How does the Xist activator Rlim/Rnf12 regulate Xist expression?

The long non-coding RNA (lncRNA) Xist is crucially involved in a process called X chromosome inactivation (XCI), the transcriptional silencing of one of the two X chromosomes in female mammals to achieve X dosage compensation between the sexes. Because Xist RNA silences the X chromosome from which it is transcribed, the activation of Xist transcription marks the initiation of the XCI process and thus, mechanisms and players that activate this gene are of central importance to the XCI process. During female mouse embryogenesis, XCI occurs in two steps. At the 2-4 cell stages imprinted XCI (iXCI) silences exclusively the paternally inherited X chromosome (Xp). While extraembryonic cells including trophoblasts keep the Xp silenced, epiblast cells that give rise to the embryo proper reactivate the Xp and undergo random XCI (rXCI) around implantation. Both iXCI and rXCI are dependent on Xist. Rlim, also known as Rnf12, is an X-linked E3 ubiquitin ligase that is involved in the transcriptional activation of Xist. However, while data on the crucial involvement of Rlim during iXCI appear clear, its role in rXCI has been controversial. This review discusses data leading to this disagreement and recent evidence for a regulatory switch of Xist transcription in epiblasts of implanting embryos, partially reconciling the roles of Rlim during Xist activation.

Heat stress induced piRNA alterations in pachytene spermatocytes and round spermatids.

BACKGROUND: Spermatogenesis is a temperature-sensitive process, and elevation in temperature hampers this process quickly and significantly. We studied the molecular effects of testicular heating on piRNAs and gene expression in rat testicular germ cells. METHODS: We generated a cryptorchid rat model by displacing the testis from the scrotal sac (34 °C) to the abdominal area (37 °C) and sacrificed animals after 1 day, 3 days, and 5 days. Pachytene spermatocytes and round spermatids were purified using elutriation centrifugation and percoll gradient methods. We performed transcriptome sequencing in pachytene spermatocytes and round spermatids to identify differentially expressed piRNAs and their probable targets, i.e., TE transcripts and mRNAs. RESULTS: As a result of heat stress, we observed significant upregulation of piRNAs and TE transcripts in testicular germ cells. In addition to this, piRNA biogenesis machinery and heat shock proteins (Hsp70 and Hsp90 family members) were upregulated. mRNAs have also been proposed as targets for piRNAs; therefore, we shortlisted certain piRNA-mRNA pairs with an inverse relationship of expression. We observed that in testicular heat stress, the heat shock proteins go hand-in-hand with the upregulation of piRNA biogenesis machinery. The dysregulation of piRNAs in heat-stressed germ cells, increased ping-pong activity, and disturbed expression of piRNA target transcripts suggest a connection between piRNAs, mRNAs, and TE transcripts. CONCLUSIONS: In heat stress, piRNAs, piRNA machinery, and heat shock proteins are activated to deal with low levels of stress, which is followed by a rescue approach in prolonged stressaccompained by high TE activity to allow genetic mutations, perhaps for survival and adaptability.

Exome sequencing identified mutations in the WNT1 and COL1A2 genes in osteogenesis imperfecta cases.

BACKGROUND: Osteogenesis imperfecta (OI) is a heritable connective tissue disorder characterized by bone deformities, fractures and reduced bone mass. OI can be inherited as a dominant, recessive, or X-linked disorder. The mutational spectrum has shown that autosomal dominant mutations in the type I collagen-encoding genes are responsible for OI in 85% of the cases. Apart from collagen genes, mutations in more than 20 other genes, such as CRTAP, CREB3L1, MBTPS2, P4HB, SEC24D, SPARC, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, TMEM38B, and IFITM5 have been reported in OI. METHODS AND RESULTS: To understand the genetic cause of OI in four cases, we conducted whole exome sequencing, followed by Sanger sequencing. In case #1, we identified a novel c.506delG homozygous mutation in the WNT1 gene, resulting in a frameshift and early truncation of the protein at the 197th amino acid. In cases #2, 3 and 4, we identified a heterozygous c.838G > A mutation in the COL1A2 gene, resulting in a p.Gly280Ser substitution. The clinvar frequency of this mutation is 0.000008 (GnomAD-exomes). This mutation has been identified by other studies as well and appears to be a mutational hot spot. These pathogenic mutations were found to be absent in 96 control samples analyzed for these sites. The presence of these mutations in the cases, their absence in controls, their absence or very low frequency in general population, and their evaluation using various in silico prediction tools suggested their pathogenic nature. CONCLUSIONS: Mutations in the WNT1 and COL1A2 genes explain these cases of osteogenesis imperfecta.

Description of massage interventions in randomised clinical trials for neck pain; a review using the TIDieR checklist.

OBJECTIVE: How interventions are reported can impact the ability to implement these intervention in clinical practice. Therefore, our aim is to assess the reporting of massage interventions in randomised controlled trials for patients with neck pain. DATA SOURCES: This manuscript concerns a secondary analysis of trials evaluating massage for neck pain selected for a scoping review. An updated literature search was completed using four databases to 31 July 2023. REVIEW METHODS: Trials were selected that evaluate massage interventions. Two independent assessors extracted descriptive information, methodological quality (PEDro-scale) and assessed completeness of reporting of the intervention using the Template for Intervention Description and Replication (TIDier-checklist). We present frequencies of the extracted data. RESULTS: We included 35 trials (2840 patients) with neck pain. Most trials (n = 23) included patients with chronic non-specific neck pain. We found a wide variety of massage interventions from Chinese massage, Swedish massage to myofascial release. In addition, the dose, number of sessions and the duration of the intervention varied widely. The methodological quality overall was fair to good (varied between 4-8/10), and we found a moderate completeness of reporting. All trials provided the name of the intervention, 30 (86%) provided a rationale and 26 (74%) trials described details of the massage intervention. CONCLUSION: The massage interventions were moderately described in trials in patients with neck pain, but provided enough information to guide the decision making for designing future Network Meta-analysis as to what trials need to be considered when grouping massage interventions in a clinically relevant way.

Clinical validation of grouping conservative treatments in neck pain for use in a network meta-analysis: a Delphi consensus study.

BACKGROUND: A network meta-analysis aims to help clinicians make clinical decisions on the most effective treatment for a certain condition. Neck pain is multifactorial, with various classification systems and treatment options. Classifying patients and grouping interventions in clinically relevant treatment nodes for a NMA is essential, but this process is poorly defined. OBJECTIVE: Our aim is to obtain consensus among experts on neck pain classifications and the grouping of interventions into nodes for a future network meta-analysis. DESIGN: A Delphi consensus study involving neck pain experts worldwide. METHODS: We invited authors of neck pain clinical practice guidelines published from 2014 onwards. The Delphi baseline questionnaire was developed based on the findings of a scoping review, including four items on classifications and 19 nodes. Participants were asked to record their level of agreement on a seven-point Likert scale or using Yes/No/Not sure answer options for the various statements. We used descriptive analysis to summarise the responses on each statement with content analysis of the free-text comments. RESULTS: In total, 18/80 experts (22.5%) agreed to participate in one or more Delphi rounds. We needed three rounds to reach consensus for two classification of neck pain: one based on aetiology and one on duration. In addition, we also reached consensus on the grouping of interventions, including a definition of each node, with the number of nodes reduced to 17. CONCLUSION: With this consensus we clinically validated two neck pain classifications and grouped conservative treatments into 17 well-defined and clinically relevant nodes.

Small RNAs, spermatogenesis, and male infertility: a decade of retrospect.

Small non-coding RNAs (sncRNAs), being the top regulators of gene expression, have been thoroughly studied in various biological systems, including the testis. Research over the last decade has generated significant evidence in support of the crucial roles of sncRNAs in male reproduction, particularly in the maintenance of primordial germ cells, meiosis, spermiogenesis, sperm fertility, and early post-fertilization development. The most commonly studied small RNAs in spermatogenesis are microRNAs (miRNAs), PIWI-interacting RNA (piRNA), small interfering RNA (siRNA), and transfer RNA-derived small RNAs (ts-RNAs). Small non-coding RNAs are crucial in regulating the dynamic, spatial, and temporal gene expression profiles in developing germ cells. A number of small RNAs, particularly miRNAs and tsRNAs, are loaded on spermatozoa during their epididymal maturation. With regard to their roles in fertility, miRNAs have been studied most often, followed by piRNAs and tsRNAs. Dysregulation of more than 100 miRNAs has been shown to correlate with infertility. piRNA and tsRNA dysregulations in infertility have been studied in only 3-5 studies. Sperm-borne small RNAs hold great potential to act as biomarkers of sperm quality and fertility. In this article, we review the role of small RNAs in spermatogenesis, their association with infertility, and their potential as biomarkers of sperm quality and fertility.

COVID-19 vaccination does not affect male sexual functions.

BACKGROUND: COVID-19 infection has been linked with erectile dysfunction, which has also raised apprehensions about the impact of COVID-19 vaccination on male sexual functions. The purpose of this study was to investigate the impact of COVID-19 vaccination on male sexual functions, such as erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction. METHODS: We used International Index of Erectile Function (IIEF) questionnaire for data collection. Mixed methods were adopted for this study, which consisted of Google online form distribution and the distribution of hard copies of the form to those who were not internet friendly. All data were entered in a spreadsheet and scores were assigned to each response according to the standard scores given in the IIEF questionnaire. Fifteen questions, one corresponding to each question in the IIEF questionnaire, were included to assess the impact of COVID-19 vaccination on each sexual function. RESULTS: In the first part of analysis, we calculated sexual function scores and men reporting low sexual function scores (~ 15%) were excluded, providing us with 465 individuals for further analysis. Regarding the impact of COVID-19 vaccination on male sexual functions, 71% individuals reported no impact, 3% reported a decline, 2.7% reported an improvement, and 23.3% could not assess the impact. We also performed analysis on the basis of age-groups of the participants and the duration after vaccination, finding that there was no impact irrespective of the age of subjects or the length of period after vaccination. CONCLUSIONS: COVID-19 vaccination does not affect male sexual functions, including erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall sexual satisfaction.

Social support during COVID-19: Exploring the psychometric properties of the PSS-JSAS and its relationship with job search activities.

The COVID-19 pandemic has highlighted the importance of social support for everyone. Supports from relatives, neighbors, and friends are more significant for a job seeker, especially during the pandemic. Accordingly, the present study explored the psychometric properties of the Perceived Social Support for Job Search Activities Scale (PSS-JSAS) in the Indian context with the help of two independent samples. First sample of 518 respondents was randomly divided into two subsamples using the random case selection feature in the statistical package for social sciences (SPSS). The exploratory factor analysis (EFA) was performed on the first subsample, which yielded a one-factor model explaining 47.23% of variations. The confirmatory factor analysis (CFA) conducted on the second subsample concluded a good model fit of PSS-JSAS. In the second sample, Cronbach's alpha and composite reliability values (greater than 0.70) established the scale's reliability. Results also revealed that the correlation coefficients between PSS-JSAS score, hope, self-efficacy, resilience, and optimism were 0.470, 0.552, 0.621, and 0.5 at p < 0.01. It also revealed a negative association with job search anxiety scores (r = -0.549, p < 0.01). Thus, PSS-JSAS was positively associated with PsyCap and negatively correlated with job search anxiety behaviors. It concluded the criterion validity of PSS-JSAS in the Indian context. Multigroup factor analysis concludes that the scale is equally valid for both Indian males and females. Hence, results reported adequate reliability and validity of the scale in the Indian context. These findings will encourage future researchers to investigate the phenomena of social support in the job search.

Proposing a clinical algorithm for better diagnosis of hypophosphatasia in resource-limiting situations.

Early diagnosis of hypophosphatasia (HPP) is challenging. Here, we propose to broaden the diagnostic criteria of HPP by reviewing published data on BMD and fractures in HPP patients. Non-osteoporotic fractures and higher than normal lumbar BMD were recurrent in HPP patients and could be included as diagnostic criteria. HPP is a genetic disorder caused by autosomal recessive or dominant loss-of-function mutations in the ALPL gene that encodes for tissue-nonspecific alkaline phosphatase (TNSALP). Expressive genetic heterogeneity and varying severity of TNSALP deficiency lead to a wide-ranging presentation of skeletal diseases at different ages that coupled with HPP's rarity and limitation of biochemical and mutational studies present serious hurdles to early diagnosis and management of HPP. To widen the scope of HPP diagnosis, we assessed the possibility of areal bone mineral density (BMD) as an additional clinical feature of this disease. PubMed, Web of Science, and ScienceDirect were searched with the following keywords: ("Hypophosphatasia OR HPP") AND ("Bone Mineral Density OR BMD") AND "Human". Studies and case reports of subjects with age ≥ 18 years and having BMD data were included. We pooled data from 25 publications comprising 356 subjects (90 males, 266 females). Only four studies had a control group. Biochemical hallmarks, pyridoxal 5'-phosphate (PLP) and phosphoethanolamine (PEA), were reported in fifteen and six studies, respectively. Twenty studies reported genetic data, nineteen studies reported non-vertebral fractures, all studies reported lumbar spine (LS) BMD, and nineteen reported non-vertebral BMD. Higher than normal and normal BMD at LS were reported in three and two studies, respectively. There was marked heterogeneity in BMD at the non-vertebral sites. Higher than normal or normal LS BMD in an adult with minimal or insufficient fractures, pseudofractures, non-healing fractures, fragility fractures, and stress fractures may be included in the diagnostic protocol of HPP. However, genetic testing is recommended for a definitive diagnosis.

Polymorphisms in the HSF2, LRRC6, MEIG1 and PTIP genes correlate with sperm motility in idiopathic infertility.

The aim of this study was to investigate the association of 24 functionally important single nucleotide polymorphisms (SNPs) with male infertility. In this cross-sectional study, we genotyped 24 functionally important single nucleotide polymorphisms in 24 infertility candidate genes in 500 oligo-/astheno-/oligoastheno-/normo-zoospermic infertile men with idiopathic infertility. Sequenom iPlex gold assay was used for genotyping. Sperm count and motility were compared between prevalent genotypes at each test locus. We did not observe any significant difference in the average sperm count between the alternate genotypes for the loci in the KLK3, LRRC6, MEIG1, HSF2, ESR2 and PTIP genes. However, we observed a significant difference in sperm motility between the alternate genotypes for the loci in the LRRC6, MEIG1, HSF2 and PTIP genes. Polymorphisms in the LRRC6 (rs200321595), MEIG1 (rs150031795), HSF2 (rs143986686) and PTIP (rs61752013) genes show association with sperm motility.

HCG therapy in azoospermic men with lower or borderline testosterone levels and the prognostic value of Y-deletion analysis in its outcome.

The purpose of this study was to investigate the efficacy of hCG therapy in hypogonadotropic hypogonadic (HH) azoospermic males along with dissecting the prognostic value of Y-deletion analysis in these patients. Fifty-eight azoospermic infertile males with diminished testosterone levels (≤400 ng/dl) and hypogonadism symptoms were subjected to human chorionic gonadotropin (hCG) therapy, and Y-deletion analysis was undertaken. Post-treatment, 43% (25/58) patients showed improvement in sperm count with 8.6% (5/58) turning severe oligozoospermic, 24.14% (14/58) patients turning oligozoospermic and 10.54% (6/58) turning normozoospermic. Among responders, the mean sperm concentration was 8.47 ± 13.16 million/ml, sperm count was 17.05 ± 26.17 million, sperm motility was 52.59% ± 25.09% and sperm progressive motility was 26.91% ± 20.51%. Seventeen out of 25 (68%) responders and 11/33 (33%) nonresponders showed an improvement in libido post-therapy. A Y-deletion was observed in 8% (2/25) responders and in 39.39% (13 out of 33) nonresponders. The Y-deletions were more often found in nonresponders in comparison with the responders (Fisher's exact probability test, p = .007, one tailed). We conclude that hCG therapy in hypogonadotropic azoospermic males is effective in improving andrological parameters and sperm production and that Y-chromosome deletion analysis has prognostic significance in predicting the success of hCG therapy.

Human Relevance of Preclinical Studies on the Skeletal Impact of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Inflammatory bowel disease (IBD) is a relapsing chronic idiopathic inflammatory condition. The increased risks of fractures in the spine and decreased BMD at all weight-bearing skeletal sites have been reported in IBD patients. The understanding of the mechanisms of IBD-induced bone loss is far from complete. Appropriate animal models are a prerequisite for studying IBD-induced bone loss, which prompted us to undertake quantitative meta-analyses by pooling data from the available IBD models that assessed various bone parameters. Sufficient data for meta-analysis are obtained from chemically- but not genetically induced models. Among the chemically induced models, only the effects of dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) on bone parameters have been reported. Meta-analysis showed that both DSS (Hedge's g = 2.124, p = 0.001) and TNBS (Hedge's g = 6.292, p = 0.000) increased inflammatory disease severity. In pooled analysis, bone volumes in femur (Hedge's g = - 3.42, p = 0.000) and tibia (Hedge's g = - 2.49, p = 0.000) showed significant losses upon DSS administration. Similarly, bone formation rate was significantly reduced upon IBD induction (Hedge's g = - 3.495, p = 0.006). Besides, cortical thickness was reduced and trabecular microstructure deteriorated by IBD induction. Insufficient data precluded us from determining the effect of IBD on bone strength and calciotropic hormones, as well as the impact of proinflammatory cytokines on bone turnover. This meta-analysis showed that IBD induction in rodents causes significant bone loss. Impaired osteoblast function appears to be the cause of this impact.

Exome sequencing identified compound heterozygous mutations in the SRD5A2 gene in a case of 46,XY ambiguous genitalia.

The disorders of sexual development (DSD) represent an array of phenotypes with ambiguous genitalia. The present case had microphallus with fused and bifid scrotum and was initially assigned androgen insensitivity syndrome; however, sequencing of the complete coding region of the androgen receptor gene failed to identify a causative mutation. We undertook whole exome sequencing for identification of the pathogenic mutation. The most promising pathogenic variants were genotyped using Sanger sequencing to confirm the genotypes. We found compound heterozygous mutations, c.169G>T and c.586G>A in the SRD5A2 gene in this case, resulting in a nonsense (p.Glu57Ter) and a nonsynonymous substitution (p.Gly196Ser), respectively. While the nonsense mutation would result in a truncated protein, p.Gly196Ser substitution has been previously reported to be pathogenic. The mutations were confirmed by Sanger sequencing. Sequencing of 96 normal male individuals did not show the above mutations, suggesting their pathogenic nature. In conclusion, we identified compound heterozygous pathogenic mutations, c.169G>T (p.Glu57Ter) and c.586G>A (p.Gly196Ser), in the SRD5A2 gene in a case of ambiguous genitalia. p.Glu57Ter is a novel mutation, which in compound heterozygote combination with Gly196Ser causes 5a reductase deficiency.

Mutations in the desert hedgehog (DHH) gene in the disorders of sexual differentiation and male infertility.

PURPOSE: To identify the contribution of mutations in the Desert Hedgehog (DHH) gene to the disorders of sexual differentiation (DSD) and male infertility. METHODS: The study included a total 430 subjects, including 47 gonadal dysgenesis cases, 6 patients with undescended testis and infertility characterized by azoospermia, 125 infertile male patients characterized by oligoasthenozoospermia, 24 patients with oligoasthenoteratozoospermia, and 200 ethnically matched normozoospermic fertile men who had fathered a child in the last two years. Sequencing of the complete coding region of the DHH gene was undertaken to find its contribution to the DSD and male infertility. RESULTS: We observed four novel mutations in the DHH gene in the cases with different reproductive anomalies. A synonymous substitution, c. 543C>T (p.His181His) was observed in 6.6% oligoasthenozoospermic infertile males and 1.5% normozoospermic fertile control samples (RR = 4.4077, 95%CI 1.19-16.29). Another synonymous substitution, c.990G>A (p.Ala330Ala) was observed in an infertile patient with unilateral undescended testis (case #12). Insertion of G at c.1156insG (p.Arg385fs) was observed in a case with bilateral undescended testis and azoospermia (case #23). In gonadal dysgenesis category, two mutations, insertion of G at c.1156insG (p.Arg385fs) and c.997A>G (p.Thr333Ala) substitution were observed in one case (case #34). These mutations were completely absent in control samples. CONCLUSION: Mutations in the DHH gene impact reproduction with mild mutations affecting fertility, and severe or multiple mutations resulting in gonadal dysgenesis.

Efficacy of low-temperature plasma-activated gas disinfection against biofilm on contaminated GI endoscope channels.

BACKGROUND AND AIMS: It has been increasingly recognized that the safety of GI endoscopes needs to be improved by addressing the small margin of safety of high-level disinfectants (HLDs) and the failure of HLDs to clear multidrug-resistant organisms and biofilms. There is also an unmet need for effective low-temperature sterilization techniques that have a clear pathway for U.S. Food and Drug Administration clearance. Here, we report the results of our investigation of a novel argon plasma-activated gas (PAG) for disinfection and potentially sterilization of biofilm-contaminated endoscopic channels. METHODS: Test polytetrafluoroethylene channel segments were contaminated with 4-, 24- and 48-hour luminal biofilms of methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, or Escherichia coli and were treated by PAG flowing for up to 9 minutes. After PAG treatment, inactivation and dispersal of luminal bacterial biofilms and their regrowth in 48 hours were evaluated. Reactive species induced by PAG were measured with colorimetric probes and electron spin resonance spectrometry. Surface morphology and elemental composition of PAG-treated channel material were analyzed with scanning electron microscopy. RESULTS: PAG treatment for 9 minutes led to more than 8 log reduction of viable cells and dispersal of 24- and 48-hour luminal biofilms of all 3 bacteria and to suppression of their regrowth, whereas it resulted in little morphologic abnormalities in channel material. Ozone concentration of PAG fell to below .01 ppm within 30 seconds of switching off the plasma. PAG-treated deionized water was acidified with numerous types of reactive species, each with a concentration some 3 orders of magnitude or more below its bacterial inhibition concentration. CONCLUSIONS: PAG is capable of effectively and rapidly disinfecting luminal bacterial biofilms and offers an alternative to the step of HLDs and/or ethylene oxide in the endoscope reprocessing procedure with safety to personnel and environment.

Antimicrobial Efficacy and Safety of a Novel Gas Plasma-Activated Catheter Lock Solution.

Antimicrobial lock solutions are important for prevention of microbial colonization and infection of long-term central venous catheters. We investigated the efficacy and safety of a novel antibiotic-free lock solution formed from gas plasma-activated disinfectant (PAD). Using a luminal biofilm model, viable cells of methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans in mature biofilms were reduced by 6 to 8 orders of magnitude with a PAD lock for 60 min. Subsequent 24-h incubation of PAD-treated samples resulted in no detectable regrowth of viable bacteria or fungi. As a comparison, the use of a minocycline-EDTA-ethanol lock solution for 60 min led to regrowth of bacteria and fungi, up to 107 to 109 CFU/ml, in 24 h. The PAD lock solution had minimal impact on human umbilical vein endothelial cell viability, whereas the minocycline-EDTA-ethanol solution elicited cell death in nearly half of human endothelial cells. Additionally, PAD treatment caused little topological change to catheter materials. In conclusion, PAD represents a novel antibiotic-free, noncytotoxic lock solution that elicits rapid and broad-spectrum eradication of biofilm-laden microbes and shows promise for the prevention and treatment of intravascular catheter infections.

Pain and Physical Functioning in Neuropathic Pain: A Systematic Review of Psychometric Properties of Various Outcome Measures.

INTRODUCTION: A range of outcome measures across various domains are used to evaluate change following an intervention in clinical trials on chronic neuropathic pain (NeP). However, to capture a real change in the variable of interest, the psychometric properties of a particular measure should demonstrate appropriate methodological quality. Various outcome measures in the domains of pain and physical functioning have been used in the literature for NeP, for which individual properties (eg, reliability/validity) have been reported. To date, there is no definitive synthesis of evidence on the psychometric properties of those outcome measures; thus, the aim of this systematic review was to evaluate the methodological quality [COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) guidelines] of studies that evaluated psychometric properties of pain and physical functioning outcome measures used for NeP. METHODS: Specific MeSH/keywords related to 3 areas (pain and/or physical functioning, psychometric properties, and NeP) were used to retrieve relevant studies (English language) in key electronic databases (MEDLINE (Ovid), CINAHL (EBSCO), Scopus, AMED, and Web of Science) from database inception-July 2012. Articles retrieval/screening and quality analysis (COSMIN) were carried out by 2 independent reviewers. RESULTS: Twenty-four pain and thirty-seven physical functioning outcome measures were identified, varying in methodological quality from poor-excellent. CONCLUSION: Although a variety of pain and physical functioning outcome measures have been reported in the literature, few have demonstrate methodologically strong psychometric properties. Thus, future research is required to further investigate the psychometric properties of existing pain and physical functioning outcome measures used for clinical and research purposes.

Systematic review of the psychometric properties of balance measures for cerebellar ataxia.

OBJECTIVE: To review systematically the psychometric properties of balance measures for use in people with cerebellar ataxia. DATA SOURCES: Medline, AMED, CINAHL, Web of Science and EMBASE were searched between 1946 and April 2014. REVIEW METHODS: Two reviewers independently searched data sources. Cerebellar-specific and generic measures of balance were considered. Included studies tested psychometric properties of balance measures in people with cerebellar ataxia of any cause. Quality of reported studies was rated using the Consensus Based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. RESULTS: Twenty-one articles across which 16 measures had been tested were included for review. Using the COSMIN, quality of methodology in studies investigating psychometric properties of generic balance measures (n=10) was rated predominantly as 'poor'. Furthermore, responsiveness has not been tested for any generic measures in this population. The quality of studies investigating psychometric properties of balance sub-components of the cerebellar-specific measures (n=6) ranged from 'poor' to 'excellent'; however, Minimally Clinically Important Difference has not been determined for these cerebellar-specific measures. CONCLUSION: The Posture and Gait (PG) sub-component of the International Cooperative Ataxia Rating Scale (ICARS) demonstrates the most robust psychometric properties with acceptable clinical utility.

Small RNAs: an ideal choice as sperm quality biomarkers.

Spermatozoa were classically known as vehicles for the delivery of the paternal genome to the oocyte. However, in 1962, spermatozoa were discovered to carry significant amounts of RNA in them, which raised questions about the significance of these molecules in such a highly specialized cell. Scientific research in the last six decades has investigated the biological significance of sperm RNAs by various means. Irrespective of what sperm RNAs do, their presence in spermatozoa has attracted attention for their exploitation as biomarkers of fertility. Research in this direction started in the year 2000 and is still underway. A major hurdle in this research is the definition of the standard human sperm RNAome. Only a few normozoospermic samples have been analyzed to define the normal sperm RNAome. In this article, we provide a perspective on the suitability of sperm RNAs as biomarkers of fertility and the importance of defining the normal sperm RNAome before we can succeed in identifying RNA-based biomarkers of sperm quality and fertility. The identification of sperm RNA biomarkers of fertility can be exploited for quality screening of donor sperm samples, explain infertility in idiopathic cases, and RNA therapeutics for the treatment of male infertility.

SPEM1 Gene Mutation in a Case with Sperm Morphological Defects Leading to Male Infertility.

The present study aimed at identifying the genetic mutation responsible for teratozoospermic infertility in a case with coiled sperm tails. A 33-year-old infertile male was diagnosed with teratozoospermic infertility, with sperm head in coiled (HIC) tail as the most common deformity. We employed whole exome sequencing to identify the genetic cause in this case. Exome sequencing data was filtered using the following criteria: MAF (< 0.003), ALFA project (< 0.001), 1000 Genomes (< 0.003), Granthem (> 50), Polyphen-2 (> 0.70), SIFT (< 0.03), and PhyloP (> = 0) scores. Shortlisted variants were looked in the in-house 29 exomes data available with us, and the variants that affected conserved amino acid residues or led to insertion/deletion or to protein-truncation with a Combined Annotation Dependent Depletion (CADD) score ≥ 10 were shortlisted. The variants thus populated were prioritized according to their roles in spermiogenesis. The study identified a heterozygous mutation c.826C > T (Arg276Trp) in the SPEM1 gene as a potential pathogenic variant that led to teratozoospermic infertility in the case under investigation. The mutation had a minor allele frequency of 0.00008176 in the gnomAd database and was absent in the Indian Genome Variations database. This is the first human study reporting a mutation in the SPEM1 gene as a cause of coiled sperm tails.