ALBERT

Description: Influenza viruses cause respiratory tract infections and substantial health concerns. Infection may result in mild to severe respiratory disease associated with morbidity and some mortality. Several anti-influenza drugs are available, but these agents target viral components and are susceptible to drug resistance. There is a need for new antiviral drug strategies that include repurposing of clinically approved drugs. Drugs that target cellular machinery necessary for influenza virus replication can provide a means for inhibiting influenza virus replication. We used RNA interference screening to identify key host cell genes required for influenza replication, and then FDA-approved drugs that could be repurposed for targeting host genes. We examined the effects of Clopidogrel and Triamterene to inhibit A/WSN/33 (EC50 5.84 uM and 31.48 uM, respectively), A/CA/04/09 (EC50 6.432 uM and 3.32 uM, respectively), and B/Yamagata/16/1988 (EC50 0.28 uM and 0.11 uM, respectively) replication. Clopidogrel and Triamterene provide a druggable approach to influenza treatment across multiple strains and subtypes.

Description: Introduction Pregnant and postpartum women face major psychological stressors that put them at higher risk of developing common mental disorders, such as depression and anxiety. Yet, their limited access to and uptake of traditional mental health care is inequitable, especially during the COVID-19 pandemic. Mobile interventions emerged as a potential solution to this discontinued healthcare access, but more knowledge is needed about their effectiveness and impact on health equity. This equity-focused systematic review examined the effectiveness and equity impact of mobile interventions targeting common mental disorders among pregnant and postpartum women. Methods and results We systematically searched MEDLINE, EMBASE, PsychINFO and 3 other databases, from date of database inception and until January 2021, for experimental studies on mobile interventions targeting pregnant and postpartum women. We used pooled and narrative synthesis methods to analyze effectiveness and equity data, critically appraised the methodological rigour of included studies using Cochrane tools, and assessed the certainty of evidence using the GRADE approach. Our search identified 6148 records, of which 18 randomized and non-randomized controlled trials were included. Mobile interventions had a clinically important impact on reducing the occurrence of depression (OR = 0.51 [95% CI 0.41 to 0.64]; absolute risk reduction RD: 7.14% [95% CI 4.92 to 9.36]; p

Description: Background Migrants are not routinely screened for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in the Netherlands. We estimated the prevalence and determined factors associated with HBV, HCV and/or HIV infections among undocumented migrants and uninsured legal residents. Methods In this cross-sectional study, undocumented migrants and uninsured legal residents were recruited at a non governmental organization (NGO), healthcare facility in the Netherlands and were invited to be tested for hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibodies (anti-HBcAb), HCV-RNA, and anti-HIV antibodies or HIV antigen at a local laboratory. Results Of the 1376 patients invited, 784 (57%) participated. Participants originated from Africa (35%), Asia (30%) and North/South America (30%). 451/784 (58%) participants went to the laboratory for testing. Of participants 30% were HBV exposed (anti-HBcAb-positive), with 27% (n = 119/438, 95% CI 23.1% to 31.6%) having resolved HBV infection (HBsAg-negative) and 2.5% (n = 11/438, 95%CI 1.3% to 4.5%, 64% new infection) having chronic HBV infection (HBsAg-positive). Compared to HBV non-exposed, HBV exposed individuals were older (p = 0.034) and more often originated from Africa (p

Description: Fungal infection and synthesis of mycotoxins in coffee leads to significant economic losses. This study aimed to investigate the prevalence of toxigenic fungi, their metabolites, and the effect of traditional roasting and brewing on ochratoxin A (OTA) and aflatoxins (AFs) contents of naturally contaminated coffee samples. In addition, in vivo biocontrol assays were performed to explore the antagonistic activities of Bacillus simplex 350–3 (BS350-3) on the growth and mycotoxins synthesis of Aspergillus ochraceus and A. flavus. The relative density of A. niger, A. flavus, Penicillium verrucosum and A. carbonarius on green coffee bean was 60.82%, 7.21%, 3.09% and 1.03%, respectively. OTA contents were lowest in green coffee beans (2.15 μg/kg), followed by roasted (2.76 μg/kg) and soluble coffee (8.95 μg/kg). Likewise, AFs levels were highest in soluble coffee (90.58 μg/kg) followed by roasted (33.61 μg/kg) and green coffee (9.07 μg/kg). Roasting naturally contaminated coffee beans at three traditional methods; low, medium and high, followed by brewing resulted in reduction of 58.74% (3.50 μg/kg), 60.88% (3.72 μg/kg) and 64.70% (4.11 μg/kg) in OTA and 40.18% (34.65 μg/kg), 47.86% (41.17 μg/kg) and 62.38% (53.73 μg/kg) AFs contents, respectively. Significant inhibitions of AFs and OTA synthesis by A. flavus and A. carbonarius, respectively, on infected coffee beans were observed in presence of Bacillus simplex BS350-3 volatiles. Gas chromatography mass spectrochemistry (GC-MS/MS) analysis of head-space BS350-3 volatiles showed quinoline, benzenemethanamine and 1-Octadecene as bioactive antifungal molecules. These findings suggest that marketed coffee samples are generally contaminated with OTA and AFs, with a significant level of roasted and soluble coffee contaminated above EU permissible limits for OTA. Further, along with coffee roasting and brewing; microbial volatiles can be optimized to minimize the dietary exposure to mycotoxins.

Description: This paper uses publicly available data and various statistical models to estimate the basic reproduction number (R0) and other disease parameters for Ghana’s early COVID-19 pandemic outbreak. We also test the effectiveness of government imposition of public health measures to reduce the risk of transmission and impact of the pandemic, especially in the early phase. R0 is estimated from the statistical model as 3.21 using a 0.147 estimated growth rate [95% C.I.: 0.137–0.157] and a 15-day time to recovery after COVID-19 infection. This estimate of the initial R0 is consistent with others reported in the literature from other parts of Africa, China and Europe. Our results also indicate that COVID-19 transmission reduced consistently in Ghana after the imposition of public health interventions—such as border restrictions, intra-city movement, quarantine and isolation—during the first phase of the pandemic from March to May 2020. However, the time-dependent reproduction number (Rt) beyond mid-May 2020 does not represent the true situation, given that there was not a consistent testing regime in place. This is also confirmed by our Jack-knife bootstrap estimates which show that the positivity rate over-estimates the true incidence rate from mid-May 2020. Given concerns about virus mutations, delays in vaccination and a possible new wave of the pandemic, there is a need for systematic testing of a representative sample of the population to monitor the reproduction number. There is also an urgent need to increase the availability of testing for the general population to enable early detection, isolation and treatment of infected individuals to reduce progression to severe disease and mortality.

Description: Serum Paraoxonase 2 (PON2) level is a potential biomarker owing to its association with a number of pathophysiological conditions such as atherosclerosis and cardiovascular disease. Since cholinergic deficiency is closely linked with Alzheimer’s disease (AD) progression, acetylcholinesterase inhibitors (AChEIs) are the treatment of choice for patients with AD. However, there is a heterogenous response to these drugs and mostly the subjects do not respond to the treatment. Gene polymorphism, the simultaneous occurrence of two or more discontinuous alleles in a population, could be one of the important factors for this. Hence, we hypothesized that PON2 and its polymorphic forms may be hydrolyzing the AChEIs differently, and thus, different patients respond differently. To investigate this, two AChEIs, donepezil hydrochloride (DHC) and pyridostigmine bromide (PB), were selected. Human PON2 wildtype gene and four mutants, two catalytic sites, and two polymorphic sites were cloned, recombinantly expressed, and purified for in vitro analysis. Enzyme activity and AChE activity were measured to quantitate the amount of DHC and PB hydrolyzed by the wildtype and the mutant proteins. Herein, PON2 esterase activity and AChE inhibitor efficiency were found to be inversely related. A significant difference in enzyme activity of the catalytic site mutants was observed as compared to the wildtype, and subsequent AChE activity showed that esterase activity of PON2 is responsible for the hydrolysis of DHC and PB. Interestingly, PON2 polymorphic site mutants showed increased esterase activity; therefore, this could be the reason for the ineffectiveness of the drugs. Thus, our data suggested that the esterase activity of PON2 was mainly responsible for the hydrolysis of AChEI, DHC, and PB, and that might be responsible for the variation in individual response to AChEI therapy.

Description: Multidrug-resistant tuberculosis (MDR-TB) has become a major threat to the control of tuberculosis globally. Uganda is among the countries with a relatively high prevalence of tuberculosis despite significant control efforts. In this study, the drug resistance of Mycobacterium tuberculosis to rifampicin (RIF) and isoniazid (INH) was investigated among patients diagnosed with pulmonary tuberculosis in Southwestern Uganda. A total of 283 sputum samples (266 from newly diagnosed and 17 from previously treated patients), collected between May 2018 and April 2019 at four different TB diagnostic centres, were assessed for RIF and INH resistance using high-resolution melt curve analysis. The overall prevalence of monoresistance to INH and RIF was 8.5% and 11% respectively, while the prevalence of MDR-TB was 6.7%. Bivariate analysis showed that patients aged 25 to 44 years were at a higher risk of developing MDR-TB (cOR 0.253). Furthermore, among the newly diagnosed patients, the prevalence of monoresistance to INH, RIF and MDR-TB was 8.6%, 10.2% and 6.4% respectively; while among the previously treated cases, these prevalence rates were 5.9%, 23.5% and 11.8%. These rates are higher than those reported previously indicating a rise in MTB drug resistance and may call for measures used to prevent a further rise in drug resistance. There is also a need to conduct frequent drug resistance surveys, to monitor and curtail the development and spread of drug-resistant TB.

Description: During the Paleolithic period, bone marrow extraction was an essential source of fat nutrients for hunter-gatherers especially throughout cold and dry seasons. This is attested by the recurrent findings of percussion marks in osteological material from anthropized archaeological levels. Among them some showed indicators that the marrow extraction process was part of a butchery cultural practice, meaning that the inflicted fracturing gestures and techniques were recurrent, standardized and counter-intuitive. In order to assess the weight of the counter-intuitive factor in the percussion mark pattern distribution, we carried out an experiment that by contrast focuses on the intuitive approach of fracturing bones to extract marrow, involving individual without experience in this activity. We wanted to evaluate the influence of bone morphology and the individuals’ behaviour on the distribution of percussion marks. Twelve experimenters broke 120 limb bones, a series of 10 bones per individual. During the experiment, information concerning the fracture of the bones as well as individual behaviour was collected and was subsequently compared to data from the laboratory study of the remains. Then, we applied an innovative GIS (Geographic Information System) method to analyze the distribution of percussion marks to highlight recurrent patterns. Results show that in spite of all the variables there is a high similarity in the distribution of percussion marks which we consider as intuitive patterns. The factor influenced the distribution for the humerus, radius-ulna and tibia series is the bone morphology, while for the femur series individual behaviour seems to have more weight in the distribution. To go further in the subject we need to compare the intuitive models with the distributions of percussion marks registered in fossil assemblages. Thus, it would be possible to propose new hypotheses on butchering practices based on the results presented in this work.

Description: Introduction Sex-based clinical outcome differences in sickle cell disease (SCD) remain largely unknown despite evidence that female sex is associated with an increased lifespan. To better characterize sex-based differences in SCD, we assessed pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. Methods The SCDIC consists of eight comprehensive SCD centers and one data coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Eligibility criteria included: 15 to 45 years of age and a confirmed diagnosis of SCD. Self-report surveys were completed and data were also abstracted from the participants’ medical records. Results A total of 2,124 participants were included (mean age: 27.8 years; 56% female). The majority had hemoglobin SS SCD genotype. Females had worse reports of pain severity (mean (SD) T-score 51.6 (9.6) vs 49.3 (10), p

Description: Background Worldwide, strict infection control measures including visitation regulations were implemented due to the COVID-19 pandemic at Neonatal Intensive Care Units (NICUs). These regulations gave restricted access for parents to their hospitalized infants. The consequence was limited ability to involve in the care of their infants. At Oslo University Hospital entry to NICU was denied to all except healthy mothers in March 2020. The absolute access ban for fathers lasted for 10 weeks. The aim of this study was to explore parental experiences with an infant hospitalized in the NICU during this absolute visitation ban period. Methods We invited post discharge all parents of surviving infants that had been hospitalized for at least 14 days to participate. They were interviewed during autumn 2020 using an explorative semi-structured interview approach. Data were analyzed via inductive thematic analysis. Results Nine mothers and four fathers participated. The COVID-19 regulations strongly impacted the parent’s experiences of their stay. The fathers’ limited access felt life-impacting. Parents struggled to become a family and raised their voices to be heard. Not being able to experience parenthood together led to emotional loneliness. The fathers struggled to learn how to care for their infant. The regulations might lead to a postponed attachment. On the other hand, of positive aspect the parents got some quietness. Being hospitalized during this first wave was experienced as exceptional and made parents seeking alliances by other parents. Social media was used to keep in contact with the outside world. Conclusions The regulations had strong negative impact on parental experiences during the NICU hospitalization. The restriction to fathers’ access to the NICU acted as a significant obstacle to early infant-father bonding and led to loneliness and isolation by the mothers. Thus, these COVID-19 measures might have had adverse consequences for families.