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Objective This longitudinal study examined changes in psychological outcomes of perioperative frontline healthcare workers at one of Australia’s most COVID-19 affected hospitals, following the surge and decline of a pandemic wave. Method A single-centred longitudinal online survey was conducted between 26 May and 17 November 2020. Recruitment was via poster advertisement and email invitation. The survey was sent out every 4 weeks, resulting in seven time-points. Results In total, 385 survey results were analysed from 193 staff (about 64% response rate), 72 (37%) of whom completed the survey more than once. The prevalence of moderate-to-severe anxiety and depressive symptoms peaked at 27% and 25%, respectively, during the pandemic surge. Up to 35% displayed post-traumatic stress disorder (PTSD) symptoms. Although not statistically significant, the trend of depressive and PTSD symptoms worsened over time, especially among females and anaesthetic/surgical trainees, despite subsidence of the pandemic curve. Technicians and anaesthetic/scrub nurses were the at-risk groups with worst psychological outcomes. Conclusion We found persistent mental health impacts on frontline perioperative HCWs despite subsidence of the pandemic wave. Further research is needed to determine the extent and trajectory of such impacts with larger sample sizes to determine generalisability to frontline HCWs in general.

To compare the performance of four N95 respirator types with respect to quantitative fit test pass rate and health care worker-rated usability and comfort.Health care workers who participated in the respiratory protection program at the Royal Melbourne Hospital, 1 October 2020 - 31 May 2021. Participants underwent quantitative N95 respirator fit testing (at least three of four types: semi-rigid cup, flat-fold cup, duckbill, and three-panel flat-fold types), and were invited to complete an online usability and comfort assessment for respirators for which their fit test results were passes.Fit test pass rate, and user-rated overall comfort and assessment ratings (five-point Likert scales), by N95 respirator type.A total of 2161 health care workers underwent quantitative fit testing (women, 1586 [73.4%]; nurses, 1271 [58.8%]). The overall fit test pass rates were 65.0% for the semi-rigid cup respirators (1029/1583 tests), 32.4% for the flat-fold respirator (660/2035 tests), 59.2% for the duckbill respirators (2005/3387 tests), and 96.4% for the three-panel flat-fold respirator (1876/1946 tests). 378 health care workers completed the comfort and usability survey. Overall comfort and assessment ratings each differed by respirator group (P 0.001); the median overall comfort (4; IQR, 3-4) and overall assessment values (4; IQR, 3-5) were highest for the three-panel flat-fold respirator and lowest for the semi-rigid cup respirators (comfort: 2 [IQR, 1-3]; assessment: 2 [IQR, 2-3]).The three-panel flat-fold N95 respirator outperformed the three alternative types with regard to fit test pass rate and user-rated comfort and usability. To maximise respiratory protection for health care workers, these factors should be considered when making respirator procurement decisions.

Aim We investigated whether acute carbohydrate ingestion reduced arterial potassium concentration ([K+]) during and after intense exercise and delayed fatigue. Methods In a randomized, double‐blind crossover design, eight males ingested 300 ml water containing 75 g glucose (CHO) or placebo (CON); rested for 60 min, then performed high‐intensity intermittent cycling (HIIC) at 130% V˙O2peak, comprising three 45‐s exercise bouts (EB), then a fourth EB until fatigue. Radial arterial (a) and antecubital venous (v) blood was sampled at rest, before, during and after HIIC and analyzed for plasma ions and metabolites, with forearm arteriovenous differences (a‐v diff) calculated to assess inactive forearm muscle effects. Results Glucose ingestion elevated [glucose]a and [insulin]a above CON (p = .001), being, respectively, ~2‐ and ~5‐fold higher during CHO at 60 min after ingestion (p = .001). Plasma [K+]a rose during and declined following each exercise bout in HIIC (p = .001), falling below baseline at 5 min post‐exercise (p = .007). Both [K+]a and [K+]v were lower during CHO (p = .036, p = .001, respectively, treatment main effect). The [K+]a‐v diff across the forearm widened during exercise (p = .001), returned to baseline during recovery, and was greater in CHO than CON during EB1, EB2 (p = .001) and EB3 (p = .005). Time to fatigue did not differ between trials. Conclusion Acute oral glucose ingestion, as used in a glucose tolerance test, induced a small, systemic K+‐lowering effect before, during, and after HIIC, that was detectable in both arterial and venous plasma. This likely reflects insulin‐mediated, increased Na+,K+‐ATPase induced K+ uptake into non‐contracting muscles. However, glucose ingestion did not delay fatigue., Acute glucose intake substantially elevated insulin, with a systemic K+‐lowering effect evident in arterial and antecubital venous plasma before, during, and post‐exercise. An increased arterio‐venous K+ difference across the relatively inactive forearm musculature with glucose ingestion was consistent with increased K+ uptake in non‐active muscle; this was likely mediated via insulin‐induced activation of sodium‐potassium ATPase.

Author(s): Brunt, Elizabeth; Aishima, Shinichi; Clavien, Pierre-Alain; Fowler, Kathryn; Goodman, Zachary; Gores, Gregory; Gouw, Annette; Kagen, Alex; Klimstra, David; Komuta, Mina; Kondo, Fukuo; Miksad, Rebecca; Nakano, Masayuki; Nakanuma, Yasuni; Ng, Irene; Paradis, Valerie; Nyun Park, Young; Quaglia, Alberto; Roncalli, Massimo; Roskams, Tania; Sakamoto, Michiie; Saxena, Romil; Sempoux, Christine; Sirlin, Claude; Stueck, Ashley; Thung, Swan; Tsui, WMS; Wang, Xin-Wei; Wee, Aileen; Yano, Hirohisa; Yeh, Matthew; Zen, Yoh; Zucman-Rossi, Jessica; Theise, Neil | Abstract: Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as "combined (or mixed) hepatocellular-cholangiocarcinoma." These tumors, although described over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency and clinical recognition. Currently, because of a lack of common terminology in the literature, effective treatment and predictable outcome data have been challenging to accrue. This article represents a consensus document from an international community of pathologists, radiologists, and clinicians who have studied and reported on these tumors and recommends a working terminology for diagnostic and research approaches for further study and evaluation.ConclusionIt is recommended that diagnosis is based on routine histopathology with hematoxylin and eosin (HaE); immunostains are supportive, but not essential for diagnosis. (Hepatology 2018;68:113-126).

The ursane triterpenoids, asiatic acid 1 and madecassic acid 2, are the major pharmacological constituents of Centella asiatica, commonly known as Gotu Kola, which is used traditionally for the treatment of anxiety and for the improvement of cognition and memory. Using the two-electrode voltage-clamp technique, these triterpenes, and some semisynthetic derivatives, were found to exhibit selective negative modulation of different subtypes of the GABAA receptor expressed in Xenopus laevis oocytes. Despite differing by only one hydroxyl group, asiatic acid 1 was found to be a negative modulator of the GABA-induced current at α1 β2 γ2L, α2 β2 γ2L and α5 β3 γ2L GABAA receptors, while madecassic acid 2 was not. Asiatic acid 1 exhibited the greatest effect at α1 β2 γ2L (IC50 37.05 μm), followed by α5 β3 γ2L (IC50 64.05 μm) then α2 β2 γ2L (IC50 427.2 μm) receptors. Conversion of the carboxylic acid group of asiatic acid 1 to a carboxamide group (2α,3β,23-trihydroxy-urs-12-en-28-amide 5) resulted in enhanced inhibition at both the α1 β2 γ2L (IC50 14.07 μm) and α2 β2 γ2L receptor subtypes (IC50 28.41 μm). The results of this study, and the involvement of α5 -containing GABAA receptors in cognition and memory, suggest that asiatic acid 1 may be a lead compound for the enhancement of cognition and memory.

The common law presumption that a boy under the age of 14 is incapable of sexual intercourse has provoked controversial debates in Hong Kong. This article describes a 6-step advocacy journey to examine how community efforts have helped modify this law so that juvenile male sexual offenders under the age of 14 who have committed the crime of having sexual intercourse with underage females can be sentenced to receive appropriate treatment. Seven court cases provided by the magistrates' courts in Hong Kong were used in this advocacy effort for the removal of the presumption in July 2012. Although this effort has yet to reveal signs of effectiveness, it represents greater public awareness about providing rehabilitation appropriate for juvenile sex offenders through a formal sentence. Restorative justice, as opposed to retributive or punitive justice, places an emphasis on rehabilitation of the offender and restoration of victims to a place of wholeness.

We investigated whether potassium (K+) disturbances during and following intense exercise may be pronounced when utilizing a large contracting muscle mass, examining maximal 2,000-m rowing exercise effects on radial arterial plasma K+ concentration ([K+]a) in 11 healthy adults. Blood was sampled at baseline, preexercise, each 30 s during rowing, and for 30 min postexercise. Time to complete 2,000 m was 7.26 ± 0.59 min; power output at 30 s was 326 ± 81 W (mean ± SD). With exercise time expressed in deciles, power output fell 16.5% from the first to fourth decile ( P < 0.05) and 19.9% at the ninth decile ( P < 0.05); EMG median frequency declined 4.6% by the third decile and 5.5% by the eighth decile ( P < 0.05). Plasma [K+]a increased from 3.89 ± 0.13 mM at rest to 6.13 ± 0.46 mM by 90 s rowing ( P < 0.001) and was then sustained until end exercise ( P < 0.001). In recovery, [K+]a decreased abruptly, reaching 3.33 ± 0.22 mM at 5 min postexercise ( P < 0.001) and remaining below preexercise after 30 min ( P < 0.005). At end exercise, blood [lactate]a (preexercise 0.64 ± 0.18 mM) reached 10.87 ± 1.33 mM, plasma volume decreased 9.7 ± 2.3% from preexercise, and pHa decreased to 7.10 ± 0.07 units ( P < 0.001). In conclusion, arterial hyperkalemia was sustained during exhaustive rowing reflecting a balance between K+ release and reuptake in contracting muscles and K+ uptake by inactive muscles. While high, the [K+]a was lower than anticipated compared with maximal cycling or sprinting, possibly reflecting greater adrenergic response and Na+,K+-ATPase activity in contracting muscles; fatigue was evidenced by reduced power output and EMG median frequency. A prolonged hypokalemia after rowing likely reflected continuing muscular Na+,K+-ATPase activity.

A novel paradigm in tumor biology suggests that cancer growth is driven by stem-like cells within a tumor, called tumor-initiating cells (TICs) or cancer stem cells (CSCs). Here we describe the identification and characterization of such cells from hepatocellular carcinoma (HCC) using the marker CD133. CD133 accounts for approximately 1.3%-13.6% of the cells in the bulk tumor of human primary HCC samples. When compared with their CD133⁻ counterparts, CD133(+) cells not only possess the preferential ability to form undifferentiated tumor spheroids in vitro but also express an enhanced level of stem cell-associated genes, have a greater ability to form tumors when implanted orthotopically in immunodeficient mice, and can be serially passaged into secondary animal recipients. Xenografts resemble the original human tumor and maintain a similar percentage of tumorigenic CD133(+) cells. Quantitative PCR analysis of 41 separate HCC tissue specimens with follow-up data found that CD133(+) tumor cells were frequently detected at low quantities in HCC, and their presence was also associated with worse overall survival and higher recurrence rates. Subsequent differential microRNA expression profiling of CD133(+) and CD133⁻ cells from human HCC clinical specimens and cell lines identified an overexpression of miR-130b in CD133(+) TICs. Functional studies on miR-130b lentiviral-transduced CD133⁻ cells demonstrated superior resistance to chemotherapeutic agents, enhanced tumorigenicity in vivo, and a greater potential for self renewal. Conversely, antagonizing miR-130b in CD133(+) TICs yielded an opposing effect. The increased miR-130b paralleled the reduced TP53INP1, a known miR-130b target. Silencing TP53INP1 in CD133⁻ cells enhanced both self renewal and tumorigenicity in vivo. Collectively, miR-130b regulates CD133(+) liver TICs, in part, via silencing TP53INP1.

The outcomes of hepatitis B virus (HBV)-related hepatitis after liver transplantation (LT) without hepatitis B immune globulin (HBIG) is not well documented. This study aims to determine the outcomes of chronic hepatitis B (CHB) patients using an HBIG-free regimen. All biopsies performed 3 months or more after LT in consecutive CHB patients transplanted from 2003 to 2012 were reviewed. None of the patients received HBIG. Results of all liver histologies were reviewed to determine the cause of graft dysfunction. Of the 435 patients transplanted during this period, 263 liver biopsies were performed in 144 patients. Thirty-six patients were positive for hepatitis B surface antigen (HBsAg) with undetectable HBV DNA at the time of biopsy, and none had histological evidence of HBV infection. Of the 263 biopsies, 44 (17%) had evidence of fibrosis. There was a significantly higher rate of fibrosis in those with large duct obstruction compared to those without (51% versus 9%, respectively; P

Background and Aim: Decrease in expression of the E-cadherin–catenin complex is an important element in gastric carcinogenesis. However, the expression of the complex in gastric precancerous lesions has not been well studied. The present study aimed to examine the serial change in expression of E-cadherin–catenin complex in the precancerous lesions of gastric cancer patients. Methods: Gastrectomy specimens of 40 patients with gastric cancer were retrieved. Areas with chronic gastritis, atrophic gastritis, intestinal metaplasia and adenocarcinoma were identified and immunostained for α-catenin, β-catenin and E-cadherin. The results were scored semiquantitatively by two independent pathologists using a validated scoring system. Results: A significant decrease in score was observed in 5% (1/22) of α-catenin, 0% (0/22) of β-catenin and 9% (2/22) of E-cadherin in chronic atrophic gastritis patients, and in 28% (5/18) of α-catenin, 67% (10/15) of β-catenin and 57% (8/14) of E-cadherin in intestinal metaplasia patients. The scoring of α-catenin, β-catenin and E-cadherin correlated with each other. Forty-three percent of patients had concordant changes of scores along the gastritis–adenocarcinoma sequence. There was no association between Helicobacter pylori status and E-cadherin–catenin complex expression. Conclusion: Deregulation of the E-cadherin–catenin complex was observed in the majority of precancerous lesions in patients with gastric adenocarcinoma, which has potential diagnostic and therapeutic implications. © 2003 Blackwell Publishing Asia Pty Ltd

The course of gastritis and Campylobacter pylori was studied in a single-blind randomized trial comparing cimetidine 200 mg three times a day and 400 mg at night and sucralfate 1 g four times a day orally for four weeks in 140 patients with proved duodenal ulcer. At least two antral biopsies were performed during endoscopy before entry and at the end of four weeks. The activity and the degree of chronic inflammation, as assessed histologically by the degree of infiltration of, respectively, polymorphs and chronic inflammatory cells, were graded blindly by two pathologists as nil, mild, moderate, or severe. The density of C. pylori, as assessed after Warthin-Starry stain, was similarly graded. Ulcer-healing rates were comparable in the cimetidine (73.2 percent) and sucralfate (79.7 percent) groups. Improvement of the activity of gastritis occurred significantly (p less than 0.05) more frequently in the sucralfate (33.3 percent) than in the cimetidine group (18.3 percent), and remained so (p less than 0.05) when only patients with healed ulcer were compared. The density of C. pylori decreased significantly in the sucralfate group after treatment (p less than 0.01) but not in the cimetidine group. The 12-month ulcer relapse rates were significantly (p less than 0.05) lower by life-table analysis in patients healed with sucralfate than in those healed with cimetidine and were unaffected by either the density of Campylobacter in either group or the improvement of the gastritis. It is concluded that sucralfate improves duodenal ulcer-associated antral gastritis and decreases the density of C. pylori, and that factors other than bacterial density and antral gastritis may be responsible for the advantage of sucralfate over cimetidine in ulcer relapse.

SUMMARY Campylobacter pylori has been associated closely with active antral gastritis and duodenal ulcer but its pathogenetic role remains uncertain. The present longitudinal study examined, prospectively, the endoscopic antral biopsies of 45 patients with duodenal ulceration, taken before and after healing of the duodenal ulcer, during remission and at relapse. The biopsies were examined for the activity and degree of chronic inflammation of the gastritis and for the occurrence and density of C. pylori by Warthin-Starry stain. Before treatment the frequency of chronic active antral gastritis was 100% and the occurrence of C. pylori was 97%. Compared with the pre-treatment state, there was no significant change in either the frequency and severity of antral gastritis, or in the occurrence and density of the bacteria in the antral mucosa at the time the duodenal ulcer healed, during remission, or at relapse. The occurrence of the bacteria was significantly more frequent during remission, than at the time when the ulcer had healed initially (P < 0.05). These results suggest that the bacterium may not play an important pathogenetic role in ulcer healing and relapse, when patients are managed using an H2-blocker.