Lower body mass index and higher height are correlated with increased varicocele risk

To evaluate the anthropometric indexes in subjects with varicocele compared to controls and the incidence of varicocele in different body mass index (BMI) groups for the purpose of exploring the association between varicocele and anthropometric indexes. A comprehensive literature search was conducted by using PubMed, MEDLINE, EMBASE databases and Cochrane Library up to February 2019. A systematic review and meta‐analysis was conducted by STATA, and Newcastle–Ottawa Scale was utilised for assessing risk of bias. Ultimately, 13 articles containing seven case–control studies and six cross‐sectional studies with 1,385,630 subjects were involved in our study. Pooled results demonstrated that varicocele patients had a lower BMI (WMD = ?0.77, 95% CI = ?1.03 to ?0.51) and a higher height than nonvaricocele participants, especially in grade 3 varicocele patients. Subgroup analyses showed that normal BMI individuals had a higher risk of varicocele than obese or overweight individuals and a lower risk than underweight individuals. In conclusion, this study indicates that varicocele patients have a lower BMI and a higher height than nonvaricocele participants. Moreover, men with excess bodyweight have a lower incidence of varicocele compared to normal weight or underweight people. That is to say, high BMI and adiposity protect against varicocele and high BMI is associated with a decreased risk of varicocele.     

Association of meibomian gland architecture and body mass index in a pediatric population

PurposeTo determine if meibomian gland architecture in a pediatric population is impacted by body mass index (BMI).MethodsProspective evaluation of 175 eyes of 175 pediatric patients from two clinics. Demographic and clinical information were reviewed. Symptoms of dry eye were assessed with the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Meibography was performed and grading of images was performed by a masked rater using a previously validated 5-point meiboscale (0–4) for gland atrophy and a 3-point score (0–2) for gland tortuosity.Results175 eyes of 175 participants aged 4–17 years (11.6 ± 3.7 years) were imaged. The mean meiboscore was 0.82 ± 0.94 (range 0–4) and the mean gland tortuosity score was 0.53 ± 0.70 (range 0–2). Ninety-six patients (56%) showed evidence of gland atrophy (meiboscore greater than 0) and the majority of patients (n=50, 29%) had a gland tortuosity score of 1. The mean BMI was 20.5 ± 4.86 kg/m² with 39.4% of patients (n = 69) above the 85th percentile. BMI percentile was not found to be a significant predictor of a meiboscore greater than 0 (odds ratio (OR) 1.004 95% confidence interval (CI) (0.99–1.10, p = 0.41). However, BMI percentile was found to be a significant predictor of gland tortuosity score (OR 1.01 95% CI (1.00–1.02), p = 0.02). Patients with BMI percentiles between 41 and 60 were 3.79 times more likely to have a gland tortuosity score of greater than 0 than patients with BMI percentiles between 0 and 20 (OR 3.789 CI (1.17–12.24)). No significant associations were found between age, race, or sex and meiboscore or tortuosity. There was a trend towards reduction in lipid layer thickness with increasing BMI percentile (p = 0.028, r² = 0.04).ConclusionIn this pediatric population, there was an association between meibomian gland tortuosity and higher percentiles of BMI. Future studies are needed to elucidate the pathogenesis of meibomian gland tortuosity and atrophy in pediatric patients.     

Sudden Cardiac Death in Patients With Type 1 Versus Type 2 Diabetes

ObjectiveTo investigate the association between type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) with risk of sudden cardiac arrest (SCA).MethodsIn a prospective community-based study of SCA from February 1, 2002, through November 30, 2019, we ascertained 2771 cases age 18 years of age or older and matched them to 8313 controls based on geography, age, sex, and race/ethnicity. We used logistic regression to evaluate the independent association between diabetes, T1D, T2D, and SCA.ResultsPatients had a mean age of 64.5±15.9 years, were 33.3% female and 23.9% non-White race. Overall, 36.7% (n=1016) of cases and 23.8% (n=1981) of controls had diabetes. Among individuals with diabetes, the proportion of T1D was 6.5% (n=66) among cases and 2.0% among controls (n=40). Diabetes was associated with 1.5-times higher odds of SCA. Compared with those without diabetes, the odds ratio and 95% CI for SCA was 4.36 (95% CI, 2.81 to 6.75; P<.001) in T1D and 1.45 (95% CI, 1.30 to 1.63; P<.001) in T2D after multivariable adjustment. Among those with diabetes, the odds of having SCA were 2.41 times higher in T1D than in T2D (95% CI, 1.53 to 3.80; P<.001). Cases of SCA with T1D were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with T2D.ConclusionType 1 diabetes was more strongly associated with SCA compared with T2D and had less favorable outcomes following resuscitation. Diabetes type could influence the approach to risk stratification and prevention of SCA.     

Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

表观遗传调控与青光眼发病机制研究进展

表观遗传学主要机制包括DNA甲基化、组蛋白修饰和miRNAs等。这些机制将环境与基因相联系，在基因的特异性表达过程中发挥重要作用，影响疾病的表型。青光眼是全球第一大不可逆致盲眼病，其发病机制复杂，受遗传和环境的共同影响。本文分别对DNA甲基化、组蛋白修饰和miRNAs参与青光眼发病的机制进行综述，以期为临床诊治提供参考。     

Correcting forensic DNA errors

DNA mixture interpretation can produce opposing conclusions by qualified forensic analysts, even within the same laboratory. The long-delayed publication of the National Institutes of Standards and Technology (NIST) study of 109 North American crime laboratories in this journal demonstrates this most clearly. This latest study supports earlier work that shows common methods such as the Combined Probability of Inclusion (CPI) have wrongly included innocent people as contributors to DNA mixtures. The 2016 President's Council of Advisors on Science and Technology report concluded, “In summary, the interpretation of complex DNA mixtures with the CPI statistic has been an inadequately specified—and thus inappropriately subjective—method. As such, the method is clearly not foundationally valid” [7]. The adoption of probabilistic genotyping by many laboratories will certainly prevent some of these errors from occurring in the future, but the same laboratories that produced past errors can also now review old cases with their new software—without additional bench work. It is critical that laboratories adopt procedures and policies to do this.     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

Developmental validation of the ANDE™ rapid DNA system with FlexPlex™ assay for arrestee and reference buccal swab processing and database searching

A developmental validation was performed to demonstrate reliability, reproducibility and robustness of the ANDE System with the FlexPlex assay, including an integrated Expert System, across a number of laboratories and buccal sample variations. Previously, the related DNAscan™/ANDE 4C Rapid DNA System using the PowerPlex^®16 assay and integrated Expert System Software received NDIS approval in March 2016. The enhanced ANDE instrument, referred to as ANDE 6C, and the accompanying 6-dye, 27-locus STR assay, referred to as FlexPlex, have been developed to be compatible with all widely used global loci, including the expanded set of the CODIS core 20 loci.Six forensic and research laboratories participated in the FlexPlex Rapid DNA developmental validation experiments, testing a total of 2045 swabs, including those obtained from 1387 unique individuals. The goal of this extensive and comprehensive validation was to thoroughly evaluate and document the ANDE System and its internal Expert System to reliably genotype reference buccal swab samples in a manner compliant with the FBI’s Quality Assurance Standards and the NDIS Operational Procedures.The ANDE System, including automated Expert System analysis, generated reproducible and concordant results for buccal swabs when testing various instruments at different laboratories by a number of different operators. When testing a number of non-human DNAs, including oral bacteria, the ANDE System and FlexPlex assay demonstrated limited cross-reactivity. Potential PCR inhibitors were evaluated as part of the validation and no inhibition was detected. Reproducible and concordant profiles were generated from buccal swab samples collected with a limit of detection appropriate for buccal swab collections from arrestees. The precision and resolution of the System met industry standards for detection of microvariants and single base resolution.The integrated Expert System appropriately demonstrated the ability to correctly pass or fail profiles for CODIS upload without human review. During this comprehensive developmental validation, the ANDE System successfully interpreted over 2000 samples tested with over 99.99% concordant alleles. The data package described herein led to the ANDE System with the FlexPlex assay receiving NDIS approval in June 2018.     

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.