Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke

Background

The role of platelets and important effect modifiers on the risk of first stroke is unknown.

Clinicopathological Features and Prognostic Factors of Young Patients With Surgically Treated Liver Cancer

This article compares the clinical characteristics and prognosis of young patients in different age groups with liver cancer (LC).In this retrospective study, we searched the Surveillance, Epidemiology, and End Results population-based database and identified 2641 patients who had been diagnosed with LC between 1988 and 2005. These patients were categorized into 2 different age ranges: Group 1 (≤35 years) and Group 2 (36–45 years). Five-year cancer-specific survival (CSS) data were obtained. Kaplan–Meier methods and multivariable Cox regression models were used to analyze the long-term survival outcomes and risk factors.There were significant differences between the age groups for stage and tumor size (P < 0.001). The 5-year liver CSS rate was 20.4% and 14.5%, respectively (P < 0.001). Univariate and multivariate analysis also confirmed the difference (P < 0.001). Further analysis showed that this significant difference existed in localized, regional, and distant-stage patients.Young patients with LC of age 18 to 45 years are inherently heterogeneous. Patients aged ≤35 years have better CSS than those aged 36 to 45 years, despite exhibiting unfavorable clinicopathological characteristics.     

Novel bi-allelic variants in DNAH2 cause severe asthenoteratozoospermia with multiple morphological abnormalities of the flagella

Research questionMultiple morphological abnormalities of the flagella (MMAF) is characterized by excessive immotile spermatozoa with severe flagellar abnormalities in the ejaculate. Previous studies have reported a heterogeneous genetic profile associated with MMAF. What other genetic variants might explain the cause of MMAF?DesignWhole-exome sequencing was conducted in a cohort of 90 Chinese patients with MMAF. The pathogenicity of identified mutations was assessed through electron microscopy and immunofluorescent examinations.ResultsThree unrelated men with bi-allelic DNAH2 variants were identified. Sanger sequencing verified that the six novel variants originated from every parent. All these variants were located at the conserved domains of DNAH2 and predicted to be deleterious by bioinformatic tools. Haematoxylin and eosin staining and scanning electron microscopy revealed that spermatozoa harbouring DNAH2 variants displayed severely aberrant morphology mainly with absent and short flagella (≥78%). Moreover, transmission electron microscopy revealed the obvious absence of a central pair of microtubules and inner dynein arms in the spermatozoa with mutated DNAH2. Immunofluorescence data further validated these findings, showing reduced DNAH2 protein expression in the spermatozoa with DNAH2 variants, compared with normal spermatozoa. Intracytoplasmic sperm injection using spermatozoa from the three men with mutated DNAH2 resulted in blastocyst formation in all cases. Embryo transfer was carried out in two couples, both resulting in clinical pregnancy.ConclusionsThese experimental and clinical data suggest that bi-allelic DNAH2 variants might induce MMAF-associated asthenoteratozoospermia, which can be overcome through intracytoplasmic sperm injection. These findings contribute to the knowledge of the genetic landscape of asthenoteratozoospermia and clinical counselling of male infertility.     

Endogenous Deficiency of Brain-Derived Neurotrophic Factor Induces the Downregulation of Tryptophan Hydroxylase-2 Expression in Raphe Nuclei of Rapid Ejaculator Rats

BackgroundPremature ejaculation (PE) is one of the most common ejaculatory disorders. Recent studies have suggested a close relationship between the serotonin (5-hydroxytryptamine [5-HT]) system and brain-derived neurotrophic factor (BDNF), raising the question of whether BDNF plays a role in ejaculation regulation. To our knowledge, no previous studies have explored BDNF level of the central nervous system in ejaculatory disorders. At the same time, the interaction of central BDNF and 5-HT systems has not been undertaken in ejaculation regulation field.AimThe aim of this study was to investigate the interaction between BDNF and 5-HT levels in raphe nuclei which contains the serotonergic neurons in a rat animal model with different ejaculatory behavior.MethodsEighteen male rats were selected and classified as “sluggish,” “normal,” and “rapid” ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. BDNF and 5-HT levels were determined by enzyme-linked immunosorbent assay (ELISA). Real-Time Quantitative PCR and Western blot analyses were used to measure the mRNA level of Tryptophan Hydroxylase-2 (TPH2) gene and the expression of TPH2 protein (the rate-limiting enzyme in central 5-HT synthesis) in raphe nuclei, respectively.OutcomesMale rat sexual behavior, the levels of BDNF and 5-HT in raphe nuclei of rats with different ejaculatory behavior, the mRNA level of gene encoding TPH2 and the expression of TPH2 protein in raphe nuclei.ResultsThe primary finding of our study was that BDNF concentration was significantly decreased in raphe nuclei of rapid ejaculators. There was a strong positive correlation between the levels of BDNF and 5-HT (r = 0.944, P < .001). Further results showed that decreased TPH2 gene expression accompanied by TPH2 protein was shown in rapid ejaculators with lower BDNF level.Clinical ImplicationsWith refinement of current knowledge, BDNF may eventually serve as a promising biomarker in patients with PE.Strengths & LimitationsThere are no previous studies examining the interaction of the brain BDNF and 5-HT in ejaculation regulation field. The main limitation is the limited sample size.ConclusionBDNF may act via increasing the synthesis of central 5-HT in the process of ejaculation regulation. Our results suggest lack of endogenous BDNF induces the downregulation of TPH2 gene expression and the decrease of 5-HT synthesis in raphe nuclei of rapid ejaculator rats. Huang Y, Peng D, Geng H, et al. Endogenous Deficiency of Brain-Derived Neurotrophic Factor Induces the Downregulation of Tryptophan Hydroxylase-2 Expression in Raphe Nuclei of Rapid Ejaculator Rats. J Sex Med 2021;18:1491–1499.     

The integrity of cfDNA in follicular fluid and spent medium from embryo culture is associated with embryo grade in patients undergoing in vitro fertilization

Journal of Assisted Reproduction and Genetics - This study was conducted to verify if the cfDNA integrity (cfDI) in follicular fluid and subsequent spent embryo medium (SEM) could serve as...     

Exophiala dermatitidis pneumonia successfully treated with long-term itraconazole therapy

Exophiala dermatitidis pneumonia is extremely rare. Here we report a case of E. dermatitidis pneumonia successfully treated with long-term itraconazole therapy. A 63-year-old woman without a remarkable medical history developed a dry and chest pain. Chest radiographs revealed consolidation in the middle lobe of the lung. Cytologic examination by bronchoscopy showed filamentous fungi and E. dermatitidis was detected in the bronchoalveolar lavage fluid. After 5 months of itraconazole therapy, her symptoms improved and the area of consolidation diminished. Two weeks after discontinuing the itraconazole therapy, the area of consolidation reappeared. Itraconazole therapy was restarted and continued for 7 months. The abnormal shadow observed on the chest X-ray gradually diminished. Over a 27-month follow-up with periodic examination, there was no relapse and the patient had a favorable clinical course.