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Physical activity improves myocardial structure, function, and resilience via complex, incompletely defined mechanisms. We explored the effects of 1- to 2-wk swim training on cardiac and systemic phenotype in young male C57Bl/6 mice. Two-week forced swimming (90 min twice daily) resulted in cardiac hypertrophy (22% increase in heart:body weight, P < 0.01), with improved inotropy (22% higher left ventricular +dP/d t , P < 0.01) and functional tolerance to ischemia-reperfusion (I-R) (40%-50% reductions in stunning and diastolic dysfunction, P < 0.01; without changes in cell death assessed from enzyme loss) in Langendorff perfused hearts. Initial Western immunoblot analysis indicated no shifts in cardiac expression of determinants of autophagy (LC3A/B), mitochondrial biogenesis/dynamics (PGC-1α, MFN-1, and OPA-1), or stress signaling (caveolin-3 and GSK-3β). Furthermore, no changes in cardiac cytokines (IL-1b, IL-6, IL-10, IL-12, GM-CSF, TNF-α, and IFN-γ) were detected in multiplex immunoassays. Exploratory profiling of RTK phosphorylation provided evidence for moderately increased activity of receptors involved in cardiac/coronary growth and protection (insulin, IGF-1, FGF R2, Tie-2, PDGFβ, and EphB4), together with a fall in M-CSF R and ephrin sub-type receptor phosphorylation. Swimming increased growth factor while reducing inflammatory mediators across extracardiac tissues [brain, pancreas, thymus, lymph nodes, and white adipose tissue (WAT)]. This included a pattern of increased LIF, VEGF, and pentraxin-2 versus reduced CXCL2/MIP-2a, chitinase 3-like 1, CCL6, MMP9, CD40/TNFRSF5, and IGFBP6 in multiple tissues, and a shift to a pro-browning profile in WAT. In summary, swimming produces integrated systemic benefits, improving cardiac growth, inotropy, and resilience in association with increased growth factor and reduced inflammatory and lipogenic mediators in multiple tissues. NEW & NOTEWORTHY Swimming may induce cardiac and systemic benefits distinct from other modes of physical activity. We show that 2-wk forced swim training increases cardiac growth, contractility, and functional resilience to ischemia in hearts of male mice. This is associated with increased growth factor levels and reduced inflammatory and lipogenic protein profiles in peripheral tissues.

Background: Achieving critical view of safety is a key for a successful laparoscopic cholecystectomy (LC) procedure. Near-infrared fluorescence cholangiography using indocyanine green (NIF-ICG) in LC has been extensively used and accepted as beneficial auxiliary tool to visualize extrahepatic biliary structures intraoperatively. This study aimed to analyze its safety and efficacy. Materials and Methods: Searching for potential articles up to March 25, 2022 were conducted on PubMed, Europe PMC, and ClinicalTrials.gov databases. Articles on the near infrared fluorescence during laparoscopy cholecystectomy were collected. Review Manager 5.4 software was utilized to perform the statistical analysis. Results: Twenty-two studies with a total of 3457 patients undergo LC for the analysis. Our meta-analysis revealed that NIF-ICG technique during LC was associated with shorter operative time (Std. Mean Difference -0.86 [95% confidence interval (CI) -1.49 to -0.23], P  = .007, I 2  = 97%), lower conversion rate (risk ratio [RR] 0.28 [95% CI 0.16-0.50], P  < .0001, I 2  = 0%), higher success in identification of cystic duct (CD) (RR 1.24 [95% CI 1.07-1.43], P  = .003, I 2  = 94%), higher success in identification of common bile duct (CBD) (RR 1.31 [95% CI 1.07-1.60], P  = .009, I 2  = 90%), and shorter time to identify biliary structures (Std. Mean Difference -0.52 [95% CI -0.78 to -0.26], P  < .0001, I 2  = 0%) compared with not using NIF-ICG. Conclusions: NIF-ICG technique beneficial for early real-time visualization of biliary structure, shorter operative time, and lower risk of conversion during LC. Larger randomized clinical trials are still needed to confirm the results of our study.

Laser hemorrhoidoplasty (LHP) is known as a new minimally invasive and painless procedure for symptomatic hemorrhoids. However, Milligan-Morgan (MM) may offer the best result of long-term cure rates. In this study, we aim to compare the efficacy between LHP and MM for hemorrhoidal disease treatment. Using specific keywords, we comprehensively go through the potential articles on PubMed, Europe PMC, and Google Scholar sources until April 19, 2022. All published studies on LHP and MM hemorrhoidectomy were collected. Statistical analysis was done by using Review Manager 5.4 software. Twelve studies with a total of 1756 patients with hemorrhoid grades II-IV were included for the analysis. Our pooled analysis revealed that LHP was associated with shorter operative time (p < 0.00001), shorter length of hospital stay (p = 0.0005), lower risk of urinary retention (p = 0.005) and anal stenosis (p = 0.0004), and lower VAS 24-h post-operative (p < 0.00001) when compared with MM. However, LHP and MM did not differ in terms of recurrence rate (p = 0.70). LHP was superior to MM procedure in terms of shortening the recovery time and minimizing post-operative complications for patients with hemorrhoidal disease., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Skeletal muscle unloading due to joint immobilization induces muscle atrophy, which has primarily been attributed to reductions in protein synthesis in humans. However, no study has evaluated the skeletal muscle proteome response to limb immobilization using SWATH proteomic methods. This study characterized the shifts in individual muscle protein abundance and corresponding gene sets after 3 and 14 d of unilateral lower limb immobilization in otherwise healthy young men. Eighteen male participants (25.4 ±5.5 y, 81.2 ±11.6 kg) underwent 14 d of unilateral knee-brace immobilization with dietary provision and following four-weeks of training to standardise acute training history. Participant phenotype was characterized before and after 14 days of immobilization, and muscle biopsies were obtained from the vastus lateralis at baseline (pre-immobilization) and at 3 and 14 d of immobilization for analysis by SWATH-MS and subsequent gene-set enrichment analysis (GSEA). Immobilization reduced vastus group cross sectional area (-9.6 ±4.6%, P <0.0001), immobilized leg lean mass (-3.3 ±3.9%, P = 0.002), unilateral 3-repetition maximum leg press (-15.6 ±9.2%, P <0.0001), and maximal oxygen uptake (-2.9 ±5.2%, P = 0.044). SWATH analyses consistently identified 2281 proteins. Compared to baseline, two and 99 proteins were differentially expressed (FDR <0.05) after 3 and 14 d of immobilization, respectively. After 14 d of immobilization, 322 biological processes were different to baseline (FDR <0.05, P <0.001). Most (77%) biological processes were positively enriched and characterized by cellular stress, targeted proteolysis, and protein-DNA complex modifications. In contrast, mitochondrial organization and energy metabolism were negatively enriched processes. This study is the first to use data independent proteomics and GSEA to show that unilateral lower limb immobilization evokes mitochondrial dysfunction, cellular stress, and proteolysis. Through GSEA and network mapping, we identify 27 hub proteins as potential protein/gene candidates for further exploration., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Umbilical hernia usually manifests as a bulging of umbilicus. Invisible incarcerated umbilical hernia has never been reported., Case Presentation: A 53-years-old obese woman admitted to hospital with abdominal pain and vomitus one day after discharged from other hospital, was managed conservatively as an adhesion small bowel obstruction (ASBO) for seven days. There was history of caesarean section 20 years ago. Abdomen was bloated, there was transverse scar wound in hypogastric region and no signs of external abdominal hernia. Plain abdominal x-ray showed dilated small bowel located in the central part of the abdomen. Abdominal CT scan was done to determine the other cause besides adhesion, it showed incarcerated umbilical hernia and gallbladder stone. Herniorrhaphy and laparoscopic cholecystectomy were performed. During surgery, there was a loop of vital small bowel, trapped in the umbilical defect. Mayo method was performed to close the defect., Discussion: The other causes of small bowel obstruction should be determined besides adhesion, infectious disease and trauma. Umbilical hernia should be considered in obese women even without bulging in the umbilicus. Abdominal CT scan with oral water-soluble contrast is preferred as diagnostic tool to identify the cause of small bowel obstruction., Conclusion: Invisible incarcerated umbilical hernia is possible in obese patients. Routine palpation on potential sites of developing hernia and abdominal CT Scan are necessary to be done in obese patients with small bowel obstruction., (© 2022 The Authors.)

Skeletal muscle atrophy is a physiological response to disuse, aging, and disease. We compared changes in muscle mass and the transcriptome profile after short-term immobilization in a divergent model of high and low responders to endurance training to identify biological processes associated with the early atrophy response. Female rats selectively bred for high response to endurance training (HRT) and low response to endurance training (LRT; n = 6/group; generation 19) underwent 3 day hindlimb cast immobilization to compare atrophy of plantaris and soleus muscles with line-matched controls (n = 6/group). RNA sequencing was utilized to identify Gene Ontology Biological Processes with differential gene set enrichment. Aerobic training performed prior to the intervention showed HRT improved running distance (+60.6 ± 29.6%), while LRT were unchanged (-0.3 ± 13.3%). Soleus atrophy was greater in LRT vs. HRT (-9.0 ±8.8 vs. 6.2 ±8.2%; P<0.05) and there was a similar trend in plantaris (-16.4 ±5.6% vs. -8.5 ±7.4%; P = 0.064). A total of 140 and 118 biological processes were differentially enriched in plantaris and soleus muscles, respectively. Soleus muscle exhibited divergent LRT and HRT responses in processes including autophagy and immune response. In plantaris, processes associated with protein ubiquitination, as well as the atrogenes (Trim63 and Fbxo32), were more positively enriched in LRT. Overall, LRT demonstrate exacerbated atrophy compared to HRT, associated with differential gene enrichments of biological processes. This indicates that genetic factors that result in divergent adaptations to endurance exercise, may also regulate biological processes associated with short-term muscle unloading., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Giant duodenal diverticulum is a very rare case. There are only few cases reported. We reported a case of giant duodenal diverticulum with biliary obstruction caused by mucinous carcinoma of distal common bile duct (CBD), that mimicking Lemmel syndrome., Case Presentation: A 68-years-old man admitted to hospital with recurrent epigastric pain, jaundice and fever. Magnetic resonance cholangiopancreatography showed dilated intrahepatic and extrahepatic biliary tree, dilated gallbladder and cystic mass in pancreatic head that pushed the pancreatic duct ventrally. Emergency laparotomy was performed. Distended edematous gallbladder with necrotic spot, dilated of CBD and compressible bulging of the pancreatic head were found. Duodenotomy in 2nd-3rd part was made and found a giant duodenal diverticulum filled with food and mucus. Tight adhesion to the ampula of Vater, common bile duct, and pancreas due to fibrosis, met difficulties in dissection with a lot of bleeding, hence the diverticulum was not removed. Gastrojejunostomy, cholecystectomy and choledocho-duodenostomy were also done. Pathologic examination of CBD mucus was accordance with mucinous carcinoma., Discussion: Periampullary duodenal diverticulum can cause obstructive jaundice, known as Lemmel syndrome. This case was different as the giant duodenal diverticulum located in the 3rd part filled with food and mucin that compressed both distal CBD and pancreatic duct. The cause of obstructive jaundice could be fibrotic tissue in distal CBD and mucinous carcinoma., Conclusion: Giant duodenal diverticulum with bile obstruction is very rare and challenging in diagnosis and treatment. The other cause of obstruction should be considered such as mucinous carcinoma of distal CBD., (© 2022 The Authors.)

Introduction: Coronavirus disease 2019 (COVID-19) is an acute respiratory tract infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). Recent evidences mentioned the possibility of COVID-19 as a systemic infectious and inflammatory disease. Signs and symptoms of liver and gastrointestinal system are often found in post-acute COVID-19 patients. However, there are only few data found about liver abscess and necrosis in post COVID-19 patients., Case Presentation: A 49-year-old man admitted to the hospital with dyspnea, nausea, loss of appetite and epigastric pain, post confirmed SARS CoV-2 severe pneumonia 1 month ago in ICU with noninvasive ventilator (NIV), enoxaparin, tocilizumab, azithromycin, levofloxacin, hydroxychloroquine, and no preexisting liver condition. Swab PCR result was negative. The result of abdominal computed tomography (CT) scan with contrast was liver abscess formation with hemorrhages measuring about 16 × 12 × 11 cm & 10 × 9x9 cm occupying most of the right lobe liver. The patient underwent exploratory laparotomy, there were multiple liver abscesses in segment 8 with parenchymal liver necrosis and abscesses in segment 7 of liver. Necrosectomy and liver abscess drainage was performed., Clinical Discussion: Pathophysiology of liver damage in post COVID-19 are direct cytotoxicity of SARS-CoV2, immune-mediated due to severe systemic inflammatory response syndrome (SIRS) in COVID-19, hypoxemia, vascular changes due to coagulopathy, endothelitis or congestion from right heart failure, and drug-induced liver injury (DILI)., Conclusion: The possible pathophysiology of liver abscess and necrosis in post COVID-19 should be considered in monitoring and management for both COVID-19 patients and post COVID-19 patients., (© 2021 The Authors.)

Aim: Exercise is cardioprotective, though optimal interventions are unclear. We assessed duration dependent effects of exercise on myocardial ischemia-reperfusion (I-R) injury, kinase signaling and gene expression., Methods: Responses to brief (2 day; 2EX), intermediate (7 and 14 day; 7EX and 14EX) and extended (28 day; 28EX) voluntary wheel running (VWR) were studied in male C57Bl/6 mice. Cardiac function, I-R tolerance and survival kinase signaling were assessed in perfused hearts., Key Findings: Mice progressively increased running distances and intensity, from 2.4 ± 0.2 km/day (0.55 ± 0.04 m/s) at 2-days to 10.6 ± 0.4 km/day (0.72 ± 0.06 m/s) after 28-days. Myocardial mass and contractility were modified at 14-28 days VWR. Cardioprotection was not 'dose-dependent', with I-R tolerance enhanced within 7 days and not further improved with greater VWR duration, volume or intensity. Protection was associated with AKT, ERK1/2 and GSK3β phosphorylation, with phospho-AMPK selectively enhanced with brief VWR. Gene expression was duration-dependent: 7 day VWR up-regulated glycolytic (Pfkm) and down-regulated maladaptive remodeling (Mmp2) genes; 28 day VWR up-regulated caveolar (Cav3), mitochondrial biogenesis (Ppargc1a, Sirt3) and titin (Ttn) genes. Interestingly, I-R tolerance in 2EX/2SED groups improved vs. groups subjected to longer sedentariness, suggesting transient protection on transition to housing with running wheels., Significance: Cardioprotection is induced with as little as 7 days VWR, yet not enhanced with further or faster running. This protection is linked to survival kinase phospho-regulation (particularly AKT and ERK1/2), with glycolytic, mitochondrial, caveolar and myofibrillar gene changes potentially contributing. Intriguingly, environmental enrichment may also protect via similar kinase regulation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

New Findings: What is the central question of this study? The extent to which genetics determines adaptation to endurance versus resistance exercise is unclear. Previously, a divergent selective breeding rat model showed that genetic factors play a major role in the response to aerobic training. Here, we asked: do genetic factors that underpin poor adaptation to endurance training affect adaptation to functional overload? What is the main finding and its importance? Our data show that heritable factors in low responders to endurance training generated differential gene expression that was associated with impaired skeletal muscle hypertrophy. A maladaptive genotype to endurance exercise appears to dysregulate biological processes responsible for mediating exercise adaptation, irrespective of the mode of contraction stimulus., Abstract: Divergent skeletal muscle phenotypes result from chronic resistance-type versus endurance-type contraction, reflecting the principle of training specificity. Our aim was to determine whether there is a common set of genetic factors that influence skeletal muscle adaptation to divergent contractile stimuli. Female rats were obtained from a genetically heterogeneous rat population and were selectively bred from high responders to endurance training (HRT) or low responders to endurance training (LRT; n = 6/group; generation 19). Both groups underwent 14 days of synergist ablation to induce functional overload of the plantaris muscle before comparison to non-overloaded controls of the same phenotype. RNA sequencing was performed to identify Gene Ontology biological processes with differential (LRT vs. HRT) gene set enrichment. We found that running distance, determined in advance of synergist ablation, increased in response to aerobic training in HRT but not LRT (65 ± 26 vs. -6 ± 18%, mean ± SD, P < 0.0001). The hypertrophy response to functional overload was attenuated in LRT versus HRT (20.1 ± 5.6 vs. 41.6 ± 16.1%, P = 0.015). Between-group differences were observed in the magnitude of response of 96 upregulated and 101 downregulated pathways. A further 27 pathways showed contrasting upregulation or downregulation in LRT versus HRT in response to functional overload. In conclusion, low responders to aerobic endurance training were also low responders for compensatory hypertrophy, and attenuated hypertrophy was associated with differential gene set regulation. Our findings suggest that genetic factors that underpin aerobic training maladaptation might also dysregulate the transcriptional regulation of biological processes that contribute to adaptation to mechanical overload., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

The obesity epidemic has increased type II diabetes mellitus (T2DM) across developed countries. Cardiac T2DM risks include ischemic heart disease, heart failure with preserved ejection fraction, intolerance to ischemia-reperfusion (I-R) injury, and refractoriness to cardioprotection. While opioids are cardioprotective, T2DM causes opioid receptor signaling dysfunction. We tested the hypothesis that sustained opioid receptor stimulus may overcome diabetes mellitus-induced cardiac dysfunction via membrane/mitochondrial-dependent protection. In a murine T2DM model, we investigated effects of morphine on cardiac function, I-R tolerance, ultrastructure, subcellular cholesterol expression, mitochondrial protein abundance, and mitochondrial function. T2DM induced 25% weight gain, hyperglycemia, glucose intolerance, cardiac hypertrophy, moderate cardiac depression, exaggerated postischemic myocardial dysfunction, abnormalities in mitochondrial respiration, ultrastructure and Ca 2+ -induced swelling, and cell death were all evident. Morphine administration for 5 days: (1) improved glucose homeostasis; (2) reversed cardiac depression; (3) enhanced I-R tolerance; (4) restored mitochondrial ultrastructure; (5) improved mitochondrial function; (6) upregulated Stat3 protein; and (7) preserved membrane cholesterol homeostasis. These data show that morphine treatment restores contractile function, ischemic tolerance, mitochondrial structure and function, and membrane dynamics in type II diabetic hearts. These findings suggest potential translational value for short-term, but high-dose morphine administration in diabetic patients undergoing or recovering from acute ischemic cardiovascular events., (© 2021 Federation of American Societies for Experimental Biology.)

Ample evidence identifies strong links between major depressive disorder (MDD) and both risk of ischemic or coronary heart disease (CHD) and resultant morbidity and mortality. The molecular mechanistic bases of these linkages are poorly defined. Systemic factors linked to MDD, including vascular dysfunction, atherosclerosis, obesity and diabetes, together with associated behavioral changes, all elevate CHD risk. Nonetheless, experimental evidence indicates the myocardium is also directly modified in depression, independently of these factors, impairing infarct tolerance and cardioprotection. It may be that MDD effectively breaks the heart's intrinsic defense mechanisms. Four extrinsic processes are implicated in this psycho-cardiac coupling, presenting potential targets for therapeutic intervention if causally involved: sympathetic over-activity vs. vagal under-activity, together with hypothalamic-pituitary-adrenal (HPA) axis and immuno-inflammatory dysfunctions. However, direct evidence of their involvement remains limited, and whether targeting these upstream mediators is effective (or practical) in limiting the cardiac consequences of MDD is unknown. Detailing myocardial phenotype in MDD can also inform approaches to cardioprotection, yet cardiac molecular changes are similarly ill defined. Studies support myocardial sensitization to ischemic insult in models of MDD, including worsened oxidative and nitrosative damage, apoptosis (with altered Bcl-2 family expression) and infarction. Moreover, depression may de-sensitize hearts to protective conditioning stimuli. The mechanistic underpinnings of these changes await delineation. Such information not only advances our fundamental understanding of psychological determinants of health, but also better informs management of the cardiac consequences of MDD and implementing cardioprotection in this cohort., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: We examined coupling of myocardial ischaemic tolerance to physical activity and inactivity, and whether this involves modulation of survival (AKT, AMPK, ERK1/2, HSP27, EGFR) and injury (GSK3β) proteins implicated in ischaemic preconditioning and calorie restriction., Methods: Proteomic modifications were assessed in ventricular myocardium, and tolerance to 25-min ischaemia in ex vivo perfused hearts from C57Bl/6 mice subjected to 14-day voluntary activity in running-naïve animals (Active); 7 days of subsequent inactivity (Inactive); brief (day 3) restoration of running (Re-Active); or time-matched inactivity., Results: Active mice increased running speed and distance by 75-150% over 14 days (to ~40 m min(-1) and 10 km day(-1) ), with Active hearts resistant to post-ischaemic dysfunction (40-50% improvements in ventricular pressure development, diastolic pressure and dP/dt). Cardioprotection was accompanied by ~twofold elevations in AKT, AMPK, HSP27 and GSK3β phosphorylation and EGFR expression. Ischaemic tolerance was reversed in Inactive hearts, paralleling reduced EGFR expression and GSK3β and ERK1/2 phosphorylation (AKT, AMPK, HSP27 phosphorylation unaltered). Running characteristics, ischaemic tolerance, EGFR expression and GSK3β phosphorylation returned to Active levels within 1-3 days of restored activity (without changes in AKT, AMPK or HSP27 phosphorylation). Transcriptional responses included activity-dependent Anp induction vs. Hmox1 and Sirt3 suppression, and inactivity-dependent Adora2b induction., Conclusions: Data confirm the sensitive coupling of ischaemic tolerance to activity: voluntary running induces cardioprotection that dissipates within 1 week of inactivity yet recovers rapidly upon subsequent activity. While exercise in naïve animals induces a molecular profile characteristic of preconditioning/calorie restriction, only GSK3β and EGFR modulation consistently parallel activity- and inactivity-dependent ischaemic tolerance., (© 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Exercise triggers hormesis, conditioning hearts against damaging consequences of subsequent ischemia-reperfusion (I/R). We test whether "low-stress" voluntary activity modifies I/R tolerance and molecular determinants of cardiac survival. Male C57BL/6 mice were provided 7-day access to locked (7SED) or rotating (7EX) running-wheels before analysis of cardiac prosurvival (Akt, ERK 1/2) and prodeath (GSK3β) kinases, transcriptomic adaptations, and functional tolerance of isolated hearts to 25-min ischemia/45-min reperfusion. Over 7 days, 7EX mice increased running from 2.1 ± 0.2 to 5.3 ± 0.3 km/day (mean speed 38 ± 2 m/min), with activity improving myocardial I/R tolerance: 7SED hearts recovered 43 ± 3% of ventricular force with diastolic contracture of 33 ± 3 mmHg, whereas 7EX hearts recovered 63 ± 5% of force with diastolic dysfunction reduced to 23 ± 2 mmHg (P < 0.05). Cytosolic expression (total protein) of Akt and GSK3β was unaltered, while ERK 1/2 increased 30% in 7EX vs. 7SED hearts. Phosphorylation of Akt and ERK 1/2 was unaltered, whereas GSK3β phosphorylation increased ∼90%. Microarray interrogation identified significant changes (≥1.3-fold expression change, ≤5% FDR) in 142 known genes, the majority (92%) repressed. Significantly modified paths/networks related to inflammatory/immune function (particularly interferon-dependent), together with cell movement, growth, and death. Of only 14 induced transcripts, 3 encoded interrelated sarcomeric proteins titin, α-actinin, and myomesin-2, while transcripts for protective actin-stabilizing ND1-L and activator of mitochondrial biogenesis ALAS1 were also induced. There was no transcriptional evidence of oxidative heat-shock or other canonical "stress" responses. These data demonstrate that relatively brief voluntary activity substantially improves cardiac ischemic tolerance, an effect independent of shifts in Akt, but associated with increased total ERK 1/2 and phospho-inhibition of GSK3β. Transcriptomic data implicate inflammatory/immune and sarcomeric modulation in activity-dependent protection.