Notes

Characteristics of Guillain-Barré syndrome inside a Lebanese tertiary treatment center.
Total plasma cell-free DNA (cfDNA) levels were recently shown to be prognostic in two large phase III trials of taxane chemotherapy in metastatic castration-resistant prostate cancer (mCRPC). However, whether cfDNA concentration is predictive of treatment outcomes with androgen receptor pathway inhibitors (ARPIs) is unknown. We quantified plasma cfDNA levels at baseline (n = 74) and 4 weeks on treatment (n = 56) in a prospective cohort of mCRPC patients treated with the ARPIs abiraterone acetate or enzalutamide. Elevated total cfDNA concentration (log10) at both baseline (hazard ratio [HR] 5.5, p less then 0.001) and week 4 (HR 7.5, p less then 0.001) was a significant negative prognostic factor for overall survival (OS), a finding maintained after adjustment for plasma circulating tumour DNA fraction. Unexpectedly, a rise in cfDNA concentration from baseline to week 4 was also associated with significantly improved OS (HR 0.14, p = 0.003). Conversely, patients with ≥29.8% decrease in cfDNA from baseline w patients will respond to treatment in metastatic prostate cancer.Cenicriviroc (CVC) is a small-molecule chemokine receptor antagonist with highly potent and selective anti-human immunodeficiency virus type 1 (HIV-1) activity through antagonizing C-C chemokine receptor type 5 (CCR5) as a coreceptor of HIV-1. CVC also strongly antagonizes C-C chemokine receptor type 2b (CCR2b), thereby it has potent anti-inflammatory and immunomodulatory effects. CVC is currently under clinical trials in the patients for treatment of nonalcoholic steatohepatitis, in which immune cell activation and dysregulation of proinflammatory cytokines play an important role in its pathogenesis. In this study, CVC was examined for its inhibitory effect on the replication of SARS-CoV-2, the causative agent of COVID-19, in cell cultures and found to be a selective inhibitor of the virus. The 50% effective concentrations of CVC were 19.0 and 2.9 μM in the assays based on the inhibition of virus-induced cell destruction and viral RNA levels in culture supernatants of the infected cells, respectively. Interestingly, the CCR5-specific antagonist maraviroc did not show any anti-SARS-CoV-2 activity. Although the mechanism of SARS-CoV-2 inhibition by CVC remains to be elucidated, CCR2b does not seem to be its target molecule. Considering the fact that the regulation of excessive immune activation is required to treat COVID-19 patients at the late stage of the disease, CVC should be further pursued for its potential in the treatment of SARS-CoV-2 infection.
To monitor bilateral corneal parameters after unilateral Baerveldt 350 tube-shunt implantation (Advanced Medical Optics, Santa Ana, CA) through the ciliary sulcus.

Retrospective, interventional case series.

Patients from 1 private glaucoma practice with severe uncontrolled glaucoma treated with sulcus tube-shunt implantation in 1 pseudophakic eye.

Specular microscopy data were collected before and after unilateral sulcus tube-shunt implantation from the surgical and the glaucomatous fellow eyes.

Central corneal endothelial cell density (CECD), coefficient of variation (CV), percent of hexagonal cells, central corneal thickness (CCT), intraocular pressure (IOP), IOP-lowering medications, visual acuity, and complications.

Forty-six patients (mean age, 69.9 years; standard deviation [SD], 4.6 years; range, 20-88 years; male gender, 41.3%) were identified. After surgery, IOP and the number of IOP-lowering medications decreased significantly by 42.3% (P < 0.0001) and 32.1% (P < 0.0001), respectivt disruption to corneal endothelial cell morphologic features, increased corneal thickness, or corneal failures were found during the 24-month follow-up period. A prospective head-to-head comparison to assess the effects of the various methods of tube-shunt implantation on the corneal endothelium is needed.
Tube-shunt implantation through the ciliary sulcus in pseudophakic eyes appears relatively safe to the corneal endothelium, demonstrating a small and nonsignificant decline in central CECD compared with baseline and with glaucomatous fellow eyes. No significant disruption to corneal endothelial cell morphologic features, increased corneal thickness, or corneal failures were found during the 24-month follow-up period. A prospective head-to-head comparison to assess the effects of the various methods of tube-shunt implantation on the corneal endothelium is needed.Ralstonia solanacearum is a soil-borne pathogen that causes bacterial wilt worldwide. The virulence-attenuated mutants were able to combat the soil-borne plant diseases. In this study, we screened the virulence-attenuated mutant PRS-84-4-49 of Ralstonia solanacearum and demonstrated that this strain showed a significant biocontrol effect against patchouli bacterial wilt. Three putative virulence-attenuated mutants obtained in our previous preliminary screen were individually tested for their pathogenicity to patchouli plants. Mutant PRS-84-4-49 showed significantly less virulence to patchouli plants than the other investigated mutants. The virulence-attenuated mutant PRS-84-4-49 was then evaluated for its potential to control patchouli bacterial wilt. The results revealed that the biocontrol treatment significantly reduced disease severity compared with the inoculated control plants, their highest disease incidence were 33% and 63%, respectively, at 5 days post-inoculation. Mutant PRS-84-4-49 exhibited less motility and produced fewer biofilms than the wild-type strain. Therefore, our results demonstrate that virulence-attenuated mutant of Ralstonia solanacearum has potential as biological control agent capable of suppressing patchouli bacterial wilt.Hydropericardium-hepatitis syndrome (HHS) is an important emerging disease responsible for huge economic losses to the poultry industry in China. HHS primarily affects 20 to 60-day-old broilers and rarely occurs in laying flock. In this study, the highly pathogenic fowl adenovirus (FAdV) strain, AH-F19, was isolated from the liver samples of 120-day-old laying flock with HHS and its phylogenetic information, genetic mutations, and pathogenicity was evaluated. The phylogenetic analysis revealed that AH-F19 belonged to the FAdV serotype 4 (FAdV-4) cluster, however, 100K differs from the other FAdV-4 strains and is divided into different branches. Amino acid variations in fiber-2 for pathogenic isolates and non-pathogenic isolates indicated that D219, T300, and T380 may not be responsible for virulence. Animal experiments revealed AH-F19 to be a highly pathogenic isolate that can cause 100% mortality in three-week-old specific pathogen-free (SPF) chickens, which exhibited typical hydropericardium and hepatitis. Microscopically, the presence of basophilic intranuclear inclusion bodies in hepatocytes, fractured heart muscle fibers, as well as kidney degeneration and necrosis was observed. Collectively, these findings enriched our understanding of FAdV-4 pathogenicity and provided a reference for further exploration into its pathogenicity.The protein kinase TNK2 (ACK1) is an emerging drug target for a variety of indications, in particular for cancer where it plays a key role transmitting cell survival, growth and proliferative signals via modification of multiple downstream effectors by unique tyrosine phosphorylation events. Scaffold morphing based on our previous TNK2 inhibitor XMD8-87 identified urea 17 from which we developed the potent and selective compound 32. A co-crystal structure was obtained showing 32 interacting primarily with the main chain atoms of an alanine residue of the hinge region. Additional H-bonds exist between the urea NHs and the Thr205 and Asp270 residues.
Aberrant fetal programming in gestational diabetes mellitus seems to increase the risk of obesity, type 2 diabetes, and cardiovascular disease. The inability to accurately identify gestational diabetes mellitus in the first trimester of pregnancy has thwarted ascertaining whether early therapeutic interventions reduce the predisposition to these prevalent medical disorders.

A metabolomics study was conducted to determine whether advanced analytical methods could identify accurate predictors of gestational diabetes mellitus in early pregnancy.

This nested observational case-control study was composed of 92 gravidas (46 in the gestational diabetes mellitus group and 46 in the control group) in early pregnancy, who were matched by maternal age, body mass index, and gestational age at urine collection. Gestational diabetes mellitus was diagnosed according to community standards. A comprehensive metabolomics platform measured 626 endogenous metabolites in randomly collected urine. Consensus multivariate crittermine whether therapeutic interventions in the first trimester of pregnancy for gestational diabetes mellitus reduce short- and long-term morbidity.
This study aimed to conduct a systematic review of the current literature to determine estimates of vertical transmission of coronavirus disease 2019 based on early RNA detection of severe acute respiratory syndrome coronavirus 2 after birth from various neonatal or fetal sources and neonatal serology.

Eligible studies published until May 28, 2020, were retrieved from PubMed, EMBASE, medRxiv, and bioRxiv collection databases.

This systematic review included cohort studies, case series, and case reports of pregnant women who received a coronavirus disease 2019 diagnosis using severe acute respiratory syndrome coronavirus 2 viral RNA test and had reported data regarding the testing of neonates or fetuses for severe acute respiratory syndrome coronavirus 2 immediately after birth and within 48 hours of birth. A total of 30 eligible case reports describing 43 tested neonates and 38 cohort or case series studies describing 936 tested neonates were included.

The methodological quality of all included studier data, no assessment can yet be made regarding the rates of vertical transmission in early pregnancy and potential risk for consequent fetal morbidity and mortality.
Coronavirus Disease 2019 (COVID-19) has rapidly become a global pandemic, with over 1.8 million confirmed cases worldwide to date. Preliminary reports suggest that the disease may present in diverse ways, including with neurological symptoms, but few published reports in the literature describe seizures in patients with COVID-19.

The objective of the study was to characterize the risk factors, clinical features, and outcomes of seizures in patients with COVID-19.

This is a retrospective case series. Cases were identified through a review of admissions and consultations to the neurology and neurocritical care services between April 1, 2020 and May 15, 2020.

The study setting was in a tertiary care, safety-net hospital in Boston, MA.

Patients presenting with seizures and COVID-19 during the study period were included in the study.

Seven patients met inclusion criteria (5 females, 71%). Patients ranged in age from 37 to 88 years (median 75 years). FR 180204 mouse Three patients had a prior history of well-controlledicians should be vigilant for the infection in patients who present with seizures, which may precede respiratory symptoms or prompt presentation to medical care. Early testing, isolation, and contact tracking of these patients can prevent further transmission of the virus.
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