Extending colonic mucosal microbiome analysis - Assessment of colonic lavage as a proxy for endoscopic colonic biopsies

This study was supported through GI Research funds and MRC Grant Ref: MR/M00533X/1 to GH.Peer reviewedPublisher PD

Nano-mechanical properties of Fe-Mn-Al-C lightweight steels

High Al Low-density steels could have a transformative effect on the light-weighting of steel structures for transportation and achieving the desired properties with the minimum amount of Ni is of great interest from an economic perspective. In this study, the mechanical properties of two duplex low-density steels, Fe-15Mn-10Al-0.8C-5Ni and Fe-15Mn-10Al-0.8C (wt.%) were investigated through nano-indentation and simulation through utilization of ab initio formalisms in Density Functional Theory (DFT) in order to establish the hardness resulting from two critical structural features (ߢ-carbides and B2 intermetallic) as a function of annealing temperature (500 − 1050 ℃) and the addition of Ni. In the Ni-free sample, the calculated elastic properties of kappa-carbides were compared with those of the B2 intermetallic Fe3Al − L12, and the role of Mn in the kappa structure and its elastic properties were studied. The Ni-containing samples were found to have a higher hardness due to the B2 phase composition being NiAl rather than FeAl, with Ni-Al bonds reported to be stronger than the Fe-Al bonds. In both samples, at temperatures of 900 ℃ and above, the ferrite phase contained nano-sized discs of B2 phase, wherein the Ni-containing samples exhibited higher hardness, attributed again to the stronger Ni-Al bonds in the B2 phase. At 700 ℃ and below, the nano-sized B2 discs were replaced by micrometre sized needles of kappa in the Ni-free sample resulting in a lowering of the hardness. In the Ni-containing sample, the entire alpha phase was replaced by B2 stringers, which had a lower hardness than the Ni-Al nano-discs due to a lower Ni content in B2 stringer bands formed at 700 ℃ and below. In addition, the hardness of needle-like kappa-carbides formed in alpha phase was found to be a function of Mn content. Although it was impossible to measure the hardness of cuboid kappa particles in gamma phase because of their nano-size, the hardness value of composite phases, e.g. gamma + kappa was measured and reported. All the hardness values were compared and rationalized by bonding energy between different atoms

Survey on disease insight and prevalence of urinary incontinence in women

Purpose: With a rapidly aging population in Korea, the number of patients with lower urinary tract symptoms is increasing. Therefore, it is important to determine the current extent of incontinence among Korean women to establish future plans. We attempted to create reference materials for organizing public relations and educational activities by investigating the effect of age on incontinence and quality of life in women. Materials and Methods: The participants comprised women aged 30 years and older who visited a tertiary center for health screening from September 1 to October 31, 2016. The survey included a questionnaire consisting of 12 questions that took approximately 10 minutes to complete. We analyzed the responses and assessed the prevalence of the disease and its rate of recognition. Results: A total of 509 women completed the survey. Irrespective of age, 76.8% of all respondents were aware of urinary incontinence (UI) and 57.4% of the women exhibited lower urinary tract symptoms. The most prevalent symptom was UI (45.8%), and the incidence rates of stress and urge UI were identified as 33.6% and 12.2%, respectively. Only 8.0% of the women had visited a hospital; 38.3% had awaited spontaneous symptom improvement. Many participants (61.2%) answered that a urology clinic is suitable for treating UI, while 58.9% chose a gynecology clinic. Conclusions: Our study showed that more than 75% of women are aware of UI, but their perception of the disease mechanism and treatment options was low. We suggest that continuous education and publicity are necessary

Huntington's disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database.

BACKGROUND: Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner. METHODS: To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies. RESULTS: Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling), but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling). For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are associated with HD, at http://hdtt.sysbiolab.eu Additionally, we derived a candidate set of 24 novel genetic modifiers, including histone deacetylase 3 (HDAC3), metabotropic glutamate receptor 1 (GRM1), CDK5 regulatory subunit 2 (CDK5R2), and coactivator 1ß of the peroxisome proliferator-activated receptor gamma (PPARGC1B). CONCLUSIONS: The results of our study give us an intriguing picture of the molecular complexity of HD. Our analyses can be seen as a first step towards a comprehensive list of biological processes, molecular functions, and pathways involved in HD, and may provide a basis for the development of more holistic disease models and new therapeutics

Mitochondrial complex I deficiency enhances skeletal myogenesis but impairs insulin signaling through SIRT1 inactivation.

To address whether mitochondrial biogenesis is essential for skeletal myogenesis, C2C12 myogenesis was investigated after knockdown of NADH dehydrogenase (ubiquintone) flavoprotein 1 (NDUFV1), which is an oxidative phosphorylation complex I subunit that is the first subunit to accept electrons from NADH. The NDUFVI knockdown enhanced C2C12 myogenesis by decreasing the NAD(+)/NADH ratio and subsequently inactivating SIRT1 and SIRT1 activators (pyruvate, SRT1720, and resveratrol) abolished the NDUFV1 knockdown-induced myogenesis enhancement. However, the insulin-elicited activation of insulin receptor β (IRβ) and insulin receptor substrate-1 (IRS-1) was reduced with elevated levels of protein-tyrosine phosphatase 1B after NDUFV1 knockdown in C2C12 myotubes. The NDUFV1 knockdown-induced blockage of insulin signaling was released by protein-tyrosine phosphatase 1B knockdown in C2C12 myotubes, and we found that NDUFV1 or SIRT1 knockdown did not affect mitochondria biogenesis during C2C12 myogenesis. Based on these data, we can conclude that complex I dysfunction-induced SIRT1 inactivation leads to myogenesis enhancement but blocks insulin signaling without affecting mitochondria biogenesis

Epithelioma of Malherbe: new ultrasound patterns

<p>Abstract</p> <p>Backround</p> <p>Calcifying epithelioma of Malherbe, or Pilomatricoma, is considered an uncommon cutaneous neoplasia, normally occurring in children as a solitary, firm, asymptomatic, hard, subcutaneous, slowly growing nodule on the face, neck, or proximal upper extremity. In literature, two Pilomatricoma ultrasound patterns are described: the totally calcified nodule and the hypoechoic nodule with internal calcific foci. High frequency ultrasound has not yet been applied for routine diagnosis of Pilomatricoma. The aim of the study was to retrospectively identify specific ultrasound features.</p> <p>Methods</p> <p>We retrieved 124 histologically Pilomatricoma cases: 28 patients with 32 lesions were preoperatively evaluated with ultrasound.</p> <p>Results</p> <p>22/32 have shown a solid formation, hypoechoic, with a sharp outline. Of these 22, 10 lesions were completely calcifying and 12 partially calcified. In 3/32 lesions with uncertain diagnosis, ultrasounds showed a complex/mixed pattern with pseudo-fluid areas and microspots. 7/32 lesions with US different diagnosis included 3 complex lesions, 2 cystic lesions and 2 solid nodular lesions.</p> <p>Conclusion</p> <p>In addition to well-known ultrasound patterns (completely calcified and partially calcified) we identified three new, not yet described, patterns that constitute the 31% of the cases: complex, pseudocistyc and pseudotumoral.</p

Recommendations for Adult Immunization by the Korean Society of Infectious Diseases, 2023: Minor Revisions to the 3rd Edition

The Korean Society of Infectious Diseases has been regularly developing guidelines for adult immunization since 2007. In 2023, the guidelines for the following seven vaccines were revised: influenza, herpes zoster, pneumococcal, tetanus-diphtheria-pertussis (Tdap), human papillomavirus (HPV), meningococcal, and rabies vaccines. For the influenza vaccine, a recommendation for enhanced vaccines for the elderly was added. For the herpes zoster vaccine, a recommendation for the recombinant zoster vaccine was added. For the pneumococcal vaccine, the current status of the 15-valent pneumococcal conjugate vaccine and 20-valent PCV was described. For the Tdap vaccine, the possibility of using Tdap instead of tetanus-diphtheria vaccine was described. For the HPV vaccine, the expansion of the eligible age for vaccination was described. For the meningococcal vaccine, a recommendation for the meningococcal B vaccine was added. For the rabies vaccine, the number of pre-exposure prophylaxis doses was changed. This manuscript documents the summary and rationale of the revisions for the seven vaccines. For the vaccines not mentioned in this manuscript, the recommendations in the 3rd edition of the Vaccinations for Adults textbook shall remain in effect

Influence of lesion and disease subsets on the diagnostic performance of the quantitative flow ratio in real-world patients

The quantitative flow ratio (QFR) is a novel angiography-based computational method assessing functional ischemia caused by coronary stenosis. This study aimed to evaluate the diagnostic performance of quantitative flow ratio (QFR) in patients with angina and acute myocardial infarction (AMI) and to identify the conditions with low diagnostic performance. We assessed the QFR for 1077 vessels under fractional flow ratio (FFR) evaluation in 915 patients with angina and AMI. The diagnostic accuracies of the QFR for identifying an FFR ≤ 0.8 were 95.98% (95% confidence interval [CI] 94.52 to 97.14%) for the angina group and 92.42% (95% CI 86.51 to 96.31%) for the AMI group. The diagnostic accuracy of the QFR in the borderline FFR zones (&gt; 0.75, ≤ 0.85) (91.23% [95% CI 88.25 to 93.66%]) was significantly lower than that in others (difference: 4.32; p = 0.001). The condition accompanying both AMI and the borderline FFR zone showed the lowest QFR diagnostic accuracy in our data (83.93% [95% CI 71.67 to 92.38]). The diagnostic accuracy was reduced for tandem lesions (p = 0.04, not correcting for multiple testing). Our study found that the QFR method yielded a high overall diagnostic performance in real-world patients. However, low diagnostic accuracy has been observed in borderline FFR zones with AMI, and the hybrid FFR approach needs to be considered

Alpha-Blocker Treatment Response in Men With Lower Urinary Tract Symptoms Based on Sympathetic Activity: Prospective, Multicenter, Open-Labeled, Observational Study.

PURPOSE: In this study, we compared the treatment outcomes for an α-blocker between 2 groups of men, one with high sympathetic activity (HSA) and another with low sympathetic activity (LSA) or normal sympathetic activity. METHODS: A total of 159 men (≥50 years of age) with lower urinary tract symptoms resulting from benign prostatic hyperplasia were analyzed. We assigned patients to groups according to their sympathetic activity, which was evaluated by heart ratevariability measurements. HSA was defined as a low frequency/high frequency ratio greater than 1.6. All patients received 10mg of alfuzosin once a day for 12 weeks. The primary end point was a change in the total International Prostate SymptomScore (IPSS) at 12 weeks from baseline. RESULTS: Sixty-seven men were assigned to the HSA group and 92 men were assigned to the LSA group. The baseline characteristics were not significantly different between the 2 groups, and the response to alfuzosin was good in both groups. Themean total IPSS change was not different between the groups. Both groups were not significantly different with respect to the changes in maximal flow rate, IPSS voiding or storage symptom subscores, quality of life, and rates of adverse drug events. TheHSA group showed a similar willingness to continue treatment compared to the LSA group, although their treatment satisfaction rating was lower. CONCLUSIONS: The therapeutic effects of alfuzosin did not differ in regards to the differences in sympathetic activity, but treatment satisfaction ratings were lower in the HSA group

Hepatitis C Virus Infection in Phenotypically Distinct Huh7 Cell Lines

In 2005, the first robust hepatitis C virus (HCV) infectious cell culture system was developed based on the HCV genotype 2a JFH-1 molecular clone and the human-derived hepatoma cell line Huh7. Although much effort has been made to dissect and expand the repertoire of JFH-1-derived clones, less attention has been given to the host cell despite the intriguing facts that thus far only Huh7 cells have been found to be highly permissive for HCV infection and furthermore only a limited number of Huh7 cell lines/stocks appear to be fully permissive. As such, we compiled a panel of Huh7 lines from disparate sources and evaluated their permissiveness for HCV infection. We found that although Huh7 lines from different laboratories do vary in morphology and cell growth, the majority (8 out of 9) were highly permissive for infection, as demonstrated by robust HCV RNA and de novo infectious virion production following infection. While HCV RNA levels achieved in the 8 permissive cell lines were relatively equivalent, three Huh7 lines demonstrated higher infectious virion production suggesting these cell lines more efficiently support post-replication event(s) in the viral life cycle. Consistent with previous studies, the single Huh7 line found to be relatively resistant to infection demonstrated a block in HCV entry. These studies not only suggest that the majority of Huh7 cell lines in different laboratories are in fact highly permissive for HCV infection, but also identify phenotypically distinct Huh7 lines, which may facilitate studies investigating the cellular determinants of HCV infection