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Hormonal changes around ovulation divide the menstrual cycle (MC) into the follicular and luteal phases. In addition, oral contraceptives (OCs) have active (higher hormone) and placebo phases. Although there are some MC-based effects on various physiological outcomes, we found these differences relatively subtle and difficult to attribute to specific hormones, as estrogen and progesterone fluctuate rather than operating in a complete on/off pattern as observed in cellular or preclinical models often used to substantiate human data. A broad review reveals that the differences between the follicular and luteal phases and between OC active and placebo phases are not associated with marked differences in exercise performance and appear unlikely to influence muscular hypertrophy in response to resistance exercise training. A systematic review and meta-analysis of substrate oxidation between MC phases revealed no difference between phases in the relative carbohydrate and fat oxidation at rest and during acute aerobic exercise. Vascular differences between MC phases are also relatively small or nonexistent. Although OCs can vary in composition and androgenicity, we acknowledge that much more work remains to be done in this area; however, based on what little evidence is currently available, we do not find compelling support for the notion that OC use significantly influences exercise performance, substrate oxidation, or hypertrophy. It is important to note that the study of females requires better methodological control in many areas. Previous studies lacking such rigor have contributed to premature or incorrect conclusions regarding the effects of the MC and systemic hormones on outcomes. While we acknowledge that the evidence in certain research areas is limited, the consensus view is that the impact of the MC and OC use on various aspects of physiology is small or nonexistent. [ABSTRACT FROM AUTHOR]

The age‐related loss of skeletal muscle mass and functionality, known as sarcopenia, is a critical risk factor for morbidity and all‐cause mortality. Resistance exercise training (RET) is the primary countermeasure to fight sarcopenia and ageing. Altered intercellular communication is a hallmark of ageing, which is not well elucidated. Circulating extracellular vesicles (EVs), including exosomes, contribute to intercellular communication by delivering microRNAs (miRNAs), which modulate post‐translational modifications, and have been shown to be released following exercise. There is little evidence regarding how EVs or EV‐miRNAs are altered with age or RET. Therefore, we sought to characterize circulating EVs in young and older individuals, prior to and following a 12‐week resistance exercise programme. Plasma EVs were isolated using size exclusion chromatography and ultracentrifugation. We found that ageing reduced circulating expression markers of CD9, and CD81. Using late‐passage human myotubes as a model for ageing in vitro, we show significantly lower secreted exosome‐like vesicles (ELVs). Further, levels of circulating ELV‐miRNAs associated with muscle health were lower in older individuals at baseline but increased following RET to levels comparable to young. Muscle biopsies show similar age‐related reductions in miRNA expressions, with largely no effect of training. This is reflected in vitro, where aged myotubes show significantly reduced expression of endogenous and secreted muscle‐specific miRNAs (myomiRs). Lastly, proteins associated with ELV and miRNA biogenesis were significantly higher in both older skeletal muscle tissues and aged human myotubes. Together we show that ageing significantly affects ELV and miRNA cargo biogenesis, and release. RET can partially normalize this altered intercellular communication. Key points: We show that ageing reduces circulating expression of exosome‐like vesicle (ELV) markers, CD9 and CD81. Using late‐passage human skeletal myotubes as a model of ageing, we show that secreted ELV markers are significantly reduced in vitro.We find circulating ELV miRNAs associated with skeletal muscle health are lower in older individuals but can increase following resistance exercise training (RET).In skeletal muscle, we find altered expression of miRNAs in older individuals, with no effect of RET.Late‐passage myotubes also appear to have aberrant production of endogenous myomiRs with lower abundance than youthful counterpartsIn older skeletal muscle and late‐passage myotubes, proteins involved with ELV‐ and miRNA biogenesis are upregulated [ABSTRACT FROM AUTHOR]

Objective: ST3GAL3‐related developmental and epileptic encephalopathy (DEE‐15) is an autosomal recessive condition characterized by intellectual disability, language and motor impairments, behavioral difficulties, stereotypies, and epilepsy. Only a few cases have been reported, and the epilepsy phenotype is not fully elucidated. Methods: A retrospective chart review of two siblings with ST3GAL3‐related DEE was completed. In addition, we reviewed all published cases of ST3GAL3‐related congenital disorder of glycosylation. Results: Two brothers presented with global developmental delay, motor and language impairment, hypotonia, and childhood‐onset seizures. Seizures started between 2.5 and 5 years and had tonic components. Both siblings had prolonged periods of seizure freedom on carbamazepine. Tremor was present in the younger sibling. Whole exome sequencing revealed two novel pathogenic variants in ST3GAL3, (a) c.302del, p.Phe102Serfs*34 and (b) c.781C>T, p.Arg261*, which were inherited in trans. Magnetic resonance imaging showed T2 hyperintensities and restricted diffusion in the brainstem and middle cerebellar peduncle in the older sibling, also described in two reported cases. A review of the literature revealed 24 cases of ST3GAL3‐related CDG. Twelve cases had information about seizures, and epilepsy was diagnosed in 8 (67%). The median age of seizure onset was 5.5 months. Epileptic spasms were most common (67%). Four children were diagnosed with Infantile Epileptic Spasms syndrome and Lennox Gastaut syndrome (57%). Most children (n = 6, 75%) had seizures despite anti‐seizure medication treatment. Significance: Seizures related to ST3GAL3‐related DEE often occur in infancy and may present as epileptic spasms. However, seizure onset may also occur outside of infancy with mixed seizure types and show good response to treatment with prolonged seizure freedom. Tremor may also be uniquely observed in this condition. [ABSTRACT FROM AUTHOR]

Background: Loss of function variants and whole gene deletions of ZNF462 has been associated with a novel phenotype of developmental delay/intellectual disability and distinctive facial features. Over two dozen cases have been reported to date and the condition is now known as Weiss‐Kruszka syndrome (OMIM# 618619). There are several older reports in the literature and DECIPER detailing individuals with interstitial deletions of 9q31 involving the ZNF462 gene. Many of the characteristic facial features described in these microdeletion cases are similar to those who have been diagnosed with Weiss‐Kruszka syndrome. Methods: We describe three additional patients with overlapping 9q31 deletions and compare the phenotypes of the microdeletion cases reported in the literature to Weiss‐Kruszka syndrome. Results: Phenotypic overlap was observed between patients with 9q31 deletions and Weiss‐Kruszka syndrome. Several additional features were noted in 9q31 deletion patients, including hearing loss, small head circumference, palate abnormalities and short stature. Conclusions: The common region of overlap of microdeletion cases implicates ZNF462 as the main driver of the recognizable 9q31 microdeletion phenotype. The observation of additional features in patients with 9q31 microdeletions that are not reported in Weiss‐Kruszka syndrome further suggests that other genes from the 9q31 region likely act synergistically with ZNF462 to affect phenotypic expression. [ABSTRACT FROM AUTHOR]

Objective: The rationale for this study was based on reports that valosin‐containing protein (VCP) mutations are found in hereditary inclusion body myositis (IBM) and VCP was detected in rimmed vacuoles of sporadic IBM (sIBM) muscle biopsies. Autoantibodies to VCP have not been reported in sIBM or other inflammatory myopathies (IIMs). The aim of this study was to determine the frequency and clinical significance of anti‐VCP antibodies in sIBM and other IIMs. Methods: Sera were collected from 73 patients with sIBM and 383 comparators or controls, including patients with IIM (n = 69), those with juvenile dermatomyositis (JDM) (n = 67), those with juvenile idiopathic arthritis (JIA) (n = 47), those with primary biliary cholangitis (PBC) (n = 105), controls that were age matched to patients with sIBM (similarly aged controls [SACs]) (n = 63), and healthy controls (HCs) (n = 32). Immunoglobulin G antibodies to VCP were detected by addressable laser bead immunoassay using a full‐length recombinant human protein. Results: Among patients with sIBM, 26.0% (19/73) were positive for anti‐VCP. The frequency in disease controls was 15.0% (48/320). Among SACs, the frequency was 1.6% (1/63), and in HCs 0% (0/32). Frequencies were 17.5% (11/63) for IIM, 25.7% (27/105) for PBC, 3.0% (2/67) for JDM, and 17.0% (8/47) for JIA. The sensitivity, specificity, positive predictive value, and negative predictive value of anti‐VCP for sIBM were 26.0%, 87.2%, 28.4%, and 85.9%, respectively. Of patients with sIBM, 15.1% (11/73) were positive for both anti‐VCP and anti–cytosolic 5′‐nucleotidase 1A (NT5c1A). Eleven percent of patients (8/73) were positive for anti‐VCP, but negative for anti‐NT5c1A. Conclusion: Anti‐VCP has low sensitivity and moderate specificity for sIBM but may help fill the seronegative gap in sIBM. Further studies are needed to determine whether anti‐VCP is a biomarker for a clinical phenotype that may have clinical value. [ABSTRACT FROM AUTHOR]