Haneyamstrup2041

Immunodeficiency and hyperinflammation are responsible for the most frequent and life-threatening forms of coronavirus disease 2019 (COVID-19). Therefore, cytokine-based treatments targeting immuno-inflammatory mechanisms are currently undergoing clinical scrutiny in COVID-19-affected patients. In addition, COVID-19 patients also exhibit a wide range of neurological manifestations (neuro-COVID), which may also benefit from cytokine-based treatments. In fact, such drugs have shown some clinical efficacy also in neuroinflammatory diseases. On the other hand, anti-cytokine drugs are endowed with significant neurological risks, mainly attributable to their immunodepressant effects. Therefore, the aim of the present manuscript is to briefly describe the role of specific cytokines in neuroinflammation, to summarize the efficacy in preclinical models of neuroinflammatory diseases of drugs targeting these cytokines and to review the clinical data regarding the neurological effects of these drugs currently being investigated against COVID-19, in order to raise awareness about their potentially beneficial and/or detrimental neurological consequences.

Human papillomavirus (HPV) is the causative agent of precancerous lesions and cervical cancer, cervical cancer being the leading cause of deaths in Tanzanian women. Early detection and treatment of precancerous lesions are important in the prevention of cervical cancer cases.

We conducted a cross-sectional study among 3390 Tanzanian women aged 25-60years. Information on lifestyle habits was collected, and women underwent gynecological examination with collection of cervical cells for conventional cytological and HPV testing. Atezolizumab Blood samples were tested for HIV. The association between cervical high-grade cytology (HGC) and potential risk factors was examined using multivariable logistic regression adjusting for age and high-risk HPV (HR-HPV).

The prevalence of HGC was 3.6% and of low-grade cytology was 8.3%. In women who were both HR-HPV-positive and HIV-positive, the prevalence of HGC was 28.3%. It increased by age and was 47% among women aged 50-60years. Women, who had their sexual debut at age 9-15years and 16-18years, respectively, had 2.5 and 2.4 times increased odds of HGC compared with women whose sexual debut was at age 21years and older. HIV-positive women had increased odds of HGC in comparison with HIV-negative women after adjustment for age (odds ratio [OR] 2.95, 95% CI 1.92-4.54). HR-HPV-positive women had nearly 100-fold increased odds of HGC compared with HR-HPV-negative women (OR 96.6, 95% CI 48.0-194), and this estimate was higher among HIV-positive women (OR 152.2, 95% CI 36.1-642.0).

Increasing age, early age at first intercourse, HR-HPV, and HIV infections were associated with a substantially increased risk of HGC.

Increasing age, early age at first intercourse, HR-HPV, and HIV infections were associated with a substantially increased risk of HGC.

To assess and compare the oral health status and parental perception of child oral health-related quality of life (OHRQoL) among children with and without cerebral palsy (CP).

A cross-sectional comparative study was conducted among 300 children aged 5-15 years with and without CP in Bangalore city. Oral health status was assessed using WHO 2013 criteria, and malocclusion was assessed using Angle's classification of malocclusion. Parental perception of child OHRQoL was assessed using parental caregivers perceptions questionnaire. Chi-square test, Student's t-tests and logistic regression were applied. Majority of the study participants were males with a mean age of 10 years. Caries experience, gingivitis, dental trauma, and dental erosion were significantly higher among children with CP than the comparison group. Mean parental perception of child OHRQoL score among CP was significantly higher than that of comparison group (P<.001). Odds of having caries experience, gingivitis, dental trauma, and Angle's Class II/III malocclusion were significantly higher among CP children with poor OHRQoL compared to those without these conditions.

Oral health status among children with CP was poor than the children without CP. Parents perceived poor OHRQoL among children with CP when compared to those without CP. Hence CP has an impact on oral health necessitating preventive care.

Oral health status among children with CP was poor than the children without CP. Parents perceived poor OHRQoL among children with CP when compared to those without CP. Hence CP has an impact on oral health necessitating preventive care.Maleate is one of the most important unsaturated four-carbon dicarboxylic acids. It serves as an attractive building block in cosmetic, polymer, and pharmaceutical industries. Currently, industrial production of maleate relies mainly on chemical synthesis using benzene or butane as the starting materials under high temperature, which suffers from strict reaction conditions and low product yield. Here, we propose a novel biosynthetic pathway for maleate production in engineered Escherichia coli. We screened a superior salicylate 5-hydroxylase that can catalyze hydroxylation of salicylate into gentisate with high conversion rate. Then, introduction of salicylate biosynthetic pathway and gentisate ring cleavage pathway allowed the synthesis of maleate from glycerol. Further optimizations including enhancement of precursors supply, disruption of competing pathways, and construction of a pyruvate recycling system, boosted maleate titer to 2.4 ± 0.1 g/L in shake flask experiments. Subsequent scale-up biosynthesis of maleate in a 3-L bioreactor under fed-batch culture conditions enabled the production of 14.5 g/L of maleate, indicating a 268-fold improvement compared with the titer generated by the wildtype E. coli strain carrying the entire maleate biosynthetic pathway. This study provided a promising microbial platform for industrial level synthesis of maleate, and demonstrated the highest titer of maleate production in microorganisms so far.Efforts are underway to develop and implement nonanimal approaches which can characterize acute systemic lethality. A workshop was held in October 2019 to discuss developments in the prediction of acute oral lethality for chemicals and mixtures, as well as progress and needs in the understanding and modeling of mechanisms of acute lethality. During the workshop, each speaker led the group through a series of charge questions to determine clear next steps to progress the aims of the workshop. Participants concluded that a variety of approaches will be needed and should be applied in a tiered fashion. Non-testing approaches, including waiving tests, computational models for single chemicals, and calculating the acute lethality of mixtures based on the LD50 values of mixture components, could be used for some assessments now, especially in the very toxic or non-toxic classification ranges. Agencies can develop policies indicating contexts under which mathematical approaches for mixtures assessment are acceptable; to expand applicability, poorly predicted mixtures should be examined to understand discrepancies and adapt the approach.