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Enteroendocrine cells (EECs) are specialized sensory cells in the intestinal epithelium that sense and transduce nutrient information. Consumption of dietary fat contributes to metabolic disorders, but EEC adaptations to high fat feeding were unknown. Here, we established a new experimental system to directly investigate EEC activity in vivo using a zebrafish reporter of EEC calcium signaling. Our results reveal that high fat feeding alters EEC morphology and converts them into a nutrient insensitive state that is coupled to endoplasmic reticulum (ER) stress. We called this novel adaptation 'EEC silencing'. Gnotobiotic studies revealed that germ-free zebrafish are resistant to high fat diet induced EEC silencing. High fat feeding altered gut microbiota composition including enrichment of Acinetobacter bacteria, and we identified an Acinetobacter strain sufficient to induce EEC silencing. These results establish a new mechanism by which dietary fat and gut microbiota modulate EEC nutrient sensing and signaling.

The intestinal microbiota influences the development and function of myeloid lineages such as neutrophils, but the underlying molecular mechanisms are unresolved. Using gnotobiotic zebrafish, we identified the immune effector Serum amyloid A (Saa) as one of the most highly induced transcripts in digestive tissues following microbiota colonization. Saa is a conserved secreted protein produced in the intestine and liver with described effects on neutrophils in vitro, however its in vivo functions remain poorly defined. We engineered saa mutant zebrafish to test requirements for Saa on innate immunity in vivo. Zebrafish mutant for saa displayed impaired neutrophil responses to wounding but augmented clearance of pathogenic bacteria. At baseline, saa mutants exhibited moderate neutrophilia and altered neutrophil tissue distribution. Molecular and functional analyses of isolated neutrophils revealed that Saa suppresses expression of pro-inflammatory markers and bactericidal activity. Saa's effects on neutrophils depended on microbiota colonization, suggesting this protein mediates the microbiota's effects on host innate immunity. To test tissue-specific roles of Saa on neutrophil function, we over-expressed saa in the intestine or liver and found that sufficient to partially complement neutrophil phenotypes observed in saa mutants. These results indicate Saa produced by the intestine in response to microbiota serves as a systemic signal to neutrophils to restrict aberrant activation, decreasing inflammatory tone and bacterial killing potential while simultaneously enhancing their ability to migrate to wounds.

This study aimed to explore factors shaping the decision to undergo Human Immunodeficiency Virus (HIV) testing among men in rural Burkina Faso. The study took place in 2009 in the Nouna Health District and adopted a triangulation mixed methods design. The quantitative component relied on data collected through a structured survey on a representative sample of 1130 households. The qualitative component relied on 38 in-depth interviews, with men purposely selected to represent variation in testing decision, age, and place of residence. A two-part model was conducted, with two distinct outcome variables, i.e. \"being offered an HIV test\" and \"having done an HIV test\". The qualitative data analysis relied on inductive coding conducted by three independent analysts. Of the 937 men, 357 had been offered an HIV test and 97 had taken the test. Younger age, household wealth, living in a village under demographic surveillance, and knowing that HIV testing is available at primary health facilities were all positively associated with the probability of being offered an HIV test. Household wealth and literacy were found to be positively associated, and distance was found to be negatively associated with the probability of having taken an HIV test. Qualitative findings indicated that the limited uptake of HIV testing was linked to poor knowledge on service availability and to low risk perceptions. With only 10% of the total sample ever having tested for HIV, our study confirmed that male HIV testing remains unacceptably low in Sub-Saharan Africa. This results from a combination of health system factors, indicating general barriers to access, and motivational factors, such as one's own knowledge of service availability and risk perceptions. Our findings suggested that using antenatal care and curative services as the exclusive entry points into HIV testing may not be sufficient to reach large portions of the male population. Thus, additional strategies are urgently needed to increase service uptake.

The skin harbors diverse communities of microorganisms, and alterations to these communities can impact the effectiveness of the skin as a barrier to infectious organisms or injury. As the global availability and adoption of antibacterial products increases, it is important to understand how these products affect skin microbial communities of people living in rural areas of developing countries, where risks of infection and injury often differ from urban populations in developed countries. We investigated the effect of antibacterial soap on skin microbial communities in a rural Malagasy population that practices subsistence agriculture in the absence of electricity and running water. We quantified the amount of soap used by each participant and obtained skin swab samples at three time points: prior to soap use, immediately after one week of soap use, and two weeks after soap use was discontinued. Soap use did not significantly impact ecological measures of diversity and richness (alpha diversity). However, the amount of soap used was a predictor of community-level change (beta diversity), with changes persisting for at least two weeks after subjects stopped using soap. Our results indicate that the overall species richness of skin microbial communities may be resistant to short-term use of antibacterial soap in settings characterized by regular contact with the natural environment, yet these communities may undergo shifts in microbial composition. Lifestyle changes associated with the use of antibacterial soap may therefore cause rapid alterations in skin microbial communities, with the potential for effects on skin health.

Background Well-functioning surveillance systems are crucial for effective disease control programs. The Integrated Disease Surveillance and Response (IDSR) strategy was developed and adopted in 1998 for Africa as a comprehensive public health approach and subsequently, Ghana adopted the IDSR technical guidelines in 2002. Since 2012, the IDSR data is reported through the new District Health Information Management System II (DHIMS2) network. The objective was to evaluate the Integrated Disease Surveillance and Response (IDSR) system in northern Ghana. Methods This was an observational study using mixed methods. Weekly and monthly IDSR data on selected infectious diseases were downloaded and analyzed for 2011, 2012 and 2013 (the years before, of and after DHIMS2 implementation) from the DHIMS2 databank for the Upper East Region (UER) and for two districts of UER. In addition, key informant interviews were conducted among local and regional health officers on the functioning of the IDSR. Results Clinically diagnosed malaria was the most prevalent disease in UER, with an annual incidence rate close to 1. Around 500 suspected HIV/AIDS cases were reported each year. The highest incidence of cholera and meningitis was reported in 2012 (257 and 392 cases respectively). Three suspected cases of polio and one suspected case of guinea worm were reported in 2013. None of the polio and guinea worm cases and only a fraction of the reported cases of the other diseases were confirmed. A major observation was the large and inconclusive difference in reported cases when comparing weekly and monthly reports. This can be explained by the different reporting practice for the sub-systems. Other challenges were low priority for surveillance, ill-equipped laboratories, rare supervision and missing feedback. Conclusions The DHIMS2 has improved the availability of IDSR reports, but the quality of data reported is not sufficient. Particularly the inconsistencies between weekly and monthly data need to be addressed. Moreover, support for and communication within the IDSR system is inadequate and calls for attention.

We consider three examples of functors from Lorentzian categories and their applications in finiteness results, singularity theorems and boundary constructions. The third example is a novel functor from the category of ordered measure spaces to the category of Lorentzian pre-length spaces in the sense of Kunzinger–Sämann.

Cryptococcus gattii is a basidiomycetous human fungal pathogen that typically causes infection in tropical and subtropical regions and is responsible for an ongoing outbreak in immunocompetent individuals on Vancouver Island and in the Pacific Northwest of the US. Pathogenesis of this species may be linked to its sexual cycle that generates infectious propagules called basidiospores. A marked predominance of only one mating type (α) in clinical and environmental isolates suggests that a-α opposite-sex reproduction may be infrequent or geographically restricted, raising the possibility of an alternative unisexual cycle involving cells of only α mating type, as discovered previously in the related pathogenic species Cryptococcus neoformans. Here we report observation of hallmark features of unisexual reproduction in a clinical isolate of C. gattii (isolate 97/433) and describe genetic and environmental factors conducive to this sexual cycle. Our results are consistent with population genetic evidence of recombination in the largely unisexual populations of C. gattii and provide a useful genetic model for understanding how novel modes of sexual reproduction may contribute to evolution and virulence in this species.

Since 1999 a lineage of the pathogen Cryptococcus gattii has been infecting humans and other animals in Canada and the Pacific Northwest of the USA. It is now the largest outbreak of a life-threatening fungal infection in a healthy population in recorded history. The high virulence of outbreak strains is closely linked to the ability of the pathogen to undergo rapid mitochondrial tubularisation and proliferation following engulfment by host phagocytes. Most outbreaks spread by geographic expansion across suitable niches, but it is known that genetic re-assortment and hybridisation can also lead to rapid range and host expansion. In the context of C. gattii, however, the likelihood of virulence traits associated with the outbreak lineages spreading to other lineages via genetic exchange is currently unknown. Here we address this question by conducting outgroup crosses between distantly related C. gattii lineages (VGII and VGIII) and ingroup crosses between isolates from the same molecular type (VGII). Systematic phenotypic characterisation shows that virulence traits are transmitted to outgroups infrequently, but readily inherited during ingroup crosses. In addition, we observed higher levels of biparental (as opposed to uniparental) mitochondrial inheritance during VGII ingroup sexual mating in this species and provide evidence for mitochondrial recombination following mating. Taken together, our data suggest that hypervirulence can spread among the C. gattii lineages VGII and VGIII, potentially creating novel hypervirulent genotypes, and that current models of uniparental mitochondrial inheritance in the Cryptococcus genus may not be universal.

Outpatient care is made up of medical procedures, tests, and services that can be provided to the patient in a setting that doesn’t involve an overnight hospital stay. In China, tertiary hospitals are medical services centers of health care systems, and some tertiary hospitals had more than 20,000 outpatient visits per day. However, a systematic review of existed evidence on factors influencing the outpatient satisfaction in tertiary hospitals in China could inform the efforts and does not yet exist. Therefore, in order to better understand the outpatient satisfaction provided by tertiary hospitals in China, we carried out a systematic review following PRISMA guidelines. Studies reporting on the level of and factors associated with outpatient satisfaction in Chinese tertiary hospitals were systematically searched in both Chinese and English electronic databases. A total of 36 articles reported 35 studies that met the inclusion criteria. Out of these eight were household surveys covering 12,119 residents, and another 27 directly interviewed 45,930 outpatients during their hospital visits from 185 hospitals. The included studies generally used self-designed questionnaire and indicated there is a lack of standardized questionnaire for investigating outpatient satisfaction in China. The outpatients showed the highest satisfaction with the doctors and nurses and the lowest satisfaction with the hospital hygiene and outpatient procedures, especially with the long waiting time. The socio-demographic characteristics (e.g., age, marital status, income and education levels), professional skills and service attitudes of medical staff were reported to be associated with outpatient satisfaction. The results indicated that in China, the outpatient satisfaction can be largely improved. Firstly, the attitude of medical service providers, especially the pre-diagnosis nurses, registration officers, and pharmaceutical counters should be improved. Furthermore, to shorten the waiting time, policies should be developed to guide patients with common diseases and slight discomforts to community health systems to alleviate the overload in tertiary hospitals. Considering the strained relations between the doctors and patients in the clinical practice, improving patient satisfaction in China deserves more attention and research.

Abstract Background Imported malaria cases continue to pose major challenges in China as well as in other countries having achieved elimination. Our study aims to identify the factors influencing the timing of care-seeking after symptom onset among migrant workers with imported malaria, in order to develop innovative interventions to improve access and provision of post-travel healthcare for returning migrants. Methods We analysed the timing and types of healthcare service utilization after symptom onset among patients with imported malaria between 2012 and 2019 in Jiangsu Province, China. Moreover, decision tree models were used to explore the factors influencing the care-seeking timing after symptom onset among patients with imported malaria. Results A total of 2255 cases of imported malaria were identified from 1 June 2012 through 31 December 2019. Patients with malaria imported into China were mainly male migrant labourers returning from sub-Saharan Africa (96.8%). A substantial number of patients with imported malaria sought healthcare >3 days after symptom onset, which clearly represented delayed healthcare-seeking behaviour. According to the decision tree analysis, initial healthcare seeking from healthcare facilities at higher administrative levels, infection with Plasmodium vivax and absence of malaria infection history were significantly associated with delayed healthcare seeking in patients with imported malaria. Conclusion The delay in seeking of medical care among migrant workers with imported malaria should be considered and addressed by specific interventions. In addition to increasing awareness about these issues among health care professionals, improved access to healthcare facilities at higher administrative levels as well as improved diagnostic capacity of healthcare facilities at lower administrative levels should be developed. Moreover, education programs targeting populations at risk of malaria importation and delayed healthcare seeking should be improved to facilitate early healthcare seeking and service use.