Autophagy is an important mechanism to maintain homeostasis in cells. It has been linked with ageing and many currently incurable diseases, including heart disease, cancer, myopathies, neurodegeneration, and diabetes. Autophagy research is very important for identifying better treatments. This study aimed to explore the hotspots of autophagy research published from different countries, organizations, and authors.Between 1962 and 2018, articles published about autophagy were identified in the Web of Science database. The total and annual number of articles, citations, impact factor, Hirsch (H)-index, number of article citations, productive authors, and involved journals were collected for quantitative and qualitative comparisons.Autophagy published the most articles , followed by Plos One (585) and Oncotarget (392). Daniel Klionsky was the most productive author, with 171 publications. The article “LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing” was cited most frequently. The top-ranked keyword was “degradation” of macroautophagy.From 1962 to 2018, 18,811 autophagy-related articles written in English were published. Most were from China . The United States dominated in citation frequency  and h-index (264). Among related journals, Publication of articles about autophagy has increased notably from 1962 to 2018, and has increased annually. The general quality of publications from China is still in need of improvement. Autophagy research has shifted gradually from basic studies to clinical studies in recent years. Autophagy is a highly conserved mechanism of the controlled digestion of damaged organelles that is a common phenomenon in eukaryotes . It was Bibliometric analysis is an important tool that can help assess new trends in current scientific research . This teThis study used bibliometric tools to analyse autophagy-related articles retrieved from several databases. The aim was to provide a retrospective and contemporary view of the mainstream research on autophagy globally from 1962 to 2018.The online literature search was done on March 25, 2019 using the Web of Science (Thomas Reuters Company) citation indexing service that allowed access to the Essential Science Indicators (ESI) and Science Citation Index Expanded databases. Articles and reviews were included in the analysis, because they generally accounted for the majority of document types that also included complete research ideas and results. Terms used during the search were: TI = autophag* AND publishing year = (1962–2018) AND Language = English. Data entry and collecting were verified by two authors (Feng XZ and Tong WW). The txt data downloaded from the Web of Science were imported into Microsoft Excel 2013 and VOSviewer. The data were analysed quantitatively and qualitatively.The Web of Science allows the analyses of many publication characteristics, including countries or regions, institutions, publication time, authors, citation frequency, ESI top papers, and the Hirsch (H)-index. The latter is often applied to evaluate a scholar’s academic level more scientifically. The definition of the index is that a scholar with an index of H has published H papers, each of which has been cited in other papers at least H times . It is of(x) = ax3 + bx2 + cx + d was used to predict the future trend of papers in this field. The publication year is denoted by x and f(x) is the total number of publications in any one year. The plotted data can also be analysed to understand the difference of publication outputs between different countries or institutions through column diagrams or line charts.Microsoft Excel 2013 was used to chart the trend of publications according to the Web of Science data. The equation http://www.gopubmed.org/web/gopubmed/) was harnessed to count the data of relative research interest.The VOSviewer software tool is used to construct and visualize bibliometric networks, which include journals, researchers, or individual publications. The constructs can be based on citations, bibliographic coupling, co-citation, or co-authorship relations . In addiA total of 18,811 articles met the search criteria from 1962 to the end of 2018 ; Fig. S1R2 = 1.00) between the cumulative number of publications and publication year. According to the statistics of the past 15 years, we forecast that there will be approximately 3,500 autophagy-related articles published in 2019.Substantial progress in the molecular study of autophagy has taken place during only the past 15 years , so we sThe 18,811 publications focusing on autophagy research were contributed by 100 countries/territories . Figure Autophagy with 1,388 articles , followed by Plos One  and Oncotarget , which are also US journals.The 10 most prolific authors contributed a total of 1,201 articles relating to autophagy, accounting for 6.38% of all published literature relating to the field. Daniel J. Klionsky from the University of Michigan in the US has published the most articles (171), followed by Mizushima Noboru of Tokyo Medical Dental University (Japan) with 140 publications and Ohsumi Yoshinori of the Tokyo Institute of Technology (Japan) with 133 publications. Dr. Klionsky has been the only person to publish more than 150 articles on autophagy from 1962 to 2018. Authors from the US and Japan make up the majority of the top 10 authors rankings. Of the top 10 authors, six are from universities and four are from institutes . MizushiThe Web of Science analysis revealed that articles related to autophagy had been cited 793,192 times from 1962 to 2018 . Each article was cited 42.17 times. The top 10 countries ranked by the citation and H-index on autophagy research were determined.The H-index positively correlated with the sum of citations . The H-iThe top 10 cited articles about autophagy are listed in EMBO Journal ; “Autophagy in the pathogenesis of disease” by Beth Levine, published in 2008 in Cell ; and “Autophagy fights disease through cellular self-digestion” by Noboru Mizushima, published in 2008 in Nature . Overall, articles from the US and Japan have been the most highly cited. Almost all the top 10 cited articles are from these two countries.Among these 18,811 articles, the three most frequently cited are: “LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing” by Yukiko Kabeya, published in 2000 in Keywords of all the 18,811 original articles and reviews were evaluated using VOSviewer. The three types of autophagy are completely different, so we separately searched for publications concerning macroautophagy, microautophagy, and chaperone-mediated autophagy. The article numbers were 1,552, 99, and 722, respectively. The content of the remaining articles was indistinguishable. Macroautophagy is the main form of autophagy and has been studied most thoroughly. As shown in The keywords of microautophagy were obviously less than keywords of chaperone-mediated autophagy and macroautophagy. More keywords were used for chaperone-related autophagy compared to microautophagy, but their use grew with time  and S5.The quantity of global publications on autophagy has increased rapidly year-by-year from 2003 to 2018. Since 2012, the total number of articles on autophagy has increased rapidly. It can be speculated that there was a big breakthrough in autophagy research around 2012. Graphing the data highlights that autophagy research is a hotspot at the present time. Recent times have been a golden period of the development of autophagy research. China is by far the most productive country, followed by the US and Japan. Although these countries have published many papers, the indicators of H-index and sum of citations are different from each other.The US ranks first among all countries in H-index and total number of publications. This suggests the high-quality and numbers of documents from the US. There are several potential reasons. The GDP of the US is the highest globally. Thus, the US is able to fund the necessary scientific research. Secondly, the finding that three of the top 10 researchers are Americans, second only to Japan, is consistent with the view that American scientists have conducted in-depth studies of autophagy for a long time, with the discoveries laying a solid foundation for later research . MoreoveJournal of Cell Biology reported for the first time that autophagy occurs in yeast under conditions of starvation, and that autophagy is essential for yeast survival  in 2018. Since 2014, China has been publishing more articles each year than any other country. In 2004, there were no articles published from China, with the US and Japan respectively publishing 12 and 27 articles. These findings provide more evidence that research on autophagy in Japan and the US began sooner than elsewhere. The US, Japan, England, France, and Germany published articles with a higher H-index than China.Autophagy plays an important role in nervous system diseases and tumours . Along wAutophagy was by far the most pre-eminent journal, with 1,388 articles, followed by Plos One, Oncotarget, and Journal of Biological Chemistry. They are expected to be the sources of many more articles about autophagy.The journal With respect to authors and publications, highly cited articles were mainly written by the 10 most prolific authors. Their research focused on the mechanisms of autophagy.Autophagy-related documents that were cited the most will provide the fundamental basis for further studies. Additionally, they provide a reasonable prediction of research frontiers. According to the main conclusions of the top two highly cited reviews, the current focus of research is the link between autophagy and disease. Many of the documents that have been cited most often were published in 2010. This likely reflects the advances being made on the mechanism of autophagy at that time. Reading articles about autophagy published at that time could meaningfully inform future research.Autophagy is the only journal that specially publishes articles on all aspects of autophagic processes. Most of the other journals almost logically belong to the “Multidisciplinary Sciences” JCR category, confirming the important role that Autophagy plays in the dissemination of information of autophagy research in the life sciences community.Among the 10 most productive journals, Autophagy research has shifted gradually from basic studies to clinical studies in recent years. Initially, autophagy in yeast cells was the main focus . With fuAutophagy has published the largest number of articles in autophagy research. Daniel Klionsky, Noboru Mizushima, and Ohsumi Yoshinori may be good candidates for collaborative research in this field based on the H-index and citation frequency of their publications. The article“LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing” is the most cited publication. All publications can be divided into three clusters. The “Treatment related”, “Cell related”, and “Disease related” clusters may be the latest hotspots of study, and research in these areas may drive the field of autophagy in the next few years.This is the first bibliometric study assessing the worldwide productivity in the field of autophagy research. Publications on autophagy will continue to grow rapidly. The United States has been the most productive country as measured by total citations and H-index. Among related journals, 10.7717/peerj.7103/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.7103/supp-2Supplemental Information 2Click here for additional data file.10.7717/peerj.7103/supp-3Supplemental Information 3Click here for additional data file.10.7717/peerj.7103/supp-4Supplemental Information 4Click here for additional data file.10.7717/peerj.7103/supp-5Supplemental Information 5Click here for additional data file.10.7717/peerj.7103/supp-6Supplemental Information 6Click here for additional data file.10.7717/peerj.7103/supp-7Supplemental Information 7Click here for additional data file.10.7717/peerj.7103/supp-8Supplemental Information 8Click here for additional data file.


Dendrobium officinale extract shows potent anti-fatigue effects; however, the active substance responsible for these effects remains undetermined. A glucomannan with a huge molecular size of 730 kDa, called DOP, was identified as the unique authentication marker of this expensive herb. DOP exhibited immunomodulating effects on macrophages and lymphocytes in our previous study. Clinical reports also showed that people with fatigue syndrome have a disturbed immune system. Because DOP is the unique and dominant component of D. officinale, we hypothesize that DOP may also have anti-fatigue activity. The present study aims to evaluate the anti-fatigue activity of DOP on BALB/c mice, with Rhodiola rosea extract as a positive control. DOP and Rhodiola rosea extract were orally administered at doses of 50 mg/kg and 100 mg/kg, respectively, for four weeks, and the anti-fatigue activity of DOP on BALB/c mice was evaluated using the weight-loaded swimming test. The contents of lactic dehydrogenase (LDH), creatine phosphokinase (CK), triglyceride (TG), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA), lactic acid (LD), and glutathione peroxidase (GSH-Px) in serum, glycogen of liver and gastrocnemius muscle were also determined. Their effects on variability of T cells and B cells were determined by using tetrazolium compound (MTS) method. The weight-loaded swimming exercise caused fatigue syndrome, mainly including the decreases of serum SOD/GSH-Px and gastrocnemius glycogen, as well as the increases of LDH, BUN, MDA, CK, TG, and LD in serum. All of these indicators of fatigue were inhibited to a certain extent by both DOP and Rhodiola rosea extract; however, the effects of DOP were much stronger than those of Rhodiola rosea extract. Compared to the positive control, mice dosed with DOP showed increases in endurance, body weight, and food intake. Furthermore, DOP-feeding mice significantly increased the cell variability of T lymphocytes and B lymphocytes, compared with that of mice in control group. This study indicates that the unique and dominant polysaccharide DOP of D. officinale has stronger anti-fatigue activity than Rhodiola rosea extract. As such, DOP has promising potential for pharmaceutical development into health products to reduce fatigue. Fatigue syndrome refers to difficulty in initiating or sustaining voluntary activities . It is aRhodiola L. extract of which salidroside is the main functional component, showed anti-fatigue effects [Rhodiola L. may result in hypoglycemia, which compromises recovery from fatigue. Therefore, safe and effective anti-fatigue natural products are still desired.Another source of fatigue in modern populations is exercise. More and more people now exercise regularly to enhance their health. Excessive exercise also causes fatigue and even various types of damage to the body. Therefore, in the past few decades, health scholars and athletic physiologists have been looking for natural active compounds that can improve athletic ability, postpone fatigue, and accelerate the body’s recovery from physical exertion. However, many of the active substances reported to address fatigue have side effects. For instance,  effects ,5, but eVarious studies have sought evidence that people with fatigue syndrome have a disturbed immune system, such as dysfunction of natural killer cell activity ,7, redunTiepi Fengdou, the stem of Dendrobium officinale, has been used for thousands of years as a health tea herb in East Asia. It ranks as the first of “nine kinds of Chinese medicinal herbs” and is traditionally recorded as a tonic to nourish Yin, supply body fluids, strengthen immunity, and benefit gastric tonicity in traditional Chinese medicine theory [e theory . Its wate theory , howeverD. officinale [In our previous studies, a unique polysaccharide marker  was identified for the authentication of ficinale . DOP is ficinale ,15,16,17Rhodiola extract significantly increased the swimming time  in comparison with control group (557 ± 45.42 s) at day 20 (p < 0.05), compared to the first time. The PC group did not show such a decrease and remained at the same level. Instead, strikingly, the swimming time of DOP group continued to increase to around 956.75 s. These results suggest that DOP is a better anti-fatigue substance than Rhodiola extract.The weight-loaded forced swimming endurance test, one of the commonly-used anti-fatigue test models, was chosen to evaluate the anti-fatigue effect of DOP ,19. The t day 20 . The DOPRhodiola extract group all increased during the experiment. When compared to the control group and PC group, DOP had an obvious effect on body weight gain (p < 0.05). Consistently, the food consumption rate of the DOP group increased during the course of the experiment when compared to the food consumption rate of control group, positive group, and normal group (p < 0.05).As shown in Rhodiola extract at 50 mg/kg and 100 mg/kg, respectively, for four weeks and swimming test slightly, but not significantly, ameliorated the organ index of heart (Rhodiola extract remarkably increased the organ index of spleen in comparison with that of control group (p < 0.01).The organ indexes of liver, heart, kidney, and spleen were further evaluated. Oral administration of DOP and of heart , liver . DOP also boosted glycogen in the gastrocnemius muscle of mice compared to that of control group (p < 0.05). In contrast, Rhodiola extract did not significantly increase the glycogen in the gastrocnemius muscle of mice in the study.Glycogen in liver and gastrocnemius muscle were determined by hepatic glycogen/muscle glycogen assay kits. As shown in Rhodiola extract for 30 days, the lymphocytes from spleens of each group were subjected to a lymphocyte proliferation assay to assess the physical immunity. As shown in p < 0.05), but it was not detected in the positive control group (Rhodiola extract), compared to the control group.After feeding mice with DOP and Rhodiola extract in mice. DOP and Rhodiola extract extend the weight-loaded swimming time and facilitate oxidative enzyme activity and storage of hepatic glycogen. In addition, mice in the DOP group had a higher proliferation rate of T cells and B cells to mitogens, suggesting that both DOP and Rhodiola extract contribute to enhancement of physical strength and endurance.The present study evaluated the anti-fatigue effects and underlying mechanism of DOP and D. officinale, D. officinale health tea, and compounds containing D. officinale have anti-fatigue and immunomodulating effects [D. officinale is responsible for this anti-fatigue activity. The results of this study, in particular the increased swimming time, demonstrate that DOP treatment enhanced fatigue-resistance. This swimming test is a reliable measure of anti-fatigue treatment as established in both laboratory animals and humans [Rhodiola L. has anti-fatigue effects.Many Chinese research groups have demonstrated that  effects ,20,21,22d humans ,24,25. IRhodiola extract increased spleen index significantly; this result was consistent with the previous study showing that Rhodiola enhanced cellular immunity in mice and rats [Rhodiola extract did not significantly increase proliferation rates of T cells and B cells compared with those of the control group. There is a study showing that a higher dose (200 μg) of Rhodiola extract was ineffective to enhance chemokinetic activity of spleen lymphocytes in mice [Rhodiola extract was used as the positive control. Thus, too high a dosage may be the reason for the lack of response of B cells and T cells of mice in the Rhodiola extract group to mitogens in this study.Stress represents the reaction of the body to stimuli that disturb its normal physiological equilibrium or homeostasis, often with detrimental effects. The weight of spleen, thymus, and thyroid of the immune system are decreased by immobilized stress . Resultsand rats ,28,29. H in mice . In thisFatigue syndrome is a worldwide problem, with a prevalence rate of 0.4%–1%. More than 70 million people worldwide are affected by fatigue. No physical examination signs are specific to fatigue and no diagnostic tests identify this syndrome. The pathophysiological mechanism of fatigue is also unclear.Rhodiola is that DOP and Rhodiola extract enhance triglyceride (TG) (or fat) mobilization during exercise, as indicated by the decrease in TG. Energy for muscular exercise is derived initially from the breakdown of muscle glycogen, and later from circulating glucose released by the liver and from non-esterified fatty acids [Rhodiola extract increased TG mobilization might become advantageous during prolonged exercise, since better utilization of TG saves consumption of glycogen and protein, and therefore delays fatigue.Our results suggest that the mechanism of DOP against fatigue probably included three aspects. One possible explanation for the anti-fatigue effects of DOP and ty acids . After tRhodiola extract, MDA, CK, and LDH levels were decreased and SOD and GSH-Px levels were increased thereby protecting the membrane structure and resisting oxidative damage.The other possible explanation for the anti-fatigue effect of DOP is that it modifies several enzymes thereby preventing lipid oxidation which protects corpuscular membranes. Fatigue results in the release of reactive oxygen species (ROS) which cause lipid peroxidation of membrane structure. In fatigue conditions, MDA level is increased and is accompanied by a decrease in levels of the antioxidant enzymes GSH-Px and even SOD (with only an insignificant decrease trend). These conditions are also marked by the release of LDH and CK into the serum, serving as an indirect index of damage to membranes. Some reports showed that various antioxidant drugs—such as carvedilol, melatonin, and quercetin—have anti-fatigue effects because of their antioxidant activity . After iD. officinale is the ability to modulate immune function [The third reason for fatigue relief effect of DOP is that it has an immunomodulating effect. Although DOP did not increase the spleen index significantly, it significantly enhanced responses of B cells and T cells to mitogens in vivo compared with those of control group. The immunomodulating effects of DOP may be one of the key reasons it relieves fatigue. Various studies have sought evidence that people with fatigue syndrome have a disturbed immune system. Alteration of diverse immunological indicators, such as cytokine profile, function of natural killer cells, and responses of T cells to mitogens, has been reported . The prefunction ,15,16,34The increase in body weight and food intake may explain the slight increase of the spleen index which may be relevant to the anti-fatigue effects of DOP observed in this study. Some reports showed that patients with fatigue syndrome have a disturbed immune system. A slight decrease of spleen index was also observed in the control group, which is associated with the fatigue caused by the swimming test. After treatment with DOP, the spleen index was increased, and this index may be related to the fatigue resistance.Rhodiola rosea extract product containing 1% salidroside was used as the positive control. Triglyceride assay kits, lactic dehydrogenase assay kits, malonaldehyde assay kits, superoxide dismutase assay kits, glutathione peroxidase assay kits, lactic acid assay kits, urinary nitrogen assay kits, hepatic glycogen/muscle glycogen assay kits, creatine kinase assay kits were all purchased from Nanjing Jiancheng Bioengineering Institute . LPS (from Escherichia coli 0111:B4) and Concanavalin A (Con A) were purchased from Sigma-Aldrich . CellTiter 96® AQueous One Solution Cell Proliferation kit was purchased from Promega Inc. . Polysaccharide marker DOP of Dendrobium officinale was prepared in our previous study [A commercial us study .Inbred strain male  BALB/c mice were purchased from the Laboratory Animal Services Centre of The Chinese University of Hong Kong. The animals were provided with standard pellet diet and water ad libitum and maintained under controlled conditions of temperature and humidity, with 12 h light/dark cycles. All experiments with animals were carried out in accordance with the Animals Ordinance, Department of Health, Hong Kong Special Administration Region, China for the care and use of experimental animals. All of the experimental protocols were first approved by the Committee on Use of Human and Animal Subjects in Teaching and Research of the Hong Kong Baptist University. The animals were used for weight-loaded swimming experiments after seven days of adaptation to the environment and the standard diet. Mice were trained to accustom themselves to swimming twice (10 min per time) in the first week. Mice which could not learn to swim were screened out. Trained mice were randomly divided into four groups, each consisting of eight mice.Group 1 . Mice did not receive any treatment.Group 2 (Control). Mice were given distilled water for 30 days, as a negative control.Group 3 (DOP). Mice were treated with DOP (50 mg/kg) for 30 days.Rhodiola rosea extract (100 mg/kg *) for 30 days, as a positive control.Group 4 (PC). Mice were treated with Rhodiola rosea extract product.* This dose corresponds to a typical human dose of 600 mg given to a 60 kg person  according to the instruction of the Rhodiola rosea extract were dissolved in distilled water and fed by gavage to mice once a day. Changes in the body weight of the mice were observed every seven days. The above method of grouping and feeding was repeated to determine related indicators. Mice were anesthetized with chloral hydrate and blood samples were collected from each treatment group. Serum samples were obtained by centrifugation  and stored at −80 °C for further analysis. The spleens, hearts, and livers were weighed and their weights relative to the final body weights (organ index) were calculated.DOP and The procedure used in this assay followed a previous study described by Chen  and was Rhodiola rosea extract, the mice were forced to swim in the swimming pool (weight-loaded) for a 6 min session according to the method in After 28 days, the mice were taken out from each group for analyses of hepatic glycogen, muscle glycogen, and blood biochemical parameters. 1 h after the last intragastric administration of DOP and g for 15 min, the supernatants were discarded. 0.5 mL of distilled water and 1 mL of 0.2% anthrone were added, and the vials were placed in a boiling-water bath for 20 min. The absorbance at 620 nm of the solutions in vials was determined by UV/VIS spectrophotometer .After the blood was collected, the livers and the gastrocnemius muscles of the mice were immediately dissected, frozen in liquid nitrogen, and kept at −80 °C until analysis of glycogen concentration. The concentration of hepatic glycogen was tested following the recommended procedures provided by the hepatic glycogen/muscle glycogen assay kits. Briefly, alkaline solutions were added to liver and gastrocnemius muscle samples for hydrolysis at 100 °C for 30 min. After centrifugation at 4000× 6 cells/mL with RPMI-1640 after the cell viability was assessed by trypan blue exclusion. The 100 μL cell suspension was incubated in 96-well culture plates. It is known that LPS and Con A stimulate B cells and T cells, respectively [® AQueous One Solution Cell Proliferation reagent was added into each well at 4 h before the end of incubation. The absorbance of cells in each well was measured by Benchmark Plus microplate reader  at a wavelength of 490 nm.Spleens were collected from BALB/c mice of each group after killing them by cervical dislocation. Single cell suspension of splenocytes was prepared according to the method described by Busse . Brieflyectively . Thus, tp < 0.05.All values are expressed as means ± standard error (S.E.) in the tables and are indicated by vertical bars in the figures. Data were analyzed by one-way ANOVA, and then differences among means were analyzed using Fisher’s protected least significant differences (LSD) multi-comparison test. Differences were considered significant at Dendrobium Officinale, named DOP, have been used to study the anti-fatigue effect on BALB/c mice. Using the weight-loaded swimming test, DOP shows stronger anti-fatigue activity than that of positive control (Rhodiola rosea extract). In addition, the several serum parameters, indicating the fatigue symptom, were blocked to a certain extent by both DOP and Rhodiola rosea extract, compared with those of the control group. Furthermore, DOP-feeding mice significantly increased the cell variability of T lymphocytes and B lymphocytes, compared with that of mice in control group. These results indicate that the anti-fatigue effects of DOP due to the enhanced triglyceride (TG) (or fat) mobilization, decreased lipid oxidation and elevated immunomodulating activity during exercise in mice. Although our work is limited to the mechanism study, we can expect that DOP has the promising potential for pharmaceutical development into health products to reduce fatigue.In this paper, unique polysaccharide marker of


Human trafficking is a crime against humanity. It is also a serious threat to global health and security. Globalization has made human trafficking an easier task for the criminal organizations. No data are available on the volume, research trends, and key players in this field. Therefore, the aim of this study was to assess the research activity and research trends on human trafficking.A bibliometric method was adopted. Literature published in academic journals indexed in Scopus database was retrieved. The study period was set from 2000 to 2017.n = 771; 37.7%) of the retrieved documents were about sex trafficking, 616 (30.1%) were about labor trafficking/forced labor, 199 (9.7%) were about child trafficking, and 138 (6.8%) were about organ trafficking. One third  of the documents were in health-related fields while 1526 (74.7%) were in social sciences and humanities. The USA ranked first  regarding the number of published documents. Geographic distribution of the retrieved document showed that world regions with a high prevalence of human trafficking had the least research contribution. International research collaboration has a limited contribution to the retrieved literature. The Harvard University (USA) was the most active institution . International Migration  was the most active journal in publishing documents on HT. Documents published in Transplantation journal received the highest number of citations per document (25.5) and two of the most cited documents were about organ trafficking.Two thousand forty-four documents were retrieved. The average number of authors per document was 1.9. Over one third  contains supplementary material, which is available to authorized users. Trafficking Protocol [International Agreement for the Suppression of White Slave Traffic (1904) [International Agreement for the Suppression of Traffic in Women and Children (1927) [Trafficking Protocol (2000), and the Protocol against Smuggling of Migrants by Land, Sea, and Air (2000) [Trafficking Protocol to develop criminal codes for HT. As of 2016, over 150 countries had criminal laws for HT [Office to Monitor and Combat Trafficking in Persons releases an annual report (TIP Report) about international efforts to combat trafficking. The European Union adopted the Brussels Declaration on Preventing and Combating Trafficking in Human Beings which aimed to fight HT in Europe [Human trafficking (HT), or modern slavery, is an old problem . HoweverProtocol . Human tc 1904) , Internan 1927) , the Tra , Intern , the Trs for HT . In the n Europe .Sex trafficking is one of the most common forms of HT with more than half a million women being trafficked every year . Forced Human trafficking has a global dimension despite that trafficking could occur within the same country . Human tThe International Labor Organization (ILO) reported 12.3 million trafficking victims in 2005, 21 million victims in 2012, and 40.3 million victims in 2016 . The 201Bibliometric analysis is a research method used to shed light on research activity –31. It dh-index metrics for documents [In the current study, SciVerse Scopus was selected to accomplish the objectives. Scopus is a bibliographic database created by Elsevier in November 2004 . With 22ocuments , 47.Trafficking Protocol ratified in December 2000.A bibliometric method was implemented. The study period was set from 2000 to 2017. The study period was determined based on the assumption that HT has attracted a lot of public attention after the introducing the UN ). Keywords were obtained from previously published literature on HT [In bibliometric analysis, selection of keywords is of utmost importance, as these keywords have a direct impact on the findings and results. In the current study, search strategy was based on title or title/abstract search with certain constraints to minimize false-positive results Table . Keywordre on HT , 48–51. Journal of Social Medicine which is categorized in both social science and medicine. Health-related documents were further divided into different domains such as mental health, health policy and systems, maternal and reproductive health, non-communicable diseases, and infectious diseases [Using the function designated as “subject area”; it was possible to estimate the number of HT documents in health field, defined as documents in the following subject areas: medicine, nursing, psychology, pharmacology, neuroscience, general health, microbiology/immunology, biochemistry, and dentistry. The total number of health and non-health documents was greater than the total number of the retrieved documents because some journals are indexed in both medicine and social sciences; e.g. the diseases .In the current study, bibliometric indicators were presented as ten most active countries, institutions, journals, authors, and ten most cited documents. The choice of number ten as a threshold to list the results was an arbitrary selection that has been used in previously published bibliometric studies , 52–54.Research collaboration was assessed using author affiliation. For example, documents with authors having different country affiliations represent international research collaboration while documents with authors having the same country affiliation represent intra-country collaboration. Scopus allows for segregation of documents based on authoraffiliation. Therefore, for each country, the number of documents with international authors was calculated as a percentage of the total number of documents published by that country. Documents with international authors were referred to as multiple country publications (MCP) and represented the extent of international collaboration –58.Co-authorship analysis, international collaboration, and keyword analysis were presented as network visualization maps using VOSviewer  , 60.The In total, 2044 documents were retrieved .In total, 707 34.6%) documents were in the health field while 1526 (74.7%) were in social sciences and humanities taking into consideration certain limited overlap between the health and health research domains. Analysis of the retrieved showed that 971 (47.5%) documents were about law and criminology, 238 (11.6%) were about health policy and systems, 200 (9.8%) were about social work, and 183 (9.0%) were about mental health  documents  with international research collaboration. In contrast, Brazil had the least percentage of documents (12%) with international research collaboration. For the US, which led in the number of publications, only 12.5% of documents with US authors included authors from other countries. Of the 1478 publications produced by the top 10 active countries, there were only 238 (16.1%) publications with international collaboration.Harvard University (USA)  was the most active institution in this field followed by University of British Columbia (Canada) and London School of Hygiene & Tropical Medicine (UK) (Table USA) n = 9; 1.9% wn = 1250) documents were single-authored publications, 20.0% (n = 408) were two-authored publications, while the remaining 18.9% (n = 386) were multi-authored publications (≥ 3 authors per document). Professor Cathy Zimmerman (UK) was the most active author . Professor Jay Silverman (USA) ranked second   journal received the highest number of citations per article followed by those published in International Migration (22.5).The retrieved documents were published in 998 different journals. The ts Table . The majh-index of the retrieved documents was 48. The document that received the highest number of citations was published in 2007 in Politics and Society. Top ten cited documents discussed topics about organ trafficking, mental health, and HIV infections of HT victims. Table The retrieved documents received 15,505 citations giving a mean of 7.6 citations per document. The The current study aimed to assess and analyze published literature on HT. Quantitative analysis of literature on HT is complicated by the lack of academic and legal consensus on the definition of HT as well as the unclear distinction between trafficked victims, exploited people, and vulnerable migrants . For exaThe findings of the current study showed that the total number of retrieved documents on HT was low when compared to the size of literature on the 21 million people described as refugees . The numThe current study showed that there was an underrepresentation of health-related research on HT despite the potential threat of HT to national health security . Health The findings of the current study regarding the under-representation of labor trafficking relative to sex trafficking were in agreement several previously published studies , 82. ProThe current study showed that the bulk of the retrieved literature and the topics discussed represent the perspective of the destination rather than source countries. It is believed that the source countries are ones with no or minimum level of democracy, high levels of corruption, and poor economic growth, which make engagement in research and academic investigation an unaffordable luxury. The source countries might not have enough public health researchers or experts HT, which influence their contribution to literature in this field. It is recommended that the source countries place migration and trafficking in their national and foreign policy agendas. Healthcare professionals, social care specialists, and experts in global health diplomacy in source countries need to get engaged in developing evidence-based information about methods used by traffickers in recruiting their victims from source countries . Legal aIn the current study, published literature on sex trafficking dominated the field of HT. The over-representation of sex trafficking suggests that research related to other forms of trafficking, particularly labor trafficking is being under-researched. Trafficked laborers live and work in harsh and mostly unhealthy conditions that might involve confiscation of passports, low wages, sex slavery, and deprivation of basic health need –94. ReseThe current study has a few limitations. Using Scopus database to retrieve literature on HT created a certain bias toward countries with a large number of journals indexed in Scopus. Scopus is biased toward academic journals in which documents are published in English. Therefore, documents in HT published in non-English were not retrieved. The current study, like all other bibliometric studies, did not include grey literature. The search strategy used in this study might have led to some false-negative or false-positive results. Therefore, interpretation of the results should take into consideration these limitations.The current study is the first to assess research activity in the field of HT. The current study showed that health aspects of HT were under-represented compared to criminal, legal, and social aspects of HT. Similarly, research on labor trafficking was under-represented compared to sex trafficking and exploitation. The literature on HT represents the agendas of destination countries with limited contribution of countries in Asia, Latin America, Africa, the Middle East, and Eastern European. Future research plans should shed light on trafficking for non-sexual purposes. Furthermore, research networks need to be strengthened by including scholar from source and destination countries to investigate health conditions of trafficking survivors or exploited migrants. Greater investments in international research collaborations and research networks should be encouraged to help prioritize research on HT in various world regions.Additional file 1:Scheme of the sequence of data extraction and analysis. Number of documents retrieved using Scopus at each step in the search strategy used to obtain the required data. (DOCX 30 kb)


It explores the utility of simple anthropometric measures (the waist height ratio (WHtR) and waist circumference (WC)) for the assessment of obesity. In the morning after an overnight fast (10 h), 30 participants underwent a body composition DXA (GE iDXA) scan, BIA (seca 515), and anthropometric measures. Compared to the DXA reference measure, the BIA underestimated fat mass (FM) by 0.32 kg ; overestimated fat free mass (FFM) by 0.43 kg . Some of the variation was explained by body mass index (BMI), as for FM, the mean difference of the normal range BMI group was smaller than for the overweight/obese group  with wider limits of agreement . There were significant differences in visceral adipose tissue (VAT) volume measurements between methods with BIA systematically overestimating VAT compared to DXA. WC was more strongly correlated with DXA FM  than WHtR . BIA had some agreement with DXA; however, they are not equivalent measures for the range of BMIs explored, with DXA remaining the more informative tool. WC is a useful and simple assessment tool for obesity.This study aimed to compare the use of the bioelectrical impedance device (BIA) seca With gr, BMI, . 2, BMI), . VAT is 2, BMI), ,8. This 2, BMI), ,11,12,132 utilized to discriminate individuals of normal weight from overweight and obese individuals [BMI is a widely used method for the assessment of obesity, with a cut-off of ≥25 kg/mividuals . Althougividuals ,16. Assessment of body composition is used in a variety of settings, from weight management clinics to sports performance, and screening at a population level for risk of obesity complications . TherefoDual X-ray absorptiometry (DXA) is a commonly used method for the assessment of body composition, especially bone density and soft tissue . The GE ® mBCA 515 Analyser  offers the additional calculation of VAT volume through an in-house developed proprietary algorithm [Bioelectrical impedance devices (BIA) are smaller, some being hand-held, and faster, and require little training for their use. They use a harmless electrical current, rather than radiation, to assess body composition. BIA measures the opposition (impedance or resistance) to the flow of an electric current through the body, and uses this information to predict total body water (TBW). Predictions are made via the use of algorithms, often empirically derived and device-specific, in order to quantify FFM, calculated as TBW/0.732 where 0.732 is an assumed hydration fraction of the FFM. FM is obtained by subtracting FFM from total mass. The secalgorithm . Current literature suggests that BIA could be a viable alternative to DXA for determining body composition, with BIA offering an inexpensive, faster, and less invasive option. However, to date, studies have not investigated its utility across a wide spectrum of body sizes (BMI) ,23. ShafThere is a clear need for a better understanding of the strengths and weaknesses of different techniques of body composition instruments, which is particularly true when proprietary algorithms are incorporated into simple devices but with little explanation, such as with the seca 515 mBCA Analyzer. Often, BIA devices are used interchangeably with other body composition methods, and so there is a need to explore whether this is appropriate. Other simple measures include WHtR and WC, which are quick and simple anthropometric measures often used to assess central adiposity, and can be surrogate indicators of disease risk in both adults and children ,29. The There is a need to quantify VAT, as it is potentially a more precise screening measurement for identifying those at risk of metabolic disorders associated with obesity. The reference methods for the quantification of VAT is MRI or CT scanning. The GE iDXA with CoreScan technology is widely used for body composition assessment, and also reports the quantification of VAT; this has been confirmed against CT scanning . BetweenThe aims of this study were: to compare the use of the seca mBCA 515 Analyzer for body composition (FM and FFM) against a body composition scan, using the GE Lunar iDXA as a reference method; to explore the VAT measures across both instruments; and to assess the utility of WHtR and WC as indicators of body fatness. 2 and 50 kg/m2; and those who reported to have a stable weight and were not actively attempting to lose or gain weight. Exclusion criteria included: pregnant women; anyone who had exposure to radiation three months prior to study enrolment; and those with standard exclusions for DXA and/or BIA, such as those with implanted defibrillator devices or prostheses. Thirty participants enrolled in this observational study. Recruitment commenced in October 2015 and concluded in September 2016. Participants were recruited through online staff and student forums and poster advertisements at Monash University, Melbourne, Australia. Inclusion criteria were: healthy adults, who were able to comprehend and consent to the study in English; being aged between 18 and 65 years; having a BMI between 18.5 kg/mParticipants were required to attend one three-hour session in the morning after an overnight fast. All subjects gave their full informed consent for inclusion before participation in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol and supporting documents were approved by the Monash University Human Research Ethics Committee (CF15/2790-2015001139).2).Height was measured using a Holtain fixed stadiometer  to the nearest 0.1 cm . Weight The DXA scan was conducted on a GE Lunar iDXA . Each participant received a total body scan, conducted by a single qualified radiographer (AE) who was experienced in DXA scanning. Participants were scanned in the supine position and VAT was estimated using the android region (from the ribs to the iliac crest) via the inbuilt CoreScan software . FFM was determined by the sum of bone mineral content and lean soft tissue values, and FM was also determined. The coefficient of the variations were 0.74% for FM, 0.48% for lean mass, and 11.84% for VAT volume. The seca mBCA 515  uses multi-frequency 8-point stand-on bioelectrical impedance analysis to measure TBW by applying an electrical current of 100 µA to the body. The drop in voltage between sensor electrodes at the hands and feet is used to determine total body water. The manufacturer’s operating instructions and proprietary software calculated FM, FFM, and VAT volume from total body water, weight, WC, height, age, and gender . The BIA2 and <25 kg/m2) and those with a weight in the overweight or obese range (BMI ≥ 25 kg/m2), as defined by BMI. Descriptive characteristics are displayed as means ± the standard deviation for the total sample, both males and females. For FM, FFM, and VAT, one-sample t-tests were performed to initially assess the variation from zero for the difference between methods. If the variation was not significantly different from zero, a Bland-Altman plot was created to assess the agreement between methods and determine the limits of agreement for each variable [All statistics were analyzed using IBM SPSS Statistics 24 . The sample was analyzed as a whole group and then split into those with a weight within the normal range , 47% were classified as overweight (n = 14), and 20% were obese (n = 6), as defined by the World Health Organization’s cutpoints for BMI. Height (cm) and weight (kg) were significantly different between males and females , as well as BIA FFM (kg) and WHtR . There was a strong correlation between BIA and DXA for FM (kg),  and between WC and BIA VAT (cm3) . For each variable, BIA and DXA were more strongly correlated with WC than WHtR; in the normal weight group, there were no significant relationships between these variables . Again, in this group, BIA and DXA were more strongly correlated with WC than WHtR for all measures. Concordance was strong between BIA and DXA for FM and FFM ; however, concordance was poor for VAT measured by BIA and DXA (−0.016).ariables . For thet-test demonstrated that the difference between methods for VAT measurement was significantly different from zero  for the total sample and when the sample was split into normal weight and overweight/obese groups; therefore, it was not appropriate to construct Bland-Altman plots for this variable. Linear regression analysis showed that BIA significantly overestimated VAT compared to DXA . A Bland-Altman plot determined the level of agreement for FM measurements  compared with DXA. For the normal weight group, BIA underestimated FM by 0.25 kg  compared with DXA, and for the overweight and obese group, BIA underestimated fat mass by 0.35 kg  compared with DXA. There was good agreement between the methods for FM, and whilst the mean difference was smaller for the normal weight group, the limits of agreement were narrower for the overweight and obese group . Regression analysis showed that there was no proportional bias between measures of FM or FFM for the whole group or either of the normal weight or overweight/obese groups (data not shown). BIA overestimated FFM by 0.43 kg, and whilst the limits of agreement were larger, this represented a smaller proportion of mean FFM  than for FM . The meaThis study aimed to better understand the strengths and weaknesses of two relatively new instruments that purport to measure body composition, as well as VAT in adults across the spectrum of the BMI range. Both devices, the GE iDXA and seca BIA instruments, incorporate proprietary algorithms into simple-to-use instruments, but with little explanation as to their measurement derivation. A strength of the seca 515 BIA is its non-invasive nature and ease of use; however, our results indicate that the seca BIA device showed greater agreement with DXA for FM measurements, especially in individuals with larger amounts of FM. The two methods did not demonstrate clinically relevant equivalence for measures of FM or FFM; this highlights that different devices for body composition are not interchangeable.VAT volume is an independent risk factor for a host of lifestyle-related diseases ,10. QuanWaist circumference is a valuable tool in assessing central adiposity and, as such, this simple anthropometric measure should not be overlooked, as it is an informative indicator of obesity and risk of related diseases ,43. AlthThe limitations of this study were the small sample size, especially in the normal weight group, with the majority of the participants being of Caucasian descent; and not being able to draw conclusions on the generalizability of the instruments for use in body composition assessment across other ethnic groups, due to body composition variability observed between ethnicities . HoweverThe limits of agreement were larger than those previously reported ,28, withWC and WHtR are quick, simple, and cheap methods of assessing body fatness . WC is a


To investigate the characteristics of blood in nonsyndromic retinitis pigmentosa (RP) and reveal the pathogenesis of blood cells involved in blood stasis in RP.  This is a retrospective observational study.  We collected vein blood from 101 cases of patients with nonsyndromic RP and 120 cases of normal individuals according to a single-blind study and used routine clinical examination to detect the indicators of blood. All the subjects were mainly from the central south of China. Data were analyzed statistically between the RP group and normal control. p < 0.01). There were no statistical differences in the other indicators between the RP and normal group.  The indicator of platelet distribution width (PDW) in patients with RP was higher than that in the normal group; the indicators of red blood cell (RBCs), hemoglobin (HGB), hematocrit (HCT), basophils (BASs), platelets (PLTs), and plateletcrit (PCT) in the RP group were lower than those in the normal control. The differences were statistically very significant between the RP group and normal group ( The changes in RBCs and PLTs in patients with RP implied that RP induces RBC aggregation and platelet activation, leading to blood stasis which in turn initiates more apoptosis. Retinitis pigmentosa (RP) is a group of heterogeneous inherited retinal degeneration disease . ExtensiHuman blood is composed of plasma and several kinds of cells such as red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). Blood performs many important roles within the body, such as supplying oxygen and nutrients to cells and tissues, removing wastes, transporting hormones and signaling, regulating body pH and temperature, and helps in immunological functions and coagulation. Blood rheological behavior affects the vascular system, especially microcirculation and tissue perfusion . Risk fat = 1.222, p > 0.05) and sex ratio  between the two groups. According to the clinical routine blood examination, all blood samples from patients and normal individuals were taken from the vein in the elbow by professionals in hospitals according to the single-blind study.Our study retrospectively analyzed two datasets of blood samples from patients with nonsyndromic RP diagnosed by First Affiliated Hospital Ophthalmology of Hunan University of Chinese Medicine and Hunan Provincial Hospital of Chinese Medicine from 2012 to 2018. Blood samples were collected from 101 patients with primary nonsyndromic RP and without other system diseases. For these patients, this should be their first medical visit or they have not undergone systemic therapy for RP. The collected 101 samples, including unrelated probands of familial and sporadic cases, were mainly from Hunan, Hubei, Jiangxi, and other provinces, mainly located in the central south of China, including 44 males and 57 females, aged from 8 to 59 (average age of 43.02 ± 13.07). On the other hand, 120 normal individuals who were examined at the physical examination center of the First Affiliated Hospital of Hunan University of Chinese Medicine were selected as the control group, including 63 males and 57 females, aged from 9 to 69 (average age of 40.35 ± 12.50). There was no significant difference in age , hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell width variation coefficient (RDW-cv), white blood cells (WBCs), lymphocytes (LYMs), monocytes (MONs), neutrophils (NEUs), eosinophils (EOSs), basophils (BASs), platelets (PLTs), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW).T-tests for comparing RP group with the normal group when the quantitative data were normally distributed; median and interquartile range were used in two independent samples rank sum test for comparing RP group with the normal group when the quantitative data were not normally distributed. p < 0.05 was considered statistically significant; p < 0.01 was considered statistically very significant.We used SPSS 22.0 software to perform statistical analysis. Mean and standard deviation were used in two independent samples p < 0.01). However, the difference in MCV, MCH, and MCHC was not significant between the RP group and normal group (p > 0.05). Data are presented in The indicators of RBCs, HGB, HCT, MCV, MCH, MCHC, and RDW-cv both in the RP group and normal control were in accordance with the normal distribution. RDW-cv in patients with RP was higher than that in the normal individuals. The indicators of RBC, HGB, and HCT in the RP group were lower than those of the normal control. The differences were statistically very significant . However, there were no statistically significant differences in the count of WBC, NEU, LYM, MON, and EOS between the RP group and the normal control (p > 0.05). Data are presented in The indicators of WBC counts and NEU counts were in accordance with the normal distribution, and two independent T-test was performed. The other data both in RP group and normal group were not in accordance with the normal distribution, and two independent samples rank sum test was performed. PDW in patients with RP was higher than that in the normal control. PLT counts and PCT in patients with RP were lower than those in the normal control. The differences in PLT counts, PCT, and PDW between the RP group and normal control were statistically very significant (p < 0.01). There were no statistically significant differences in the MPV between the RP group and normal group (p > 0.05). Data are presented in The count of PLT both in the RP group and normal group was in accordance with the normal distribution, and two independent samples p < 0.01). There were no statistically significant differences in the other indicators between the RP group and normal group (p > 0.05). The results indicated that RBCs and PLTs may be involved in abnormal blood flow in RP.In this study, we retrospectively analyzed two datasets of blood samples from 101 patients with nonsyndromic RP; these patients included unrelated probands of familial and sporadic cases and were from two hospitals, and they were mainly from the central south of China. One major drawback of this approach is the limited sample size; selection bias is another potential concern because the samples come from the adjacent areas. The indicator of PDW in patients with RP was higher than that in the normal group; the indicators of RBCs, HGB, HCT, BASs, PLTs, and PCT in the RP group were lower than those in the normal group. The differences were statistically very significant  adhesion: the platelets attach to the interrupted endothelium; (ii) activation: they change shape, turn on receptors, and secrete chemical messengers; and (iii) aggregation: they connect to each other through receptor bridges . When thThe changes occurred in the blood of patients with RP in our research implied that RBCs and PLTs are involved in vascular atrophy and blood stasis in RP. The indicator of PDW in patients with RP was higher than that in the normal control. The indicators of RBC counts, HGB, HCT, BASs, PLTs, and PCT in patients with RP were lower than those in the normal group. In summary, the cell degeneration and abnormal retina vessel in RP induced RBC aggregation, extracellular calcium reduction, platelet consumption, and platelet activation; all the changes lead to blood stasis. It is expected that keeping under control the RBC aggregation and platelet consumption and activation may help in the reduction of peripheral vascular resistance and in increment of blood flow to ameliorate the blood stasis in RP. However, the mechanism of blood stasis in RP remains unknown; the relationship between the characteristics of blood in a hypercoagulable state in RP needs to be further studied.


Background: Previous studies have focused on left and right ventricular remodeling in cystic fibrosis (CF), whereas atrial function has not been assessed in detail so far. We sought to investigate left and right atrial (LA and RA) function in patients with CF. Methods: This retrospective investigation included 82 CF patients (64 survivors and 18 non-survivors) who were referred to CF department over the period of four years, as well as 32 control subjects matched by age and gender. All participants underwent an echocardiographic examination including a strain analysis, which was performed offline and blinded for groups. Results: LA and RA volume indexes were significantly higher in CF patients than in controls and were particularly high in CF non-survivors. LA conduit and reservoir functions were significantly worse in CF survivors and non-survivors, compared with control subjects. RA phasic function was not different between controls, CF survivors and non-survivors. The parameters of lung function  and forced expiratory volume in the first second (FEV1)) and the LA and RA volume indexes were predictors of mortality in CF patients. However, in a multivariate analysis, only FVC was an independent predictor of mortality in CF patients. Conclusions: Our results suggest that both atria are enlarged, but only LA function is impaired in CF patients. LA reservoir and conduit function is particularly deteriorated in CF patients. Though statistical significance was not reached due to our limited sample size, there was a trend of deterioration of LA and RA function from controls across CF survivors to CF non-survivors. LA and RA enlargement represented predictors of mortality in CF patients. Cystic fibrosis (CF) is the most frequent life-threatening autosomal recessive disease in the Caucasian race, occurring in 1 out of 2500 newborns. CF is caused by almost 2000 various mutations of the CF transmembrane conductance regulator gene, located on the seventh chromosome. Previously, chronic cor pulmonale was present in 70% of infants and children dying from CF [Studies conducted in the CF population have reported significant heart remodeling and, particularly, right ventricular (RV) hypertrophy and dysfunction in the advanced stages of disease ,3,4,5,6.Atrial remodeling is usually underestimated and neglected in patients with various cardiovascular diseases. However, left atrial (LA) enlargement and dysfunction is related with both cardiovascular and overall mortality . Right aThe aim of the present study was to evaluate LA and RA phasic function using the strain method in CF patients. Additionally, we sought to investigate if LA and RA function and volume represent predictors of lethal outcome in CF patients.n = 15).This is a retrospective study that involved 82 consecutive CF patients who were referred to the CF department in the period between October 2012 and December 2016. The diagnosis of CF was confirmed via a documented positive sweat chloride test or by the identification of two genetic mutations known to cause CF. Controls were recruited from the echocardiography department among the patients who were referred to a regular check-up examination, palpitations or innocent heart murmur. Control subjects were matched with the CF group by age and gender. Patients with symptoms or signs of coronary artery disease, valve heart disease more than mild, atrial fibrillation, congenital heart disease, liver or kidney failure were excluded from this study. All study participants underwent an echocardiographic examination, and one researcher (AD) performed an offline strain analysis. This investigator was blinded to which group study participant belonged . All CF patients had spirometry before their echocardiographic examination. Patients with inadequate echocardiographic images were excluded  and laboratory analyses  were obtained from all the participants. Body mass index (BMI) and body surface area (BSA) were calculated for each subject. The study was approved by the local ethics committee.Echocardiographic examinations were performed by a Vivid 7  ultrasound machine. LV diameters, posterior wall and septum thickness were measured, and relative wall thickness was calculated according to the current recommendations . The LV A pulsed-wave Doppler evaluation of transmitral LV was obtained in the apical 4-chamber view according to guidelines . Tissue LA volumes (LAVs) were measured just before the mitral valve opening. The LA volume was determined according to the biplane method in the 4-and 2-chamber views, and it was indexed for BSA  .2D LA strain imaging was performed in the apical 4- and 2-chamber views , and comThe RV internal diameter was measured in the apical four-chamber view . RV globRA volume was evaluated just before the tricuspid valve opening and indexed for BSA . RA strap < 0.1 in the univariate logistic regression analysis. The p-value < 0.05 was considered statistically significant.Continuous variables are presented as mean ± standard deviation, showed a normal distribution, and were compared by the analysis of equal variance (ANOVA). An LSD post hoc analysis was used for the comparison between different groups. Differences in proportions were compared by the χ² test. Univariate and multivariate logistic regression analyses were used for the determination of predictors of mortality in the CF patients. A multivariate logistic regression analysis included variables that showed There was no significant difference in age and sex distribution between controls, CF survivors and CF non-survivors . BMI was2) was significantly higher in CF non-survivors than in controls and CF survivors (Left ventricular diameter was significantly higher in the control group than in the two CF groups . Interveurvivors . LV diasurvivors .2 for women and > 26 mL/m2) between controls and CF patients  and two chamber (2Ch)) were evaluated . DiffereThe RA strains  and strain rates were similar between controls, CF survivors and CF non-survivors .p = 0.004).Parameters of lung function (FVC and FEV1), the LA and RA volume indexes were predictors of mortality in CF patients . PAPs waOur investigation provided several important findings: (i) Both atria were significantly enlarged in CF patients—particularly in CF non-survivors; (ii) LA conduit and reservoir functions were significantly lower in CF survivors and non-survivors than in controls; (iii) RA function was not impaired in CF patients; (iv) the atrial volume indexes (LAVI and RAVI) were predictors of mortality in CF patients.Most investigations about CF performed in the last three decades have been focused on RV structure, RV function, and, more recently, RV mechanics ,12,14. L2) was almost equal to the cut-off value for LA dilatation in the general population (≥ 34 mL/m2). This shows that left heart must not be forgotten in the assessment of CF patients, and this evaluation cannot be based solely on the calculation of the LV ejection fraction. LA dilatation in our CF patients was associated with a significant increase in the mitral E/e’ ratio and a decrease in the mitral E/A ratio. Both parameters are associated with an increased LV filling pressure that could be explained by an increased LV preload, a low pulmonary blood flow, an increased pulmonary pressure, an impaired RV performance, and interventricular interdependence throughout interventricular septum [Our findings revealed significant LA and RA enlargement in CF patients. Namely, LA and RA volumes gradually increased from controls, across CF survivors to CF non-survivors. Interestingly, LA dilatation was a bit more pronounced than RA dilatation, and in CF non-survivors, the LA volume index function . There aLA conduit and reservoir functions assessed by strain were significantly lower in CF patients than in the control group. In fact, LA conduit function was impaired in CF patients, and LA booster pump function was similar between the observed groups. As the result, LA reservoir function was also impaired in CF patients comparing with controls. There was a trend of the gradual deterioration of the LA reservoir and conduit functions from controls across CF survivors to CF non-survivors. However, a statistical significance in LA function between CF survivors and non-survivors was not reached due to the limited sample size. The deterioration of LA conduit and reservoir functions in our study indicated the presence of LV diastolic dysfunction, even though parameters for LV diastolic dysfunction were still in normal range. However, it must be underlined that these differences in LA phasic function between CF patients and controls were obtained only in the four-chamber view and not in the two-chamber view, and, subsequently, they were also not observed in global values—obtained as the average between the four- and two-chamber views. These regional differences are not an exception because other authors also did not find a statistically significant difference in global LV and RV strains, but significant differences were found in some LV and RV segments ,14. ThisRA phasic function was not significantly deteriorated in CF patients compared with controls. However, RA was significantly larger in CF patients than in controls. Sciatti et al. recently reported significantly larger RA area in CF patients than in controls . RA voluThe LA and RA volume indexes were significant predictors of mortality among our patients with CF. This showed the great importance of the evaluation of LA and RA volumes in the CF population. Besides the LA and RA volume indexes, the only predictors of mortality in the CF population were lung function parameters (FVC and FEV1). LA and RA strain parameters were not predictors of a lethal outcome in CF patients. The only independent predictor of mortality was lung function (FVC).The most relevant clinical implication of the current study is underlined importance of a bi-atrial echocardiographic evaluation, which involves the assessment of the LA and RA volume indexes. This is not time-consuming and is widely available because an atrial volume assessment does not require any additional equipment besides a basic echocardiographic machine, which makes it favorable from a cost-effectiveness perspective. An additional evaluation of LA and RA strains would be beneficial and also recommended, because it provides better insight in atrial function and remodeling.Our study has several limitations. First, our sample size was limited and a statistical significance was not reached in many comparisons where obvious trend existed. Second, this was a retrospective study, and the echocardiographic exam was not optimized for the research, which resulted in the exclusion of some patients due to a lack of adequate images. Third, diabetes was very prevalent in CF patients and could contribute to atrial remodeling. However, CF induces diabetes in more than 50% of adult patients, and it also represents a characteristic of CF in a certain age group. Fourth, biomarkers related to RV or LV dysfunction were not available for this study, and these would have been helpful to reach a conclusion.LA and RA were enlarged in CF patients. The dilatation was more remarkable in CF non-survivors than in CF survivors and controls. LA conduit and reservoir functions, evaluated by strain, were deteriorated in CF patients in comparison with controls. RA phasic function in CF patients was not significantly different from controls, even though there was an obvious trend of RA function impairment from controls to CF non-survivors. The LA and RA volume indexes, but not strain, were predictors of mortality in CF patients. This study underlines the importance of a bi-atrial assessment in CF patients, which involves the evaluation of, at least, LA global strain, as well as atrial volume indexes whenever is feasible. Further follow-up studies with larger numbers of patients are necessary to determine the predictive value of LA and RA phasic function and strain on the outcome in CF patients.


To investigate the factors associated with a higher risk of noncompliance to tuberculosis (TB) treatment in Porto Alegre, Brazil.We identified 478 adult patients for this case-control study undergoing treatment for confirmed pulmonary TB. Cases (noncompliance) were defined as patients who stopped treatment for more than 30 consecutive days (n = 118). Controls were defined as all patients who completed treatment and were cured (n = 360). Factors associated with noncompliance were calculated with unadjusted and adjusted odds ratio (OR).The rate of noncompliance in our study was 25%. The factors of noncompliance after adjustments in the overall population were, in order of magnitude, living in an area of lower income , abuse of drugs , nonadherence to a previous treatment regimen , and history of smoking . Age, race, gender, level of education, HIV infection or diabetes status were not associated with a higher risk of noncompliance. In the subgroup of re-treatment cases, poverty , smoking history , male gender , and younger age  were also associated with a higher risk of dropout.Predictors of poor compliance to TB treatment were low income, abuse of drugs, re-treatment cases and history of smoking. Tuberculosis (TB) remains as an important cause of death from an infective agent in the world . ParadoxSeveral strategies have been proposed to improve treatment compliance, such as a fixed-dose combination therapy, directly observed therapy (DOT), and ensuring access to medication at the time of diagnosis . In BrazThe goal of this study was to investigate the factors associated with a higher risk of noncompliance to tuberculosis treatment dropout in Porto Alegre, southern Brazil. We further stratified the cases of noncompliance between treatment-naïve patients and re-treatment cases to identify the differences in risk factors between these groups.Mycobacterium tuberculosis, or at least two smear-positive results for acid-fast bacilli, or one smear positive for bacilli plus evidence of TB on diagnostic chest x-ray), (3) and treatment with standard antituberculous drug scheme followed in Brazil  for at least 6 months. Information regarding recommended routine ATT regimens, duration of treatment, and alternative regimens in consideration of comorbidities is provided in We retrospectively identified consecutive adult patients referred for pulmonary TB treatment in Porto Alegre, southern Brazil, from January 2014 to December 2014. The city has four referral tuberculosis centers (RTC), and patients from all centers were included in this study. The inclusion criteria were: (1) Age ≥ 18 years; (2) confirmed diagnosis of pulmonary TB  were defined as all confirmed bacteriologically pulmonary TB (criteria above) who had dropped out from the routine treatment scheme. Dropout was considered when the patient did not show up in the last medical office visit and stopped the treatment for at least 30 consecutive days. Controls were defined as all patients with confirmed bacteriologically pulmonary TB (criteria above) who had completed the same treatment and were cured. Cure was defined as two negative smear bacilloscopy (one in the attendance phase and the other at the end of the treatment) or completion of therapy in addition to clinical and radiological recovery in the absence of sputum during the treatment. Both cases and controls were further stratified as “new cases”, those treatment naïve or in-therapy for less than a month; and “re-treatment cases”, individuals who relapsed before complete cure despite of a previous adequate treatment in the last 5 years, or when the patient spontaneously dropped out of treatment after 30 days of therapy and was again referred to restart treatment.The following independent variables were analyzed in this study: sex, age, self-reported ethnicity, level of education (in years), human development index income at the municipal level (HDI-M), homeless status, and presence of other associated health problems such as HIV infection, smoking status, drug use, and diabetes. The income of the participants was defined based according to the location of the basic health unit where the patient was first diagnosed with TB, considering the income dimension of the Human Development Index at the municipal level (HDI-M) of the city of Porto Alegre in the state of Rio Grande do Sul, Brazil. The HDI-M was obtained from the Brazilian Human Development Atlas, produced by the United Nations Development Programme (UNDP).The HIV seropositivity was confirmed by at least two positive ELISA tests followed by a positive western blot test as confirmation. Tobacco smoking was defined as smoking at least 100 cigarettes in a lifetime. Drug use refers to the harmful or hazardous use of psychoactive substances, not occasionally.Descriptive statistics were used to describe the characteristics of the total sample and by the cases (tuberculosis treatment dropout) and controls (tuberculosis cure). The distribution of the characteristics was described by absolute and relative numbers between cases and controls, using the Fisher's exact test to explore the heterogeneity of proportions. To investigate the potential factors associated with tuberculosis treatment dropout, an unadjusted and adjusted OR with 95% confidence intervals were calculated by unconditional logistic regression. Wald test for heterogeneity of proportions  and linear trend  was obtained. Only the characteristics associated with the tuberculosis treatment dropout that showed a p-value lower than 0.20 in unadjusted analysis were considered confounding factors and were included in the multivariable analysis. Additionally, we explored the individual analysis stratified by new cases of tuberculosis and re-treatment cases. A two-tailed statistical significant difference was defined at p<0.05. The data analysis was performed using Stata, version 12.0 .The characteristics of the study subjects are shown in Discontinuation of treatment was higher among re-treatment cases compared to the treatment-naïve subjects . Most cases were male (66.1%), were aged 31–49 years (45.8%), non-white (55.9%), had 5–10 years of education (50%), were assisted in an area with higher HDI-M (46.6%), were not homeless (92.4%), were non-smokers (66.1%), HIV positive (66.1%), had no diabetes (95.8%) and were new treatment cases (53.4%). Except for gender (p = 0.08) and diabetes status (p = 0.87), there was a significant difference in all other demographic characteristics between cases and controls. In comparison to controls, the cases were more likely to be from low-income regions (42.4% vs. 14.7%), drug users (33.9% vs. 12.2%), smokers (44.1% vs. 28.3%) and re-treatment cases (46.6% vs. 23.6%). Of note, the proportion of subjects with HIV was lower in the cases when compared to controls .The factors associated with noncompliance to ATT are described in We stratified the sample into new cases and re-treatment cases to investigate the factors associated with noncompliance to ATT in each category . For newWe have shown that the incidence of noncompliance among treatment-naïve and re-treatment patients referred to TB treatment in Porto Alegre was approximately 19% and 40%, respectively. The factors associated with a higher chance of noncompliance after adjustments were, in order of magnitude, living in an area of lower income, abuse of drugs, cases of re-treatment, and history of smoking. Age, race, gender, level of education, HIV infection or DM status were not associated with a higher risk of noncompliance in the overall population.In 2008, Porto Alegre had the highest annual incidence of tuberculosis among Brazilian capitals, with a ratio of 101 cases per 100.000 inhabitants ,10. AlthIn the present study, there was a clear difference in the risk factors associated with treatment compliance when patients were stratified into “new cases” and “re-treatment cases”. We believe these differences can be used in clinical practice to select which patient would benefit from more closely supervised treatment, such as DOT. In the multivariate analysis of treatment-naïve patients, living in an area of low income and drug use were the only factors significantly associated with a higher risk of dropout in the multivariate. These two variables are consistently reported as risk factors by previous studies ,13,14. OOn the other hand, when considering the “re-treatment cases,” three other variables became significantly associated with poor compliance: young age, male gender and low level of education (<4 years). Thus, these factors should be considered by the provider when restarting treatment for a patient with a previous history of relapse, but not for treatment-naïve patients. Drug use was not significantly associated with poor adherence in this group, which could be explained by the lack of power to demonstrate its significance in the subgroup analysis. Similarly, homeless status appeared as a non-significant trend toward a higher risk of dropout in all analysis, possibly due to the low number of homeless people in our cohort. However, previous studies have reported this variable as a risk of noncompliance ,13,15.Other variables have been described in the literature as associated with poor compliance. Lack of effective social support networks and unstable living circumstances are unfavorable for adherence , whereasThe strengths of this work include a large sample of 478 cases and the exploration of specific risk factors associated with poor compliance in the subgroup of patients with a previous history of dropout. Most of the previous works were developed with treatment-naïve patients only or did not specify if re-treatment cases were included ,7,13,21.The factors associated with a higher chance of noncompliance to ATT were, after adjustments, living in an area of low income, abuse of drugs, poor compliance to previous ATT regimen, and history of smoking. Among re-treatment patients three other variables were associated with higher risk of noncompliance: young age, being a male, and low education level.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(XLSX)Click here for additional data file.


The adjusted Cox proportional hazard regression showed that DLC was associated with a significantly higher risk of DNI . The mortality rate in cirrhotic patients with DNI was not significantly higher than that in noncirrhotic patients with DNI . Conclusions: This study is the first to investigate the correlation between DLC and DNI. The study findings strongly indicate that DLC is an independent risk factor for DNI. Cirrhotic patients with DNI do not have a significantly poorer survival rate than noncirrhotic patients with DNI. Therefore, physicians should be alert to potential DNI occurrence in DLC patients. Besides this, intensive care and appropriate surgical drainage can yield similar survival outcomes in DLC-DNI and noncirrhosis-DNI patients.Background: Deep neck infection (DNI) can progress to become a life-threatening complication. Liver cirrhosis, which is related to poor immune conditions, is a likely risk factor for DNI. This study investigated the risk and mortality of DNI in patients with decompensated liver cirrhosis (DLC). Methods: We performed a nationwide cohort study using the National Health Insurance Research Database (NHIRD) in Taiwan. We included a total of 33,175 patients with DLC between 2000 and 2013, from the Catastrophic Illness Patient Database, a subsection of the NHIRD, along with 33,175 patients without cirrhosis who were matched in a 1:1 proportion for age, sex, and socioeconomic status. The occurrence of DNI was the primary study outcome. The risk, treatment, and mortalities of DNI were evaluated in the study and comparison cohorts. Results: DLC Patients had a significantly higher incidence of DNI than noncirrhotic patients ( Deep neck infection (DNI) occurs in cervical fascial spaces. The incidence rate of DNI is 20.88 per 100 thousand persons; years are reported in a recent population-based study in Taiwan . These sAccording to our review of the relevant literature, despite some case reports, the incidence and mortality of DNI among patients with decompensated or compensated cirrhosis remained unknown ,15,16,17We performed a nationwide cohort study using population-based data from the National Health Insurance Research Database (NHIRD) in Taiwan. The National Health Insurance (NHI) program is a single-payer and compulsory health insurance that, at present, covers all forms of healthcare services for 99.6% of the population in Taiwan ,21,22. TThe Institutional Review Board of Chang Gung Memorial Hospital approved this study (CGMH-IRB No.201601249B1). Following strict confidentiality guidelines in accordance with the personal electronic data protection regulations, the personal information of all patients in the NHIRD was encrypted. We matched each patient with DLC with one comparison patient without cirrhosis selected from the Longitudinal Health Insurance Database in 2000 (LHID2000), a representative database of 1 million random patients from the 2000 registry of all NHI enrollees, which contained all claim data for 1996–2013 ,30,33. APatients were followed until death or the end of the study period (31 December 2013) ,35. The For patients who finally developed DNI, the treatment modalities, hospitalization duration, tracheostomy, intensive care unit (ICU) care, mediastinitis , and mortalities were investigated. The patients who underwent surgical drainage were categorized into the “surgery group”, and those who received abscess aspiration or antibiotics without surgery were categorized into the “non-surgery group”.Patient sociodemographic information, including age, sex, socioeconomic status, and urbanicity level, was obtained from enrollment data files. The comorbidities of patients, including DM, chronic kidney disease (CKD), and autoimmune disease, were retrieved from the ambulatory and inpatient claims data. We included these comorbidities if they were observed either in inpatient settings or in three or more outpatient claims. Each comorbidity was analyzed as a binominal variable.Continuous variables and descriptive statistics were analyzed using the independent student t test and Pearson chi-squared test, respectively, to compare the cirrhosis and noncirrhosis groups in terms of their sociodemographic characteristics and comorbidities. The Kaplan–Meier method was used to calculate the cumulative incidences of DNI, and the log-rank test was applied to compare the differences between each curve. The adjusted hazard ratio (HR) for DNI was estimated using the Cox proportional hazard regression models. SAS  was used for statistical analysis, and a two-sided p value of <0.05 was considered statistically significant.The present study included 33,175 patients with DLC and 33,175 comparison patients without cirrhosis between 2000 and 2013 in Taiwan. After matching for sex, age, and socioeconomic status, the results revealed that the cirrhosis group was more likely to develop autoimmune disease, DM, and ESRD than the noncirrhosis group . The meap < 0.001; Using the Kaplan–Meier method, the cumulative incidence of DNI was observed to be significantly higher in the cirrhosis group than in the noncirrhosis group (p < 0.001). The ‘No. at risk’ is the number of patients who were still alive and whose follow-up extended at least that far into the curve.The Kaplan–Meier analysis demonstrated the cumulative DNI identified in the study and comparison cohorts, respectively, during the follow-up period (1997–2013). The log-rank test revealed a significantly higher cumulative incidence in the DLC cohort (p < 0.001).Multivariate analysis was conducted to compare the risk of DNI in the study and comparison cohorts across different sexes, age groups, urbanicity levels, socioeconomic statuses, and comorbidities . No signp = 0.651), respectively, in the DLC-DNI and noncirrhosis-DNI groups.We analyzed the treatment modalities and mortalities of those patients in the study and comparison cohorts who finally developed DNI. The ratios of patients receiving surgical drainage, tracheostomy, mean hospitalization duration, mediastinitis, and three-month mortality did not differ significantly between the DLC-DNI and noncirrhosis-DNI groups . The ratp < 0.001). In our study, the mean (standard deviation) follow-up time was 5.8 (3.9) and 9.2 (3.1) years in the study and comparison cohorts, respectively. This observation duration was adequate to assess the risk of DNI among each group. Furthermore, the treatment modalities did not differ significantly among cirrhotic and noncirrhotic patients with DNI. The three-month mortality rates of DNI in the cirrhosis group were not significantly higher than in the non-cirrhosis group.According to our review of the relevant literature, this study is the first to investigate the risk and mortality of DNI in patients with liver cirrhosis. Our study showed that patients with DLC were at a significantly increased DNI risk than those without cirrhosis. In our study, the 4, 8, and 12-year death-adjusted cumulative incidences of DNI in the cirrhosis group were 0.435%, 0.946%, and 1.651%, respectively. This study is the first to estimate these indices. After adjusting for the potential confounders, the HR for DNI was 4.11 , indicating that the risk of DNI increased by 311% in patients with DLC. The log-rank test results indicated that patients with DLC had a significantly higher incidence of DNI than those without cirrhosis , which is consistent with the findings of previous studies [The adjusted HR for DM in the present study was 1.81  to compare the outcomes between the study and comparison cohorts.The present study has some limitations. First, detailed data on albumin, bilirubin, and prothrombin time are not available in the NHIRD. Second, the exact etiology of cirrhosis was not identified in our study, and we were unable to evaluate the severity of cirrhosis based on the Child–Pugh scores. Third, the patients in the study cohort were selected from the RCIPD, which only included patients with DLC. Therefore, patients with compensated liver cirrhosis were not included in this study. Nonetheless, despite the aforementioned limitations, this study is the most comprehensive nationwide population-based study to prove that DLC is a risk factor for DNI. Moreover, additional investigations are warranted to determine the risk of DNI in patients with compensated cirrhosis. Finally, our study is a retrospective population-based study. Therefore, additional prospective studies are required to elucidate the relationship between cirrhosis and DNI.This study is the first to demonstrate that patients with DLC are at an increased risk of DNI. In addition, cirrhotic patients with DNI do not have a significantly poorer survival rate than noncirrhotic patients with DNI. Our study findings suggest that physicians should consider the risk of DNI while treating patients with DLC. Besides this, intensive care and appropriate surgical drainage can yield similar survival outcomes in DLC-DNI and noncirrhosis-DNI patients.