HISTAMINE IN THE BRAIN: BEYOND SLEEP AND MEMORY

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Generation of precision-cut slice cultures of human placenta.

We present a protocol to generate an advanced ex vivo model of human placenta. We use a vibrating tissue slicer to obtain precision-cut slices representative of the entire thickness of human placenta. This approach delivers standardized cultures with a preserved microstructure and cellular composition comparable to the native tissue. We applied this system to study SARS-CoV-2 infection at the maternal-fetal interface. Moreover, this system can be used to investigate the basic functions of the human placenta in health and disease. For complete details on the use and execution of this protocol, please refer to Fahmi et al. (2021)

Comparison of the estimated incidence of acute leptospirosis in the Kilimanjaro Region of Tanzania between 2007-08 and 2012-14

Background: The sole report of annual leptospirosis incidence in continental Africa of 75–102 cases per 100,000 population is from a study performed in August 2007 through September 2008 in the Kilimanjaro Region of Tanzania. To evaluate the stability of this estimate over time, we estimated the incidence of acute leptospirosis in Kilimanjaro Region, northern Tanzania for the time period 2012–2014. Methodology and Principal Findings: Leptospirosis cases were identified among febrile patients at two sentinel hospitals in the Kilimanjaro Region. Leptospirosis was diagnosed by serum microscopic agglutination testing using a panel of 20 Leptospira serovars belonging to 17 separate serogroups. Serum was taken at enrolment and patients were asked to return 4–6 weeks later to provide convalescent serum. Confirmed cases required a 4-fold rise in titre and probable cases required a single titre of ≥800. Findings from a healthcare utilisation survey were used to estimate multipliers to adjust for cases not seen at sentinel hospitals. We identified 19 (1.7%) confirmed or probable cases among 1,115 patients who presented with a febrile illness. Of cases, the predominant reactive serogroups were Australis 8 (42.1%), Sejroe 3 (15.8%), Grippotyphosa 2 (10.5%), Icterohaemorrhagiae 2 (10.5%), Pyrogenes 2 (10.5%), Djasiman 1 (5.3%), Tarassovi 1 (5.3%). We estimated that the annual incidence of leptospirosis was 11–18 cases per 100,000 population. This was a significantly lower incidence than 2007–08 (p<0.001). Conclusions: We estimated a much lower incidence of acute leptospirosis than previously, with a notable absence of cases due to the previously predominant serogroup Mini. Our findings indicate a dynamic epidemiology of leptospirosis in this area and highlight the value of multi-year surveillance to understand leptospirosis epidemiology

Risk factors for human brucellosis in northern Tanzania

Little is known about the epidemiology of human brucellosis in sub-Saharan Africa. This hampers prevention and control efforts at the individual and population levels. To evaluate risk factors for brucellosis in northern Tanzania, we conducted a study of patients presenting with fever to two hospitals in Moshi, Tanzania. Serum taken at enrollment and at 4–6 week follow-up was tested by Brucella microagglutination test. Among participants with a clinically compatible illness, confirmed brucellosis cases were defined as having a ≥ 4-fold rise in agglutination titer between paired sera or a blood culture positive for Brucella spp., and probable brucellosis cases were defined as having a single reciprocal titer ≥ 160. Controls had reciprocal titers < 20 in paired sera. We collected demographic and clinical information and administered a risk factor questionnaire. Of 562 participants in the analysis, 50 (8.9%) had confirmed or probable brucellosis. Multivariable analysis showed that risk factors for brucellosis included assisting goat or sheep births (Odds ratio [OR] 5.9, 95% confidence interval [CI] 1.4, 24.6) and having contact with cattle (OR 1.2, 95% CI 1.0, 1.4). Consuming boiled or pasteurized dairy products was protective against brucellosis (OR 0.12, 95% CI 0.02, 0.93). No participants received a clinical diagnosis of brucellosis from their healthcare providers. The under-recognition of brucellosis by healthcare workers could be addressed with clinician education and better access to brucellosis diagnostic tests. Interventions focused on protecting livestock keepers, especially those who assist goat or sheep births, are needed

Risk factors for human acute leptospirosis in northern Tanzania

Introduction: Leptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania. Methods: We enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012–2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer ≥800. Seropositive participants required a single titer ≥100, and controls had titers <100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables. Results: We identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis. Conclusions: In our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease

Meat safety in Tanzania’s value chain : experiences, explanations and expectations in butcheries and eateries

This research was funded by the Biotechnology and Biological Sciences Research Council, the Department for International Development, the Economic and Social Research Council, the Medical Research Council, the Natural Environment Research Council, and the Defence Science and Technology Laboratory, under the UK Zoonoses and Emerging Livestock Systems Initiative (Grant Numbers BB/L017679/1 and BB/L018926/1).Urbanisation is associated with changes in consumption patterns and food production processes. These patterns and processes can increase or decrease the risks of outbreaks of foodborne diseases and are generally accompanied by changes in food safety policies and regulations about food handling. This affects consumers, as well as people economically engaged in the food value chain. This study looks at Tanzania’s red meat value chain—which in its totality involves about one third of the population—and focuses on the knowledge, attitudes and reported practices of operators of butcheries and eateries with regards to meat safety in an urban and in a rural environment. We interviewed 64 operators about their experiences with foodborne diseases and their explanations and expectations around meat safety, with a particular emphasis on how they understood their own actions regarding food safety risks vis-à-vis regulations. We found operators of eateries emphasising their own agency in keeping meat safe, whereas operators of butcheries—whose products are more closely inspected—relied more on official inspections. Looking towards meat safety in the future, interviewees in rural areas were, relative to their urban counterparts, more optimistic, which we attribute to rural operators’ shorter and relatively unmediated value chains.Publisher PDFPeer reviewe

Disrupting the HDAC6-ubiquitin interaction impairs infection by influenza and Zika virus and cellular stress pathways.

The deacetylase HDAC6 has tandem catalytic domains and a zinc finger domain (ZnF) binding ubiquitin (Ub). While the catalytic domain has an antiviral effect, the ZnF facilitates influenza A virus (IAV) infection and cellular stress responses. By recruiting Ub via the ZnF, HDAC6 promotes the formation of aggresomes and stress granules (SGs), dynamic structures associated with pathologies such as neurodegeneration. IAV subverts the aggresome/HDAC6 pathway to facilitate capsid uncoating during early infection. To target this pathway, we generate designed ankyrin repeat proteins (DARPins) binding the ZnF; one of these prevents interaction with Ub in vitro and in cells. Crystallographic analysis shows that it blocks the ZnF pocket where Ub engages. Conditional expression of this DARPin reversibly impairs infection by IAV and Zika virus; moreover, SGs and aggresomes are downregulated. These results validate the HDAC6 ZnF as an attractive target for drug discovery