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IntroductionThe Latinx population has the second highest COVID-19 death rate among racial/ethnic groups in the United States and less than half of Latinx youth aged 5-17 years old completed their COVID-19 primary vaccination series as of September 2022. COVID-19 vaccine misinformation detrimentally impacts vaccination rates. In this study, we examined factors that predicted Latinx youth COVID-19 vaccine hesitancy and vaccination status.MethodsA community-based sample of 290 Latinx parent and adolescent dyads from a Southwestern metropolitan area of the United States who were recruited to complete an online survey at baseline at T1 (August 2020 -March 2021) and one year later. We tested a longitudinal mediation model in which we examined individual and family factors that would predict youth COVID-19 vaccine hesitancy and vaccination status over time.ResultsYouth's pandemic disbelief (i.e., the belief that the COVID-19 pandemic is a conspiracy or not real) predicted greater youth's COVID-19 vaccine hesitancy, and in turn, a lower likelihood of youth's COVID-19 vaccination. Youth's pandemic disbelief also predicted greater parent's vaccination hesitancy which, in turn, predicted greater youth's vaccination hesitancy and a lower likelihood of COVID-19 vaccination. Parents' pandemic disbelief predicted their own COVID-19 hesitancy, but not youth hesitancy.DiscussionOur study findings provide initial evidence that general pandemic disbelief was a significant driver of vaccine hesitancy and vaccination among Latinx families. The study contributes to the limited research investigating COVID-19 vaccination in the Latinx community and among Latinx youth, further aiding how COVID-19 vaccine disparities can be mitigated among racial/ethnic populations.

UPLC-MS/MS profiling of Cassia glauca leaves extract revealed the identification of 10 flavonoids. Kaempferol 3-O-β-D-rutinoside was isolated and studied for its cytotoxic activity. It showed high cytotoxic effects against MCF-7 (IC50 of 4.6±0.038 μg/ml) and HepG-2 (IC50 of 8.2±0.024 μg/ml) cancer cell lines, compared to the leaves extracts, their Ag nanoparticles, and doxorubicin. Moreover, Kaempferol 3-O-β-D-rutinoside exerted a synergistic cytotoxic effect with doxorubicin on MCF-7 cell lines. It was discovered as kinases and aldose reductase inhibitor while rationalizing its cytotoxic activity through molecular docking study. Thus, it is expected that the cardiotoxic effects of doxorubicin can be also decreased by using Kaempferol 3-O-β-D-rutinoside due to its aldose reductase inhibitory effect. These findings suggested that Kaempferol 3-O-β-D-rutinoside could be used in combination with chemotherapeutic drugs to increase the sensitivity to their cytotoxic activity and protect against their side effects.

Phthiocerol dimycocerosates (PDIMs) are a class of mycobacterial lipids that promote virulence in Mycobacterium tuberculosis and Mycobacterium marinum. It has recently been shown that PDIMs work in concert with the M. tuberculosis Type VII secretion system ESX-1 to permeabilize the phagosomal membranes of infected macrophages. As the zebrafish-M. marinum model of infection has revealed the critical role of PDIM at the host-pathogen interface, we set to determine if PDIMs contributed to phagosomal permeabilization in M. marinum. Using an ΔmmpL7 mutant defective in PDIM transport, we find the PDIM-ESX-1 interaction to be conserved in an M. marinum macrophage infection model. However, we find PDIM and ESX-1 mutants differ in their degree of defect, with the PDIM mutant retaining more membrane damaging activity. Using an in vitro hemolysis assay-a common surrogate for cytolytic activity, we find that PDIM and ESX-1 differ in their contributions: the ESX-1 mutant loses hemolytic activity while PDIM retains it. Our observations confirm the involvement of PDIMs in phagosomal permeabilization in M. marinum infection and suggest that PDIM enhances the membrane disrupting activity of pathogenic mycobacteria and indicates that the role they play in damaging phagosomal and red blood cell membranes may differ.

Sexually Transmitted Infections (STIs) are ambiguous burden of tremendous health, social and economic consequences. The current systematic review was conducted in order to determine awareness and knowledge of Africans toward sexually transmitted infections, not only concerning HIV/AIDS, but also other STIs such as gonorrhea, syphilis, HBV, HCV and HPV. A systematic review of literature was conducted, studies were retrieved and selected after fulfilling the inclusion criteria as well as passing the assessment procedure. Related data was extracted, quantitative analysis was conducted among participants who responded to questions related to HIV, HBV, HCV, HPV or STIs knowledge, sensitivity analysis as well as subgroup analysis were also conducted. Seventy four articles addressing knowledge among 35 African countries were included and 136 questions were analyzed and synthesized. The question "does using condom reduces HIV transmission?" was answered by 1,316,873 Africans in 35 countries, 66.8% [95% Cl; 62.6, 70.9] answered yes. While the question "is sexual contact a possible route of HBV transmission?" was answered by 7,490 participants in 5 countries; 42.5% [95% Cl; 20.4, 64.7] answered yes. The differences observed among populations are highlighting the possibility for improvement by directing light toward specific populations as well as addressing specific awareness knowledge to ensure that the general as well as the related specific preventive knowledge is improved.

Background: Coronavirus disease (COVID-19) negatively impacted tuberculosis (TB) programs which were already struggling to meet End-TB targets globally. We aimed to quantify and compare diagnosis, treatment initiation, treatment success, and losses along this TB care cascade for drug-susceptible TB in Cape Town, South Africa, prior to and during COVID-19., Methods: This observational study used routine TB data within two predefined cohorts: pre-COVID-19 (1 October 2018-30 September 2019) and during-COVID-19 (1 April 2020-31 March 2021). The numbers of people diagnosed, treated for TB and successfully treated were received from the Western Cape Provincial Health Data Centre. Pre and post treatment loss to follow up and cascade success rates (proportion of individuals diagnosed with an outcome of treatment success) were calculated and compared across cohorts, disaggregated by sex, age, HIV status, TB treatment history and mode of diagnosis., Results: There were 27,481 and 19,800 individuals diagnosed with drug-susceptible TB in the pre- and during-COVID-19 cohorts respectively, a relative reduction of 28% (95% CI [27.4% - 28.5%]). Initial loss to follow up increased from 13.4% to 15.2% (p<0.001), while post treatment loss increased from 25.2% to 26.1% (p < 0.033). The overall cascade success rate dropped by 2.1%, from 64.8% to 62.7% (p< 0.001). Pre- and during-COVID-19 cascade success rates were negatively associated with living with HIV and having recurrent TB., Conclusions: An already poorly performing TB program in Cape Town was negatively impacted by the COVID-19 pandemic. There was a substantial reduction in the number of individuals diagnosed with drug-susceptible. Increases in pre-and post-treatment losses resulted in a decline in TB cascade success rates. Strengthened implementation of TB recovery plans is vital, as health services now face an even greater gap between achievements and targets and will need to become more resilient to possible future public health disruptions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jennings et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Since March 2020, the COVID-19 pandemic has swiftly propagated, triggering a competitive race among medical firms to forge vaccines that thwart the infection. Lebanon initiated its vaccination campaign on February 14, 2021. Despite numerous studies conducted to elucidate the characteristics of immune responses elicited by vaccination, the topic remains unclear. Here, we aimed to track the progression of anti-spike SARS-CoV-2 antibody titers at two-time points (T1: shortly after the second vaccination dose, T2: six months later) within a cohort of 201 adults who received Pfizer-BioNTech (BNT162b2), AstraZeneca, or Sputnik V vaccines in North Lebanon. Blood specimens were obtained from participants, and antibody titers against SARS-CoV-2 were quantified through the Elecsys-Anti-SARS-CoV-2 S assay (Roche Diagnostics, Switzerland). We used univariate analysis and multivariable logistic regression models to predict determinants influencing the decline in immune response and the occurrence of breakthrough infections among vaccinated patients. Among the 201 participants, 141 exhibited unchanging levels of antibody titers between the two sample collections, 55 displayed waning antibody titers, and only five participants demonstrated heightened antibody levels. Notably, age emerged as the sole variable significantly linked to the waning immune response. Moreover, the BNT162b2 vaccine exhibited significantly higher efficacy concerning the occurrence of breakthrough infections when compared with the AstraZeneca vaccine. Overall, our study reflected the immune status of a sample of vaccinated adults in North Lebanon. Further studies on a larger scale are needed at the national level to follow the immune response after vaccination, especially after the addition of the third vaccination dose., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is little information on the epidemiology of enteric pathogens in Lebanon, a low- and middle-income country that suffers from a myriad of public health challenges. To address this knowledge gap, we aimed to assess the prevalence of enteric pathogens, identify risk factors and seasonal variations, and describe associations between pathogens among diarrheic patients in the Lebanese community., Methodology and Principal Findings: A multicenter cross-sectional community-based study was conducted in the north of Lebanon. Stool samples were collected from 360 outpatients suffering from acute diarrhea. Based on fecal examination using the BioFire® FilmArray® Gastrointestinal Panel assay, the overall prevalence of enteric infections was 86.1%. Enteroaggregative Escherichia coli (EAEC) was the most frequently identified (41.7%), followed by enteropathogenic E. coli (EPEC) (40.8%) and rotavirus A (27.5%). Notably, two cases of Vibrio cholerae were identified, while Cryptosporidium spp. (6.9%) was the most common parasitic agent. Overall, 27.7% (86/310) of the cases were single infections, and the majority, 73.3% (224/310), were mixed infections. Multivariable logistic regression models showed that enterotoxigenic E. coli (ETEC) and rotavirus A infections were significantly more likely to occur in the fall and winter compared to the summer. Rotavirus A infections significantly decreased with age but increased in patients living in rural areas or suffering from vomiting. We identified strong associations in the co-occurrence of EAEC, EPEC, and ETEC infections and a higher percentage of rotavirus A and norovirus GI/GII infections among EAEC-positive cases., Conclusions: Several of the enteric pathogens reported in this study are not routinely tested in Lebanese clinical laboratories. However, anecdotal evidence suggests that diarrheal diseases are on the rise due to widespread pollution and the deterioration of the economy. Therefore, this study is of paramount importance to identify circulating etiologic agents and prioritize dwindling resources to control them and limit outbreaks in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Osman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study is designed to determine the knowledge, attitude, and practice of food poisoning and its factors among postgraduate students in Universiti Putra Malaysia., Methods: A cross-sectional study was conducted among 212 respondents who were selected through simple random sampling. Data was generated using a validated and reliable self-administered questionnaire., Results: The majority of the respondents are male, aged less than 35 years old, non-Malaysian, single, first-degree holders, not working, received a monthly income of less than 3264 Malaysian Ringgit, aware of food poisoning outbreak and the sources of their information of the food poisoning outbreak were television, the internet, newspaper, Online journals, friends, Facebook, community, nurse, drinking raw milk for the second time, information from their parents, relatives, restaurant, and radio. Majority had previous history of food poisoning illness but didn't correctly confirm the causes of their food poisoning illness. Majority had poor knowledge, acceptable attitude, and good practice of food poisoning. A significant association was observed for citizen, marital status, awareness of food poisoning outbreak, and previous history of food poisoning illness with knowledge. Gender and awareness of food poisoning outbreak were significantly associated with attitude. Attitude and practice were significantly associated. Logistic regression revealed that being married, awareness of food poisoning outbreak, and previous history of food poisoning illness are predictors for good knowledge. Female respondents and awareness of food poisoning outbreak are predictors for acceptable attitude., Conclusion: Documentation of the identified poor knowledge and factors affecting knowledge, attitude, and practice provides essential information on the baseline indicators towards the risk of food poisoning among the respondents. A relevant interventional program is highly recommended to prevent the potential risks of food poisoning outbreak among them., Competing Interests: The authors have declared that no competing interests exist.

Background: Delayed linkage to tuberculosis (TB) treatment leads to poor patient outcomes and increased onward transmission. Between 12% and 25% of people diagnosed with TB are never linked to a primary health care facility for continued care. The TB health program is for creating processes that promote and facilitates easy access to care. We explored how TB patients experience TB services and how this influenced their choices around linkage to TB care and treatment., Methods: We enrolled 20 participants routinely diagnosed with TB in hospital or at primary health care facilities (PHC) in a high TB/HIV burdened peri-urban community in South Africa. Using the Western Cape Provincial Health Data centre (PHDC) which consolidates person-level clinical data, we used dates of diagnosis and treatment initiation to select participants who had been linked (immediately, after a delay, or never). Between June 2019 and January 2020, we facilitated in-depth discussions to explore both the participants' experience of their TB diagnosis and their journey around linking to TB care at a primary health care facility. We analysed the data using case descriptions., Results: Twelve of twenty (12/20) participants interviewed who experienced a delay linking were diagnosed at the hospital. Participants who experienced delays in linking or never linked explained this as a result of lack of information and support from health care providers. Unpleasant previous TB treatment episodes made it difficult to 'face' TB again and being uncertain of their TB diagnosis. In contrast, participants said the main motivator for linking was a personal will to get better., Conclusion: The health care system, especially in hospitals, should focus on strengthening patient-centred care. Communication and clear messaging on TB processes is key, to prepare patients in transitioning from a hospital setting to PHC facilities for continuation of care. This should not just include a thorough explanation of their TB diagnosis but ensure that patients understand treatment processes. Former TB patients may require additional counselling and support to re-engage in care., Competing Interests: The authors have declared that no competing interests exist.

Background: Coronavirus disease 2019 (COVID-19) has affected millions of lives globally. However, the disease has presented more extreme challenges for developing countries that are experiencing economic crises. Studies on COVID-19 symptoms and gut health are scarce and have not fully analyzed possible associations between gut health and disease pathophysiology. Therefore, this study aimed to demonstrate a potential association between gut health and COVID-19 severity in the Lebanese community, which has been experiencing a severe economic crisis., Methods: This cross-sectional study investigated SARS-CoV-2 PCR-positive Lebanese patients. Participants were interviewed and gut health, COVID-19 symptoms, and different metrics were analyzed using simple and multiple logistic regression models., Results: Analysis of the data showed that 25% of participants were asymptomatic, while an equal proportion experienced severe symptoms, including dyspnea (22.7%), oxygen need (7.5%), and hospitalization (3.1%). The mean age of the participants was 38.3 ±0.8 years, and the majority were males (63.9%), married (68.2%), and currently employed (66.7%). A negative correlation was found between gut health score and COVID-19 symptoms (Kendall's tau-b = -0.153, P = 0.004); indicating that low gut health was associated with more severe COVID-19 cases. Additionally, participants who reported unhealthy food intake were more likely to experience severe symptoms (Kendall's tau-b = 0.118, P = 0.049). When all items were taken into consideration, multiple ordinal logistic regression models showed a significant association between COVID-19 symptoms and each of the following variables: working status, flu-like illness episodes, and gut health score. COVID-19 severe symptoms were more common among patients having poor gut health scores (OR:1.31, 95%CI:1.07-1.61; P = 0.008), experiencing more than one episode of flu-like illness per year (OR:2.85, 95%CI:1.58-5.15; P = 0.001), and owning a job (OR:2.00, 95%CI:1.1-3.65; P = 0.023)., Conclusions: To our knowledge, this is the first study that showed the impact of gut health and exposure to respiratory viruses on COVID-19 severity in Lebanon. These findings can facilitate combating the pandemic in Lebanon., Competing Interests: The authors have declared that no competing interests exist.

Grounding systems are critical in safeguarding people and equipment from power system failures. A grounding system's principal goal is to offer the lowest impedance path for undesired fault current. Optimization of the grounding grid designs is important in satisfying the minimum cost of the grounding system and safeguarding those people who work in the surrounding area of the grounded installations. Currently, there is no systematic guidance or standard for grounding grid designs that include two-layer soil and its effects on grounding grid systems, particularly vertically layered soil. Furthermore, while numerous studies have been conducted on optimization, relatively limited study has been done on the problem of optimizing the grounding grid in two-layer soil, particularly in vertical soil structures. This paper presents the results of optimization for substation grounding systems using the Simulated Annealing (SA) algorithm in different soil conditions which conforms to the safety requirements of the grounding system. Practical features of grounding grids in various soil conditions discussed in this paper (uniform soil, two-layer horizontal soil, and two-layer vertical soil) are considered during problem formulation and solution algorithm. The proposed algorithm's results show that the number of grid conductors in the X and Y directions (Nx and Ny), as well as vertical rods (Nr), can be optimized from initial numbers of 35% for uniform soil, 57% for horizontal two-layer soil for ρ1> ρ2, and 33% for horizontal two-layer soil for ρ1< ρ2, and 29% for vertical two-layer soil structure. In other words, the proposed technique would be able to utilize square and rectangle-shaped grounding grids with a number of grid conductors and vertical rods to be implemented in uniform, two-layer horizontal and vertical soil structure, depending on the resistivity of the soil layer., Competing Interests: NO authors have competing interests.

Tuberculosis (TB) cases have increased drastically over the last two decades and it remains as one of the deadliest infectious diseases in Malaysia. This cross-sectional study aimed to establish the spatial distribution of TB cases and its association with the sociodemographic and environmental factors in the Gombak district. The sociodemographic data of 3325 TB cases such as age, gender, race, nationality, country of origin, educational level, employment status, health care worker status, income status, residency, and smoking status from 1st January 2013 to 31st December 2017 in Gombak district were collected from the MyTB web and Tuberculosis Information System (TBIS) database at the Gombak District Health Office and Rawang Health Clinic. Environmental data consisting of air pollution such as air quality index (AQI), carbon monoxide (CO), nitrogen dioxide (NO2), sulphur dioxide (SO2), and particulate matter 10 (PM10,) were obtained from the Department of Environment Malaysia from 1st July 2012 to 31st December 2017; whereas weather data such as rainfall were obtained from the Department of Irrigation and Drainage Malaysia and relative humidity, temperature, wind speed, and atmospheric pressure were obtained from the Malaysia Meteorological Department in the same period. Global Moran's I, kernel density estimation, Getis-Ord Gi* statistics, and heat maps were applied to identify the spatial pattern of TB cases. Ordinary least squares (OLS) and geographically weighted regression (GWR) models were used to determine the spatial association of sociodemographic and environmental factors with the TB cases. Spatial autocorrelation analysis indicated that the cases was clustered (p<0.05) over the five-year period and year 2016 and 2017 while random pattern (p>0.05) was observed from year 2013 to 2015. Kernel density estimation identified the high-density regions while Getis-Ord Gi* statistics observed hotspot locations, whereby consistently located in the southwestern part of the study area. This could be attributed to the overcrowding of inmates in the Sungai Buloh prison located there. Sociodemographic factors such as gender, nationality, employment status, health care worker status, income status, residency, and smoking status as well as; environmental factors such as AQI (lag 1), CO (lag 2), NO2 (lag 2), SO2 (lag 1), PM10 (lag 5), rainfall (lag 2), relative humidity (lag 4), temperature (lag 2), wind speed (lag 4), and atmospheric pressure (lag 6) were associated with TB cases (p<0.05). The GWR model based on the environmental factors i.e. GWR2 was the best model to determine the spatial distribution of TB cases based on the highest R2 value i.e. 0.98. The maps of estimated local coefficients in GWR models confirmed that the effects of sociodemographic and environmental factors on TB cases spatially varied. This study highlighted the importance of spatial analysis to identify areas with a high TB burden based on its associated factors, which further helps in improving targeted surveillance., Competing Interests: The authors declare no conflict of interest.

In South Africa, low tuberculosis (TB) treatment coverage and high TB case fatality remain important challenges. Following TB diagnosis, patients must link with a primary health care (PHC) facility for initiation or continuation of antituberculosis treatment and TB registration. We aimed to evaluate mortality among TB patients who did not link to a TB treatment facility for TB treatment within 30 days of their TB diagnosis, i.e. who were "initial loss to follow-up (ILTFU)" in Cape Town, South Africa. We prospectively included all patients with a routine laboratory or clinical diagnosis of TB made at PHC or hospital level in Khayelitsha and Tygerberg sub-districts in Cape Town, using routine TB data from an integrated provincial health data centre between October 2018 and March 2020. Overall, 74% (10,208/13,736) of TB patients were diagnosed at PHC facilities and ILTFU was 20.0% (2,742/13,736). Of ILTFU patients, 17.1% (468/2,742) died, with 69.7% (326/468) of deaths occurring within 30 days of diagnosis. Most ILTFU deaths (85.5%; 400/468) occurred in patients diagnosed in hospital. Multivariable logistic regression identified increasing age, HIV positive status, and hospital-based TB diagnosis (higher in the absence of TB treatment initiation and being ILTFU) as predictors of mortality. Although hospitals account for a modest proportion of diagnosed TB patients they have high TB-associated mortality. A hospital-based TB diagnosis is a critical opportunity to identify those at high risk of early and overall mortality. Interventions to diagnose TB before hospital admission, improve linkage to TB treatment following diagnosis, and reduce mortality in hospital-diagnosed TB patients should be prioritised., Competing Interests: The authors have declared that no competing interests exist.

People make judgments of others based on appearance, and these inferences can affect social interactions. Although the importance of facial appearance in these judgments is well established, the impact of the body morphology remains unclear. Specifically, it is unknown whether experimentally varied body morphology has an impact on perception of threat in others. In two preregistered experiments (N = 250), participants made judgments of perceived threat of body stimuli of varying morphology, both in the absence (Experiment 1) and presence (Experiment 2) of facial information. Bodies were perceived as more threatening as they increased in mass with added musculature and portliness, and less threatening as they increased in emaciation. The impact of musculature endured even in the presence of faces, although faces contributed more to the overall threat judgment. The relative contributions of the faces and bodies seemed to be driven by discordance, such that threatening faces exerted the most influence when paired with non-threatening bodies, and vice versa. This suggests that the faces and bodies were not perceived as entirely independent and separate components. Overall, these findings suggest that body morphology plays an important role in perceived threat and may bias real-world judgments., Competing Interests: The authors have declared that no competing interests exist.

Early clinical successes are driving enthusiasm for fecal microbiota transplantation (FMT), the transfer of healthy gut bacteria through whole stool, as emerging research is linking the microbiome to many different diseases. However, preliminary trials have yielded mixed results and suggest that heterogeneity in donor stool may play a role in patient response. Thus, clinical trials may fail because an ineffective donor was chosen rather than because FMT is not appropriate for the indication. Here, we describe a conceptual framework to guide rational donor selection to increase the likelihood that FMT clinical trials will succeed. We argue that the mechanism by which the microbiome is hypothesized to be associated with a given indication should inform how healthy donors are selected for FMT trials, categorizing these mechanisms into four disease models and presenting associated donor selection strategies. We next walk through examples based on previously published FMT trials and ongoing investigations to illustrate how donor selection might occur in practice. Finally, we show that typical FMT trials are not powered to discover individual taxa mediating patient responses, suggesting that clinicians should develop targeted hypotheses for retrospective analyses and design their clinical trials accordingly. Moving forward, developing and applying novel clinical trial design methodologies like rational donor selection will be necessary to ensure that FMT successfully translates into clinical impact., Competing Interests: EA is co-founder of Finch Therapeutics and is on the Board of Directors of OpenBiome. CZ, PP, SB, and MO are employed by OpenBiome. These commercial sources of funding do not alter our adherence to PLOS ONE policies on sharing data and materials.

This qualitative study aimed to explore the misconceptions, knowledge gaps and constructs of leptospirosis among 72 respondents from rural and urban districts in two states of Malaysia. We conducted focus group discussions and data were examined using thematic analyses. The layman term of 'rat urine disease' contributed the most to the misconceptions regarding leptospirosis. There were gaps in the knowledge among urban and rural respondents in the two states, with the majority of subjects demonstrating a poor understanding of the disease. Construction of knowledge about leptospirosis relied mostly on the information provided by mass and social media; reading materials; word-of-mouth publicity; observations; experiences; and knowledge sharing among families, friends, and communities. The study findings may provide the foundation for the development of educational materials that may reduce the gaps in knowledge, and thereby improve health literacy and enhance preventive health behaviours for avoiding leptospirosis., Competing Interests: The authors have declared that no competing interests exist.

Background: The association between Cryptosporidium and human colon cancer has been reported in different populations. However, this association has not been well studied. In order to add new strong arguments for a probable link between cryptosporidiosis and colon human cancer, the aim of this study was to determine prevalence and to identify species of Cryptosporidium among Lebanese patients., Methodology and Principal Findings: Overall, 218 digestive biopsies were collected in Tripoli, Lebanon, from three groups of patients: (i) patients with recently diagnosed colon intraepithelial neoplasia/adenocarcinoma before any treatment (n = 72); (ii) patients with recently diagnosed stomach intraepithelial neoplasia/adenocarcinoma before any treatment (n = 21); and (iii) patients without digestive intraepithelial neoplasia/adenocarcinoma but with persistent digestive symptoms (n = 125). DNA extraction was performed from paraffin-embedded tissue. The presence of the parasite in tissues was confirmed by PCR, microscopic observation and immunofluorescence analysis. We identified a high rate (21%) of Cryptosporidium presence in biopsies from Lebanese patients with recently diagnosed colonic neoplasia/adenocarcinoma before any treatment. This prevalence was significantly higher compared to 7% of Cryptosporidium prevalence among patients without colon neoplasia but with persistent gastrointestinal symptoms (OR: 4, CI: 1.65-9.6, P = 0.001). When the comparison was done against normal biopsies, the risk of infection increased 11-fold in the group of patients with colon adenocarcinoma (OR: 11.315, CI: 1.44-89.02, P = 0.003)., Conclusions: This is the first study performed in Lebanon reporting the prevalence of Cryptosporidium among patients with digestive cancer. These results show that Cryptosporidium is strongly associated with human colon cancer being maybe a potential etiological agent of this disease.

Renovascular hypertension (RVH) has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C) model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO) protects the stenotic kidney (STK) from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS) was established in Wild-type (WT) and Smad3 KO mice (129 genetic background) by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

Blastocystis sp. is a common intestinal parasite infecting humans and a wide range of animals worldwide. It exhibits an extensive genetic diversity and 17 subtypes (STs) have thus far been identified in mammalian and avian hosts. Since several STs are common to humans and animals, it was proposed that a proportion of human infections may result from zoonotic transmission. However, the contribution of each animal source to human infection remains to be clarified. Therefore, the aim of this study was to expand our knowledge of the epidemiology and host specificity of this parasite by performing the largest epidemiological survey ever conducted in animal groups in terms of numbers of species screened. A total of 307 stool samples from 161 mammalian and non-mammalian species in two French zoos were screened by real-time PCR for the presence of Blastocystis sp. Overall, 32.2% of the animal samples and 37.9% of the species tested were shown to be infected with the parasite. A total of 111 animal Blastocystis sp. isolates were subtyped, and 11 of the 17 mammalian and avian STs as well as additional STs previously identified in reptiles and insects were found with a varying prevalence according to animal groups. These data were combined with those obtained from previous surveys to evaluate the potential risk of zoonotic transmission of Blastocystis sp. through the comparison of ST distribution between human and animal hosts. This suggests that non-human primates, artiodactyls and birds may serve as reservoirs for human infection, especially in animal handlers. In contrast, other mammals such as carnivores, and non-mammalian groups including reptiles and insects, do not seem to represent significant sources of Blastocystis sp. infection in humans. In further studies, more intensive sampling and screening of potential new animal hosts will reinforce these statements and expand our understanding of the circulation of Blastocystis sp. in animal and human populations., Competing Interests: Competing Interests: C. Noël is employed by Geneius Laboratories Ltd., RM and SB by the zoo of Lille and TP by the zoo of La Palmyre. There are no patents, products in development or marketed products to declare in relation with our study. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Recent thymic emigrants (RTEs) represent a source of antigen-naïve T cells that enter the periphery throughout life. However, whether RTEs contribute to the control of chronic parasitic infection and how their potential might be harnessed by therapeutic intervention is currently unclear. Here, we show that CD4+ recent thymic emigrants emerging into the periphery of mice with ongoing Leishmania donovani infection undergo partial activation and are recruited to sites of granulomatous inflammation. However, CD4+ RTEs displayed severely restricted differentiation either into IFNγ+ or IFNγ+TNFα+ effectors, or into IL-10-producing regulatory T cells. Effector cell differentiation in the chronically infected host was not promoted by adoptive transfer of activated dendritic cells or by allowing extended periods of post-thymic differentiation in the periphery. Nevertheless, CD4+ RTEs from infected mice retained the capacity to transfer protection into lymphopenic RAG2-/- mice. Taken together, our data indicate that RTEs emerging into a chronically inflamed environment are not recruited into the effector pool, but retain the capacity for subsequent differentiation into host protective T cells when placed in a disease-free environment., Competing Interests: The authors have declared that no competing interests exist.

Background: Effective coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises is required to ensure efficiency of services, avoid duplication, and improve equity. The objective of this review was to assess how, during and after humanitarian crises, different mechanisms and models of coordination between organizations, agencies and bodies providing or financing health services compare in terms of access to health services and health outcomes., Methods: We registered a protocol for this review in PROSPERO International prospective register of systematic reviews under number PROSPERO2014:CRD42014009267. Eligible studies included randomized and nonrandomized designs, process evaluations and qualitative methods. We electronically searched Medline, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and the WHO Global Health Library and websites of relevant organizations. We followed standard systematic review methodology for the selection, data abstraction, and risk of bias assessment. We assessed the quality of evidence using the GRADE approach., Results: Of 14,309 identified citations from databases and organizations' websites, we identified four eligible studies. Two studies used mixed-methods, one used quantitative methods, and one used qualitative methods. The available evidence suggests that information coordination between bodies providing health services in humanitarian crises settings may be effective in improving health systems inputs. There is additional evidence suggesting that management/directive coordination such as the cluster model may improve health system inputs in addition to access to health services. None of the included studies assessed coordination through common representation and framework coordination. The evidence was judged to be of very low quality., Conclusion: This systematic review provides evidence of possible effectiveness of information coordination and management/directive coordination between organizations, agencies and bodies providing or financing health services in humanitarian crises. Our findings can inform the research agenda and highlight the need for improving conduct and reporting of research in this field.

Cryptosporidium, a protozoan parasite that can cause severe diarrhea in a wide range of vertebrates including humans, is increasingly recognized as a parasite of a diverse range of wildlife species. However, little data are available regarding the identification of Cryptosporidium species and genotypes in wild aquatic environments, and more particularly in edible freshwater fish. To evaluate the prevalence of Cryptosporidiumspp. in fish from Lake Geneva (Lac Léman) in France, 41 entire fish and 100 fillets (cuts of fish flesh) were collected from fishery suppliers around the lake. Nested PCR using degenerate primers followed by sequence analysis was used. Five fish species were identified as potential hosts of Cryptosporidium: Salvelinus alpinus, Esox lucius, Coregonus lavaretus, Perca fluviatilis, and Rutilus rutilus. The presence of Cryptosporidium spp. was found in 15 out of 41 fish (37%), distributed as follows: 13 (87%) C. parvum, 1 (7%) C. molnari, and 1 (7%) mixed infection (C. parvum and C. molnari). C. molnari was identified in the stomach, while C. parvum was found in the stomach and intestine. C. molnari was also detected in 1 out of 100 analyzed fillets. In order to identify Cryptosporidium subtypes, sequencing of the highly polymorphic 60-kDa glycoprotein (gp60) was performed. Among the C. parvum positive samples, three gp60 subtypes were identified: IIaA15G2R1, IIaA16G2R1, and IIaA17G2R1. Histological examination confirmed the presence of potential developmental stages of C. parvum within digestive epithelial cells. These observations suggest that C. parvum is infecting fish, rather than being passively carried. Since C. parvum is a zoonotic species, fish potentially contaminated by the same subtypes found in terrestrial mammals would be an additional source of infection for humans and animals, and may also contribute to the contamination of the environment with this parasite. Moreover, the risk of human transmission is strengthened by the observation of edible fillet contamination.

Cryptosporidium spp. represent a major public health problem worldwide and infect the gastrointestinal tract of both immunocompetent and immunocompromised persons. The prevalence of these parasites varies by geographic region, and no data are currently available in Lebanon. To promote an understanding of the epidemiology of cryptosporidiosisin this country, the main aim of this study was to determine the prevalence Cryptosporidium in symptomatic hospitalized patients, and to analyze the genetic diversity of the corresponding isolates. Fecal specimens were collected in four hospitals in North Lebanon from 163 patients (77 males and 86 females, ranging in age from 1 to 88 years, with a mean age of 22 years) presenting gastrointestinal disorders during the period July to December 2013. The overall prevalence of Cryptosporidium spp. infection obtained by modified Ziehl-Neelsen staining and/or nested PCR was 11%, and children <5 years old showed a higher rate of Cryptosporidium spp. The PCR products of the 15 positive samples were successfully sequenced. Among them, 10 isolates (66.7%) were identified as C. hominis, while the remaining 5 (33.3%) were identified as C. parvum. After analysis of the gp60 locus, C. hominis IdA19, a rare subtype, was found to be predominant. Two C. parvum subtypes were found: IIaA15G1R1 and IIaA15G2R1. The molecular characterization of Cryptosporidium isolates is an important step in improving our understanding of the epidemiology and transmission of the infection.

Background: Giant cell arteritis (GCA) and Takayasu's arteritis (TAA) are large vessel vasculitides (LVV) for which corticosteroids (CS) are the mainstay for treatment. In patients with LVV unable to tolerate CS, biological agents have been used with variable effectiveness., Objective: To systematically review the effectiveness and safety of biological agents in patients with LVV., Methods: We searched 5 electronic databases (inception to October 2012) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. Our protocol was registered in PROSPERO., Results: We included 25 studies (3 RCTs and 22 case series with ≥2 cases). 95 GCA and 98 TAA patients received biological agents. The RCTs using anti-TNF agents (infliximab, etanercept and adalimumab) did not suggest a benefit in GCA. GCA patients receiving tocilizumab, in case series, achieved remission (19 patients) and reduction of corticosteroid dose (mean difference, -16.55 mg/day (95% CI: -26.24, -6.86)). In case series, 75 patients with refractory TAA treated with infliximab discontinued CS 32% of the time. Remission was variably defined and the studies were clinically heterogeneous which precluded further analysis., Conclusion: This systematic review demonstrated a weak evidence base on which to assess the effectiveness of biological treatment in LVV. Evidence from RCTs suggests that anti-TNF agents are not effective for remission or reduction of CS use. Tocilizumab and infliximab may be effective in the management of LVV and refractory TAA, respectively, although the evidence comes from case series. Future analytical studies are needed to confirm these findings.

Current eye-tracking research suggests that our eyes make anticipatory movements to a location that is relevant for a forthcoming task. Moreover, there is evidence to suggest that with more practice anticipatory gaze control can improve. However, these findings are largely limited to situations where participants are actively engaged in a task. We ask: does experience modulate anticipative gaze control while passively observing a visual scene? To tackle this we tested people with varying degrees of experience of tennis, in order to uncover potential associations between experience and eye movement behaviour while they watched tennis videos. The number, size, and accuracy of saccades (rapid eye-movements) made around 'events,' which is critical for the scene context (i.e. hit and bounce) were analysed. Overall, we found that experience improved anticipatory eye-movements while watching tennis clips. In general, those with extensive experience showed greater accuracy of saccades to upcoming event locations; this was particularly prevalent for events in the scene that carried high uncertainty (i.e. ball bounces). The results indicate that, even when passively observing, our gaze control system utilizes prior relevant knowledge in order to anticipate upcoming uncertain event locations.

Several studies have reported that task instructions influence eye-movement behavior during static image observation. In contrast, during dynamic scene observation we show that while the specificity of the goal of a task influences observers' beliefs about where they look, the goal does not in turn influence eye-movement patterns. In our study observers watched short video clips of a single tennis match and were asked to make subjective judgments about the allocation of visual attention to the items presented in the clip (e.g., ball, players, court lines, and umpire). However, before attending to the clips, observers were either told to simply watch clips (non-specific goal), or they were told to watch the clips with a view to judging which of the two tennis players was awarded the point (specific goal). The results of subjective reports suggest that observers believed that they allocated their attention more to goal-related items (e.g. court lines) if they performed the goal-specific task. However, we did not find the effect of goal specificity on major eye-movement parameters (i.e., saccadic amplitudes, inter-saccadic intervals, and gaze coherence). We conclude that the specificity of a task goal can alter observer's beliefs about their attention allocation strategy, but such task-driven meta-attentional modulation does not necessarily correlate with eye-movement behavior.

Human reasoning is often biased by intuitive heuristics. A central question is whether the bias results from a failure to detect that the intuitions conflict with traditional normative considerations or from a failure to discard the tempting intuitions. The present study addressed this unresolved debate by using people's decision confidence as a nonverbal index of conflict detection. Participants were asked to indicate how confident they were after solving classic base-rate (Experiment 1) and conjunction fallacy (Experiment 2) problems in which a cued intuitive response could be inconsistent or consistent with the traditional correct response. Results indicated that reasoners showed a clear confidence decrease when they gave an intuitive response that conflicted with the normative response. Contrary to popular belief, this establishes that people seem to acknowledge that their intuitive answers are not fully warranted. Experiment 3 established that younger reasoners did not yet show the confidence decrease, which points to the role of improved bias awareness in our reasoning development. Implications for the long standing debate on human rationality are discussed.