Association between obesity and sperm quality

There is awareness of likelihood of abnormal spermatozoa in obese men; however, results from previous studies are inconclusive. Advances in computer‐aided sperm analysis (CASA) enable precise evaluation of sperm quality and include assessment of several parameters. We studied a retrospective cohort of 1285 men with CASA data from our infertility clinic during 2016. Obesity (BMI ≥30) was associated with lower (mean ± SE) volume (?0.28 ± 0.12, p‐value = .04), sperm count (48.36 ± 16.51, p‐value = .002), concentration (?15.83 ± 5.40, p‐value = .01), progressive motility (?4.45 ± 1.92, p‐value = .001), total motility (?5.50 ± 2.12, p‐value = .002), average curve velocity (μm/s) (?2.09 ± 0.85, p‐value = .001), average path velocity (μm/s) (?1.59 ± 0.75, p‐value = .006), and higher per cent head defects (0.92 ± 0.81, p‐value = .02), thin heads (1.12 ± 0.39, p‐value = .007) and pyriform heads (1.36 ± 0.65, p‐value = .02). Obese men were also more likely to have (odds ratio, 95% CI) oligospermia (1.67, 1.15–2.41, p‐value = .007) and asthenospermia (1.82, 1.20–2.77, p‐value = .005). This is the first report of abnormal sperm parameters in obese men based on CASA. Clinicians may need to factor in paternal obesity prior to assisted reproduction.     

In vitro biotransformation, in vivo efficacy and pharmacokinetics of antimalarial chalcones

4'-n-Butoxy-2,4-dimethoxy-chalcone (MBC) has been described as protecting mice from an otherwise lethal infection with Plasmodium yoelii when dosed orally at 50 mg/kg/dose, daily for 5 days. In contrast, we found that oral dosing of MBC at 640 mg/kg/dose, daily for 5 days, failed to extend the survivability of P. berghei-infected mice. The timing of compound administration and metabolic activation likely contribute to the outcome of efficacy testing in vivo. Microsomal digest of MBC yielded 4'-n-butoxy-4-hydroxy-2-methoxy-chalcone and 4'-(1-hydroxy-n-butoxy)-2,4-dimethoxy-chalcone. We propose that the latter will hydrolyze in vivo to 4'-hydroxy-2,4-dimethoxy-chalcone, which has greater efficacy than MBC in our P. berghei-infected mouse model and was detected in plasma following oral dosing of mice with MBC. Pharmacokinetic parameters suggest that poor absorption, distribution, metabolism and excretion properties contribute to the limited in vivo efficacy observed for MBC and its analogs.     

Risk factors for Barrett's esophagus

Barrett's esophagus (BE) is a well‐recognized precursor of esophageal adenocarcinoma (EAC) and is defined as ≥1 cm segment of salmon‐colored mucosa extending above the gastroesophageal junction into the tubular esophagus with biopsy confirmation of metaplastic replacement of the normal squamous epithelium by intestinal‐type columnar epithelium. The incidence of both BE and EAC has been increasing over the past few decades. As a result, preventing the development of BE by identifying and understanding its modifiable and non‐modifiable risk factors may help reduce the incidence of EAC. Over the recent past, a tremendous amount of progress has been made towards improving our knowledge of risk factors and pathogenesis of BE. This article reviews the evidence for the various risk factors for developing BE.     

Resection of early esophageal neoplasms: The pendulum swings from surgical to endoscopic management

Esophageal cancer is a highly lethal disease and is the sixth leading cause of cancer related mortality in the world. The standard treatment is esophagectomy which is associated with significant morbidity and mortality. This led to development of minimally invasive, organ sparing endoscopic therapies which have comparable outcomes to esophagectomy in early cancer. These include endoscopic mucosal resection and endoscopic submucosal dissection. In early squamous cell cancer, endoscopic submucosal dissection is preferred as it is associated with cause specific 5-year survival rates of 100% for M1 and M2 tumors and 85% for M3 and SM1 tumors and low recurrence rates. In early adenocarcinoma, endoscopic resection of visible abnormalities is followed by ablation of the remaining flat Barrett's mucosa to prevent recurrences.Radiofrequency ablation is the most widely used ablation modality with others being cryotherapy and argon plasma coagulation. Focal endoscopic mucosal resection followed by radiofrequency ablation leads to eradication of neoplasia in93.4% of patients and eradication of intestinal metaplasia in 73.1% of patients.Innovative techniques such as submucosal tunneling with endoscopic resection are developed for management of submucosal tumors of the esophagus. This review includes a discussion of various endoscopic techniques and their clinical outcomes in early squamous cell cancer, adenocarcinoma and submucosal tumors. An overview of comparison between esophagectomy and endoscopic therapy are also presented.     

A single-nucleotide polymorphism in the fetal catechol-O-methyltransferase gene is associated with spontaneous preterm birth in African Americans

Catechol-O-methyltransferase (COMT) activity has been reported to be higher in African Americans (AA) than Caucasians (Cau). COMT converts 2- and 4-hydroxy (OH) estrogens to 2- and 4-methoxyestrogens, respectively, and can increase estrogenic milieu locally in tissues. To assess whether the increased incidence of preterm birth (PTB) among AA women is associated with single-nucleotide polymorphism (SNP) in the COMT gene, we examined variations in maternal and fetal COMT genes and their association with pregnancy outcomes (term vs preterm pregnancies) using 4 functional SNPs: rs4633, rs4680, rs4818, and rs6269 in both AA and Cau. We analyzed samples from 267 AA women (191 term and 76 preterm pregnancies) and 339 Cau (194 term and 145 preterm pregnancies) in this study. The results showed a significant difference (P < .05) in allele and genotype frequencies between term and preterm AA and Cau women in 3 SNPs in both maternal and fetal DNA. The analysis revealed that in AA fetal COMT genes, SNP rs4818 is associated with PTB at the allele (C; P < .001), genotype (C/C; P < .01), and 2- (P < .03) and 3 (P < .04)-window haplotype levels. Multidimensionality reduction analysis also showed a significant (P < .01) association between rs4818 and PTB. In conclusion, our study demonstrated that a synonymous polymorphism, rs4818 in the fetal COMT gene, is associated with PTB in AA.     

Bioinformatics analysis of diabetic retinopathy using functional protein sequences

Diabetic retinopathy is the leading cause of blindness among patients with diabetes mellitus. We evaluated the role of several proteins that are likely to be involved in diabetic retinopathy by employing multiple sequence alignment using ClustalW tool and constructed a phylogram tree using functional protein sequences extracted from NCBI. Phylogram was constructed using Neighbor-Joining Algorithm in bioinformatics approach. It was observed that aldose reductase and nitric oxide synthase are closely associated with diabetic retinopathy. It is likely that vascular endothelial growth factor, pro-inflammatory cytokines, advanced glycation end products, and adhesion molecules that also play a role in diabetic retinopathy may do so by modulating the activities of aldose reductase and nitric oxide synthase. These results imply that methods designed to normalize aldose reductase and nitric oxide synthase activities could be of significant benefit in the prevention and treatment of diabetic retinopathy.     

Ipsi- and contralateral changes in rabbit soleus myosins by cross-reinnervation

Cross-reinnervation of soleus muscle in the adult rabbit induces changes in myosin light chain and isomyosin patterns. The transformation of the light chain pattern consists of a decrease in LC1_s and LC2_s and an induction of the three fast type myosin light chains. The transition in the isomyosin pattern consists of a decrease of the slow type isomyosin SM and an induction of fast type isomyosins FM₁, FM₂ and FM₃ normally seen in fast-twitch rabbit muscle. An additional isomyosin of intermediate electrophoretic mobility, which resembles isomyosin 4 of rat muscle, is induced. These changes are not restricted to the cross-reinnervated soleus muscle but are also seen, although to a lesser extent, in the contralateral soleus muscle. It is suggested that the altered afferent activity brought about by cross-reinnervation, is neurally transmitted to the opposite side and leads to a change in efferent activity to the contralateral muscle.     

Superficial Siderosis of the CNS and Otoneurological Manifestations

Superficial siderosis is an uncommon condition occurring in central nervous system (CNS) due to deposition of hemosiderin in the subpial meningeal layer causing progressive neurological dysfunction. The classical clinical manifestation is a triad of chronic ataxia, bipyramidal signs and progressive bilateral symmetrical sensorineural hearing loss (SNHL). It has rarely been reported in Indian literature. We report an unusual case of superficial siderosis in a 60-year-old farmer who presented with the above triad along with involvement of olfactory nerve. We present this case to highlight the fact that progressive SNHL can be an important sign for the early awareness of this rare disorder. The literature on superficial siderosis is reviewed and the pathogenesis is discussed.