Beneficial effect of branched-chain amino acid supplementation on glycemic control in chronic hepatitis C patients with insulin resistance: Implications for type 2 diabetes

Branched-chain amino acids (BCAAs) improve disorders of albumin metabolism, quality of life, subjective symptoms, and prognosis in patients with chronic hepatitis. However, it remains unclear whether they improve insulin resistance. We examined the effects of BCAAs on glucose tolerance and insulin sensitivity in patients with chronic hepatitis C and insulin resistance. Individuals with a definitive diagnosis of chronic hepatitis C and insulin resistance were eligible for participation. Eligible participants were randomly assigned to the BCAA group or a control group. Participants were then crossed over to the other treatment for a further 12 weeks. Baseline clinical features, laboratory markers, fatty acid levels, and insulin sensitivity, assessed with oral glucose tolerance tests and a hyperinsulinemic euglycemic clamp, were also examined before and 12 and 24 weeks after the beginning of the study. Of the 27 patients who completed the study, 14 began in the BCAA group and 13 began as controls. There were no significant differences in glucose metabolism parameters or lipid profiles between the groups. HbA1c values were improved in 10 patients and worsened or remained unchanged in 17 patients. The only predictive variable for change in HbA1c was the baseline Matsuda index: the lower the index, the greater the improvement in HbA1c values. BCAA therapy did not have adverse effects on glucose tolerance or insulin sensitivity in patients with chronic hepatitis C and insulin resistance. Moreover, it had a therapeutic effect on HbA1c values in patients with marked peripheral (primarily muscle) insulin resistance. © 2012 Elsevier Inc

Arthroscopic excision of unstable os acromiale associated with impingement syndrome : a case report

Os acromiale is a rare anatomical variant that is caused by failure of fusion of the acromial apophysis and is usually asymptomatic. We report a case of impingement syndrome of the left shoulder secondary to unstable os acromiale, which was initially overlooked and confirmed only during arthroscopic examination. Arthroscopic excision of the unstable fragment was successful without residual dysfunction of the deltoid muscle

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Arthroscopic Removal of a Wire Fragment from the Posterior Septum of the Knee following Tension Band Wiring of a Patellar Fracture

Tension band wiring with cerclage wiring is most widely used for treating displaced patellar fractures. Although wire breakage is not uncommon, migration of a fragment of the broken wire is rare, especially migration into the knee joint. We describe here a rare case of migration of a wire fragment into the posterior septum of the knee joint after fixation of a displaced patellar fracture with tension band wiring and cerclage wiring. Although it was difficult to determine whether the wire fragment was located within or outside the knee joint from the preoperative plain radiographs or three-dimensional computed tomography (3D CT), we found it arthroscopically through the posterior transseptal portal with assistance of intraoperative fluoroscopy. Surgeons who treat such cases should bear in mind the possibility that wire could be embedded in the posterior septum of the knee joint

B Cells Play Key Roles in Th2-Type Airway Immune Responses in Mice Exposed to Natural Airborne Allergens

<div><p>Humans are frequently exposed to various airborne allergens. In addition to producing antibodies, B cells participate in immune responses via various mechanisms. The roles of B cells in allergic airway inflammation and asthma have been controversial. We examined the functional importance of B cells in a mouse model of asthma, in which mice were exposed repeatedly to common airborne allergens. Naïve wild-type BALB/c mice or B cell-deficient JH^−/− mice were exposed intranasally to a cocktail of allergen extracts, including <i>Alternaria</i>, <i>Aspergillus</i>, and house dust mite, every other day for two weeks. Ovalbumin was included in the cocktail to monitor the T cell immune response. Airway inflammation, lung pathology, and airway reactivity were analyzed. The airway exposure of naïve wild type mice to airborne allergens induced robust eosinophilic airway inflammation, increased the levels of Th2 cytokines and chemokines in the lung, and increased the reactivity to inhaled methacholine. These pathological changes and immune responses were attenuated in B cell-deficient JH^−/− mice. The allergen-induced expansion of CD4⁺ T cells was impaired in the lungs and draining lymph nodes of JH^−/− mice. Furthermore, lymphocytes from JH^−/− mice failed to produce Th2 cytokines in response to ovalbumin re-stimulation <i>in vitro</i>. Our results suggest that B cells are required for the optimal development of Th2-type immune responses and airway inflammation when exposed to common airborne allergens. The therapeutic targeting of B cells may be beneficial to treat asthma in certain patients.</p></div

Airway reactivity is reduced in JH^-/- mice.

<p>WT or JH^-/- mice were intranasally exposed to OAAH or PBS for 2 weeks, as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121660#pone.0121660.g001" target="_blank">Fig. 1A</a>. (A) Airway reactivity to inhaled methacholine was assessed by whole-body plethysmography, as described in the Methods section. Results are presented as the percentage of baseline (i.e. before PBS or methacholine challenge) and as mean±SEM (n = 4 and 6 in PBS and OAAH, respectively). *, p<0.05, between WT mice and JH^-/- mice exposed to OAAH. (B) Lung sections were stained with the periodic acid-Schiff stain. Original magnification, 160×. Scale bars, 50 μm. Data are representative of two independent experiments.</p

Th2-type responses in draining lymph nodes are attenuated in JH^-/- mice.

<p>WT or JH-^/- mice were intranasally exposed to OAAH for 2 weeks, as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0121660#pone.0121660.g001" target="_blank">Fig. 1A</a>. (A) Mediastinal lymph nodes (MLNs) were harvested, and cells were stained with anti-CD3 and anti-CD4 antibodies and analyzed by flow cytometry. Results are presented as mean±SEM (n = 5 mice per group). *, p<0.05; **, p<0.01. Data are representative of two independent experiments. (B) MLN cells were cultured with medium alone or with OVA (100 μg/ml) in 96-well tissue culture plates for 5 days. The levels of cytokines in the culture supernatants were analyzed by ELISA. *; p<0.05 between the groups indicated by horizontal lines. Data (mean±range, n = 2) are representative of three independent experiments.</p

Allergen exposure-induced airway inflammation is attenuated in B cell-deficient JH^-/- mice.

<p>(A) The experimental protocol is shown. Wild-type (WT) or JH^-/- mice were intranasally exposed to a cocktail of allergens (OAAH; ovalbumin, <i>Alternaria</i>, <i>Aspergillus</i>, house dust mite) on days 0, 2, 4, 7, 9, 11, and 14, and they were analyzed on day 15. (B) Cell differentials in BAL fluids were counted and presented as mean±standard error of the mean (SEM; n = 4 and 6 in PBS and OAAH, respectively). **, p<0.01, between WT BALB/c and JH^-/- mice exposed to OAAH. (C) Lung sections were stained with hematoxylin and eosin stains (upper and middle panels) or with the anti-mouse MBP antibody (lower panels). Original magnification, 160×. Scale bars, 50 μm. Data are representative of two independent experiments. (D) Chemokine levels in BAL fluids were determined by ELISA. Results are presented as mean±SEM (n = 4 and 6 in PBS and OAAH, respectively).</p