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Gut Sep 2019Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in... (Review)
Review
Imaging of the living human brain is a powerful tool to probe the interactions between brain, gut and microbiome in health and in disorders of brain-gut interactions, in particular IBS. While altered signals from the viscera contribute to clinical symptoms, the brain integrates these interoceptive signals with emotional, cognitive and memory related inputs in a non-linear fashion to produce symptoms. Tremendous progress has occurred in the development of new imaging techniques that look at structural, functional and metabolic properties of brain regions and networks. Standardisation in image acquisition and advances in computational approaches has made it possible to study large data sets of imaging studies, identify network properties and integrate them with non-imaging data. These approaches are beginning to generate brain signatures in IBS that share some features with those obtained in other often overlapping chronic pain disorders such as urological pelvic pain syndromes and vulvodynia, suggesting shared mechanisms. Despite this progress, the identification of preclinical vulnerability factors and outcome predictors has been slow. To overcome current obstacles, the creation of consortia and the generation of standardised multisite repositories for brain imaging and metadata from multisite studies are required.
Topics: Big Data; Brain; Humans; Irritable Bowel Syndrome; Nerve Net; Neuroimaging; Sex Characteristics
PubMed: 31175206
DOI: 10.1136/gutjnl-2019-318308 -
The World Journal of Men's Health Apr 2024Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable...
Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.
PURPOSE
Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA.
MATERIALS AND METHODS
A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.
RESULTS
Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit.
CONCLUSIONS
This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.
PubMed: 38606867
DOI: 10.5534/wjmh.230339 -
Frontiers in Endocrinology 2021Bloom syndrome (BS) is a rare autosomal recessive disorder that causes several endocrine abnormalities. So far, only one BS pedigree, without diabetes, has been reported...
Bloom syndrome (BS) is a rare autosomal recessive disorder that causes several endocrine abnormalities. So far, only one BS pedigree, without diabetes, has been reported in the Chinese population. We presented the first case of BS with diabetes in the Chinese population and explored the clinical spectrum associated with endocrine. Possible molecular mechanisms were also investigated. Our study indicated that BS may be one rare cause of diabetes in the Chinese population. We also found a new pathogenic sequence variant in (BLM RecQ like helicase gene)(NM_000057.4) c.692T>G, which may expand the spectrum of variants.
Topics: Bloom Syndrome; Diabetes Mellitus, Type 1; Humans; Male; Mutation; RecQ Helicases; Young Adult
PubMed: 34177791
DOI: 10.3389/fendo.2021.524242 -
Environment International Feb 2020Residing in greener areas has several health benefits, but no study to date has examined the effects of greenness on metabolic syndrome (MetS). We aimed to assess...
BACKGROUND
Residing in greener areas has several health benefits, but no study to date has examined the effects of greenness on metabolic syndrome (MetS). We aimed to assess associations between residential greenness and MetS prevalence in China, and to explore whether air pollution and physical activity mediated any observed associations.
METHODS
We analyzed data from 15,477 adults who participated in the 33 Communities Chinese Health Study during 2009. We defined MetS according to standard guidelines for Chinese populations. Residential greenness was estimated using the Normalized Difference Vegetation Index (NDVI), the Soil Adjusted Vegetation Index (SAVI), and the Vegetation Continuous Field (VCF). We used generalized linear mixed models to assess the associations between greenness and MetS, and mediation analyses to explore potential mechanisms underlying the associations.
RESULTS
Higher greenness levels were associated with lower odds of MetS [e.g., for every interquartile range increase of NDVI, SAVI, and VCF, the adjusted odds ratio of MetS was 0.81 (95% confidence interval: 0.70-0.93), 0.80 (95% confidence interval: 0.69-0.93), and 0.91 (95% confidence interval: 0.83-1.00), respectively]. The direction and the magnitude of the associations persisted in several sensitivity analyses. Stratified analyses showed that age and household income modified the associations, with greater effect estimates observed in participants younger than 65 years old or those with higher household income. Particulate matter with an aerodynamic diameter ≤10 μm, nitrogen dioxide, and ozone mediated 2.1-20.3% of the associations between greenness and MetS; no evidence of mediation was observed for physical activity.
CONCLUSIONS
Our findings suggest a beneficial association for residential greenness and MetS in Chinese urban dwellers, especially for participants younger than 65 years old and those with higher household income. Particulate matter with an aerodynamic diameter ≤10 μm, nitrogen dioxide and ozone, but not physical activity, may only partially mediate the association.
Topics: Adult; Aged; Air Pollution; China; Humans; Metabolic Syndrome; Nitrogen Dioxide; Particulate Matter
PubMed: 31837524
DOI: 10.1016/j.envint.2019.105388 -
Molecular Syndromology Jun 2020Bloom syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin...
Bloom syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early-onset cancer and development of multiple malignancies. Loss-of-function variants of the gene, which codes for a RecQ helicase, cause Bloom syndrome. We report a consanguineous family, with 2 siblings showing clinical signs of suspected chromosome breakage disorder. One of them developed recurrent malignant lymphoma during lifetime. We performed next-generation sequencing analysis, focusing on cancer predisposition syndromes. We identified a homozygous pathogenic nonsense variant c.1642C>T (p.Gln548*) in the gene in the proband, associated with Bloom syndrome. Sanger sequencing validated the presence of a homozygous pathogenic variant in the proband and also in the brother with short stature. In this article, we will focus on the clinical presentation of the syndrome in this particular family as well as the characteristics of malignancies found in the proband.
PubMed: 32655338
DOI: 10.1159/000507006 -
JACC. Asia Sep 2021The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of...
BACKGROUND
The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known.
OBJECTIVES
This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia.
METHODS
The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison.
RESULTS
Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020.
CONCLUSIONS
The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.
PubMed: 36338167
DOI: 10.1016/j.jacasi.2021.06.002 -
The Journal of Clinical Investigation May 2024The gut microbiota is an integral part of the human metaorganism that is required to shape physiologic host immune responses including host defense against pathogens....
The gut microbiota is an integral part of the human metaorganism that is required to shape physiologic host immune responses including host defense against pathogens. Disease-associated gut dysbiosis has been characterized by blooms of pathobionts, which are bacterial species that can drive disease under certain conditions. Pathobionts like Enterobacteriaceae often bloom during flares of inflammatory bowel disease (IBD) and are causally linked with IBD in murine models. In this issue of the JCI, Hecht and colleagues investigated how simple carbohydrates are causally linked to the bloom of the gut pathobiont Klebsiella pneumoniae, which belong to the Enterobacteriaceae family. Notably, the presence of fiber reduced the dissemination of K. pneumoniae into the blood and liver in a colitis model. Their findings provide a diet-related mechanism for gut dysbiosis, which has implications in the management of IBD and other conditions in which gut dysbiosis is an underlying factor.
Topics: Humans; Dysbiosis; Animals; Gastrointestinal Microbiome; Klebsiella pneumoniae; Inflammatory Bowel Diseases; Mice; Dietary Carbohydrates; Klebsiella Infections; Colitis; Dietary Fiber
PubMed: 38690730
DOI: 10.1172/JCI180001 -
Molecular Biology and Evolution Apr 2023SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do...
SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.
Topics: Animals; Humans; SARS-CoV-2; COVID-19; Mutation; Mutation Rate; Severe acute respiratory syndrome-related coronavirus; Genome, Viral
PubMed: 37039557
DOI: 10.1093/molbev/msad085 -
Computational and Structural... 2022SMYD3 overexpression in several human cancers highlights its crucial role in carcinogenesis. Nonetheless, SMYD3 specific activity in cancer development and progression...
SMYD3 overexpression in several human cancers highlights its crucial role in carcinogenesis. Nonetheless, SMYD3 specific activity in cancer development and progression is currently under debate. Taking advantage of a library of rare tripeptides, which we first tested for their binding affinity to SMYD3 and then used as probes, we recently identified BRCA2, ATM, and CHK2 as direct SMYD3 interactors. To gain insight into novel SMYD3 cancer-related roles, here we performed a comprehensive analysis to cluster all potential SMYD3-interacting proteins identified by screening the human proteome for the previously tested tripeptides, based on their involvement in cancer hallmarks. Remarkably, we identified mTOR, BLM, MET, AMPK, and p130 as new SMYD3 interactors implicated in cancer processes. Further studies are needed to characterize the functional mechanisms underlying these interactions. Still, these findings could be useful to devise novel therapeutic strategies based on the combined inhibition of SMYD3 and its newly identified molecular partners. Of note, our methodology may be useful to search for unidentified interactors of other proteins of interest.
PubMed: 35495117
DOI: 10.1016/j.csbj.2022.03.037 -
Molecular Biology of the Cell Apr 2022Homology-directed repair of DNA double-strand breaks (DSBs) represents a highly faithful pathway. Non-crossover repair dominates in mitotically growing cells, likely...
Homology-directed repair of DNA double-strand breaks (DSBs) represents a highly faithful pathway. Non-crossover repair dominates in mitotically growing cells, likely through a preference for synthesis-dependent strand annealing (SDSA). How homology-directed repair mechanism choice is orchestrated in time and space is not well understood. Here, we develop a microscopy-based assay in living fission yeast to determine the dynamics and kinetics of an engineered, site-specific interhomologue repair event. We observe highly efficient homology search and homology-directed repair in this system. Surprisingly, the initial distance between the DSB and the donor sequence does not correlate with the duration of repair. Instead, we observe that repair often involves multiple site-specific and Rad51-dependent colocalization events between the DSB and donor sequence. Upon loss of the RecQ helicase Rqh1 (BLM in humans) we observe rapid repair possibly involving a single strand invasion event, suggesting that multiple strand invasion cycles antagonized by Rqh1 could reflect ongoing SDSA. However, failure to colocalize with the donor sequence and execute repair is also more likely in cells, possibly reflecting erroneous strand invasion. This work has implications for the molecular etiology of Bloom syndrome, caused by mutations in BLM and characterized by aberrant sister chromatid crossovers and inefficient repair.
Topics: DNA Breaks, Double-Stranded; DNA Helicases; DNA Repair; DNA Replication; Humans; Recombinational DNA Repair; Schizosaccharomyces; Schizosaccharomyces pombe Proteins
PubMed: 35080989
DOI: 10.1091/mbc.E20-07-0433