Substance-use and sexual harm reduction strategies of methamphetamine-using men who have sex with men and inject drugs

Research indicates that men who have sex with men (MSM), use methamphetamine, and inject drugs are at high risk of HIV infection and they employ multiple harm reduction strategies simultaneously to reduce that risk. In this study, we identified substances most commonly injected and harm reduction strategies most often employed by methamphetamine-using MSM, used latent class analysis (LCA) to identify patterns of harm reduction strategies, and differentiated MSM within each class by individual characteristics. We analyzed data from 284 participants who completed an online cross-sectional survey. Commonly injected substances were methamphetamine (93.70%), gamma-hydroxybutyrate/gamma-butyrolactone (41.55%), flunitrazepam (40.49%), and cocaine (35.56%). The substance-use strategies most often used were avoidance of sharing needles (85.92%) and use of bleach to clean drug paraphernalia (64.08%). The sexual strategy most often used was avoidance of condomless anal intercourse (CAS) while using drugs (77.11%). Using an LCA approach, we identified three classes distinguishable by age, race/ethnicity, and outness. One class (19%) employed lay strategies to reduce harm: they avoided sharing drug preparation equipment, serosorted when sharing needles and equipment or having CAS, and practiced withdrawal when having CAS. The largest class (53%) combined sexual and substance-use strategies: they avoided sharing needles, used bleach to clean needles and equipment, avoided CAS when using drugs, and used extra lubricant when having CAS. The remaining class (28%) employed only substance-use rather than sexual strategies. More MSM of color were in the substance-use class, and more young, non-Hispanic White men were in the lay class. The low utilization of sexual strategies by younger, non-Hispanic White men in the lay class is concerning as they are just as likely as older, non-Hispanic White men in the combined class to have CAS with multiple male partners. Interventionists should consider these differences when developing interventions tailored to methamphetamine-using MSM.     

HLA-genotyping of clinical specimens using Ion Torrent-based NGS

We have evaluated and validated the NXType™ workflow (One Lambda, Inc.) and the accompanying TypeStream™ software on the Ion Torrent Next Generation Sequencing (NGS) platform using a comprehensive testing panel. The panel consisted of 285 genomic DNA (gDNA) samples derived from four major ethnic populations and contained 59 PT samples and 226 clinical specimens. The total number of alleles from the six loci interrogated by NGS was 3420. This validation panel provided a wide range of HLA sequence variations including many rare alleles, new variants and homozygous alleles. The NXType™ system (reagents and software) was able to correctly genotype the vast majority of these specimens. The concordance rate between SBT-derived genotypes and those generated by TypeStream™ auto-analysis ranged from 99.5% to 99.8% for the HLA-A, B, C, DRB1 and DQB1 loci, and was 98.9% for HLA-DPB1. A strategy for data review was developed that would allow correction of most of the few remaining typing errors. The entire NGS workflow from gDNA amplification to genotype assignment could be completed within 3 working days. Through this validation study, the limitations and shortcomings of the platform, specific assay system, and software algorithm were also revealed for further evaluation and improvement.     

基于MDT的对分课堂联合CBL教学模式在软组织肿瘤临床教学中的应用

目的:探讨基于MDT的对分课堂联合CBL教学模式在软组织肿瘤临床教学中的应用效果及学员对该教学模式的评价。方法:选取2017年1月至2019年10月在我科接受住院医师规范化培训的50名学员为研究对象。随机分为对照组和实验组，每组25人。对照组授课方式为传统教学法，实验组授课采用MDT联合对分课堂和CBL教学法。教学结束后，采用命题考试进行教学效果考核；采用问卷调查的方法评估学生对教学模式的满意度。结果:实验组的选择题、简答论述、病例分析和总成绩分别为26.36±2.75、18.24±2.40、30.76±3.09、75.36±5.96，而对照组分别为24.40±3.80、16.60±2.10、29.04±2.86、70.04±6.30，两组比较有统计学差异（P<0.05）。在提高课堂学习效率、学习兴趣、自学能力、理论知识的理解和记忆能力，扩充专业知识，提高文献检索能力、分析问题和解决问题的能力、临床思维能力，这8个维度的赞成度调查中，实验组均优于对照组（P<0.05）。实验组学员对本组教学模式的接受度更高（P<0.05），但也有更多的实验组学员认为本组教学模式增加了学习负担（P<0.05）。结论:MDT联合对分课堂和CBL的教学模式应用于软组织肿瘤临床教学中，有利于提高教学效果，且接受度更高。     

Wnt/β⁃catenin信号通路参与马蹄内翻足畸形形成的研究

目的　探讨Sox9（sex determining region Y-box9）和β-catenin对先天性马蹄内翻足（congenital talipes equinovarus，CTE）的影响以及Wnt/β-catenin信号通路作用机制。 方法　将孕10 d的SD大鼠随机均分为实验组及对照组，以135 mg/kg全反式维甲酸溶于矿物油对实验组大鼠进行灌胃制作胎鼠CTE模型，对照组予以等量矿物油灌胃处理，取大鼠足踝部组织，通过免疫组化、RT-PCR、Western blot检测β-catenin、Sox9以及磷酸化β-catenin-S552的表达水平。 结果　与对照组相比，HE染色可见CTE模型组织中有较多的胶原组织沉积，免疫组化结果显示实验组标本Sox9与β-catenin表达增高，RT-qPCR表明实验组Sox9与β-catenin的mRNA水平显著增高，Western blot结果显示实验组Sox9与β-catenin的表达增高而磷酸化β-catenin-S552表达降低。 结论　CTE大鼠的足踝部组织中Sox9高表达受Wnt/β-catenin信号通路调控，该通路参与先天性马蹄内翻足畸形的形成。     

Infections caused by extended-spectrum β-lactamase-producing Enterobacterales after rectal colonization with ESBL-producing Escherichia coli or Klebsiella pneumoniae

ObjectivesInfections as a result of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) are considered infections with a high public health burden. In this study, we aimed to identify incidences of and risk factors for healthcare-associated infections (HAIs) after rectal colonization with ESBL-producing Escherichia coli (ESBL-EC) or Klebsiella pneumoniae (ESBL-KP).MethodsThis prospective cohort study was performed in 2014 and 2015. Patients colonized with ESBL-EC or ESBL-KP were monitored for subsequent HAI with ESBL-E and other pathogens. In the case of an ESBL-E infection, rectal and clinical isolates were compared using pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS) for ESBL-KP isolates. Proportional hazard models were applied to identify risk factors for HAIs, and to analyse competing risks.ResultsAmong all patients admitted to the hospital during the study period, 13.6% were rectally screened for third-generation cephalosporin-resistant Enterobacterales (3GCREB). A total of 2386 rectal carriers of ESBL-EC and 585 of ESBL-KP were included in the study. Incidence density (ID) for HAI with ESBL-E was 2.74 per 1000 patient days at risk (95% confidence interval (CI) 2.16–3.43) among carriers of ESBL-EC, while it was 4.44 per 1000 patient days at risk (95% CI 3.17–6.04) among carriers of ESBL-KP. In contrast, ID for HAI with other pathogens was 4.36 per 1000 patient days at risk (95% CI 3.62–5.21) among carriers of ESBL-EC, and 5.00 per 1000 patient days at risk (95% CI 3.64–6.69) among carriers of ESBL-KP. Cox proportional hazard regression analyses identified colonization with ESBL-KP (HR = 1.58, 95% CI 1.068–2.325) compared with ESBL-EC as independent risk factor for HAI with ESBL-E. The results were consistent over all competing risk analyses.ConclusionsClinicians should be aware of the increased risk of ESBL-E infections among patients colonized with ESBL-KP compared with ESBL-EC that might be caused by underlying diseases, higher pathogenicity of ESBL-KP and other factors.     

Plasma matrix metalloproteinase 7, CC-chemokine ligand 18, and periostin as markers for pulmonary sarcoidosis

BackgroundSome patients with sarcoidosis experience worsening of pulmonary lesions. However, no biomarker has been identified that reflects pulmonary disease status in sarcoidosis. We investigated the usefulness of potential markers of pulmonary fibrosis in patients with sarcoidosis.MethodsPlasma matrix metalloproteinase 7 (MMP-7), CC-chemokine ligand 18 (CCL-18), and periostin levels were evaluated in 60 patients with sarcoidosis and 30 healthy controls; bronchoalveolar lavage fluid levels were analyzed in 22 patients with sarcoidosis. To determine the usefulness of these markers, we explored potential correlations between these markers and sarcoidosis clinical characteristics.ResultsPlasma MMP-7, CCL-18, and periostin concentrations were significantly higher in patients with sarcoidosis than those in healthy controls. MMP-7 concentrations in plasma and bronchoalveolar lavage fluid were higher in patients with sarcoidosis with parenchymal infiltration than in those without lung lesions. Moreover, MMP-7 concentration was negatively correlated with pulmonary function.ConclusionAmong these novel biomarkers, MMP-7 most precisely reflected pulmonary sarcoidosis disease status and thus, might be useful for diagnosing and evaluating sarcoidosis, particularly in patients with pulmonary parenchymal lesions.     

Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy

Variants in RORB have been reported in eight individuals with epilepsy, with phenotypes ranging from eyelid myoclonia with absence epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and epilepsy syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of epilepsy syndromes.     

Profilin 1 knockdown prevents ischemic brain damage by promoting M2 microglial polarization associated with the RhoA/ROCK pathway

Microglial polarization to the anti-inflammatory M2 phenotype is essential in resolving neuroinflammation, making it a promising therapeutic strategy for stroke intervention. The actin cytoskeleton is known to be important for the physiological functions of microglia, including migration and phagocytosis. Profilin 1 (PFN1), an actin-binding protein, is involved in the dynamic transformation and reorganization of actin. However, the role of PFN1 in microglial polarization and ischemia/reperfusion injury is unclear. The role of PFN1 on microglial polarization was examined in vitro in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGDR) and in vivo in male mice after transient middle cerebral artery occlusion (MCAO). Knockdown of PFN1 inhibited M1 microglial polarization and promoted M2 microglia polarization 48 hr after OGDR stimulation in BV2 cells and 7 days after MCAO-induced injury in male mice. RhoA/ROCK pathway was involved in the regulation of PFN1 during microglial polarization. Knockdown of PFN1 also significantly attenuated brain infarcts and edema, improved cerebral blood flow and neurological deficits in MCAO-injured mice. Inhibition of PFN1 effectively protected the brain against ischemia/reperfusion injuries by promoting M2 microglial polarization in vitro and in vivo.