Sex chromosome complement contributes to sex differences in coxsackievirus B3 but not influenza A virus pathogenesis

<p>Abstract</p> <p>Background</p> <p>Both coxsackievirus B3 (CVB3) and influenza A virus (IAV; H1N1) produce sexually dimorphic infections in C57BL/6 mice. Gonadal steroids can modulate sex differences in response to both viruses. Here, the effect of sex chromosomal complement in response to viral infection was evaluated using four core genotypes (FCG) mice, where the <it>Sry </it>gene is deleted from the Y chromosome, and in some mice is inserted into an autosomal chromosome. This results in four genotypes: XX or XY gonadal females (XXF and XYF), and XX or XY gonadal males (XXM and XYM). The FCG model permits evaluation of the impact of the sex chromosome complement independent of the gonadal phenotype.</p> <p>Methods</p> <p>Wild-type (WT) male and female C57BL/6 mice were assigned to remain intact or be gonadectomized (Gdx) and all FCG mice on a C57BL/6 background were Gdx. Mice were infected with either CVB3 or mouse-adapted IAV, A/Puerto Rico/8/1934 (PR8), and monitored for changes in immunity, virus titers, morbidity, or mortality.</p> <p>Results</p> <p>In CVB3 infection, mortality was increased in WT males compared to females and males developed more severe cardiac inflammation. Gonadectomy suppressed male, but increased female, susceptibility to CVB3. Infection with IAV resulted in greater morbidity and mortality in WT females compared with males and this sex difference was significantly reduced by gonadectomy of male and female mice. In Gdx FCG mice infected with CVB3, XY mice were less susceptible than XX mice. Protection correlated with increased CD4+ forkhead box P3 (FoxP3)+ T regulatory (Treg) cell activation in these animals. Neither CD4+ interferon (IFN)γ (T helper 1 (Th1)) nor CD4+ interleukin (IL)-4+ (Th2) responses differed among the FCG mice during CVB3 infection. Infection of Gdx FCG mice revealed no effect of sex chromosome complement on morbidity or mortality following IAV infection.</p> <p>Conclusions</p> <p>These studies indicate that sex chromosome complement can influence pathogenicity of some, but not all, viruses.</p

Lot sizing with a Markov production process and imperfect items scrapped

This paper considers an inventory system within the economic order quantity (EOQ) model framework under random supply. The production process can go "out-of-control" with a constant probability and start producing imperfect quality items. Such a system has been studied in the literature under the assumption that defective items are reworked instantaneously and returned to inventory. In some situations, imperfect quality items are not necessarily defective and are removed from the inventory to be used elsewhere. This paper develops two models where imperfect items are removed from inventory. The first model finds the expected cost and optimal lot size assuming that imperfect quality items are removed from inventory at no cost. The second model assumes that batches of imperfect quality are consolidated and shipped together due to economies of scale in shipping. Analytical and numerical results are developed for both models revealing several managerial insights.Imperfect quality Random yield Lot sizing EOQ

Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon

Objective: This study was designed to determine the efficacy of ivermectin, an FDA-approved drug, in producing clinical benefits and decreasing the viral load of SARS-CoV-2 among asymptomatic subjects that tested positive for this virus in Lebanon. Methods: A randomized controlled trial was conducted in 100 asymptomatic Lebanese subjects that have tested positive for SARS-CoV2. Fifty patients received standard preventive treatment, mainly supplements, and the experimental group received a single dose (according to body weight) of ivermectin, in addition to the same supplements the control group received. Results: There was no significant difference (p = 0.06) between Ct-values of the two groups before the regimen was started (day zero), indicating that subjects in both groups had similar viral loads. At 72 h after the regimen started, the increase in Ct-values was dramatically higher in the ivermectin than in the control group. In the ivermectin group, Ct increased from 15.13 ± 2.07 (day zero) to 30.14 ± 6.22 (day three; mean ± SD), compared to the control group, where the Ct values increased only from 14.20 ± 2.48 (day zero) to 18.96 ± 3.26 (day three; mean ± SD). Moreover, more subjects in the control group developed clinical symptoms. Three individuals (6%) required hospitalization, compared to the ivermectin group (0%). Conclusion: Ivermectin appears to be efficacious in providing clinical benefits in a randomized treatment of asymptomatic SARS-CoV-2-positive subjects, effectively resulting in fewer symptoms, lower viral load and reduced hospital admissions. However, larger-scale trials are warranted for this conclusion to be further cemented

Retraction: Samaha et al. Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon. <em>Viruses</em> 2021, <em>13</em>, 989

The journal retracts the article, Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon [...