requires the alignment of multiple programmes and initiatives towards the overarching goal of universal health coverage.The notion of equity woven into the fabric of the NTD agenda reminds the international community that prioritisation of services and explicit consideration must be given to the most disadvantaged groups, including those living in low-income and rural communities who are most at risk of NTDs.Today, much depends on medicines donated free of charge or subsidised interventions for the very poorest people and for those living in communities that are often beyond the reach of formal health systems. The WHO Roadmap and initiatives such as the London Declaration are game-changers that share the same engagement in mainstreaming NTDs in the global public health agenda as they continue to contribute to expanding access to health.Extending universal health coverage will require a shift towards greater decentralisation of health services, including outreach beyond fixed health facilities, in order to provide people-centred integrated health services to all.Meeting the 2030 SDG targets, while “leaving no one behind,” will largely depend on how we prioritise our fight against NTDs.


This study aimed to test the diagnostic performance of a fully quantitative fibrosis assessment tool for liver fibrosis in patients with chronic hepatitis B (CHB), primary biliary cirrhosis (PBC) and non-alcoholic steatohepatitis (NASH). A total of 117 patients with liver fibrosis were included in this study, including 50 patients with CHB, 49 patients with PBC and 18 patients with NASH. All patients underwent liver biopsy (LB). Fibrosis stages were assessed by two experienced pathologists. Histopathological images of LB slices were processed by second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy without staining, a system called qFibrosis (quantitative fibrosis) system. Altogether 101 quantitative features of the SHG/TPEF images were acquired. The parameters of aggregated collagen in portal, septal and fibrillar areas increased significantly with stages of liver fibrosis in PBC and CHB (P<0.05), but the same was not found for parameters of distributed collagen (P>0.05). There was a significant correlation between parameters of aggregated collagen in portal, septal and fibrillar areas and stages of liver fibrosis from CHB and PBC (P<0.05), but no correlation was found between the distributed collagen parameters and the stages of liver fibrosis from those patients (P>0.05). There was no significant correlation between NASH parameters and stages of fibrosis (P>0.05). For CHB and PBC patients, the highest correlation was between septal parameters and fibrosis stages, the second highest was between portal parameters and fibrosis stages and the lowest correlation was between fibrillar parameters and fibrosis stages. The correlation between the septal parameters of the PBC and stages is significantly higher than the parameters of the other two areas (P<0.05). The qFibrosis candidate parameters based on CHB were also applicable for quantitative analysis of liver fibrosis in PBC patients. Different parameters should be selected for liver fibrosis assessment in different stages of PBC compared with CHB. The severity of liver fibrosis is an important factor for long-term prognosis of liver disease. Studies show that liver fibrosis is a reversible process –3. AccuLiver biopsy is still the gold standard for quantitative assessment of liver fibrosis. From the initial subjective and descriptive diagnosis to the current semi-quantitative score system, the pathological assessment of liver fibrosis has improved greatly. Several semi-quantitative staging systems exist, including Knodell staging system, Ishak staging system, Metavir staging system, and others . AlthougNoninvasive diagnostic methods for liver fibrosis, including fibroscan and MRI, have been widely used in the diagnosis of severe liver fibrosis and cirrhosis in recent years, but these methods are not effective in the diagnosis of mild or moderate liver fibrosis. So currently, the noninvasive diagnostic methods can not completely substitute liver biopsy .In recent years, a new concept of quantitative structure has been proposed, which is based on a new technology tool – qFibrosis analysis system . It reliThe aim of this study is to assess the diagnostic performance of qFibrosis for the evaluation of fibrosis and histological stages in chronic cholestatic diseases of primary biliary cirrhosis (PBC) and non-alcoholic steatohepatitis (NASH) by comparing with the results from chronic hepatitis B (CHB), to analyze the characteristics of different etiology liver fibrosis in different stages, and to provide theoretical basis and data for further clinical application of qFibrosis.Altogether 117 patients with liver fibrosis, including 50 patients with chronic hepatitis B (CHB), 49 patients with primary biliary cirrhosis (PBC), and 18 patients with non-alcoholic steatohepatitis (NASH) were retrospectively enrolled from October 2010 to October 2015, in Beijing Friendship Hospital, Capital Medical University. Patients diagnosed with a single known etiology and that underwent percutaneous liver biopsy (LB) were included in this study. Patients with other or mixed etiologies, and malignancy were excluded. Informed written consent was obtained from all patients and the study was approved by the Research Ethics Committee of the Beijing Friendship Hospital.PBC was defined according to the 2009 PBC practice guidelines from the American Association for the Study of Liver Diseases (AASLD) , as follLiver biopsy specimens were routinely fixed in formalin and paraffin embedded. Five-micron thick sections were stained with Masson trichrome for histological assessment. Biopsy specimens were analyzed independently by two experienced pathologists. Liver fibrosis of CHB and PBC were evaluated semiquantitatively according to the Metavir staging system : F0: no The embedded biopsy specimen sectioned at 5-μm thickness were dewaxed for imaging by the SHG/TPEF microscopy system . Collagen was visualized by SHG microscopy and hepatocyte morphology was acquired by the TPEF microscopy. We used the full scan method to acquire the images. Images were acquired at 20× magnification with 512×512 pixel resolutions. Image processing and analysis (threshold and SHG scoring) were routinely performed, and 101 quantitative morphological features of the SHG/TPEF image were acquired by the computer-aided system. Three main fibrosis patterns – collagen in portal area , collagen in septal area (bridging fibrosis), and collagen in fibrillar area  were evaluated in this study. Collagen features were classified into three groups: collagen proportions including total, aggregated and distributed collagen percentages; collagen string properties such as the thickness, length, and width; and ratios of different collagen string types. See The qFibrosis parameters for patients with CHB, PBC and NASH were analyzed. One-way ANOVA test was also used for parameter comparison between different fibrosis stages. In order to determine the characteristics of liver fibrosis from different etiologies, Spearman correlation analysis was used to analyze correlation between parameters and stages.Parameters of aggregated collagen in portal, septal and fibrillar areas all increased significantly with higher fibrosis stages in samples from PBC and CHB (P<0.05), but parameters of distributed collagen did not increase significantly (P>0.05). There was no significant increase in parameters in samples from NASH (P>0.05) .Spearman correlation analysis showed a significant correlation between parameters in portal, septal and fibrillar areas for both CHB and PBC samples (P<0.05), but no significant correlation was found between collagen parameters and stage of liver fibrosis for both CHB and PBC samples (P>0.05). There was no significant correlation between NASH parameters and fibrosis stages (P>0.05) .For CHB and PBC patients, the highest correlation was between the septal parameters and stages of fibrosis, in the middle was the correlation between portal parameters and stages, and the lowest correlation was between fibrillar parameters and stages, which suggest that the septal parameter is the most important for predicting liver fibrosis progression .From the second harmonic generation and two-photon excited fluorescence images, the pathological patterns of fibrosis are different in different etiologies, with collagen stained in green and liver cell structure stained in red .Liver biopsy is still the gold standard in etiology differentiation and severity evaluation of liver fibrosis, providing descriptive diagnosis. By analyzing pathological changes of liver diseases, researchers establish disease severity according to pathological characteristics, such as necrosis in portal or septal area, degeneration or foci necrosis in fibrillar area, portal veins inflammation and liver fibrosis . In ordeEffort is made to assess the progression of liver fibrosis by the proportion of collagen fibers in the liver. Morphological assay (morphometry) is frequently used in clinical studies. In this method, collagen fibers from a stained area are calculated and compared with the whole area under analysis to get the collagen proportionate area (CPA). CPA, also called collagen area ratio, is 1 to 7% in normal liver and 12 to 36% in liver cirrhosis. CPA can be further subdivided, and it is used as an independent predictor for cirrhosis . DespiteqFibrosis quantitative analysis of liver biopsies includes quantitative and structural information of fibrosis, which can reflect changes of fibrosis intensity and distribution. Combining the staging method with fully quantitative fibrosis analysis can also solve the problems of the traditional stage system - etiology differentiation and fibrosis reversion. The fully quantitative method can confirm fibrosis reversion from a pathological point of view.In this study, we assessed the performance of qFibrosis for the evaluation of fibrosis and histological stages in chronic cholestatic diseases of PBC, CHB, and NASH. We found that the parameters of aggregated collagen in portal, septal and fibrillar areas all increased significantly with higher stages of liver fibrosis in PBC and CHB, but the parameters of distributed collagen did not significantly increase in the same samples. Also, there was a significant correlation between parameters in portal, septal and fibrillar areas for both CHB and PBC, but not between the collagen parameters and the stages of liver fibrosis in those diseases. There was no significant correlation between NASH parameters and fibrosis stages. For CHB and PBC patients, the highest correlation was between septal parameters and fibrosis stages, the second highest was between portal parameters and fibrosis stages and the lowest correlation was between fibrillar parameters and fibrosis stages, which suggest that the septal parameter was the most important predictor for liver fibrosis progression.Compared with parameters of distributed collagen, parameters of aggregated collagen in portal, septal and fibrillar areas seem to be more suitable for assessment of liver fibrosis progression in PBC and CHB patients. Pathologically, for PBC patients, liver fibrosis progression happens in the septal area, although it starts in the portal area. For CHB, parameters in the portal and septal areas were strongly correlated with progression of stages, which suggests that the parameters in these two areas, particularly the aggregated collagen parameters, could be used in the assessment of liver fibrosis progression and reversion. The qFibrosis candidate parameters based on CHB are also applicable for quantitative analysis of liver fibrosis in PBC. In this study, the parameters for NASH were not significantly correlated with fibrosis stages, suggesting that the candidate parameters of qFibrosis based on CHB are not suitable for quantitative assessment of liver fibrosis in NASH. Further studies are necessary to reach a stronger conclusion, because of the small sample size of NASH cases in this study.pdf]Click here to view [


Balance in protein turnover influences the regulation of skeletal muscle mass  on skeletal muscle growth in mice. They suggested that only synchronous inhibition of both receptors induces a maximal anabolic response  was investigated on HEK293T/17 cells stably expressing Smad2/3; this effect was then compared with that of anti-ActRIIA or anti-ActRIIB antibodies. Inhibition of both receptors with a combination of these antibodies, bimagrumab, and CDD866, completely blocked Smad2/3 signaling induced by myostatin and activin A in comparison with the 30–50% inhibition with the either of the two antibodies.To compare the effect of single or synchronous blockade of ActRIIA and ActRIIB on muscle growth, mice were treated with anti-ActRIIA, anti-ActRIIB, both antibodies, or bimagrumab. Treatment with a combination of anti-ActRIIA and anti-ActRIIB antibodies or bimagrumab increased muscle strength and mass by 20–30%, compared to the control, meanwhile, treatment with individual antibodies, increased by 10%. This suggested that higher growth response results from blockade of both receptors, compared to effects of individual antibodies.Recently, both murine models of cancer cachexia and bone healing after osteotomy suggest that either CDD866 or bimagrumab protects against both body weight and muscle mass loss resulting from anti-cancer therapy, with no effects on bone fracture healing  indicates that the effect of bimagrumab was assessed in chronic obstructive pulmonary disease patients with cachexia and on weight loss in lung or pancreatic cancer patients; Bimagrumab increased muscle volume and is currently under clinical trials on patients who underwent hip fracture surgery or in patients with sarcopenia, overweight, and obesity, with type 2 diabetes.Morvan et al. reported the role of ActRIIA and ActRIIB in muscle growth, representing valuable targets for blockade in pharmacological studies, along with a potential therapeutic alternative for patients with decreased muscle strength and mass. The clinical trials resource on the NIH website  that consequently potentiate myostatin/activin ligand atrophy (Schwarz et al., Hence, important aspects regarding interactions among different muscle growth regulators and drugs that inhibit ActRIIA/IIB receptors warrant further investigation. Pharmacological and preclinical studies aimed to identify integrated regulatory mechanisms that operate on muscle metabolism and growth could be used to promote healthy muscle adaptation and delay muscle loss associated with progression of muscle-related diseases and aging.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JC and handling Editor declared their shared affiliation.


Social medical insurance schemes are crucial for realizing universal health coverage and health equity. The aim of this study was to investigate whether and how reimbursement for injury-induced medical expenses is addressed in Chinese legislative documents relevant to social medical insurance. We retrieved legislative documents from the China National Knowledge Infrastructure and the Lawyee databases. Four types of social medical insurance schemes were included: urban employee basic medical insurance, urban resident basic medical insurance, new rural cooperative medical system, and urban and rural resident medical insurance. Text analyses were conducted on all identified legislative documents. As a result, one national law and 1,037 local legislative documents were identified. 1,012 of the 1,038 documents provided for reimbursement. Of the 1,012 documents, 828 (82%) provided reimbursement only for injuries without a legally responsible person/party or not caused by self-harm, alcohol use, drug use, or other law violations, and 162 (16%) did not include any details concerning implementation. Furthermore, 760 (92%) of the 828 did not provide an exception clause applying to injuries when a responsible person/party could not be contacted or for situations when the injured person cannot obtain reimbursement from the responsible person/party. Thus, most Chinese legislative documents related to social medical insurance do not provide reimbursement for medical expenses from injuries having a legally responsible person/party or those caused by illegal behaviors. We argue that all injury-induced medical expenses should be covered by legislative documents related to social medical insurance in China, no matter what the cause of the injury. Further research is needed to explore the acceptability and feasibility of such policy changes. Social medical insurance programs have long been used by state governments to protect finances of individuals and households affected by illness and injury and to realize universal health coverage for all citizens. However,Injuries are a significant global health challenge. In 2015, injuries caused 64.1 deaths per 100,000 population and accounted for 8.5% of all deaths in the world.[China—which contains close to 1/5 of the world’s population—recently realized coverage of social medical insurance to over 95% of its residents, including to rural areas The ongoDespite this positive progress to ensure medical coverage for all citizens, the Social Insurance Law of the People’s Republic of China states that social medical insurance covers only the cost of medical care for injuries having no legally responsible person/party or injuries for which the legally responsible person/party that caused the injury cannot be reached or does not pay the medical expenses. This natOur systematic search of both the English and Chinese scientific literatures suggests scholars have written very little concerning the topic of reimbursement for injury-induced medical expenses in China’s social medical insurance schemes. Relevant publications offer only opinions and perspectives rather than presenting research evidence on reimbursement regulations for injury-induced expenses.–17 StudiThus, this study was designed to examine the extent to which national social medical insurance law in China influences the policies of local governments to provide for reimbursement of medical expenses from injuries caused by external responsible persons or parties. To address this question, we conducted a systematic review of legislative documents, assessing whether and how reimbursement for injury-induced medical expenses is addressed in local Chinese social medical insurance schemes.This study is based on open-access legal database and does not involve any private information of individuals. The research was approved by the Medical Ethics Committee of Central South University in Changsha, China.In China, national-level legislative documents are classified into three categories: (a) laws issued by the Standing Committee of the National People’s Congress, which have the strongest legislative power; (b) admihttp://law1.cnki.net/law/brief/result.aspx?dbprefix=CLKLP&catalogName=CLKL_CLS) [http://www.lawyee.net) [For this study, the China National Knowledge Infrastructure (CNKI) (available from: LKL_CLS)  and the yee.net)  were seayee.net)  The Lawyyee.net) Our search was limited to four kinds of social medical insurance schemes in China: the UEBMI for employees, NRCMS for rural residents, URBMI for urban residents, and URRMI for urban and rural residents in participating provinces. Disability insurance schemes are not part of the social insurance system according to the People’s Republic of China Social Insurance Law, and therWe used a combination of two groups of search terms to conduct our search of documents. Group A consisted of social medical insurance related terms and group B consisted of injury related terms.Group A covers the full name and abbreviations of the four types of social medical insurance schemes: urban employee basic medical insurance (UEBMI), urban resident basic medical insurance (URBMI), new rural cooperative medical system (NRCMS), and the urban and rural resident medical insurance (URRMI).Group B includes both general injury and specific injury causes, all based on the classification of external causes of injury recommended by the United States Centers for Disease Control and Prevention. FollowinCombining the terms in Groups A and B, a total of 360 search combinations were used to conduct the document search. Detailed search terms, listed in the original Chinese language, are included in the Four criteria were used to determine eligible documents:relevant to the reimbursement for injury-induced medical expenses for any of the four social medical insurance schemes;being national or local legislative documents;being valid current legislation  at the time of searching and screening legislative documents (from October 2016 to February 2017);focusing on the general population in either a national or local jurisdiction.The first author (YG) completed the document search, manual screening and information extraction. 20% of initial documents retrieved through the search were selected at random for a second review by the same researcher and the consistency coefficient for the two-round document screening was 99.8% for the CNKI and 99.4% for Lawyee.st, 2nd, 4th and 5th authors) first developed a draft data extract form  and then conducted a pilot evaluation of 157 eligible policy documents. Issues revealed in the pilot data extraction and document evaluation were resolved through email communication and face-to-face group discussion to improve the data extraction form and document evaluation indicators. Next, we used three indicators to assess our outcomes of interest, the inclusion of reimbursement for injury-induced medical expenses in each legislative document, as listed below.A group of eight postgraduates studying at the Xiangya School of Public Health, Central South University  expenses for injuries having no legally responsible person/party and not caused by self-harm, alcoholism, drug use, or other legal violations; (2) expenses for injuries having a legally responsible person/party but not caused by self-harm, alcoholism, drug use, or other legal violations; (3) expenses for specific injuries, including burns, scalds, animal bites, vaccine-related adverse reactions, and natural disasters not mentioning whether they have a legally responsible person/party; and (4) expenses for injuries are covered, but no detailed requirements are listed.Indicator C: Does the legislative document include an exception clause allowing for reimbursement of medical expenses from injuries having a legally responsible person/party or caused by self-harm, alcoholism, drug use, or other legal violations? Four options were coded: (1) no exception clause included; (2) an exception clause is present and applies to injuries whose legally responsible person/party cannot be reached; (3) an exception clause is present and applies to situations when the injured person does not receive reimbursement from the legally responsible person/party; (4) an exception clause is present and applies to injuries whose legally responsible person/party cannot be reached or the injured person does not receive reimbursement from the legally responsible person/party.In addition to collecting data concerning the three indicators, we extracted the following information from all eligible documents: full-text transcription of relevant clauses, name of the document, type of legislative document , administrative level , issue date, and type of social medical insurance scheme or schemes involved . All potentially related document texts were extracted from each eligible document for formal evaluation.st, 4th, 5th and 6th authors) was held. This step was required for only 2 of 2878 judgments (0.07%) among the 1038 eligible documents. Note that 1038 documents were evaluated for indicator A, 1012 documents for indicator B and 828 documents for indicator C.The evaluation of policy documents was completed by the first author (YG). On rare occasions when the researcher felt she could not make a judgment with confidence, group discussion among nine researchers  legislative documents allowed for reimbursement of injury-induced medical expenses . ReimburThe majority of the legislative documents  allowed for reimbursement of medical expenses from injuries having no legally responsible person/party and not caused by self-harm, alcoholism, drug use, or other legal violations (Category A). Most of the remaining documents  provided no detailed requirements, although they did allow for reimbursement of injury-induced medical expenses . Data paOf the 828 legislative documents not covering injuries with a legally responsible person/party or caused by self-harm, alcoholism, drug use, or other legal violations, 760 (92%) had no exception clause. Twenty-three documents had an exception clause for injuries whose legally responsible person/party could not be reached, 7 had an exception clause in situations where the injured person did not receive reimbursement from the legally responsible person/party, and 38 had an exception clause applying to injuries whose legally responsible person/party could not be reached or when the injured person did not receive reimbursement from the responsible person/party . Data paFrom both moral and logical perspectives, comprehensive social medical insurance programs should cover all health and medical conditions, including those caused by injuries. We found that most Chinese regulations (97%) included reimbursement of injury-induced medical expenses. However, of the 1,012 documents covering injuries, 828 (82%) did not include coverage for injuries having a legally responsible person/party or caused by risky behaviors such as alcohol use, and 16% provided no specific details concerning reimbursement. Further, of the 828 documents not incorporating coverage for injuries having a legally responsible person/party or caused by the included risky behaviors, 92% had no exception clause to account for situations where, for example, the responsible person or party could not be reached or did not pay the expenses.Following previous research, we adoptThe exclusion of injuries from social insurance in local legislative documents can have serious impact on injured individuals and their families living in those jurisdictions. In situations where the legally responsible person/party for the injury cannot be reached or refuses to pay the expenses, substantial economic burden could fall to the injured person and his/her family. The situation also can lead to fraud in the medical community, whereby clinical diagnoses are tampered by medical personnel from injuries to other causes to help patients obtain social medical insurance reimbursement.,38–40 BeInjuries cause approximately 700,000 deaths and 620 million hospitalizations in China each year. From theSuch legal policies also could conflict with the principles of the World Health Organization Global Alliance for Care of the Injured—to ensure essential medical coverage for patients without regards to the ability to pay and achiThis study was limited by the completeness (representativeness) of national and local legislative documents in the legal document databases that we used. Some local legislative documents may not appear in databases because some local governments retain their legislation as private documents. This is especially the case at the county level, where we detected only 394 eligible documents . This impWe conclude that the majority of Chinese local legislative documents related to social medical insurance do not provide reimbursement for medical expenses from injuries having a legally responsible person/party or caused by illegal behaviors. The results likely derive from the fact that local regulations follow the national social medical law. To realize universal health coverage nationwide, China has two logical options. First, legislators could mandate that all injury-induced medical expenses are reimbursed by social medical insurance at the national level, no matter what the cause of the injury. Further scientific research could support such a policy change by assessing the economic and policy impacts of it, including the acceptability, feasibility and affordability of relevant law and policy changes . An alternative approach would be national availability of supplementary insurance (or subsidy programs) to provide injury insurance, disability insurance, poverty remedy and children’s aid. Such programs, if used widely, could relieve economic burden to injured persons and their families if they allow for reimbursements not offered by primary insurance programs. Of course, the two options also could be integrated to maximally alleviate economic burden to citizens.S1 Appendix(DOCX)Click here for additional data file.


Pain is the most reported and troublesome symptom of nearly all functional disorders affecting the genitourinary and gastrointestinal organs. Patients with irritable bowel syndrome (IBS), interstitial cystitis/painful bladder syndrome (IC/PBS), vulvodynia, and/or chronic prostatitis/chronic pelvic pain syndrome  report pain severe enough to impact quality of life and often suffer from symptoms of or are diagnosed with more than one of these syndromes. This increased comorbidity between chronic pelvic pain syndromes, and with pain disorders of disparate body regions, as well as with mood disorders, can be influenced by disruptions in the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the response to stress and influences the perception of pain. Experiencing trauma, neglect, or abuse in early life can permanently affect the functioning of the HPA axis. As such, a significant proportion of patients suffering from comorbid chronic pelvic pain syndromes report a history of early life stress or trauma. Here we will report on how these early life experiences influence chronic pelvic pain in patients. We will also discuss various rodent models that have been developed to study this phenomenon to understand the mechanisms underlying HPA axis dysfunction, as well as potential underlying mechanisms connecting these syndromes to one another. The International Association for the Study of Pain (IASP) defines “pain” as an “unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”  sensitization of primary sensory afferents innervating the viscera ; (2) hyper-excitability of ascending spinal neurons receiving synaptic input from the viscera ; and (3) dysregulation of descending pathways that modulate spinal nociceptive transmission , are also produced in stress-related brain regions. Ucn2 and Ucn3 are found in the PVN  are also abundantly expressed in the hypothalamus and limbic structures and respond to systemic and diurnal release of GCs from the adrenal cortex. The high-affinity mineralocorticoid receptor (MR) can be bound at low circulating levels of GCs, and is thus thought to be important in ambient GC signaling , whereas CRF1 is expressed in tissues such as adrenal, adipose tissue, the gonads, endometrium, myometrium, placenta, skin, spleen, and specific cells of the immune system  in rodents has been used for several decades as a model of early life stress that significantly impacts the functioning of the HPA axis -γ, as well as infiltration of mast cells, in the distal colon, all of which can sensitize peripheral nociceptors and enhance visceral perception  following reinflammation with zymosan as adults  and disruption of proper functioning of the HPA axis. Patients diagnosed with one of these disorders are very often diagnosed with, or present with symptoms of, additional functional pain syndromes and/or mood disorders, such as anxiety, panic disorder, or depression (Bullones Rodríguez et al., Patients with chronic pelvic pain disorders commonly report having experienced early life stress, trauma, or peripheral insult, including repeated infections. The strong influence that stress has on initiating and/or exacerbating symptoms associated with pelvic pain disorders further strengthens this relationship between stress and pain, likely due to the influence of the HPA axis. Development of clinical therapies and preclinical animal models should heed this important and influential relationship to improve treatment options and better understand the underlying etiology of these related disorders.IMF and JAC: equal contribution for the literature search and article preparation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This is the first structured review to identify and summarize research on lifestyle choices that improve health and have the greatest potential to mitigate climate change. Two literature searches were conducted on: (1) active transport health co-benefits, and (2) dietary health co-benefits. Articles needed to quantify both greenhouse gas emissions and health or nutrition outcomes resulting from active transport or diet changes. A data extraction tool (PRISMA) was created for article selection and evaluation. A rubric was devised to assess the biases, limitations and uncertainties of included articles. For active transport 790 articles were retrieved, nine meeting the inclusion criteria. For diet 2524 articles were retrieved, 23 meeting the inclusion criteria. A total of 31 articles were reviewed and assessed using the rubric, as one article met the inclusion criteria for both active transport and diet co-benefits. Methods used to estimate the effect of diet or active transport modification vary greatly precluding meta-analysis. The scale of impact on health and greenhouse gas emissions (GHGE) outcomes depends predominately on the aggressiveness of the diet or active transport scenario modelled, versus the modelling technique. Effective mitigation policies, infrastructure that supports active transport and low GHGE food delivery, plus community engagement are integral in achieving optimal health and GHGE outcomes. Variation in culture, nutritional and health status, plus geographic density will determine which mitigation scenario(s) best suit individual communities.  Climate change and non-communicable diseases are global crises that threaten life as we know it and require a global response. The United Nations’ sustainable development goals (SDGs) highlight the need for a multifaceted, coordinated effort to limit global temperature rise to 1.5–2 degrees Celsius and prevent the catastrophic effects of climate change [The impact of lifestyle choices on GHGE should not be underestimated or ignored. Currently, carbon-based transportation and some food’s production and transportation significantly contribute to regional and global GHGE. For example in the USA, 9% of GHGE have been attributed to the agriculture sector and 27% to the transportation sector ; whereasPublic engagement must also be fostered with respect to physical activity, diet and health. It is estimated that a third of adults and four-fifths of adolescents do not meet current public heath recommendations for physical activity . In addiIncreased physical activity, decreased sedentary time and healthy dietary choices are modifiable behaviors that can reduce morbidity and premature mortality as well as decrease GHGE when the necessary policies and infrastructure exist for sustainable choices. However, to date, lifestyle-related mitigation co-benefits appear to have received less consideration than other co-benefits strategies. Indeed, the IPCC’s recent Summary for Policy Makers lacks any discussion of active transport and diet co-benefits review articles . Though Two separate searches were conducted, one for active transport health co-benefits literature and one for dietary health co-benefits literature. In both cases, searches were performed in ScienceDirect (1995 to present), PubMed (1940s to present), and Google Scholar. The last search was performed 7 July 2014. For the active transport literature, search terms included greenhouse gas, emissions, health, co-benefits, active transport, and active travel. The primary search in ScienceDirect was as follows: (“greenhouse gas” OR emissions) AND health AND co-benefit AND (“active transport” or “active travel”). For the dietary literature, search terms included greenhouse gas, emissions, health, co-benefits, food, and diet. The primary search in ScienceDirect was as follows: (“greenhouse gas” OR emissions) AND food AND diet AND health AND (“co-benefit” or cobenefit). Articles that were deemed irrelevant based on title and abstract were excluded. The full text of the remaining, relevant articles was retrieved and further reviewed for inclusion based on the pre-defined inclusion criteria described below. Relevant articles cited within the literature were also sought out and analyzed for inclusion. Articles on greenhouse gas mitigation strategies related to lifestyle choices with health co-benefits were of interest. The lifestyle-related mitigation strategies in the existing literature include active transport and diet. For inclusion, an article must have quantified both the GHGE and the health or nutrition impact of at least one of the lifestyle-related mitigation strategies. The most common reason for exclusion was quantification of either (as oppose to both) the GHGE or the health or nutrition impact of at least one of the lifestyle-related mitigation strategies. English language articles published in peer-reviewed journals were considered without date restrictions. Review articles were not included. Due to the wide range of GHGE and health outcome measurements of interest, meta-analysis was not a goal of this review. We created a data extraction tool guided by the PRISMA guidelines. Two authors tested the tool on a subset of the literature and revisions were made until the tool design was agreed upon. The evaluation included: authors; publication date; study population description, including age, gender, time and geography; baseline data sources; study design; health and GHGE analysis methods; and outcomes. Two authors performed a second evaluation of each article using a rubric. This rubric assigned a score based on the article’s success in recognizing and addressing the biases, limitations and uncertainties of the research according to three different categories: (1) general; (2) GHGE; and (3) health . Five articles from the ScienceDirect search meet the inclusion criteria. Subsequent searches on PubMEd and Google Scholar returned two additional articles. A manual search based on articles cited in the selected literature added a further two articles. In total, literature searches produced nine articles, eight of which specifically addressed active transport, and one of which addressed both active transport and diet.2) equivalent emissions based on regional, country, or municipal models as applicable to the population of interest.Of the nine selected active transport articles, two each were based on UK, U.S., and New Zealand data, and one each on Indian, Spanish, and Organization for Economic Co-operation and Development (OECD) country data. For health outcome measures, two articles estimated the disability-adjusted life years (DALYs), another two articles evaluated monetized gains from reduced mortality or increased life expectancy, and four articles estimated all-cause mortality with or without evaluation of specific disease occurrences. One article correlated increased trends in sedentary behavior and meat consumption with obesity . IdentifThe majority of diet articles returned from the ScienceDirect search did not address greenhouse gas mitigation strategies related to diet. For relevant articles, the full text was retrieved. Most were review articles or only examined one of the two outcomes of interest . Eight articles from the ScienceDirect search were selected for inclusion. Subsequent searches on PubMed and Google Scholar resulted in ten additional articles for inclusion. A manual search based on articles cited in the selected literature added a further four articles. The Michaelowa and Dransfeld  article 2 equivalents or GHGE. Other environmental outcomes, such as change in land use, were also occasionally included.Of the 23 selected diet articles, seven were based on UK data, three were based on Swedish data, two each were based on Brazilian, French, Danish, and European data, and one each on New Zealand, Italian, Dutch, OCED, and Australian data. For health outcome measures, 18 articles evaluated intermediate determinates of health including consumption of cholesterol or saturated fats, nutrients and total calories. Several articles went further to estimate health outcomes directly. Five estimated changes in mortality or DALYs, and three evaluated the occurrence of specific diseases. All articles estimated changes to CO2eq/100 g) that was compared to the nutritional value of the item to obtain a sustainability score). González et al. [Diet articles included, with the exception of two, detailed estimates of their proposed GHGE reductions under various scenarios and therefore quantified reductions could be reported . Masset z et al.  similarlAll active transport articles considered scenarios where biking, walking or both replaced vehicular transport. In addition to active transport mitigation strategies, four articles included low emission vehicles in their transportation scenarios and two considered increased public transportation . A furthIn selected diet articles, the primary method for reducing GHGE and improving health outcomes was reduced consumption of meat and other animal products. Eleven of the articles only considered meat and other animal product reduction, while twelve considered meat and other animal product reduction amongst additional diet modifications. Further detailed information on each article is summarized in the Lifestyle-related rubric scores  are summn = 2) was 3.5/5. For Low Emissions Vehicles articles (n = 4) it was 3.25/5 and for active transport only articles (n = 4) it was 4/5. Articles that only considered active transport had better GHGE scores as GHGE were reduced more drastically than in scenarios where public transportation or low emissions vehicles were allowed to increase. For diet articles, the average GHGE rubric scores for articles where meat and animal product reduction was only considered (n = 2) was 3.9/5, whereas articles where meat and animal product reduction was considered in conjunction with more general diet modifications (n = 12) it was 4.5/5. Diet articles that considered more than reducing consumption of meat and animal products had better GHGE scores as other high GHGE producing food groups were also reduced.For active transport articles, the average GHGE rubric scores for increased public transport articles  the small number of articles found that quantified both GHGE and health impacts associated with lifestyle-related mitigation strategies; (2) the scale and range of lifestyle-related mitigation strategies examined within the literature, plus; (3) differences in model assumptions. However, following a structured review of the literature it seems that the scale of impact on health and GHGE outcomes depends predominately on the aggressiveness of the diet or active transport scenario modelled, versus the modelling technique. Implications for both researchers and policymakers are discussed below.All reviewed active transport articles concluded that their scenarios would reduce GHGE and increase physical activity resulting in net positive health outcomes. The degree to which GHGE were reduced or health was improved depended largely on the scale of the transportation modification, the range of health outcomes considered, and the assumptions of the model. In all reviewed articles physical activity was the largest determinant of health outcomes and was always positive. However, assumptions regarding the effects of traffic injury and air pollution varied between articles, resulting in a range of positive and negative health outcome predictions. Woodcock et al.  found thThe extent of emission reduction/increase for a diet scenario depended on the scale of the scenario and assumptions of the model. For example, the scenario used by Aston et al.  doubled In some articles, diet scenarios were also selected for affordability . Cost coOverall, achieving mitigation and health benefits from diet modifications requires an extensive understanding of diet and health interactions, cultural dietary traditions, plus GHGE for culturally/geographically relevant foods. Existing GHGE estimates for food items and production systems could be considered relatively narrow. Further database development of GHGE for food items and production systems would guide the development of sustainable diets  . It is eThe reviewed articles also contained parametric and structural uncertainties . ParametIn the simulation of change in a health determining exposure (point 1 above), the feasibility of widespread and extensive diet or transportation modifications over space and time must be addressed and was in some articles. Linear programming models incorporated constraints to improve the acceptability of their proposed diets, whereas, Aston et al.  and BernA change in activity level or diet (the “exposure” referred to in point 2 above) will not have an immediate effect on health, and effects may change over time. Unintended outcomes must be considered when determining changes in health or GHGE following a diet or transportation modification. Macmillian et al.  includedAs per point 3, diet and physical activity changes may affect individuals within the population differently depending on age, sex, and baseline activity and diet. Additionally, food production, automotive technology, and medical practices are continually developing, thus estimates of the impact of diet modification and active transport will change over time. The GHGE estimates produced in these articles may become less reliable as technology advances. It is also important to recognize that population-based health outcomes could improve with better medical intervention, independent of exercise or diet modification. This potential impact on the level of disease burden within a population is a source of uncertainty (point 4). Estimations of the future burden of disease were not attempted in these models, though some models incorporated this uncertainty in their future projections according to published burden of disease estimates ,25,34,41Despite the prevalence of uncertainties, the multi-potent disease prevention and treatment potential of diet and physical activity interventions should not be overlooked. Indeed, diet and physical activity/exercise interventions would make for a healthier, more resilient general population, with the likely flow-on benefit of reduce hospital admissions and reduced GHGE from the health sector. Thus, diet modifications and active transport will continue to improve GHGE and health outcomes, however, the scale of their effect will change over time and individuals will not be impacted equally by these mitigation strategies.2 equivalent emissions. Conversely, health outcomes in the dietary articles ranged from morbidity and mortality to intermediate determinants of health such as nutrient and calorie intake. In the majority of diet articles, health outcomes were associated with nutrient or calorie intake, whereby improved nutrient profiles or reduced calorie intake was associated with improved health outcomes; however, the exact impact of the diet modification on morbidity and mortality was not quantified. A few articles use previously published relative risks related to specific nutrient intake to estimate morbidity and mortality associated with proposed diet changes  into their analysis of health outcomes as a measure of pollutant exposure. Although it is not the only pollutant with a health impact, PM is considered the most relevant factor in predicting health outcomes [Active transport articles all estimated morbidity or mortality associated with physical activity, but estimations varied as to whether they also include the effects of pollutant exposure and traffic accidents on heath . The impoutcomes . Exposuroutcomes . Many mooutcomes  and Michoutcomes  were theThe majority of reviewed diet articles estimated GHGE using lifecycle assessments (LCAs) of food items or groups. Some articles used a top-down methodology with input-output analysis to scale self-reported consumption data to match food supply ,32. ThisQuantifying GHGE across stages of food production and delivery  can be complex. Each stage provides a variable, but significant contribution to GHGE. Many of the GHGE estimates in the included articles relied on previously published databases of food group’s GHGE estimates, with varying degrees of generalization regarding the source and delivery point of food items. The challenging nature of tracking the GHGE impact for individual food items likely contributes to the focus on meat production in the included dietary articles. Meat is known to be a significant contributor to agricultural and food-related GHGE and is a significant source of dietary calories, protein, and fat. It has been estimated that up to 35% of GHGE come from agriculture and land use for livestock production . The article selection may be biased as articles included were all published in English language, peer-reviewed journals. Our analysis of included articles relied heavily on the rubric of biases, uncertainties, limitations described in This review aimed to identify opportunities for health benefits and GHGE reductions through lifestyle modification. It also highlighted similarities in the two lifestyle-related mitigation strategies. The novel aspects of this review are: (1) the collective focus on both diet and transport co-benefits (2) the evaluation of similarities and differences in these bodies of literature, plus (3) the assessment of biases, limitations and uncertainties of included articles.Modeled scenarios of increased active transport conclude that health and GHGE outcomes can be improved. However, the best methods for bringing about transportation change are less clear. Macmillan et al.  used sysFor dietary interventions, the outcomes for health and GHGE are less certain. A more exhaustive list of LCAs for food items is needed in order to identify and promote low-GHGE meats and meat substitutes that best meet nutritional requirements. As far as achieving diet modification, the acceptability of taxation on high GHG emitting food will vary greatly between countries. In some countries this may provide an ideal mechanism for achieving a sustainable diet, though other strategies such as limiting meat production or placing restrictions on fats and sugars included in processed foods also have potential. Health outcome estimates could be improved with greater understanding of the effect of diet on morbidity and mortality.It is difficult to draw clear conclusions from the current body of literature regarding the scale of GHGE reductions and health improvements from potential diet and active transport interventions. Outcomes presented in the reviewed articles are difficult to compare directly due to variations in the assumptions and measurement units. More attention needs to be given to developing realistic and relevant diet and transportation modifications strategies. To date, the most effective approach proposed in the literature is the combination of a Pigouvian tax for GHGE and a “sin” tax on unhealthy food items. A tax on GHGE alone will not necessarily result in a healthier diet. Meat consumption reduction strategies may be best suited to countries with excess consumption of meat and protein, while others may need to consider developing low GHGE meat production systems that can supply their nation with a healthy protein source.


The data described in this article is related to the review article “Medicinal plants used in the traditional management of diabetes and its sequelae in Central America: a review”   Specifications TableValue of the data•Data scattered across literature compiled in one database.•Future research and analysis on the medicinal plants used to manage diabetes and its sequelae at country and regional level will be facilitated by the data included here.•Plant names validated against The Plant List, taxonomic status checked, and current accepted name provided.•Complete list of synonyms for compiled medicinal plants to facilitate research.1The data includes 1055 use reports of 537 plant taxa used to manage diabetes and its sequelae in Central America  are alsoThe data are analysed in a related article [1].2We searched publications with data on the useful plants of Central America in databases  and on relevant journals by using selected relevant keywords . We conducted the search using both English and Spanish Keywords. Then, we extracted reported uses of medicinal plants and entered the data in a bespoke Access database within the disease categories diabetes mellitus, kidney disease, urinary problems, skin diseases and infections, cardiovascular disease, sexual dysfunctions, visual loss, and nerve damage. We included in our definition of Central America the following countries: Belize, Guatemala, Honduras, El Salvador, Nicaragua, Costa Rica and Panama. Compiled data were entered in a bespoke Access database . Table 1


In older age health needs and demand for health services utilization increase. Individual’s social relationships can play a decisive role regarding the utilization of outpatient health care services. This systematic review examines the associations of structural and functional dimensions of social relationships with outpatient health services use of older adults.The databases PubMed, CINAHL, SocINDEX, PsycINFO, International Bibliography of the Social Sciences (IBSS), Sociological Abstracts, and Applied Social Sciences Index and Abstracts (ASSIA) were searched in February 2016. The methodological and reporting quality of the articles was assessed and the results were synthesized descriptively and systematically.Out of 1.392 hits, 36 articles (35 studies) were included in the systematic review. The methodological and reporting quality of the included articles was reasonable. Various structural and functional characteristics of social relationships were associated with the use (yes/no) and the frequency of using outpatient care among older adults. The majority of the associations between structural dimensions of social relationships and the use of physicians were positive and moderate in strength. The associations between functional dimensions of social relationships and the probability of using physician services were inconsistent and varied in strength. For the most part, social relationship variables assigned to the structural dimension were positively and weakly to moderately associated with the frequency of physician visits. Functional aspects of social relationships also tended to have positive associations with the frequency of physician utilization. The associations were weak to moderate in strength.Measuring social relationships and their influence on health services use is a challenging methodological endeavor indicated by the inconclusive results. The results suggest that the outpatient care utilization behavior of older individuals being structurally and functionally integrated in social relationships is different to older adults being socially isolated or having no social support. All in all, the current status of quantitative data was insufficient. Future health services research should accentuate social ties in more detail, especially according to quality aspects of social relationships. Rapidly ageing populations generate increasing health needs and chronic conditions in Western industrial countries associated with a rising demand for health services . CompareFollowing Berkman, Glass  social tTo date, no systematic review on this topic has been conducted. Therefore, the first aim of this systematic review was to provide an overview of studies dealing with outpatient care utilization among older adults associated with various dimensions of social relationships. The second aim was to evaluate magnitude and consistency of the associations between social ties and health services use.A systematic review on studies dealing with social relationships and the utilization of outpatient care physicians among older adults was conducted. The performance of this review was based on the PRISMA checklist  and a stth 2016). The databases PubMed, CINAHL, SocINDEX, PsycINFO, International Bibliography of the Social Sciences, Sociological Abstracts, and Applied Social Sciences Index and Abstracts were searched for the keywords and various synonyms “social relationships”, “utilization”, “outpatient care” and “aged” in title and abstract  screened the titles and abstracts of all articles identified by electronic and reference search. In a second step, two independent reviewers (DB and LI) applied a predefined set of inclusion criteria on all relevant articles by performing a full text screening. In case of disagreement between the reviewers, a third investigator (OK) was consulted and the study was discussed until consensus was accomplished.Within the full text screening, articles had to pass five predefined inclusion criteria. Firstly, records were controlled for the criterion “peer-reviewed journal articles in German or English”. Peer-reviewed journal articles represent good scientific practice to secure quality, to foster objectivity and to provide transparency. Due to language skills and a reasonable use of resources of the reviewers, German and English articles were screened. Secondly, records were checked for three different study designs: quantitative observational 1) cross-sectional, 2) case-control and 3) cohort studies. Thirdly, full texts were inspected for the criterion “community-dwelling or noninstitutionalized individuals fifty years and older”. The rationale behind this population was to extract a reference group still active on the labor market, and to expand the number of potentially relevant studies. Compared with younger cohorts, individuals within their fifties or older show more chronic illnesses and increased rates of health care use [The data was extracted using a standardized form including information about the author, year, country, research design, study year (follow-up if applicable), sample size, response rate, age, gender, outcome, social relationship variables, and confounders in the fully adjusted model.The quality assessment, including the methodological and reporting quality, was based on a checklist following the Newcastle-Ottawa-Scale  and its The results were descriptively and systematically synthesized. All associations between social relationships and utilization of physicians were extracted and categorized. Each social relationship variable was assigned to a social relationship category and dimension. For a better overview, closely related indicators were aggregated within categories . Moreover, social relationship variables were classified as “structural” or “functional” . The funA total of 1,392 publications were identified through database search. After removing 158 duplications, 1,234 articles remained for title and abstract screening . 1,176 pThe articles were published between 1981 and 2015 . More thThe methodological and reporting quality of 47.2% of the records was categorized as “high”, 44.4% as “medium” and 8.3% as “low” . Apart fFourty associations between social relationships and the use of physicians were found in thirteen articles . In seveSeven out of these fourteen associations included variables of the structural dimension of social ties , 38, 44.Seven out of fourteen associations included variables of the functional dimension of social relationships , 12, 50.Ninety-two associations between social relationships and the frequency of physician use were found in twenty-eight articles . In seveTwenty-two out of these thirty-seven associations included variables of the structural dimension of social ties. Three studies found positive associations between being married and the frequency of physician visits , 45, 49 Fifteen out of thirty-seven associations included variables of the functional dimension of social relationships. Two studies showed positive and weak associations between received social support and the frequency of physician utilization , 8. FinaLi and Chi  investigThis review provides a comprehensive overview and furthers the understanding of the association between social relationships and health services use among older adults (50 years and older). The first objective of this study was to systematically review social relationships associated with the utilization of outpatient care services of older people. The second aim was to evaluate magnitude and consistency of the associations between social ties and health services use.We included thirty-six records on thirty-five different studies reporting structural and functional dimensions of social relationships linked to the utilization of health services into our analyses. In most cases empirical evidence was insufficient and for several of the social tie variables inconsistent results were found. Taking into account the fully adjusted model, associations between use measures and social relationship variables were for the most part weak and statistically insignificant. Potentially, associations were underestimated by that strict criterion.Overall, most of the studies focused on associations between social ties and frequency of physician use. The structural dimension of social relationships and its association with physician visits (use and frequency of use) was investigated far more often than the functional dimension. Though a substantial number of social relationship dimensions were explored until now, none of the included studies included a holistic approach of social tie measures   and theiThe majority of the associations between structural dimensions of social relationships and the use of physicians were positive and moderate in strength. The associations between functional dimensions of social relationships and the probability of using physician services were inconsistent and varied in strength. For the most part, social relationship variables assigned to the structural dimension were positively and weakly to moderately associated with the frequency of physician visits. Functional aspects of social relationships also tended to have positive associations with the frequency of physician utilization. The associations were weak or moderate in strength. All in all, the current status of quantitative data was insufficient to draw precise and generalizable conclusions.Our review reveals that the link between various social relationship indicators and health care use as well as frequency of use have been investigated in few studies. This clearly indicates that further research is needed.Including a broad range of seven medical and sociological databases, we were able to minimize the risk of missing relevant articles. Nevertheless, the risk of publication bias is still existent. More than half of the studies (64%) were performed in North America, and therefore, findings cannot be generalized. Since the majority of included studies (61%) had cross-sectional design, conclusions concerning causal relations are not possible.Due to the fact that ten studies did not (four studies) or did not clearly meet (six studies) the quality criterion of representativeness and thirty articles did not (twelve studies) or did not clearly report (eighteen studies) information on non-respondents and response rate, the results were moderately robust. Overall, the methodological and reporting quality of the studies was mostly categorized as medium or high (92%).Most of the studies referred to one year of physician use. Still, the range of the utilization variable was substantial between the studies (from 15 days to two years). As the time span was quite long in some studies, and considering the older age of the interviewed individuals, risk of memory bias was existent, particularly, if the information on consultations was not compared to medical records (twenty-seven studies).Since there were no consistent measures of predictors  and outcome variables (use and frequency of outpatient care visits), data was analyzed systematically, but descriptively. A prerequisite of meta-analyses is a high level of accordance across the included studies regarding independent and dependent variable measures and data analysis approaches . Due to Unfortunately, analyses of group-differences concerning age, gender, and chronic conditions could not conducted on the basis of the review material.Social relationships can increase or decrease the probability to consult a physician, and they can influence the frequency of visits. All in all, older people who are structurally integrated by social relationships are more likely to consult a physician at all and to contact a physician more often. Functional aspects of social relationships, depending on the form of social support, can increase or decrease the probability of physician use. Older adults who are experiencing social support tend to have a higher rate of physician visits than older people without any or less support.On the one hand, this could be read as good news, since structural and functional aspects of social relationships tend to enable the utilization of health services, and thereby potentially foster older adults’ health. Social relationships could offer informational, instrumental and emotional resources with regard to health, health care services and treatments. On the other hand, considering increasing numbers of single-person-households and an increasing risk of loneliness and social isolation in older age , this coSocial ties have an impact on the patient’s motives for a consultation and on the patient’s compliance regarding future visits for treatment, prevention or rehabilitation , 55. ConThe variety of dimensions of social relationships presented in this review illustrates that utilization of outpatient health care services is a complex social process. Besides methodological challenges, the complex picture of social tie’s impact on health care utilization bases on the fact that relationships are not always of positive virtue , 57. In Furthermore, the inconclusive results demonstrate that measuring social relationships and their influence on health services use is a challenging methodological endeavor. Future health services research should accentuate social relationship variables more in detail, and not only in terms of structure and quantity, but also according to functional and quality aspects of social relationships.The relatively low number of included studies indicates a deficit of elaborated observational studies dealing with the role of social relationships for the utilization of health services among older populations. The majority of the identified studies have a cross-sectional design investigating a number of possible social relationships of health services use. It is crucial to determine social ties for health services use more clearly and to identify causal relations, especially in the form of prospective cohort studies.Methodologically, it can be constructive to directly connect the question of social relationships and health care utilization to the scientific debate of health care inequalities –62 by coS1 File(PDF)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.S1 Fig(DOCX)Click here for additional data file.S1 Table(DOC)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(XLSX)Click here for additional data file.S4 Table(XLSX)Click here for additional data file.S5 Table(XLSX)Click here for additional data file.


ES theory holds the promise to be a unifying concept to link across hierarchical scales of patterns and processes in ecology, but this has not been fully achieved. Therefore, we propose connecting the expertise of aquatic ecologists and biogeochemists with ES theory as a common currency to connect food webs, ecosystem metabolism, and biogeochemistry, as they are inherently concatenated by the transfer of carbon, nitrogen, and phosphorous through biotic and abiotic nutrient transformation and fluxes. Several new studies exist that demonstrate the connections between food web ecology, biogeochemistry, and ecosystem metabolism. In addition to a general introduction into the topic, this paper presents examples of how these fields can be combined with a focus on ES. In this review, a series of concepts have guided the discussion: (1) changing biogeochemistry affects trophic interactions and ecosystem processes by altering the elemental ratios of key species and assemblages; (2) changing trophic dynamics influences the transformation and fluxes of matter across environmental boundaries; (3) changing ecosystem metabolism will alter the chemical diversity of the non-living environment. Finally, we propose that using ES to link nutrient cycling, trophic dynamics, and ecosystem metabolism would allow for a more holistic understanding of ecosystem functions in a changing environment.Although aquatic ecologists and biogeochemists are well aware of the crucial importance of ecosystem functions, i.e., how biota drive biogeochemical processes and vice-versa, linking these fields in conceptual models is still uncommon. Attempts to explain the variability in elemental cycling consequently miss an important biological component and thereby impede a comprehensive understanding of the underlying processes governing energy and matter flow and transformation. The fate of multiple chemical elements in ecosystems is strongly linked by biotic demand and uptake; thus, considering elemental stoichiometry is important for both biogeochemical and ecological research. Nonetheless, assessments of ecological stoichiometry (ES) often focus on the elemental content of biota rather than taking a more holistic view by examining both elemental pools and fluxes (e.g., organismal stoichiometry  Figure 1). The magnitude of ecosystem fluxes and stoichiometric constraints on biogeochemical processes are determined by turnover of elements, including the most commonly studied, carbon (C), nitrogen (N), phosphorus (P). These basal resources can be governed by ecosystem metabolism, where the balance of gross primary production (GPP) and ecosystem respiration (ER) dictate net ecosystem production (NEP). In freshwater aquatic ecosystems, when GPP exceeds ER (NEP > 0) the ecosystem is autotrophic and when ER > GPP (NEP < 0), it is heterotrophic indicating a reliance on imported C inputs, often of terrestrial origin, for respiration , a large number of studies included any of the three terms—food webs, ecosystem metabolism, and biogeochemistry—together with ES, but only eight studies used ES in connection to all three terms. ES has the potential to be a concept unifying flux-oriented biogeochemistry, ecosystem metabolism, and population-oriented ecology, but so far only a few studies have achieved this  increased N fluxes to some invertebrate functional feeding groups . In our first case study, ES links a general trait of metabolism (body mass dependence) to trophic interactions and biogeochemistry by demonstrating changes in resource transport and N:O ratios. Secondly, ES demonstrates the interactions between trophic dynamics of benthic aquatic invertebrates and two large-scale biogeochemical fluxes. Thirdly, the addition of trace elements to the traditional C:N:P ratios improves the understanding of altered trophic interactions and nutrient fluxes. And then in the subsequent two examples, the N:P loads shift over time, allowing for the proliferation of invasive species which further impact that quality of carbon and N:P availability. Furthermore, the sixth case study uses ES to demonstrate how changes to N:P alters ecosystem metabolism through enhanced microbial respiration rates and food web interactions. Finally, the interaction between biogeochemistry with regard to changing temperature is quantified using ES and the impact on ecosystem metabolism. The diversity of our examples illustrates the potential strength of this approach for understanding relationships among and across trophic levels, including biogeochemical interactions as well as direct and indirect effects.In the following section, we exemplify how food web interactions, ecosystem metabolism, and biogeochemistry can use ES theory to integrate from microbial to ecosystem-scale processes through a series of case studies. The examples are derived from a special session at the 2016 Association for the Sciences of Limnology and Oceanography (ASLO) meeting in Santa Fe, NM, United States, with the aim to merge the fields of biogeochemistry, food webs and ecosystem metabolism by using ES as a common theoretical framework. Using the following research highlights, we convey the depth and range of approaches which have been applied, that merge these disciplines, which are conceptualized in our model (N) should also then relate to the degree of body-shape change during growth. They tested this hypothesis using literature data on bN for pelagic invertebrates across five different phyla, and found that bN is significantly positively correlated with predicted surface area enlargement, whilst also co-varying with the mass-scaling of respiration rate (bR). Indeed, intraspecific differences between bN and bR values have revealed there are shifts in the ratio of O2-consumed to N-excreted over ontogeny. This suggests that changes in the relative anabolism and catabolism of proteins and lipids over development, may cause these consumption-excretion ratios to change too. In conclusion, diverse pelagic invertebrates, that dominate vast open water ecosystems, therefore appear to falsify the predictions of general metabolic scaling theories built upon resource-transport networks, while supporting predictions of surface-area dependent theory. Furthermore, ontogenetic variation in ratios of O2 consumed to N excreted of these species, may not only provide insight into the developmental metabolism, but also the stoichiometry of ecological systems, including, for example, seasonal changes in N-budgets that are linked to pelagic animal life cycles.Body size is a “master trait” that affects all vital rates, including feeding, reproduction, excretion and metabolism . Underst2O), methane (CH4), and carbon dioxide (CO2) (Aquatic ecosystems can be sources of greenhouse gases (GHG), a process that is strongly controlled by the availability of C, N, and P, which can stimulate emission of nitrous oxide (Nde (CO2) . Howeverde (CO2) .4 produced in freshwater and marine sediments that is not released by ebullition is oxidized to CO2 or assimilated by methanotrophic bacteria  under variable conditions is important to our understanding of faunal influence on GHG fluxes in aquatic ecosystems. Since taxa such as Tubificinae have been shown to enhance GHG flux  and also43-), which shares the same chemical structure as arsenate (AsO43-), the most common form of As in oxygenated freshwaters . Members of different trophic levels were found to have different correlations with N and P, as did taxa within trophic levels. These patterns were consistent with the premise that the fish community shifted to species that were proportionately more P-rich over time as N and P ratios increased due to substantial increases in N loading and reductions in P. The patterns were also consistent with increased importance of a benthic food web following reductions in P loading. Changes in external nutrient loads also drove changes in biogeochemical fluxes at the sediment water interface, leading to increasing abundance of macrophytes, clams, and of the toxic algae Microcystis, along with more omnivorous fish fueled by a benthic food web. The picture that has emerged of this ecosystem is one where changes in the food web are now understood to follow the conceptual model of stoichiometry, and not purely stochastic events. Previously considered one of the most heavily invaded estuaries in the world, it is now clear that environmental changes, including nutrient ratios and concentrations, interact with vectors of invasion to enhance their success.ES, together with biogeochemistry has been applied to understanding invasive species and changes to aquatic food webs in the San Francisco Bay Delta . In thisDreissena rostriformis bugensis) have caused unprecedented ecological and environmental changes in Lake Michigan. Declines in primary production, fish biomass, and turbidity as well as significant changes to food web structure, phytoplankton composition, and nutrient cycling pathways have all occurred as a result of the introduction of quagga mussels . As demonstrated in the previous examples, altered nutrient concentrations, ratios or fluxes, either through anthropogenic or system-induced pathways, results in changes in ecosystem functioning . By increasing nutrient concentrations, organic matter decomposition increases and results in overall C loss in aquatic ecosystems. Furthermore, these increased nutrient concentrations may induce a shift toward favorable conditions for invasive species to persist :Along with the above examples, we have demonstrated the current state-of-the-art approaches, which link food web interactions, ecosystem metabolism, and biogeochemistry along the following concepts and processes (1.Changing biogeochemistry affects trophic interactions and ecosystem processes by altering the elemental ratios of key species and assemblages.◦The stoichiometry of biogeochemical processes links the biological turnover rates of major elements, such that changes in biodiversity result in changes in mineral nutrient ratios in biogeochemical pools and fluxes.2.Changing trophic dynamics influences the transformation and fluxes of matter across environmental boundaries.◦Through biogeochemical pathways, change in a focal group of organisms has propagating consequences on the functioning of other compartments and on the metabolism of aquatic ecosystems.◦Trophic interactions, food web structure, and mutualistic networks will result in cascading effects on ecosystem metabolism or vice versa.3.Changing ecosystem metabolism will alter the chemical diversity of the non-living environment.◦The alteration of metabolic processes in aquatic ecosystems affects the transformation and fluxes of inorganic and organic matter.◦The molecular diversity of non-living organic matter is functionally linked to the diversity of organisms. Chemical diversity influences and is influenced by shifts in biodiversity.The future goal is to use the theory of ES as a common currency to connect food web interactions, ecosystem metabolism, and biogeochemistry as they are inherently linked by the transfer of C, N, and P through biotic and abiotic nutrient transformations and fluxes in order to improve our understanding of aquatic ecosystem functioning. Given the future projections of climate change for increasing temperature and anthropogenic nutrient loading, ES can be essential to understand and predict the links between food web interactions, biogeochemistry, and ecosystem metabolism and elucidate the controls which underpin the processes that ultimately drives nutrient and energy fluxes in aquatic ecosystems.NW and MS contributed equally to this manuscript. NW, MS, and AU conceived the manuscript. All authors contributed substantially to the manuscript, revised it for important intellectual content, approved the final version, and agreed to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.