The antihypertensive agent hydralazine reduced extracellular matrix synthesis and liver fibrosis in nonalcoholic steatohepatitis exacerbated by hypertension

als.fakia shared this article with you from Inoreader The antihypertensive agent hydralazine reduced extracellular matrix synthesis and liver fibrosis in nonalcoholic steatohepatitis exacerbated by hypertension Via PLOS ONE Alerts: New Articles by Yuan Yuan, Hisao Naito, Kazuya Kitamori, Sayuki Hashimoto, Tomomi Asano, Tamie Nakajima Hypertension is an important risk factor for nonalcoholic steatohepatitis. We have previously demonstrated that hypertensive rats fed a high fat and cholesterol (HFC) diet incurred a more severe hepatic inflammatory response and fibrosis. Here we investigated the role of hypertension in NASH by comparing HFC-induced hepatic fibrogenesis between spontaneously hypertensive rats (SHRs) and their normotensive Wistar Kyoto counterpart. Compared to the counterpart, the HFC diet led to stronger aggregation of CD68-positive macrophages in SHRs. HFC feeding also resulted in significantly higher upregulation of the fibrosis-related gene alpha-smooth muscle actin in SHR. The HFC diet induced higher overexpression of serum tissue inhibitor of metalloproteinase-1 (TIMP1) and greater suppression of matrix metalloproteinase-2 (MMP2):TIMP1, MMP8:TIMP1, and MMP9:TIMP1 ratios, as a proxy of the activities of these MMPs in SHR. Administration of the antihypertensive agent hydralazine to SHRs significan tly ameliorated HFC-induced liver fibrosis; it suppressed the aggregation of CD68-positive macrophages and the upregulation of platelet-derived growth factor receptor beta, and collagen, type 1, alpha-1 chain. In conclusion, a hypertensive environment exacerbated the hepatic fibrogenetic effects of the HFC diet; while the effects were partially reversed by the antihypertensive agent hydralazine. Our data suggest that antihypertensive drugs hold promise for treating NASH exacerbated by hypertension. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Patient-reported physical functioning is limited in almost half of critical illness survivors 1-year after ICU-admission: A retrospective single-centre study

als.fakia shared this article with you from Inoreader Patient-reported physical functioning is limited in almost half of critical illness survivors 1-year after ICU-admission: A retrospective single-centre study Via PLOS ONE Alerts: New Articles by Lise F. E. Beumeler, Anja van Wieren, Hanneke Buter, Tim van Zutphen, Nynke A. Bruins, Corine M. de Jager, Matty Koopmans, Gerjan J. Navis, E. Christiaan Boerma Post-intensive care unit (ICU) sequelae, including physical and mental health problems, are relatively unexplored. Characteristics commonly used to predict outcome lack prognostic value when it comes to long-term physical recovery. Therefore, the objective of this study was to assess the incidence of non-recovery in long-stay ICU-patients. In this single-centre study, retrospective data of adults with an ICU stay >48 hours who visited the specialized post-ICU clinic, and completed the Dutch RAND 36-item Short Form questionnaire at 3 and 12 months post-ICU, were retrieved from electronic patient records. In cases where physical functioning scores at 12 months were below reference values, patients were allocated to the physical non-recovery (NR) group. Significantly different baseline and (post-)ICU-characteristics were assessed for correlations with physical recovery at 12 months post-ICU. Of 250 patients, 110 (44%) fulfilled the criteria for the NR-group. Neither the severity of i llness, type of admission, nor presence of sepsis did not differ between groups. However, NR-patients had a higher age, were more often female, and had a higher incidence of co-morbidities. Shorter LOS ICU, lower incidence of medical comorbidities, and better physical performance at 3 months were significantly correlated with 1-year physical recovery. Comorbidities and reduced physical functioning at 3 months were identified as independent risk-factors for long-term physical non-recovery. In conclusion, a substantial proportion of long-stay ICU-patients who visited the standard care post-ICU clinic did not fulfil the criteria for full physical recovery at 12 months post-ICU. Commonly used ICU-characteristics, such as severity of illness, do not have sufficient prognostic value when it comes to long-term recovery of health-related quality of life. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Interrater reliability of novice examiners using A-mode ultrasound and skinfolds to measure subcutaneous body fat

als.fakia shared this article with you from Inoreader Interrater reliability of novice examiners using A-mode ultrasound and skinfolds to measure subcutaneous body fat Via PLOS ONE Alerts: New Articles by Dale R. Wagner, Masaru Teramoto Examiners with minimal training and skill are often called upon to make body composition assessments using field methods. This study compared the interrater reliability of novice examiners for the skinfold (SKF) and A-mode ultrasound (US) methods of body composition assessment. Undergraduate Kinesiology majors (48 males, 32 females) with minimal training took both SKF and US measurements at three sites (males: chest, abdomen, thigh; females: triceps, suprailiac, thigh). Interrater reliability was significantly better for US compared to SKF at the thigh (ICCUS = 0.975, ICCSKF = 0.912) and abdomen (ICCUS = 0.984, ICCSKF = 0.693) for men and suprailiac (ICCUS = 0.978, ICCSKF = 0.883) for women. Additionally, interrater reliability of the US method was superior to the SKF method for the estimate of male body fat percentage (ICCUS = 0.990, ICCSKF = 0.862). The 95% CI was generally narrower for the US m ethod than the SKF method at each site. The interrater reliability of the US method was superior to or equal to the SKF method for measuring subcutaneous body fat when novice examiners took the measurements. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Acid-base variables in acute and chronic form of nontuberculous mycobacterial infection in growing goats experimentally inoculated with Mycobacterium avium subsp. hominissuis or Mycobacterium avium subsp. paratuberculosis

als.fakia shared this article with you from Inoreader Acid-base variables in acute and chronic form of nontuberculous mycobacterial infection in growing goats experimentally inoculated with <i>Mycobacterium avium subsp</i>. <i>hominissuis</i> or <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> Via PLOS ONE Alerts: New Articles by Stefanie Bassis, Sina Fischer, Heike Köhler, Petra Reinhold In current literature, data assessing the acid-base equilibrium in animals and humans during bacterial infection are rare. This study aimed to evaluate acid-base deteriorations in growing goats with experimentally induced NTM (nontuberculous mycobacteria) infections by application of the traditional Henderson-Hasselbalch approach and the strong ion model. NTM-challenged animals were orally inoculated with either Mycobacterium avium subsp. hominissuis (MAH; n = 18) or Mycobacterium avium subsp. paratuberculosis (MAP; n = 48). Twenty-five goats served as non-infected controls. Until 51st week post-inoculation (wpi), blood gas analysis, serum biochemical analysis, and serum electrophoresis were performed on venous blood. Fifty percent (9/18) of goats inoculated with MAH developed acute clinical signs like apathy, fever, and diarrhea. Those animals died or had to be euthanized within 11 weeks post-inoculation. This acute form of NTM-infection was ch aracterized by significantly lower concentrations of sodium, calcium, albumin, and total protein, as well as significantly higher concentrations of gamma globulin, associated with reduced albumin/globulin ratio. Acid-base status indicated alkalosis, but normal base excess and HCO3- concentrations, besides significantly reduced levels of SID (strong ion difference), Atot Alb (total plasma concentration of weak non-volatile acids, based on albumin), Atot TP (Atot based on total protein) and markedly lower SIG (strong ion gap). The remaining fifty percent (9/18) of MAH-infected goats and all goats challenged with MAP survived and presented a more sub-clinical, chronic form of infection mainly characterized by changes in serum protein profiles. With the progression of the disease, concentrations of gamma globulin, and total protein increased while albumin remained lower compared to controls. Consequently, significantly reduced album in/globulin ratio and lower Atot Alb as well as higher Atot TP were observed. Changes were fully compensated with no effect on blood pH. Only the strong ion variables differentiated alterations in acid-base equilibrium during acute and chronic NTM-infection. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinicopathologic Significance of EGFR Mutation and HPV Infection in Sinonasal Squamous Cell Carcinoma

a.sfakia shared this article with you from Inoreader Clinicopathologic Significance of EGFR Mutation and HPV Infection in Sinonasal Squamous Cell Carcinoma Via The American Journal of Surgical Pathology - Current Issue Sinonasal squamous cell carcinoma (SNSCC) is sometimes associated with high-risk human papillomavirus (HR-HPV) infection and inverted sinonasal papilloma or oncocytic sinonasal papilloma. Frequent mutations of EGFR and KRAS are reported in inverted sinonasal papilloma–related sinonasal squamous cell carcinoma (ISP-SCC) and oncocytic sinonasal papilloma–related SNSCC, respectively. Here, we attempted to determine the prevalence and the prognostic significances of these alterations in SNSCC. We retrospectively collected 146 SNSCCs, including 14 ISP-SCCs, and comprehensively analyzed the HR-HPV infection by human papillomavirus (HPV)-RNA in sit u hybridization, EGFR gene copy number gain (CNG) by chromogenic in situ hybridization, and gene mutations in EGFR and KRAS by Sanger sequencing. HR-HPV was detected in 11 cases (7.5%), whereas all 14 ISP-SCCs were negative. EGFR mutations were present in 21 (14.7%) of 143 SNSCCs, including 13/14 (92.9%) ISP-SCCs and 8/129 (6.2%) non–ISP-SCCs (P View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Malignant Mesothelioma of the Peritoneum in Women: A Clinicopathologic Study of 164 Cases

a.sfakia shared this article with you from Inoreader Malignant Mesothelioma of the Peritoneum in Women: A Clinicopathologic Study of 164 Cases Via The American Journal of Surgical Pathology - Current Issue Malignant mesothelioma of the peritoneum in women is an uncommon tumor. In this study, we present the clinicopathologic features of 164 such cases seen in our institution over a period of 42 years (1974-2016). Clinical information, pathologic findings, immunohistochemical results, and follow-up were recorded. Hematoxylin and eosin–stained slides were reviewed in all cases. Patients ranged in age from 3 to 85 years, median: 49 years. Most patients presented with abdominal/pelvic pain, although some were asymptomatic, presented with paraneoplastic syndromes or cervical lymphadenopathy. Overall, 9% of patients had a history of direct or indirec t exposure to asbestos. In total, 31% and 69% of patients had either a personal or family history of other tumors; most of these tumors are currently recognized as part of a syndrome. Genetic testing information was available in 5 patients: BAP-1 germline mutation (1), type 2 neurofibromatosis (1), Lynch syndrome (1), McCune-Albright syndrome (1), no BAP-1 or TP53 mutation (1). Most cases had gross and microscopic features typical of malignant mesothelioma of the peritoneum in women; however, some had confounding features such as gelatinous appearance, signet ring or clear cells, and well-differentiated papillary mesothelioma-like areas. Calretinin and WT-1 were the markers more frequently expressed, and up to 23% of the cases showed PAX-8 expression. Patients' treatments predominantly included: chemotherapy, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy. On multivariate analysis, the predominance of deciduoid cells, nuclear grade 3, and the absence of surgi cal treatment were associated with worse overall survival (OS). For all patients, the 3- and 5-year OS were 74.3% and 57.4%, respectively. The 3- and 5-year OS for patients treated with cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy were 88.9% and 77.8%, respectively. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Immunohistochemical Characterization of Giant Cell Tumor of Bone Treated With Denosumab: Support for Osteoblastic Differentiation

a.sfakia shared this article with you from Inoreader Immunohistochemical Characterization of Giant Cell Tumor of Bone Treated With Denosumab: Support for Osteoblastic Differentiation Via The American Journal of Surgical Pathology - Current Issue Giant cell tumor of bone is a locally aggressive, rarely metastasizing neoplasm. Evidence suggests that the neoplastic cells may be osteoblastic in differentiation. Standard treatment is surgical removal, but medical therapy with denosumab, an inhibitor of receptor activator of nuclear factor-κβ ligand, has become a component of patient management in select cases. Denosumab-treated giant cell tumor of bone (DT-GCTB) shows drastic morphologic changes including the presence of abundant bone. To further determine the relationship of the neoplastic cells to osteoblast phenotype, we performed a morphologic and immunohistochemical study on a seri es of DT-GCTB. Cases of DT-GCTB were retrieved from surgical pathology files, available slides were reviewed, and immunohistochemistry for H3.3 G34W, SATB2, and p63 was performed. The cohort included 31 tumors from 30 patients (2:3 male:female), ages 15 to 73 years (median=36 y). The morphology of post–denosumab-treated tumors ranged from tumors composed of an abundant bone matrix with few spindle cells to spindle cell-predominant tumors. Five had focal residual classic CGTB, and 2 manifested mild nuclear atypia. The majority expressed all markers: 86.2% for H3.3 G34W, 96.7% for SATB2, and 100% for p63. All markers stained the various tumor components including spindle cells and the cells on the surface of and within the treated tumor bone matrix. Most markers were also positive in reactive-appearing woven bone adjacent to tumor: 84.6% for H3.3 G34W, 100% for SATB2, and 68% for p63. These findings suggest that denosumab treatment of giant cell tumor of bone results in osteoblast ic differentiation with bone production. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.