Effects of Mouse Kidney Parvovirus on Pharmacokinetics of Chemotherapeutics and the Adenine Model of Chronic Kidney Disease.

Mouse kidney parvovirus (MKPV) causes inclusion body nephropathy in severely immunocompromised mice and renal interstitial inflammation in immunocompetent mice. Here we sought to determine the effects of MKPV on pre-clinical murine models that depend on renal function. To assess the effects of MKPV infection on the pharmacokinetics of 2 renally excreted chemotherapeutic agents, methotrexate and lenalidomide, we measured drug concentrations in the blood and urine of MKPV-infected or uninfected immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) and immunocompetent C57BL/6NCrl (B6) female mice. No differences in plasma pharmacokinetics were observed for lenalidomide. However, the AUC of methotrexate was 1.5-fold higher in uninfected NSG mice compared with infected NSG mice, 1.9-fold higher in infected B6 mice compared with uninfected B6 mice, and 4.3-fold higher in uninfected NSG mice compared with uninfected B6 mice. MKPV infection did not significantly affect the renal clearance of either drug. To assess effects of MKPV infection on the adenine diet model of chronic kidney disease, MKPV-infected and uninfected B6 female mice were fed a 0.2% adenine diet, and clinical and histopathologic features of disease were assessed over 8 wk. MKPV infection did not significantly alter urine chemistry results, hemogram findings, or serum concentrations of BUN, creatinine, or symmetric dimethylarginine. However, infection did influence histologic outcomes. As compared with uninfected mice, MKPV-infected mice had more interstitial lymphoplasmacytic infiltrates after 4 and 8 wk of diet consumption and less interstitial fibrosis at week 8. Macrophage infiltrates and renal tubular injury were similar between in infected and uninfected mice. These findings indicate that MKPV infection had minimal effects on the renal excretion of 2 chemotherapeutics and on serum biomarkers of renal function. However, infection significantly influenced two histologic features of the adenine diet model of chronic renal disease. MKPV-free mice are critically important in studies evaluating renal histology as an experimental outcome.

Mechanical Washing Prevents Transmission of Bacterial, Viral, and Protozoal Murine Pathogens from Cages.

Infectious agents have varying susceptibilities to thermal inactivation and/or mechanical removal from cages by the use of heated, pressurized water. In this study, we tested whether 5 specific infectious organisms (Candidatus savagella [segmented filamentous bacterium (SFB)], Helicobacter sp., mouse norovirus (MNV), Tritrichomonas sp., and Entamoeba muris) could survive the cage wash process and still infect naïve mice. These 5 organisms were chosen due to their prevalence in rodent colonies, environmental stability, and/or potential to influence experimental outcomes. Cages that had housed mice shedding all 5 organisms were assigned to 1 of 3 treatment groups: 1) sanitization in a tunnel washer followed by autoclaving (121 °C [250 °F] for 20 min; n = 40 cages); 2) sanitization in a tunnel washer (82 °C [180 °F] for an average of 30 s; n = 40 cages); or 3) control (bedding change only; n = 40 cages). The presence of these agents in the cage was assessed by performing PCR on swabs of the empty soiled cage interior before and after the treatment. In addition, to determine if any residual nucleic acid was infectious, 2 Swiss outbred (J:ARC(S)) female mice were housed for 7 d in cages from each treatment group. The above procedures were then repeated so that every week each pair of J:ARC(S) mice ( n = 10 pairs of mice/treatment group) were housed in another cage that underwent the same treatment; this was done for a total of 4 consecutive, 1-wk-long periods. Swabs collected from soiled cages were PCR-positive for SFB, Helicobacter, MNV, Tritrichomonas, and Entamoeba in 99%, 97%, 39%, 63%, and 73% of the cages tested, respectively. Cages in the tunnel wash group that were PCR-positive for SFB, Helicobacter, Tritrichomonas, and Entamoeba before treatment remained PCR-positive in 8%, 15%, 43%, and 10% of positive cages, respectively. None of the cages from the autoclave group were PCR-positive for any of the agents after treatment. None of the mice housed in cages in either the autoclave or tunnel wash groups became infected with any of the agents. However, 80%, 60%, and 100% of the pairs of mice housed in untreated cages were PCR-positive for SFB, MNV, and Entamoeba, respectively. None of the mice housed in untreated cages were positive for Helicobacter or Tritrichomonas. Our results suggest that nucleic acids from these bacterial and protozoal organisms may remain in cages after mechanical cage washing, but these nucleic acids are not infectious, and autoclaving is not necessary to prevent transmission.

Healthcare of pregnant women with diabetes during the COVID-19 pandemic: a Southern Brazilian cross-sectional panel data.

OBJECTIVES: To evaluate the indirect effects of the COVID-19 pandemic on the care of women with pregnancies complicated by gestational or pre-existing diabetes, and their maternal-fetal outcomes. METHODS: A cross-sectional panel data conducted in a University Hospital in Southern Brazil. Maternal-fetal outcomes and predictors of care from 235 pregnant women with type 1, type 2, or gestational diabetes were evaluated. Two time periods were compared: six months preceding the pandemic, in 2019, and the COVID-19 period from September 2020 to March 2021. Comparisons were performed using analysis of variance, Mann-Whitney U, Fisher's exact and T-tests. Risks were calculated using the Poisson regression with robust estimates. RESULTS: Maternal age was lower (32.1 ± 6.8 vs. 34.4 ± 6.6, p=0.009) and rates of depression/anxiety were higher (16.5 vs. 7.4%, p=0.046) in the group evaluated during the COVID-19. Neonatal hypoglycemia (RR 4.04; 95% CI 1.37-11.98, p=0.012), and SGA rates (RR 4.29; 95% CI 1.93-9.54, p<0.001) were higher in the group assessed before the pandemic. CONCLUSIONS: Despite economic, social and structural impacts of the pandemic, parameters of maternal care were similar; diabetes control improved, and neonatal hypoglycemia and SGA rates were lower among pregnant women with diabetes during the pandemic.

Prehospital emergency obstetric and neonatal care train-the-trainers program in Rwanda.

OBJECTIVE: To improve maternal mortality rates, our collaboration developed and implemented a context-specific, prehospital Emergency Obstetrics and Neonatal Course (EONC) and train-the-trainers program in Rwanda. METHODS: Two cohorts of staff participated in the program-the SAMU emergency medical service and staff from district hospitals. A 2-day course was developed, consisting of skills stations, simulations, and didactics. A 50-question assessment was administered to both cohorts before and after the courses. Student's t test and matched paired t tests were used to evaluate the assessments through retrospective analysis of the data. RESULTS: EONC1 median scores were 60% versus 92% (pre vs post), using matched-pair analysis of 20 participants. EONC2 median scores were 52% versus 96% (pre vs post), using matched-pair analysis of participants. A one-way analysis of variance mean square analysis showed that regardless of the baseline level of training for each participant, all trainees reached similar post-course assessment scores (F(1)  = 8.35, P = 0.0059). CONCLUSION: Optimal prehospital management of obstetric emergencies is essential to prevent needless mortality and morbidity. This study demonstrated that a context-appropriate prehospital obstetric and neonatal training program could be effectively developed and implemented for the SAMU team in Kigali, Rwanda.

Group B streptococcal colonization: Prevalence and impact of smoking in women delivering term or near term neonates in a large tertiary care hospital in the southern United States.

BACKGROUND AND HYPOTHESIS: The role of smoking as a risk factor for group B streptococcal (GBS) colonization in women during pregnancy has not been previously adequately explored. We hypothesized that women of term or near term neonates who smoked during pregnancy were more likely to have GBS colonization than their non-smoking counterparts. METHODS: The electronic health records (EHRs) of a convenience sample of women delivering in an inner-city university tertiary care center were reviewed. The outcome variable of interest was maternal GBS colonization during pregnancy. The primary independent variable of interest was tobacco smoking during pregnancy, determined from the EHRs by the number of cigarettes smoked during gestation. Descriptive statistics were conducted and categorical data were compared by the Fischer's exact test. Multiple logistic regression analysis was further conducted to determine the independent impact of tobacco smoke exposure on GBS colonization. RESULTS: The prevalence of maternal GBS colonization was 35% among the study population. In the univariate analyses, factors associated with maternal GBS colonization were tobacco smoking during pregnancy (P of trend <0.001), Race (P<0.001), maternal age <20 years (P = 0.006), low birthweight <2500 gm (P = 0.020), maternal drug use (P = 004), and gestational age <37 (P = 0.041). In a multiple logistic regression analysis, tobacco smoking during pregnancy remained the most significant predictor of GBS colonization. Women who smoked during pregnancy were more than twice more likely to be colonized than their non-smoking counterparts (OR = 2.6; 95% CI = 1.5-4.6; p<0.001). Maternal age was the only other significant predictor with younger mothers more than one and a half time more likely to be colonized than their older counterparts (OR = 1.65; 95% CI = 1.02-2.68; P = 0.04). CONCLUSION: The prevalence of GBS colonization in this institution was consistent with recent national rates. Smoking and maternal age were identified as two independent risk factors for GBS colonization during pregnancy. Further studies are needed to confirm these findings.

Colonización por ESKAPES y características clínicas de pacientes en estado crítico / Colonization by ESKAPES and clinical characteristics of critically ill patients / Colonização por ESKAPES e características clínicas de pacientes críticos

OBJETIVO: Identificar la colonización por ESKAPES y las características clínicas de los pacientes hospitalizados en una Unidad de Cuidados Intensivos para Adultos de un hospital mixto en Paraná. MÉTODO: Investigación de campo, descriptiva, documental y experimental con enfoque cuantitativo, desarollada en una Unidad de Cuidados Intensivos adultos de un hospital mixto en el suroeste de Paraná, Brasil. La población del estudio consistió en pacientes con ingreso de 48 horas en la Unidad de Cuidados Intensivos, de abril a agosto de 2018 y de abril a agosto de 2019. La muestra totalizó 102 individuos. Para la recopilación de datos clínicos, se utilizó un Checklist y para el análisis microbiológico se recogieron muestras de las cavidades nasales y orales y la secreción traqueal. El análisis de los datos clínicos se produjo a través del software Statistical Package for the Social Sciences. Se realizaron pruebas de frecuencia y chi-cuadrado, teniendo en cuenta la p < 0,05 significativa. RESULTADOS: Se evaluaron un total de 102 pacientes ingresados en la Unidad de Cuidados Intensivos durante el período estudiado. De ellos, 57 (55,8%) fueron colonizados por microorganismos patógenos. En cuanto a la colonización por microorganismos, predominan Staphylococcus aureus (61,4%), seguido de Klebsiella pneumoniae (40,4%), Pseudomonas aeruginosa (26,3%) y Staphylococcus epidermidis (21,1%). Cabe destacar que Klebsiella pneumoniae y Staphylococcus aureus estuvieron presentes en las tres regiones evaluadas. CONCLUSIÓN: El estudio identificó la presencia de colonización en pacientes en estado crítico estudiados, siendo esta colonización, en su mayoría, por bacterias resistentes pertenecientes al grupo ESKAPE

OBJECTIVE: To identify colonization by ESKAPES and clinical characteristics of patients admitted in Adult Intensive Care Unit of a mixed hospital in Paraná. METHOD: Field research, descriptive, documentary and experimental quantitative approach, developed in adult Intensive Care Unit of a mixed hospital in Southwest Paraná, Brazil. The study population consisted of patients with admission from 48 hours in the Intensive Care Unit, from April to August 2018 and April to August 2019. The sample has 102 individuals. For the collection of clinical data, a checklist was used and for microbiological analysis the sample was collected from nasal and oral cavities and tracheal secretion. The analysis of clinical data occurred through the Statistical Package for the Social Sciences software. Descriptive frequency and chi-square test, considering significant p <0,05. RESULTS: A total of 102 patients admitted to the Intensive Care Unit during the period studied were evaluated. On these ones, 57 (55,8%) were colonized by pathogenic microorganisms. Regarding the colonization of microorganisms, there was predominance of Staphylococcus aureus (61,4%), followed by Klebsiella pneumoniae (40,4%), Pseudomonas aeruginosa (26,3%) and Staphylococcus epidermidis (21,1%). It is noteworthy that Klebsiella pneumoniae and Staphylococcus aureus were present in the three regions evaluated. CONCLUSION: The study identified the presence of colonization in critically ill patients studied, being this colonization, mostly, resistant bacteria belonging to the ESKAPE group

OBJETIVO: Identificar a colonização por ESKAPES e características clínicas de pacientes internados em uma Unidade de Terapia Intensiva Adulto de um hospital misto do Paraná. MÉTODO: Pesquisa de campo, descritiva, documental e experimental com abordagem quantitativa, desenvolvida em uma Unidade de Terapia Intensiva adulto de um hospital misto do Sudoeste do Paraná, Brasil. A população do estudo constituiu-se pelos pacientes com admissão a partir de 48 horas na Unidade de Terapia Intensiva, no período de abril a agosto de 2018 e de abril a agosto de 2019. A amostra totalizou 102 indivíduos. Para a coleta de dados clínicos foi utilizado um Checklist e para a análise microbiológica foram coletadas amostras das cavidades nasal e oral e secreção traqueal. A análise dos dados ocorreu por meio do software Statistical Package for the Social Sciences. Realizou-se frequência descritiva e teste de qui-quadrado, considerando significativo p <0,05. RESULTADOS: Foram avaliados 102 pacientes admitidos na Unidade de Terapia Intensiva durante o período pesquisado. Destes, 57 (55,8%) estavam colonizados por microrganismos patogênicos. Em relação à colonização de microrganismos, houve predominância de Staphylococcus aureus (61,4%), seguido por Klebsiella pneumoniae (40,4%), Pseudomonas aeruginosa (26,3%) e Staphylococcus epidermidis (21,1%). Vale ressaltar que, Klebsiella pneumoniae e Staphylococcus aureus estiveram presentes nas três regiões avaliadas. CONCLUSÃO: O estudo identificou a presença de colonização nos pacientes criticamente enfermos pesquisados, sendo essa colonização, em sua maioria, por bactérias resistentes pertencentes ao grupo ESKAPE

Single-Dose Levonorgestrel Emergency Contraception and Silent Barriers to Its Access: Is It Really Just One Step?

BACKGROUND: Single-dose levonorgestrel has been legally available over the counter in the United States without age restriction since 2013. The objective of this study was to discover if there are barriers to access and to determine if such barriers vary based on the gender of the person making the purchase. MATERIALS AND METHODS: A male and female caller contacted 146 Richmond, Virginia pharmacies listed on the Plan B One Step® website. Ultimately, these callers interviewed 90 pharmacies via phone and used a rehearsed standardized script to ask eight questions regarding emergency contraception (EC) in relation to availability, age restrictions, parental consent, counseling requirements, and a male's ability to purchase the product. The statistical data were analyzed using Fisher's exact test. RESULTS: Pharmacy employees provided incorrect information to both men and women regarding age restrictions for purchasing Plan B One Step 51% of the time. However, only seven of the pharmacy employees counseled that males were unable to purchase the medication. Both callers received correct information regarding parental consent and in-store counseling at the time of purchase. Pharmacy technicians provided the majority of information, and the male caller was more likely to be transferred to another person when requesting the medication (9 vs. 0 transfers for the male and female callers, respectively). CONCLUSION: Given the inconsistent data provided to the public regarding the purchase of EC, clinicians are obligated to convey accurate up-to-date information to patients about emergency contraceptive products as part of their counseling and should not assume that consumers receive accurate information when inquiring about over-the-counter EC.

Sox14 is required for transcriptional and developmental responses to 20-hydroxyecdysone at the onset of drosophila metamorphosis.

The steroid hormone 20-hydroxyecdysone (20E), by means of a heterodimer consisting of two nuclear receptors, the Ecdysone receptor (EcR) and Ultraspiracle (Usp), triggers the major developmental transitions in the Drosophila life cycle through the regulation of genetic hierarchies. We have previously demonstrated that the Sox14 transcription factor is a primary response gene to 20E/EcR/Usp complex. In this study, we show that mutations in sox14 result in prepupal and pupal lethality with animals displaying a multitude of defects in 20E developmentally regulated pathways. In addition, through Northern blot and microarray analyses of sox14 mutant animals, we demonstrate that Sox14 is required for the proper expression of 20E- and non-20E-regulated genes at the onset of metamorphosis. We also show that the Sox14-regulated gene set correlates well with Sox14 expression in a variety of larval and adult tissues. Thus, Sox14 is a critical transcription factor required for 20E signaling at the onset of metamorphosis.

Synthesis and evaluation of novel 8,5-fused bicyclic peptidomimetic compounds as interleukin-1beta converting enzyme (ICE) inhibitors.

An 8,5-fused bicyclic peptidomimetic ring system generated by a stereoselective ring metathesis reaction was elaborated into potent inhibitors of interleukin-1beta converting enzyme (ICE, caspase-1). Multiple compounds were found that exhibited ICE IC50 values < 10 nM and were selective over caspase-3 and caspase-8. These active analogs generally possessed good activity (IC50 values < 100 nM) in a whole cell assay measuring IL-1beta production. Pharmacokinetic analysis of the ethyl acetal prodrug form of a selected active lead revealed a compound with a reasonable plasma half-life (1.1 h) and good oral bioavailability (30%).

Synthesis and evaluation of (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones as Kv1.5 channel blockers for the treatment of atrial fibrillation.

A series of novel (2-phenethyl-2H-1,2,3-triazol-4-yl)(phenyl)methanones were prepared and examined for utility as Kv1.5 channel blockers for the treatment of atrial fibrillation.