Design and optimization of electrochemical microreactors for continuous electrosynthesis

The study focuses on the design and construction, as well as the theoretical and experimental optimization of electrochemical filter press microreactors for the electrosynthesis of molecules with a high added value. The main characteristics of these devices are firstly a high-specific electrochemical area to increase conversion and selectivity, and secondly the shape and size of themicrochannels designed for a uniform residence time distribution of the fluid. A heat exchanger is integrated into the microstructured electrode to rapidly remove (or supply) the heat required in exo- or endothermic reactions. The microreactors designed are used to perform-specific electrosynthesis reactions such as thermodynamically unfavorable reactions (continuous NADH regeneration), or reactions with high enthalpy changes

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies.

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Cost of dengue and other febrile illnesses to households in rural Cambodia: a prospective community-based case-control study

<p>Abstract</p> <p>Background</p> <p>The average annual reported dengue incidence in Cambodia is 3.3/1,000 among children < 15 years of age (2002–2007). To estimate the economic burden of dengue, accurate cost-of-illness data are essential. We conducted a prospective, community-based, matched case-control study to assess the cost and impact of an episode of dengue fever and other febrile illness on households in rural Cambodia.</p> <p>Methods</p> <p>In 2006, active fever surveillance was conducted among a cohort of 6,694 children aged ≤ 15 years in 16 villages in Kampong Cham province, Cambodia. Subsequently, a case-control study was performed by individually assigning one non-dengue febrile control from the cohort to each laboratory-confirmed dengue case. Parents of cases and controls were interviewed using a standardized questionnaire to determine household-level, illness-related expenditures for medical and non-medical costs, and estimated income loss (see Additional file <supplr sid="S1">1</supplr>). The household socio-economic status was determined and its possible association with health seeking behaviour and the ability to pay for the costs of a febrile illness.</p> <suppl id="S1"> <title> <p>Additional File 1</p> </title> <text> <p><b>2006 cost study survey questionnaire, Cambodia</b>. the questionnaire represents the data collection instrument that was developed and used during the present study.</p> </text> <file name="1471-2458-9-155-S1.pdf"> <p>Click here for file</p> </file> </suppl> <p>Results</p> <p>Between September and November 2006, a total of 60 household heads were interviewed: 30 with dengue-positive and 30 with dengue-negative febrile children. Mean total dengue-related costs did not differ from those of other febrile illnesses (31.5 vs. 27.2 US$, p = 0.44). Hospitalization almost tripled the costs of dengue (from 14.3 to 40.1 US$) and doubled the costs of other febrile illnesses (from 17.0 to 36.2 US$). To finance the cost of a febrile illness, 67$ and higher debt was associated with hospitalization compared to outpatient treatment (US$23.1 vs. US$ 4.5, p < 0.001). These costs compared to an average one-week expenditure on food of US$ 9.5 per household (range 2.5–21.3). In multivariate analysis, higher socio-economic status (odds ratio [OR] 4.4; 95% confidence interval [CI] 1.4–13.2), duration of fever (OR 2.1; 95%CI 1.3–3.5), and age (OR 0.8; 95%CI 0.7–0.9) were independently associated with hospitalization.</p> <p>Conclusion</p> <p>In Cambodia, dengue and other febrile illnesses pose a financial burden to households. A possible reason for a lower rate of hospitalization among children from poor households could be the burden of higher illness-related costs and debts.</p

Nipah Virus Transmission in a Hamster Model

Based on epidemiological data, it is believed that human-to-human transmission plays an important role in Nipah virus outbreaks. No experimental data are currently available on the potential routes of human-to-human transmission of Nipah virus. In a first dose-finding experiment in Syrian hamsters, it was shown that Nipah virus was predominantly shed via the respiratory tract within nasal and oropharyngeal secretions. Although Nipah viral RNA was detected in urogenital and rectal swabs, no infectious virus was recovered from these samples, suggesting no viable virus was shed via these routes. In addition, hamsters inoculated with high doses shed significantly higher amounts of viable Nipah virus particles in comparison with hamsters infected with lower inoculum doses. Using the highest inoculum dose, three potential routes of Nipah virus transmission were investigated in the hamster model: transmission via fomites, transmission via direct contact and transmission via aerosols. It was demonstrated that Nipah virus is transmitted efficiently via direct contact and inefficiently via fomites, but not via aerosols. These findings are in line with epidemiological data which suggest that direct contact with nasal and oropharyngeal secretions of Nipah virus infected individuals resulted in greater risk of Nipah virus infection. The data provide new and much-needed insights into the modes and efficiency of Nipah virus transmission and have important public health implications with regards to the risk assessment and management of future Nipah virus outbreaks

Identification and Characterization of a New Orthoreovirus from Patients with Acute Respiratory Infections

First discovered in the early 1950s, reoviruses (respiratory enteric orphan viruses) were not associated with any known disease, and hence named orphan viruses. Recently, our group reported the isolation of the Melaka virus from a patient with acute respiratory disease and provided data suggesting that this new orthoreovirus is capable of human-to-human transmission and is probably of bat origin. Here we report yet another Melaka-like reovirus (named Kampar virus) isolated from the throat swab of a 54 year old male patient in Kampar, Perak, Malaysia who was suffering from high fever, acute respiratory disease and vomiting at the time of virus isolation. Serological studies indicated that Kampar virus was transmitted from the index case to at least one other individual and caused respiratory disease in the contact case. Sequence analysis of the four small class genome segments indicated that Kampar and Melaka viruses are closely related. This was confirmed by virus neutralization assay, showing an effective two-way cross neutralization, i.e., the serum against one virus was able to neutralize the other. Although the exact origin of Kampar virus is unknown, epidemiological tracing revealed that the house of the index case is surrounded by fruit trees frequently visited by fruit bats. There is a high probability that Kampar virus originated from bats and was transmitted to humans via bat droppings or contaminated fruits. The discovery of Kampar virus highlights the increasing trend of emergence of bat zoonotic viruses and the need to expand our understanding of bats as a source of many unknown viruses

Changes in Cognitive Function Over 96 weeks in Naïve Patients Randomised to Darunavir-ritonavir plus either Raltegravir or Tenofovir-Emtricitabine: a substudy of the NEAT001/ANRS143 trial

BACKGROUND: Improvements in cognitive function are described after initiation of combination antiretroviral therapy (cART), with sparse data on differences between cART strategies. METHODS: We assessed changes in cognition, over 96 weeks, in therapy naïve HIV-positive adults randomised to darunavir/ritonavir (800/100mg once daily) with either raltegravir (400mg twice daily, Arm1) or tenofovir/emtricitabine (245/200mg once daily, Arm2). Seven cognitive tests were administered at baseline and week 96. Changes from baseline in individual cognitive test scores and composite score (NPZ) were assessed. Comparisons between treatment arms were by intention-to-treat and associations with immunological and virological parameters by regression models. FINDINGS: Of 343 subjects enrolled, 208 completed the week 96 cognitive assessment. Baseline median (IQR) CD4+ count and plasma HIV RNA was 348(282-398) cells/uL and 4.7(4.2-5.1) log10 copies/mL, respectively. At week 96, numbers with plasma HIV RNA undetectable and remaining on randomised cART were 85(92%) and 110(96%), and 84(90%) and 107(93%) in Arm1 and Arm2, respectively. Overall, performance significantly improved by week 96 in 5 of 7 individual tests and in NPZ. Mean change in NPZ was 0.28 versus 0.21 for Arm1 and 2, respectively (p=0.37). No statistically significant differences between study treatment arms were observed in individual cognitive domains apart from attention (greater improvement in Arm1, p=0.0499). At week 96, NPZ-score increase was associated with increase in CD4+ (p=0.001) but not HIV RNA area-under-curve (p=0.60). INTERPRETATION: Subsequent to the initiation of cART, immunological recovery rather than type of antiretroviral therapy is the major driver of changes in cognitive function

Rabies-Related Knowledge and Practices Among Persons At Risk of Bat Exposures in Thailand

Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of lyssavirus circulation has recently emerged in Southeast Asian bats. We surveyed persons regularly exposed to bats and bat habitats in Thailand to assess rabies‐related knowledge and practices. Targeted groups included guano miners, bat hunters, game wardens, and residents/personnel at Buddhist temples where mass bat roosting occurs. Of the 106 people interviewed, 11 (10%) identified bats as a source of rabies. History of a bat bite/scratch was reported by 29 (27%), and 38 (36%) expressed either that they would do nothing or that they did not know what they would do in response to a bat bite. Guano miners were less likely than other groups to indicate animal bites as a mechanism of transmission (68% vs. 90%, p=0.03) and were less likely to say they would respond appropriately to a bat bite or scratch (61% vs. 27%, p=0.003). These findings indicate a need for educational outreach in Thailand to raise awareness of bat rabies, promote exposure prevention, and ensure health‐seeking behaviors for bat‐inflicted wounds, particularly among at‐risk groups

Dengue in Thailand and Cambodia: An Assessment of the Degree of Underrecognized Disease Burden Based on Reported Cases

Dengue is a major public health problem especially in tropical and subtropical countries of Asia and Latin-America. An effective dengue vaccine is not yet available, but several vaccine candidates are currently being evaluated in clinical trials. Accurate country-level incidence data are crucial to assess the cost-effectiveness of such vaccines and will assist policy-makers in making vaccine introduction decisions. Existing national surveillance systems are often passive and are designed to monitor trends and to detect disease outbreaks. Our analyses of data from prospectively followed cohorts with laboratory confirmation of dengue cases show that, in Thailand and Cambodia, dengue incidence is underrecognized by more than 8-fold. The magnitude of the outpatient burden caused by dengue is not assessed or reflected by the national surveillance data. We estimate that a median of more than 340,000 symptomatic dengue virus infections occurred annually in children less than 15 years of age in Thailand in Cambodia between 2003 and 2007