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Background Thoracentesis and tube thoracostomy are common procedures with bleeding risks, but existing guidelines may be overly conservative. We reviewed the evidence on the safety of thoracentesis and tube thoracostomy in patients with uncorrected coagulopathy. Research Question Is it safe to perform thoracentesis and tube thoracostomy in patients with uncorrected coagulopathy? Study Design and Methods This systematic review was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. PubMed and Embase were searched from inception through December 31, 2019. Included studies involved patients with uncorrected coagulopathy because of disease (eg, thrombocytopenia, liver cirrhosis, kidney failure) or drugs (eg, antiplatelets, anticoagulants). Relevant outcomes were major bleeding and mortality. Results Eighteen studies (5,134 procedures) were included. Using random-effects meta-analysis, the pooled major bleeding and mortality rate was 0 (95% CI, 0%-1%). No publication bias was found. Excluding six studies that were in abstract form, meta-analysis of the remaining 12 full articles showed that the pooled major bleeding and mortality rate also was 0 (95% CI, 0%-2%). Subgroup analysis performed for patients with uncorrected coagulopathy resulting from disease or drugs showed similar results. Interpretation Among patients with uncorrected coagulopathy who underwent thoracentesis or tube thoracostomy, major bleeding and mortality complications were uncommon. Our results suggest that in appropriately selected patients, thoracentesis or tube thoracostomy can be performed safely. Trial Registry PROSPERO; No.: CRD42020152226; URL: www.crd.york.ac.uk/prospero/

Objective: To demonstrate differences in cardiovascular structure and function between diabetic and non-diabetic older adults. To investigate associations between acyl-carnitines and cardiovascular function as indexed by imaging measurements. Methods: A community-based cohort of older adults without cardiovascular disease underwent current cardiovascular imaging and metabolomics acyl-carnitines profiling based on current and archived sera obtained fifteen years prior to examination. Results: A total of 933 participants (women 56%, n=521) with a mean age 63±13 years were studied. Old diabetics compared to old non-diabetics had lower myocardial relaxation (0.8±0.2 vs 0.9±0.3, p=0.0039); lower left atrial conduit strain (12±4.3 vs 14±4.1, p=0.045), lower left atrial conduit strain rate (-1.2±0.4 vs -1.3±0.5, p=0.042) and lower ratio of left atrial conduit strain to left atrial booster strain (0.5±0.2 vs 0.7±0.3, p=0.0029). Higher levels of archived short chain acyl-carnitine were associated with present-day impairments in myocardial relaxation (C5:1; OR 1.03, p=0.011), worse left atrial conduit strain function (C5:1; OR 1.03, p=0.037). Increases in hydroxylated acyl-carnitines were associated with worse left atrial conduit strain [(C4-OH; OR 1.05, p=0.0017), (C16:2-OH; OR 1.18, p=0.037)]. Current, archived and changes in long chain acyl-carnitines were associated with cardiovascular functions [(C16; OR 1.02, p=0.002), (C20:3; OR 1.01, p=0.014), (C14:3; OR 1.12, p=0.033), (C18:1; OR 1.01, p=0.018), (C18:2; OR 1.01, p=0.028), (C20:4; OR 1.10, p=0.038)] (all p

Differences in dietary habits of people with vs without irritable bowel syndrome and their association with symptom and psychological status: A pilot study

Background Cryptic balanced translocations often evade detection by conventional cytogenetics. The preimplantation genetic testing (PGT) technique can be used to help carriers of balanced translocations give birth to healthy offspring; however, for carriers of cryptic balanced translocations, there is only one report about trying assisted reproduction using the PGT technique but with no pregnancy. Case presentation A couple had 3 births out of 4 pregnancies, and all died very young, with two of them having both cerebral palsy and glaucoma. The husband with oligoasthenospermia was found to be a cryptic balanced translocation carrier for t (9,13) (p24.3, q31.3) with G-banding, FISH (fluorescence in-situ hybridization), and MicroSeq techniques; live birth of a healthy baby girl was achieved with PGT/NGS (next-generation sequencing) for the couple. Conclusion Here, we report for the first time a successful live birth of a healthy baby through the PGT technique for a family in which the husband is a carrier of the cryptic balanced translocation t (9,13) (p24.3, q31.3), presumably causative for cerebral palsy and glaucoma. Our study showed that the PGT/NGS technique can effectively help families with a cryptic balanced translocation have healthy offspring.

Melanoma is the most aggressive form of skin cancer affecting patients worldwide and has the potential to metastasize to virtually any organ in the body. Early detection is of paramount importance to minimize patient morbidity and mortality. However, there has been increasing evidence highlighting that geographical and ethnic variations in the clinical presentation of melanoma do exist. Unlike the Western population, the major subtype of melanoma affecting the Asian population is in fact, acral lentiginous melanoma (ALM) and not superficial spreading melanoma (SSM).We hereby present a case of left hallux subungual melanoma with scalp metastasis. This case underscores the importance of the examination of acral skin and the nail apparatus for melanoma in Asians.

The adverse implications of obesity extend beyond physical health to include negative impact on quality of life (QoL), mood, and eating habits. While bariatric surgery provides successful weight loss and metabolic benefits, studies describe conflicting results on QoL and mood-related outcomes. Patients (n = 140) with class II/III obesity and T2DM were recruited from 2015 to 2019, and stratified based on medical or surgical treatment. Questionnaires including the Hospital Anxiety and Depression Scale, Euro QoL visual analogue scale (EQ-VAS), and Revised 21-item Three-Factor Eating Questionnaire (TFEQ-R21) were recorded at baseline, 6 months, and 12 months after treatment. At baseline, the surgical group (n = 55) and medical group (n = 85) had no significant difference in questionnaire outcomes. At 6 and 12 months, EQ-VAS was higher in the surgical group (12 months surgical 82.00 ± 12.64, medical 72.81 ± 16.56, p = 0.001), with greater improvement from baseline. HADS-D scores at 12 months were lower in the surgical group (surgical 2.60 ± 2.88, medical 3.90 ± 3.58, p = 0.025). At 12 months, the surgical group also had better TFEQ-R21 scores, with higher cognitive restraint scores (surgical 19.09 ± 3.00, medical 16.69 ± 3.61, p

Background Laparoscopic sleeve gastrectomy (LSG) has become the preferred bariatric procedure in many countries. However, there is one shortcoming of LSG in the long-term follow-up, and this is the onset of gastro-esophageal reflux disease (GERD) and erosive esophagitis (EE). Conversion to Roux-en-Y gastric bypass (RYGB) is considered an option in patients unresponsive to medical therapy. Currently, there is no evidence of EE improvement or resolution after conversion surgery. In this study, we objectively evaluate the effectiveness of RYGB in management of EE with upper endoscopy (EGD) to identify the significant variables in patients with GERD symptoms post LSG refractory to medical therapy and require conversion surgery. Methods Over a period of 11 years (2008–2019) at Singapore General Hospital, we retrospectively reviewed a prospectively collected database of a cohort of patients whom had conversion surgery to RYGB for refractory GERD and EE after LSG. Patient’s endoscopic findings and demographic and anthropometric data were analyzed. Results We identified a total of 14 patients who underwent LSG to RYGB conversions for endoscopic proven erosive esophagitis in our unit during the study period. Eight patients (57.1%) had concurrent hiatal hernia repaired. Nine (64.3%) patients were females. The median age of patients in this cohort was 44 (range 30–61) years. Mean weight and BMI were 87.7 kg (± 19.2) and 32.8 (± 3.09) kg/m2, respectively, on the day of conversion surgery. The median time between LSG and revision to RYGB was 36 (range 6–68) months. Seven patients (50%) had complete resolution of GERD symptoms after conversion, and 6 patients (42.9%) had partial resolution. Six out of 7 patients had complete resolution of EE. There were 4 anastomotic strictures (28.6%). Older patients, Indian ethnicity, present of hiatal hernia and lower weight loss after initial LSG were more likely to undergo conversion surgery. Conclusion Conversion to RYGB after LSG is clinically relevant and may be a feasible solution if patients have ongoing GERD refractory to medical therapy. Ninety-three percent of our patients achieved complete resolution of their GERD symptoms and significant improvement of erosive esophagitis with significant weight loss after conversion. This study has important implications as LSG is increasingly being performed and a proportion of these will need revision surgery for various reasons, particularly GERD which is extremely prevalent.

Purpose To investigate the therapeutic effects of vitamin A (VitA) or vitamin D (VitD) against bronchopulmonary dysplasia (BPD) and the underlying mechanism from the perspective of macrophage polarization. Methods A BPD model was established on rats. Hematoxylin and eosin staining was used to evaluate the pathological state of lung tissues. The expression of CD68 was determined by immunohistochemistry assay. The infiltration of M1 and M2 macrophages was marked by immunofluorescence. The expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-10, nitric oxide synthase (NOS), and arginase-1 (Arg-1) were evaluated by quantitative reverse transcription polymerase chain reaction assay, and the ratio of M1/M2 in the bronchoalveolar lavage fluid was determined by flow cytometry. Results Disordered alveolar structure in the lung tissue, thickened alveolar septa, and infiltration of inflammatory cells around the alveolar cavity and pulmonary septa were observed in lipopolysaccharide (LPS)-treated rats. On day 21 post-natal (PN21), the pathological state was aggravated, alveolar simplification was observed, and the expression level of CD68 in the lung tissues was significantly elevated, and these results were dramatically alleviated in the VitA, VitD, and VitA+VitD groups. However, no significant synergistic effect was observed between VitA+VitD and VitA or VitD groups. After the administration with VitA or VitD, IL-10 and Arg-1 were up-regulated on PN10. TNF-α and NOS were up-regulated on PN21. The ratio of macrophage polarization and M2 macrophages increased considerably after the stimulation with LPS, and this result was significantly reversed by VitA or VitD. A significant difference was observed on the effect of different dosages of VitA or VitD on macrophage polarization, among which moderate dosages of VitA or VitD exerted the most significant influence on macrophage polarization. Conclusion The BPD-linked pulmonary injury stimulated by LPS can be ameliorated by the introduction of VitA or VitD.

Data on attitudes and perceptions towards obesity are lacking in Asia. Participants who attended an obesity public forum were surveyed concerning obesity and its treatment options. Although obesity is generally accepted as a disease with biological underpinnings such as hormonal imbalances and slow metabolic rate, it is also regarded as an issue of personal responsibility. 65.1% believed that weight-loss medications are dangerous. 20.6% thought that pharmacotherapy is effective for weight loss, whereas 41.1% were unsure. Most believed that bariatric surgery could improve health (81.9%) and diabetes control (74.0%) although 64.1% were unsure of its risks.

Background: There is little direct or indirect evidence of the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on early childhood development.Methods: We conducted a prospective, observational cohort study in China from May 1 to October 31, 2020, that enrolled 135 mother-infant dyads: 57 dyads in the infection cohort and 78 in the non-infection cohort. Among all infants, 14.0% were preterm birth in the infection cohort and 6.4% in the non-infection cohort. Participants were followed by telephone interviews to collect demographic characteristics, medical records of coronavirus disease 2019, breastfeeding data, and early childhood development was assessed by the Age and Stage Questionnaire (ASQ-3) and Age and Stage Questionnaire Social-Emotional (ASQ:SE-2) Chinese versions at 3 months after childbirth. We used multivariable Poisson regression models to estimate the relative risk (RR) of SARS-CoV-2 infection. Multivariable linear regression models and a mediation model were used to test the direct and indirect associations between SARS-CoV-2 infection and the ASQ-3 score. This study was approved by the Peking University Third Hospital Medical Science Research Ethics Committee (No. IRB00006761-M2020127).Results: In the infection cohort, 13.6% of the children showed social–emotional developmental delay, and 13.5% showed overall developmental delay. The corresponding rates in the non-infection cohort were 23.4 and 8.1%. Compared with the non-infection cohort, SARS-CoV-2 infection during pregnancy did not increase the risk of social-emotional (RR = 0.87, 95% CI: 0.51–1.49) or overall (RR = 1.02, 95% CI: 0.60–1.73) developmental delay. The mediation model showed that SARS-CoV-2 infection indirectly affected the ASQ-3 score by increasing the length of mother–infant separation.Conclusions: SARS-CoV-2 during late pregnancy did not increase the risk of developmental delay of the offspring 3 months after delivery. However, SARS-CoV-2 may have indirect effects on early childhood development by increasing mother-infant separation.

Background: Bile acids (BAs) are traditionally associated with lipid absorption and phase II detoxification by forming various BA conjugates. Recently, it has been discovered that BAs also regulate glucose metabolism, and the increase in BAs in patients following bariatric surgery may contribute to the post-surgery improvement in insulin resistance (IR). However, while Roux-en-Y gastric bypass can increase BA concentrations post-surgery, this may not be the case after laparoscopic sleeve gastrectomy (LSG). We hypothesized that the profiling of BAs that include the conjugated BA species could detect post-surgery BA changes after LSG. To test our hypothesis, we performed comprehensive profiling of BAs in Asian individuals with morbid obesity at baseline, and at 6 months following LSG. Methods: Fourteen subjects scheduled for LSG were recruited. Anthropometric measurements, oral glucose tolerance test, and biochemistry tests were performed at baseline and at 6 months after LSG. BAs were profiled using liquid chromatography–mass spectrometry. Results: At 6 months, subjects lost significant weight from 117.4±5.4 to 92.1±3.8 kg and demonstrated significant improvement in IR. HOMA-IR decreased from 6.2±0.7 to 2.0±0.2 and the Matsuda index increased from 1.9±0.3 to 3.3±0.3. We did not detect any significant post-operative change in the levels of total BAs (5237.1±1219.4 vs. 3631.7±457.9, p=0.181) or non-sulfated BAs after LSG. However, sulfated BA species increased significantly after LSG. Conclusion: Our study showed that the serum concentrations of sulfated BA species in morbidly obese Asian individuals increased significantly 6 months after LSG; the increase in sulfated BAs after LSG might contribute to the post-surgery improvement of metabolic health.

Background Parent-child separation is a considerable adversity for left-behind children (LBC), but there is little evidence on the association between detailed characteristics of parent-child separation and social-emotional development among LBC. This study examined the characteristics of parent-child separation and its impacts on developmental delay among under-3 LBC in poor rural China. Methods We used data from 811 LBC surveyed in five poor counties in rural China in 2018. Detailed characteristics of their parental migration were recalled by their primary caregivers in face-to-face interviews. The children’s social-emotional development was measured by using the Ages and Stages Questionnaire: Social-Emotional. Logistic regression was employed to examine the association of detailed characteristics of parent-child separation with early social-emotional problems after adjusting for the children’s and primary caregivers’ sociodemographic characteristics. Results 287 (35.4%) children were left behind by fathers and cared for by mothers (FM-MC), while 524 (64.6%) were left behind by both parents and cared for by grandparents (PM-GC). The rate of social-emotional problems among LBC was 36.8% (PM-GC vs FM-MC: 40.6% vs 29.5%; aOR 1.51, 95% CI: 1.06 to 2.16). For paternal migration, the medians of the child’s age at the first migration and average duration per migration were 3 months (IQR: 1 to 9 months) and 4.48 months (IQR: 2.38 to 7.54 months), respectively. For maternal migration, the corresponding values were 9 months (IQR: 6 to 13 months) and 4.65 months (IQR: 2.71 to 7.62 months), respectively. On average, LBC had been separated from fathers for 72% of their life due to paternal migration and from mothers for 52% of their life due to maternal migration. No significant association was found between the detailed characteristics of paternal migration and social-emotional development among LBC, while social-emotional problems among LBC were significantly associated with the proportion of cumulative duration of maternal migration in the child’s lifetime (aOR 2.83; 95% CI: 1.13 to 7.10). Conclusions LBC under 3 years had a high risk of social-emotional problems in poor rural China. Cumulative exposure to maternal migration may be detrimental to LBC’s early social-emotional development. Programs are necessary to support these children as well as their families.

Objective To explore whether the whole brain resting-state functional connectivity (rs-FC) could predict episodic memory performance in individuals with subjective cognitive decline and amnestic mild cognitive impairment . Method This study included 33 cognitive normal (CN), 26 subjective cognitive decline (SCD) and 27 amnestic mild cognitive impairment (aMCI) patients, and all the participants completed resting-state fMRI (rs-fMRI) scan and neuropsychological scale test data. Connectome-based predictive modeling (CPM) based on the rs-FC data was used to predict the auditory verbal learning test-delayed recall (AVLT-DR) scores, which measured episodic memory in individuals. Pearson correlation between each brain connection in the connectivity matrices and AVLT-DR scores was computed across the patients in predementia stages of Alzheimer’s disease (AD). The Pearson correlation coefficient values separated into a positive network and a negative network. Predictive networks were then defined and employed by calculating positive and negative network strengths. CPM with leave-one-out cross-validation (LOOCV) was conducted to train linear models to respectively relate positive and negative network strengths to AVLT-DR scores in the training set. During the testing procedure, each left-out testing subject's strengths of positive and negative network was normalized using the parameters acquired during training procedure, and then the trained models were used to predict the testing participant’s AVLT-DR score. Results The negative network predictive model tested LOOCV significantly predicted individual differences in episodic memory from rs-FC. Key nodes that brain regions contributed to the prediction model were mainly located in the prefrontal cortex, frontal cortex, parietal cortex and temporal lobe. Conclusion Our findings demonstrated that rs-FC among multiple neural systems could predict episodic memory at the individual level.

Uterine rupture common in scar uterus. In invasive mole lead to uterine rupture are rarely seen. A 31-year-old woman, in a clinic was abortioned. After abortion, the patient abdomen paind and litter vaginal bleeding fivty-three days ago. Then, the Human Chorionic Gonadotrophin(HCG) was rised and MR imaging showed a mass in myometrium. Suddenly, the uterine ruptured and shock. The patient was operated on for a hysterectomy of Gynaecologist. The pathological result is invasive mole.

Diabetic keratopathy (DK) is a common, but underdiagnosed, ocular complication of diabetes mellitus (DM) that has a significant economic burden. It is characterised by progressive damage of corneal nerves, due to DM-induced chronic hyperglycaemia and its associated metabolic changes. With advances in corneal nerve imaging and quantitative analytic tools, studies have shown that the severity of diabetic corneal neuropathy correlates with the status of diabetic peripheral neuropathy. The corneal nerve plexus is, therefore, considered as an important surrogate marker of diabetic peripheral neuropathy and helps in the evaluation of interventional efficacy in the management of DM. The clinical manifestations of DK depend on the disease severity and vary from decreased corneal sensitivity to sight-threatening corneal infections and neurotrophic ulcers. The severity of diabetic corneal neuropathy and resultant DK determines its management plan, and a step-wise approach is generally suggested. Future work would focus on the exploration of biomarkers for diabetic corneal neuropathy, the development of new treatment for corneal nerve protection, and the improvement in the clinical assessment, as well as current imaging technique and analysis, to help clinicians detect diabetic corneal neuropathy earlier and monitor the sub-clinical progression more reliably.

Objective: To investigate variation in the characteristics of regional cerebral blood flow (rCBF), brain activity, and intrinsic functional connectivity (FC) across the Alzheimer's disease spectrum (ADS).Methods: The study recruited 20 individuals in each of the following categories: Alzheimer's disease (AD), mild cognitive impairment (MCI), subjective cognitive decline (SCD), and healthy control (HC). All participants completed the 3.0T resting-state functional MRI (rs-fMRI) and arterial spin labeling scans in addition to neuropsychological tests. Additionally, the normalized CBF, regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) of individual subjects were compared in the ADS. Moreover, the changes in intrinsic FC were investigated across the ADS using the abnormal rCBF regions as seeds and behavioral correlations. Finally, a support-vector classifier model of machine learning was used to distinguish individuals with ADS from HC.Results: Compared to the HC subjects, patients with AD showed the poorest level of rCBF in the left precuneus (LPCUN) and right middle frontal gyrus (RMFG) among all participants. In addition, there was a significant decrease in the ALFF in the bilateral posterior cingulate cortex (PCC) and ReHo in the right PCC. Moreover, RMFG- and LPCUN-based FC analysis revealed that the altered FCs were primarily located in the posterior brain regions. Finally, a combination of altered rCBF, ALFF, and ReHo in posterior cingulate cortex/precuneus (PCC/PCUN) showed a better ability to differentiate ADS from HC, AD from SCD and MCI, but not MCI from SCD.Conclusions: The study demonstrated the significance of an altered rCBF and brain activity in the early stages of ADS. These findings, therefore, present a potential diagnostic neuroimaging-based biomarker in ADS. Additionally, the study provides a better understanding of the pathophysiology of AD.

IntroductionLower extremity amputation uniformly impairs a person’s vocational, social and recreational capacity. Rehabilitation in traditional socket prostheses (TSP) is associated with a spectrum of complications involving the socket-residuum interface which lead to reduced prosthetic use and quality of life. Osseointegration has recently emerged as a novel concept to overcome these complications by eliminating this interface and anchoring the prosthesis directly to bone. Though the complications of TSPs affect both transfemoral and transtibial amputees, Osseointegration has been predominantly performed in transfemoral ones assuming a greater benefit/risk ratio. However, as the safety of the procedure has been established, we intend to extend the concept to transtibial amputees and document the outcomes.Methods and analysisThis is protocol for a prospective cohort study, with patient enrolment started in 2014 and expected to be completed by 2022. The inclusion criteria are age over 18 years, unilateral, bilateral and mixed transtibial amputation and experiencing socket-related problems. All patients receive osseointegrated implants, the type of which depend on the length of the residuum and quality of bone, which are press-fitted into the residual bone. Objective functional outcomes comprising 6-Minute Walk Test, Timed Up-and-Go test and K-level, subjective patient-reported-quality-of-life outcomes (Short Form Health Survey 36, daily prosthetic wear hours, prosthetic wear satisfaction) and adverse events are recorded preoperatively and at postoperative follow-up intervals of 3, 6, 12 months and yearly, and compared with the preoperative values using appropriate statistical tests. Multivariable multilevel logistic regression will be performed with a focus to identify factors associated with outcomes and adverse events, specifically infection, periprosthetic fracture, implant fracture and aseptic loosening.Ethics and disseminationThe Ethics approval for the study has been received from the University of Notre Dame, Sydney, Australia (014153S). The outcomes of this study will be disseminated by publications in peer-reviewed academic journals and scientific presentations at relevant orthopaedic conferences.

BACKGROUND Plasma concentrations of branched-chain amino acids (BCAAs) are elevated in obese individuals with insulin resistance (IR) and decrease after bariatric surgery. However, the metabolic mechanisms are unclear. OBJECTIVES Our objectives are to compare leucine kinetics between morbidly obese and healthy-weight individuals cross-sectionally, and to prospectively evaluate changes in the morbidly obese after sleeve gastrectomy. We hypothesized that leucine oxidation is slower in obese individuals and increases after surgery. METHODS Ten morbidly obese [BMI (in kg/m2) ≥32.5, age 21-50 y] and 10 healthy-weight participants (BMI

Background: Whether a vegetarian diet is appropriate for pregnancy remains unclear.Objective: This study aimed to determine the association between vegetarian diet during pregnancy and various maternal–fetal outcomes.Method: PubMed-Medline, EMBASE, and Cochrane Library databases were searched for relevant articles published by August 30, 2017. Quantitative data were analyzed by a random-effects model with pooled odds ratios or weighted mean difference (WMD) and 95% confidence interval as aggregate estimations.Results: A total of 19 observational studies were identified for each of meta-analysis and narrative review. The overall estimated relation between vegetarian pregnancy and low birth weight (LBW) was marginally significant (1.27 (0.98, 1.65), P = 0.07, I2 = 0%). Asian (India/Nepal) vegetarian mothers exhibited increased risks to deliver a baby with LBW (1.33 (1.01, 1.76), P = 0.04, I2 = 0%). However, the WMD of neonatal birth weight in five studies suggested no difference between vegetarians ...

Methionine is one of the most limited factors in plant-based feed for fish. It plays critical roles in fish growth performance and feed utilization. However, little is known about its effects on amino acid metabolism and intestinal homeostasis in turbot. In this study, an 8-week feeding trial was conducted to examine the nutritional physiology of turbot fed with diets containing deficient (0.85%, LM), adequate (1.82%, MM) or excess (2.80%, HM) levels of methionine respectively. After the feeding trial, fish growth and feed efficiency were significantly reduced by LM diet while no significant difference was observed between MM group and HM group. Methionine deficiency diet also led to a reduction of free Met, Cys, Thr, Arg and His levels in plasma, while an elevation of Gly, Lys and Ala concentrations. The Asp and Gly levels in HM group were significantly lower than other groups. The mRNA expression of cystathionine β-synthase (cbs) and s-adenosylmethionine decarboxylase (samdc) in LM group were up-regulated while the expression of methionine synthase (ms) in LM group was depressed. The expression of ornithine decarboxylase (odc) was not affected by dietary methionine levels. Furthermore, methionine deficiency decreased the height of intestinal villus and microvilli, as well as the number of goblet cells. The mRNA expression of proliferating cell nuclear antigen (pcna) and mucin-2 (muc-2), as well as the content of glutathione, were also induced with the methionine level in the diets. These results provide important new clues in methionine function in teleost.

Background Branched-chain amino acids (BCAAs) are elevated in the insulin-resistant (IR) state. The reasons for this increase remain unclear, but it may be related to abnormalities in BCAA metabolism and free fatty acid (FFA) metabolism. Objective In this study, we quantified BCAA and FFA kinetics of IR and insulin-sensitive (IS) nonobese Asian men with the use of stable-isotope tracers. We hypothesized that in addition to greater substrate flux, the BCAA oxidative pathway is also impaired to account for the higher plasma BCAA concentration in the IR state. Design We recruited 12 IR and 14 IS nonobese and healthy Asian men. Oral-glucose-tolerance tests (OGTTs) were performed to quantify insulin sensitivity, and subjects underwent 2 stable-isotope infusion studies. [U-13C6]Leucine was infused to measure leucine flux and oxidation as indexes of BCAA metabolism, whereas [U-13C16]palmitate was infused to measure palmitate flux and oxidation to represent FFA metabolism, The 2H2O dilution method was used to estimate body composition. Results IR subjects had greater adiposity and significantly higher fasting and post-OGTT glucose and insulin concentrations compared with the IS group. However, none of the subjects were diabetic. Despite similar dietary protein intake, IR subjects had a significantly higher plasma BCAA concentration and greater leucine flux. Leucine oxidation was also greater in the IR group, but the relation between leucine oxidation and flux was significantly weaker in the IR group than in the IS group (r = 0.530 compared with 0.695, P

Laparoscopic sleeve gastrectomy (LSG) has become the preferred bariatric procedure in many countries. However, there is one shortcoming of LSG in the long-term follow-up and this is the onset of GERD and erosive esophagitis (EE). Current evidence of the effect of SG on GERD did not consolidate to a consensus. In this study, we objectively evaluate the incidence of EE 1 year post-LSG with upper endoscopy (EGD) and try to identify the significant variables and possible underlying mechanisms of the EE post-LSG. Over a period of 5 years (2011–2016) at Singapore General Hospital, we retrospectively reviewed a prospectively collected database of a cohort of patients whom had LSG by a single surgeon who routinely performed EGD pre-operative and 1 year post-operative to assess EE and hiatal hernia. Patient’s endoscopic findings and demographic and anthropometric data were analyzed. We identified a total of 97 obese patients who underwent LSG at our hospital by studied surgeon. Sixty-three patients (64.9% of original sample) were finally evaluated in the present study, 40 (59.7%) of whom were female. The mean (range) age of patients was 38.2 (18–66) years, and mean BMI was 36.3 ± 4.1 kg/m2. Median time to follow-up EGD was 13 months (range, 12–15). Following LSG, there was a significant decrease in both BMI (42.1 ± 1.2 vs. 29.9 ± 1.0 kg/m2) and percentage excess weight loss of 56.6 ± 3.6%. The prevalence of EE on endoscopy increased from 9 (14.3%) to 28 (44.4%) patients. Of which 15 (23.8%) were grade A, 11 (17.5%) were grade B, and 2 (3.2%) were grade C. There was no correlation between GERD symptoms with EE; however, our study found a trend suggesting higher prevalence of EE with a sleeve diameter measuring > 2 cm wide (p = 0.069). Although LSG is effective in treating obesity and its metabolic syndromes, the prevalence of EE increased significantly 1 year after the surgery. Since we do not fully understand the long-term impact of chronic esophagitis in post-sleeve population, we recommend follow-up EGD assessment post-operatively and treat the esophagitis if present.

INTRODUCTION Obesity is a key risk factor in the development of Type 2 diabetes mellitus (T2DM). Bariatric surgery causes a large amount of durable weight loss in those with clinically severe obesity. We reported the effect of weight loss via bariatric surgery on DM prevention in those at high risk of developing DM. METHODS This was a retrospective cohort study of 44 patients with obesity (mean body mass index 43.8 kg/m2) and pre-DM who underwent bariatric surgery and were followed up for up to three years. We also reviewed a non-surgical cohort of patients with obesity and pre-DM seen at the weight management clinic. RESULTS 91% of patients attained normal glycaemic status at one year after bariatric surgery. At the three-year follow-up, 87.5% of the patients maintained normoglycaemia. None of the patients developed T2DM after surgery. 26.9% of patients achieved absolute weight loss at one year after bariatric surgery and maintained this at two and three years post surgery (p < 0.001 vs. baseline). The homeostatic model assessment-insulin resistance index in patients also decreased from 5.50 at baseline to 1.20, 1.14 and 1.44 at one, two and three years, respectively (p < 0.001). CONCLUSION Bariatric surgery produces significant weight loss, and leads to reversion from the pre-diabetic state to normal glycaemic status and reduction of the incident DM rate in those with pre-DM and morbid obesity.

Aims/Introduction Indian individuals are more insulin resistant (IR) than Chinese individuals, even among those with a non‐obese body mass index (BMI). However, BMI often underestimates body fat in Indian individuals, and it remains unclear whether Indians would remain more IR than Chinese individuals when both BMI and body fat are equally matched. Materials and Methods Using the hyperinsulinemic‐euglycemic clamp with stable‐isotope infusion, we comprehensively assessed IR between 13 non‐obese Indian men with 13 Chinese men matched for age, BMI and body fat. We further compared the differences in insulin metabolic clearance rate (MCR) between the two groups and its relationship with various metabolic parameters. The response of lipid and amino acid metabolism to insulin stimulation was also evaluated using metabolomic profiling. Results The rates of endogenous glucose production during fasting were similar, and endogenous glucose production was completely suppressed during insulin clamp for both ethnic groups. Glucose disappearance during insulin clamp was also similar between the two groups, even after accounting for differences in insulin concentration. Metabolomic profiles of amino acids and various acylcarnitines were similar during both fasting and insulin clamp. However, plasma insulin during clamp was significantly higher in Indian men, indicating that insulin MCR was lower. Insulin MCR correlated significantly with total adiposity and skeletal muscle insulin sensitivity. Conclusion When equally matched for body fat, non‐obese Indian men had similar skeletal muscle insulin sensitivity and endogenous glucose production to Chinese men. The effects of insulin on lipid and amino acid metabolism were also similar. Low insulin MCR is associated with greater adiposity and lower skeletal muscle insulin sensitivity.

In Asia, metabolic-bariatric surgery (MBS) rates have grown rapidly in parallel with rising prevalence of obesity and type 2 diabetes (T2D). The objective of this study was to identify factors that influence glycemic outcomes and diabetes remission 12 months after sleeve gastrectomy (SG) or gastric bypass (GB) in a multiethnic Asian cohort. The study’s setting was in a tertiary hospital in Singapore. Data from 145 T2D patients who had SG (37%) or GB (63%) and at least 1-year follow-up were analyzed. Diabetes remission was defined as hemoglobin A1c ≤ 6.0% without diabetes medications. Analysis involved binary logistic regression to identify predictors and general linear regression for variables associated with glycemic improvement after surgery. Baseline parameters are as follows: BMI 40.0 ± 7.6 kg/m2, A1c 8.4 ± 1.6%, diabetes duration 9.3 years, ethnic composition: Chinese (51.7%), Malay (23.4%), Indian (20.7%), Others (4.1%). 55.9% achieved diabetes remission at 1 year. Baseline A1c, baseline BMI, and diabetes duration were significant pre-operative factors for remission (cumulative R 2 = 0.334). At 12 months, percentage weight loss was similar after SG (24.1 ± 7.4%) and GB (25.4 ± 7.4%, p = 0.31). Greater A1c decrease was seen with GB compared to SG (2.7 ± 1.6 vs 2.0 ± 1.5%, p = 0.006), significant even after adjustment for weight loss, age, BMI, baseline A1c, and diabetes duration (p = 0.033). Weight loss at 12 months also correlated independently with A1c reduction. Ethnicity did not influence weight loss, diabetes remission, or glycemic control after MBS. Baseline A1c, baseline BMI, and diabetes duration independently predict diabetes remission after MBS. GB is more effective in controlling T2D compared to SG despite similar weight loss, whereas ethnicity does not play a significant role in the multiethnic Asian cohort.

Purpose: Many genes have been associated with primary open-angle glaucoma (POAG). This study was conducted to investigate whether catalase (CAT) polymorphisms play a significant role in POAG in a Chinese population. Methods: A cohort of 416 unrelated POAG patients and 997 unrelated control subjects was included in this case–control association study. CAT functional single-nucleotide polymorphisms (SNPs), including rs1001179, rs7943316, and rs769217, were genotyped by SNaPshot method. The genotype and allele frequencies were evaluated using the χ2 tests. The linkage disequilibrium (LD) and haplotype block structure association were examined using the program Haploview (Broad Institute, Cambridge, MA). Results: There was a statistically significant difference for CAT functional SNP rs769217 between POAG cases and controls in the allelic model (p = 0.004, OR = 1.27, 95% CI 1.08–1.49). At this SNP, the allele frequency of the C allele in POAG cases was 0.587, which was higher than that in controls (0.528). However, no association was found for rs1001179 and rs7943316 with POAG. Pairwise LD analysis showed high LD between rs769217 and rs7943316 (D’ = 0.857, r2 = 0.252, confidence bounds 0.71–0.93). After the association analysis for haplotype block structure generated from rs769217 with rs7943316, the data showed no significant association between the cases and controls. Conclusions: This study showed that CAT functional SNP rs769217 was significantly associated with POAG, implying that the CAT gene variants may play a role in the pathogenesis of POAG in the Chinese population.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is increasingly widespread with an overall global estimated prevalence of 25%. Type 2 diabetes Mellitus (T2DM) is a key contributor to NAFLD progression and predicts moderate-severe liver fibrosis and mortality. However, there is currently no uniform consensus on routine NAFLD screening among T2DM patients, and the risk factors of NAFLD and advanced fibrosis among T2DM patients remain to be clarified fully.AimWe explored the prevalence, clinical spectrum, and risk factors of NAFLD and liver fibrosis among T2DM patients.MethodsThis is a cross-sectional study that enrolled subjects from a primary care clinic and a diabetes centre in Singapore. Subjects aged 21 to 70 years of all ethnic groups with an established T2DM diagnosis were included. Subjects with chronic liver diseases of other aetiologies were excluded. All subjects underwent transient elastography for hepatic steatosis and fibrosis assessment. Their demographics, anthropometric measurements and clinical parameters were collected. Statistical analysis was performed using STATA/SE16.0 software.ResultsAmong 449 enrolled T2DM subjects, 436 with complete data and valid transient elastography results were analysed. Overall, 78.72% (344/436) of the T2DM subjects had NAFLD, of which 13.08% (45/344) had increased liver stiffness. Higher ALT level (OR = 1.08; 95% CI: 1.03-1.14; p = 0.004), obesity (BMI ≥ 27.5 kg/m2, OR = 2.64; 95% CI: 1.28-5.44; p = 0.008) and metabolic syndrome (OR = 4.36; 95% CI 1.40-13.58; p = 0.011) were independent factors associated with increased CAP (NAFLD). Higher AST level (OR = 1.06; 95% CI: 1.02-1.11; p = 0.008), CAP value (OR = 1.02; 95% CI: 1.00-1.03; p = 0.003), lower platelet count (OR = 0.99; 95% CI: 0.98-1.00; p = 0.009) and concomitant hypertension (OR = 4.56; 95% CI: 1.18-17.62; p = 0.028) were independent factors associated with increased liver stiffness.ConclusionsOur study demonstrated a considerably high prevalence of NAFLD among T2DM patients, with the proportion of advanced liver fibrosis among T2DM NAFLD patients much higher than the general population. Given that NAFLD is largely asymptomatic, increased awareness and vigilance for identifying NAFLD and increased liver stiffness among T2DM patients should be advocated.

Background: Accelerated lipolysis and the accumulation of incomplete products of fatty acid metabolism may contribute to insulin resistance (IR). It remains unclear whether the improvement in IR during the early period following bariatric surgery could be related to changes in lipid metabolism. Aims and Hypothesis: In this study, we compared the rates of lipolysis, lipid-related acylcarnitines (ACs) and IR in morbidly obese individuals at baseline, 6-months after bariatric surgery and with lean controls. Methods: 10 morbidly obese individuals scheduled for sleeve gastrectomy and 14 lean controls were recruited. IR was quantified using OGTT while body composition was measured using the 2H2O technique or DXA scans. Glycerol flux represents whole-body lipolysis and was measured using 2H5-glycerol infusion. Plasma lipid-derived ACs were measured using mass spectrometry as an indicator of complete fatty acid oxidation. Obese subjects were reassessed 6-months after bariatric surgery. Results: Compared to lean controls, obese subjects had significantly higher fat mass (50.7 ± 1.9 vs. 16.8 ± 1.0 kg) and were significantly more IR. They had higher HOMA-IR (6.6 ± 1.0 vs. 1.43 ± 0.31), glucose and insulin AUC after OGTT. Glycerol flux (16098.1 ± 1136.2 vs. 7266.20± 497.66 umol/h), plasma glycerol (117.13 ± 10.96 vs, 46.79± 3.15 umol/L), C14 (0.225 ± 0.079 vs. 0.042± 0.012) and C16 (0.136 ± 0.016 vs. 096 ± 0.003 umol/L) ACs were significantly higher in the obese individuals. 8 subjects returned at 6-months and lost 19% of their total weight, 29% of fat mass and had a 68% decrease in HOMA-IR. Glycerol flux, plasma glycerol, C14 and C18 ACs however did not show any difference compared to baseline and remained significantly higher compared to the lean controls. Conclusion: IR improved 6-months following sleeve gastrecotmy despite accelerated lipolysis and accumulation of byproducts of incomplete fatty acid metabolism. Disclosure H. Tan: None. J.W. Hsu: None. J. Kovalik: None. C. Khoo: None. S. Chacko: None. S. Ganguly: None. E. Tai: Advisory Panel; Self; Amgen Inc., BASF. O. Lai: None. E. Lim: None. F. Jahoor: None.

Purpose The aim of this study was to evaluate the role of mesh technique in the reconstruction of the extensor mechanism after resection of proximal tibial tumors. Methods We retrospectively analyzed the cases of 14 patients who were diagnosed with proximal tibial tumors at our center and reconstructed with tumor prosthesis, gastrocnemius muscle, and mesh between 2012 and 2017. The treatment strategies for patellar tendon reconstruction primarily involve gastrocnemius reconstruction to cover the tumor prosthesis and mesh reconstruction for the patellar ligament. Results Among the 14 patients, the mean was 1.57° (range 0–12°) for active extension versus 105.00° (range 80–120°) for active flexion. The mean for passive extension was 0°. The passive flexion mean was 115.00° (range 90–120°). The extensor lag averaged 1.57° (range 0–12°), and the mean Musculoskeletal Tumor Society score (MSTS) was 23.57 (range 19–27). The average follow-up for all patients was 23.50 months (range 14–37). During the recent follow-up, all patients were able to walk without crutches. Two patients underwent above-the-knee amputation for local recurrence of the tumor, and lung metastasis occurred in three patients after operation. There were no postoperative complications. Conclusions Extensor lag was remarkably reduced in the surgery group in comparison to previous study reports. Surgical resection is a simple, reliable, and effective method to remove and control the tumor. Mesh reconstruction of patellar ligament is effective to reconstruct the extensor mechanism of the knee after excision of tumor.

Introduction: Obesity increases the risk of incident chronic kidney disease (CKD), being one of the strongest risk factors for new-onset CKD even in the metabolically normal obese. Weight loss has been shown to reduce renal hyperfiltration and proteinuria. Metabolic Bariatric Surgery (MBS) remains an effective treatment for obesity and its metabolic related complications. However, literature on its impact on long term renal function remains limited. Methods: This was an observational retrospective study in a tertiary centre in Singapore. MBS cases performed at the centre between 2008 and 2019 were included. The primary outcome measure was estimated Glomerular Filtration Rate (eGFR), calculated using the CKD Epidemiology Collaboration equation, and albuminuria (defined as urine Albumin-Creatinine Ratio (uACR) >3.5 mg/mmol) at baseline and at one-year post surgery. Results: 557 patients were included. Baseline parameters are as follows: mean age 41.7 ±10.1 years; female 65.4%; ethnic composition: Chinese (35.2%), Malay (33.0%), Indian (26.9%); BMI 42.5 ±7.9 kg/m²; glycaemic status: Diabetes Mellitus (34.5%), Pre-diabetes (13.5%), Non-diabetic (52.1%); Hypertensive status: Hypertension (55.2%), Pre-Hypertension (1.9%), Normotensive (42.9%). Median eGFR was 110.9 (92.4 - 121.5) mL/min/1.73 m² and median uACR was 1.00 (0.40 - 3.55) mg/mmol. At one-year post surgery, patients achieved statistically significant reductions in mean BMI (-11.3 ±4.2 kg/m2), systolic BP (-3.24 ±19.3 mmHg), diastolic BP (-5.23 ±13.8 mmHg), fasting glucose (-1.95 ±2.89 mmol/L) and improvement in HDL (0.29 ±0.26 mmol/L). In addition, statistically significant reductions in the proportion of patients on anti-hypertensive (48.8% to 14.4%), anti-diabetic (34.1% to 12.7%) and lipid-lowering medications (37.8% to 20.4%) were seen. In particular, ACE-inhibitor and/or angiotensin receptor blocker (32.9% to 9.2%, p< 0.001) usage was reduced. At one-year post surgery, median eGFR increased by 1.66 mL/min/1.73 m² (p Conclusions: Metabolic bariatric surgery had a positive impact on renal function as shown by the improvement in eGFR in the non-diabetic group, and the reduction in albuminuria in the diabetes and pre-diabetes group at one-year post surgery. More adequately powered, longer-term data is required to investigate the durability of this impact.

Obesity-induced insulin resistance leads to abnormalities in glucose, lipid, and amino acid metabolism. Our study examined the differences in insulin-mediated glucose, amino acid, and lipid metabolism between morbidly obese subjects with non-obese controls and the associated changes following sleeve gastrectomy (SG). Non-obese controls and individuals with morbid obesity and scheduled for SG were recruited. Metabolic assessments were performed for all subjects at baseline and at 6 months after SG for eight subjects. The hyperinsulinemic-euglycemic clamp technique together with comprehensive metabolomic profiling was used to quantify insulin-mediated glucose, amino acid, and lipid metabolism. Eleven morbidly obese non-diabetic subjects scheduled for SG and nine non-obese controls were recruited. Compared to controls, obese subjects had significantly lower glucose uptake (4.4 ± 0.6 vs. 17.3 ± 2.4 mg/kg FFM/min per μU/mL·100) and higher concentration of branched-chain amino acids (BCAAs, 332.5 ± 26.8 vs. 235.3 ± 11.0 μM), non-esterified fatty acid (52.9 ± 9.9 vs. 25.6 ± 6.7 μM), and lipid-related acylcarnitines (intermediate chain 389.8 ± 32.5 vs. 285.9 ± 20.5; long chain 301.7 ± 22.1 vs. 236.0 ± 13.3 nM) during insulin clamp. Body weight significantly reduced at 6 months after bariatric surgery (92.5 ± 6.3 vs. 115.2 ± 6.9 kg), together with improvements in insulin-mediated glucose uptake, and suppression of BCAAs, non-esterified fatty acids, and lipid-related metabolites. Morbid obesity in Asian individuals was associated with impairment in the regulatory actions of insulin on glucose, amino acid, and lipid metabolism, and these obesity-induced regulatory dysfunctions improved significantly 6 months after SG.

INTRODUCTION We aimed to compare the malignancy risk stratification of histologically proven thyroid nodules using the 2015 American Thyroid Association (ATA) Management Guidelines, 2014 British Thyroid Association (BTA) Guidelines for the Management of Thyroid Cancer and the Thyroid Imaging Reporting and Data System (TIRADS). METHODS Thyroid nodules measuring > 1 cm resected over 5.5 years were retrospectively studied. Demographic information as well as cytology and histopathology results were collected. Static ultrasonography (US) images and radiologists' reports of each resected nodules were reviewed and classified based on the above risk classification systems. RESULTS A total of 167 thyroid nodules from 150 patients were examined. More malignant nodules were solid (78.4% vs. 62.5%; p = 0.049) or hypoechoic (70.6% vs. 28.6%; p < 0.001), and had irregular margins (35.3% vs. 8.0%; p < 0.001), taller-than-wide morphology (9.8% vs. 2.7%; p = 0.031), microcalcifications (33.3% vs. 8.0%; p < 0.001), disrupted rim calcifications (9.8% vs. 0.9%; p = 0.012) or associated abnormal cervical lymphadenopathy (13.7% vs. 0.9%; p = 0.001) compared with benign nodules. The guidelines' diagnostic performance was: ATA - sensitivity 98.0%, specificity 17.3%, positive predictive value (PPV) 35.0%, negative predictive value (NPV) 95.0%; BTA - sensitivity 90%, specificity 50.9%, PPV 45.5%, NPV 91.8%; and TIRADS - sensitivity 94.0%, specificity 28.2%, PPV 37.3%%, NPV 91.2%. CONCLUSION Sonographic patterns outlined by the three guidelines displayed high sensitivity and NPV. Although isolated suspicious US features cannot predict malignancy risk, they should be considered when risk stratifying nodules that do not fit into particular sonographic patterns based on current guidelines.

BACKGROUND: Aerobic capacity is a powerful predictor of cardiovascular disease and all‐cause mortality, and it declines with advancing age. HYPOTHESIS: Since physical activity alters body metabolism, metabolism markers will likely differ between subjects with high vs low aerobic capacities. METHODS: Community‐based participants without physician‐diagnosed heart disease, stroke or cancer underwent same‐day multimodal assessment of cardiovascular function (by echocardiography and magnetic resonance feature tracking of left atrium) and aerobic capacity by peak oxygen uptake (VO(2)) metrics. Associations between VO(2) and cardiovascular and metabolomics profiles were studied in adjusted models including standard covariates. RESULTS: We studied 141 participants, of whom 82 (58.2%) had low VO(2), while 59 (41.8%) had high VO(2). Compared to participants with high VO(2), participants with low VO(2) had more adverse cardiovascular parameters, such as lower ratio of peak velocity flow in early diastole to peak velocity flow in late diastole by atrial contraction of >0.8 (76% vs 35%, adjusted odd ratio [OR] = 4.1, 95% confidence interval [CI] [1.7‐9.5], P = 0.001) and lower left atrial conduit strain (11.3 ± 4.0 vs 15.6 ± 6.1%, adjusted OR = 1.1, 95% CI [1.002‐1.3], P = 0.045). High VO(2) was associated with lower accumulation of wide‐spectrum acyl‐carnitines (OR = 0.6, 95% CI [0.4‐0.9], P = 0.013), alanine (OR = 0.1, 95% CI [0.01‐0.9], P = 0.044) and glutamine /glutamate (OR = 0.1, 95% CI [0.01‐0.5], P = 0.007), compared to low VO(2.) CONCLUSION: Elderly adults with low VO(2) have adverse cardiovascular and metabolic parameters compared to their counterparts with high VO(2). Combined cardiac and metabolomics phenotyping may be a promising tool to provide insights into physiological states, useful for tracking future interventions related to physical activity among community cohorts.

Objective Maternal adiposity is associated with poor offspring cardiometabolic health. We aimed to evaluate the relationship of maternal pre-pregnancy body mass index (BMI) on the BMI, body composition and cardiometabolic characteristics of the offspring. Methods Forty offspring of overweight/obese mothers (O-OW) and 28 offspring of normal weight mothers (O-NW) underwent evaluation of body composition, abdominal fat distribution, blood pressure measurement, fasting lipids and an oral glucose tolerance test. The anthropometric and cardiometabolic characteristics of O-OW were compared with those of O-NW, and the relationship to maternal BMI was evaluated. Results Subjects (mean age: 12.6 ± 0.4, female: 52.9%) had similar gestational age, birth weight, age, gender, and Tanner stage. However, O-OW had a significantly higher BMI (24.4 ± 1.2 vs. 19.7 ± 0.8 kg/m2, p = 0.001), % body fat (31.7 ± 1.6 vs. 24.6 ± 1.1%, p

We attempted to determine whether betanin (from natural pigments) that has antioxidant properties would be protective against fructose-induced diabetic cardiac fibrosis in Sprague-Dawley rats. Fructose water solution (30%) was accessed freely, and betanin (25 and 100 mg/kg/d) was administered by intra-gastric gavage continuously for 60 d. Rats were sacrificed after overnight fast. The rat blood and left ventricle were collected. In vitro antiglycation assay in bovine serum albumin/fructose system was also performed. In rats treated only with fructose, levels of plasma markers: glucose, insulin, HOMA and glycated hemoglobin rised, left ventricle collagen accumulated and cross-linked, profibrotic factor-transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF) protein expression increased, and soluble collagen decreased, compared with those in normal rats, showing fructose induces diabetic cardiac fibrosis. Treatment with betanin antagonized the changes of these parameters, demonstrating the antifibrotic role of betanin in the selected diabetic models. In further mechanistic study, betanin decreased protein glycation indicated by the decreased levels of protein glycation reactive intermediate (methylglyoxal), advanced glycation end product (N(ε)-(carboxymethyl) lysine) and receptors for advanced glycation end products (AGEs), antagonized oxidative stress and nuclear factor-κB activation elicited by fructose feeding, suggesting inhibition of glycation, oxidative stress and nuclear factor-κB activation may be involved in the antifibrotic mechanisms. Betanin also showed anitglycative effect in BSA/fructose system, which supported that anitglycation was involved in betanin's protective roles in vivo. Taken together, the potential for using betanin as an auxillary therapy for diabetic cardiomyopathy deserves to be explored further.

Purpose: To investigate whether retinal impairment was affected by age of rats in acute glaucoma model. Methods: Young adult and aged rats were randomly divided into normal control, 45 mmHg, 60 mmHg and 90 mmHg groups. Intraocular pressures (IOP) of rats were acutely elevated to 45 mmHg, 60 mmHg and 90 mmHg, respectively. Neuron loss in ganglion cell layer (GCL) and activation of retinal macrolgia and microglia 3 days after high IOP treatment were detected by immunofluorescence and further quantitatively analyzed. Results: Compared with normal control, significant loss of neurons at GCL of young adult retina wasn’t detected until IOP treatment of 90 mmHg. In contrast, obvious loss of neurons at GCL of aged retina was detected at IOP of 45 mmHg (p = 0.002 for central; p = 0.001 for peripheral). The loss level of neurons of aged retina was significantly higher than that of young adult retina at different IOP treatments. Compared with the young adult retina, high IOP induced more significant increase at area percentage of microglia and microglia number in inner part of aged retina. Activation of microglia and macroglia was either in parallel to or earlier than neuron loss of GCL of aged and young adult retina. Conclusion: Our data suggest there exists an age–related susceptibility of rat retina to the increased IOP. Therefore, the effect of ages should be considered at glaucoma study of rat models.

Commentary on : Cheung KS, Chan EW, Wong AYS, et al . Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori : a population-based study. Gut 2018; 67:28–35 Helicobacter pylori infection is the most common cause of gastric cancer. Whether H. pylori eradication reduces or eliminates the risk of gastric cancer depends on the risk at the time of cure. In those with mucosal damage and hypochlorhydria, H. pylori eradication may result in return of acid secretion. Proton pump inhibitor (PPI) therapy can profoundly reduce acid secretion after H. pylori therapy. However, the effect of PPIs on the risk of gastric cancer after H. pylori eradication is unknown. Cheung et al reported a population-based study to determine whether PPI use after H. pylori eradication altered the risk of subsequent gastric cancer.1 The study cohort consisted of Hong Kong residents whose H. pylori infection was cured using clarithromycin-containing triple therapy from 2003 to 2012. They excluded those with previous gastrectomy, gastric cancer within 1 year of H. pylori therapy, failed H. pylori eradication or incident gastric ulcer after therapy. Development of …

Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Accepted version We acknowledge H.M. Kang, S. Das, A. Tan, F. Zhang, J. Terhorst, P.-R. Loh, and G. Hellenthal for helpful discussions and support from all participants and clinical research coordinators of the contributing cohorts and studies: the TTSH Healthy Control Workgroup, the SEED cohort, the Asian Sudden Cardiac Death in Heart Failure Study, the Singapore Heart Failure Outcomes and Phenotypes (SHOP) cohort, the Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT), the Parkinson’s Disease Study, the Peranakan Genome Study, the Platinum Asian Genomes Project, the Bariatric Surgery Study, the National Heart Centre Singapore Biobank and SingHEART cohorts, and the GUSTO and S-PRESTO study groups. This study was supported by Singapore’s A*STAR (core funding and IAF-PP H17/01/a0/007), BMRC (SPF2014/001, SPF2013/002, SPF2014/003, SPF2014/004, and SPF2014/005), NMRC (CIRG/1371/2013, CIRG/1417/2015, CIRG/1488/ 2018, CSA-SI/0012/2017, CG/017/2013, CG/M006/2017_NHCS, TCR/013- NNI/2014, STaR/0011/2012, STaR2013/001, STaR/014/2013, STaR/0026/ 2015, TCR/006-NUHS/2013, TCR/012-NUHS/2014, TCR/004-NUS/2008, TCR/012-NUHS/2014, and center grants 2010-13 and 2013-2017), NRF (NRFF2016-03), National University of Singapore, SingHealth and DukeNUS, and Alexandra Health small innovative grant SIGII/15203 and funding from Huazhong University of Science and Technology, the Tanoto Foundation, the Lee Foundation, the Boston Scientific Investigator Sponsored Research Program and Bayer, the NSF (DEB-1753489), and the Alfred P. Sloan Foundation. The computation was partially performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg).

Post-operative bleeding is a major but infrequent complication in laparoscopic sleeve gastrectomy (LSG). There is paucity in the literature on management of this complication. This paper seeks to review the presentation of post-operative bleeding complications after LSG in a single cohort of patients and highlight the surgical and non-surgical methods of treatment. A retrospective study of 409 LSG patients performed in a tertiary hospital, Singapore General Hospital (SGH) since 2008. Patients who encountered post-operative bleeding complications, defined as requiring blood transfusion or re-laparoscopy for haemostasis, were identified from a prospectively recorded database. The presentation, source of bleeding and management were recorded and presented. Five out of 409 (1.2%) patients were diagnosed with post-operative bleeding. Two patients were treated conservatively requiring only blood transfusion and 3 patients were surgically explored with laparoscopy, 2 were from staple line bleeding (SLB) and suture haemostasis performed. In 1 patient, the source of bleeding was not identified intraoperatively and CT angiography performed post-operatively showed active contrast bleeding near short gastric arteries and gastroepiploic artery. Gel foam and coil embolization was performed and the bleeding was controlled. Average hospitalization stay due to post-operative bleeding was 7.3 days compared to 2.3 days for those without. Post-operative bleeding after LSG occurred at the staple line and branches of the right gastro-epiploic artery and short gastric arteries. Bleeding may stop spontaneously or require haemostasis by operative or endovascular means. CT angiogram is proposed to locate the source of bleed and subsequent embolization of bleeding arteries maybe possible, avoiding the need for re-operation. Bleeding from the staple line requires surgical haemostasis.

INTRODUCTION: Obesity is a risk factor for type 2 diabetes mellitus (T2DM). Metabolic-bariatric surgery (MBS) results in significant weight loss with dramatic improvement in T2DM. This study analysed the effects of MBS on patients with T2DM in a tertiary centre in Singapore. METHODS: Individuals with T2DM who underwent MBS in a single centre from September 2008 to May 2012, with at least 12 months of regular follow-up, were included in our study. The primary outcome measure was good glycaemic control (glycated haemoglobin [HbA1c] < 6.5%, with or without medications) 12 months after surgery. Secondary outcome measures were partial DM remission (fasting blood glucose [FBG] < 7.0 mmol/L and HbA1c < 6.5% without DM medications), complete DM remission (FBG < 5.6 mmol/L and HbA1c < 6.0% without DM medications), weight, body mass index, blood pressure, and fasting serum lipid, serum glucose and serum insulin levels. RESULTS: Of the 19 patients who met the inclusion criteria, 14 underwent gastric bypass and 5 underwent sleeve gastrectomy. At 12 months postoperatively, 17 (89.5%) patients achieved good glycaemic control. DM remission was achieved in 14 (73.7%) patients, with 10 (52.6%) attaining complete remission. CONCLUSION: In Singapore, MBS is an effective treatment modality for obese patients with T2DM. Despite the small sample size and lack of matched controls, the present study suggests that MBS is effective in achieving significant weight loss and eliciting a significant and sustainable improvement in the glycaemic control of patients with T2DM, for up to 12 months.

Bismuth type IV hilar cholangiocarcinoma (HC) tumors are usually considered unresectable. The strategies of high hilar resection while preserving liver parenchyma can achieve potentially one-stage curative resection for this condition. The aim of the present study was to investigate the feasibility and safety of available strategies. Fifty-one consecutive patients with bismuth type IV HC who underwent one-stage resection were retrospectively reviewed with regard to curative resection rate, remnant liver volume, morbidity, mortality, and survival time. The total median survival time was 29 months. The R0 (curative resection) rate was 57.8 %. The ratio of the remnant liver volume (RLV) to the standard liver volume (SLV) ranged from 35.0 to 60.6 %, with a mean of 44.5 %. The in-hospital mortality and morbidity rates were 3.9 and 37.2 %, respectively. In the R0 patients’ survival, there was not a significant difference between bilioenteric anastomosis and hepatoenteric anastomosis (P = 0.714). Combined caudate lobe and high hilar resection (CCHR) is technically safe and oncologically justifiable and could be adopted with a high cure rate as a one-stage resection procedure for most patients with Bismuth type IV HC whose total bilirubin level is less than 20 mg/L and whose direct bilirubin is more than 60 % of total bilirubin.

BACKGROUND Early post-operative hyperglycemia is commonly encountered in patients without pre-existing diabetes mellitus who are undergoing kidney transplantation. The aim of this study was to determine the effect of early post-operative hyperglycemia on graft and patient survival after kidney transplantation in our center. MATERIAL AND METHODS This was a single-center retrospective review of solitary kidney recipients transplanted in our center between January 1998 and December 2007. Of a total of 432 patients, 377 were eligible for the study. Fasting plasma glucose (FPG) levels at day 1 (D1) and day 5 (D5) after transplantation were recorded. Hyperglycemia was defined as FPG ≥ 7.0 mmol/l. Outcome events recorded included deaths and graft failures. RESULTS The mean age at transplantation was 43.2 ± 9.5 years and 50.4% were male. The mean FPG levels at D1 and D5 were 7.5 ± 1.3 mmol/L and 5.3 ± 1.3 mmol/L, respectively; 64.2% of recipients had FPG ≥ 7.0 mmol/L on D1 and this was reduced to 8.5% on D5. Recipients with D1 FPG ≥ 7.0 mmol/L had significantly poorer graft survival (39 events) compared to those without D1 hyperglycemia (6 events), with a hazard ratio of 3.708 (95% CI, 1.568-8.766, P=0.003). There was a trend towards better patients survival in recipients with D1 FPG

The serum metabolomic profile and its relationship to physiological changes during hyperthyroidism and restoration to euthyroidism are not known. This study aimed to examine the physiological, adipokine, and metabolomic changes that occur when subjects with Graves' disease transition from hyperthyroidism to euthyroidism with medical treatment.Chinese women between 21 and 50 years of age and with newly diagnosed Graves' disease attending the endocrine outpatient clinics in a single institution were recruited between July 2012 and September 2014. All subjects were treated with thioamides to achieve euthyroidism. Clinical parameters (body weight, body composition via bioelectrical impedance analysis, resting energy expenditure and respiratory quotient via indirect calorimetry, and reported total energy intake via 24 h food diary), biochemical parameters (thyroid hormones, lipid profile, fasting insulin and glucose levels), serum leptin, adiponectin, and metabolomics profiles were measured during hyperthyroidism and repeated in early euthyroidism.Twenty four Chinese women with an average age of 36.3 ± 8.6 years were included in the study. The average duration of treatment that was required to reach euthyroidism for these subjects was 38 ± 16.3 weeks. There was a significant increase in body weight (52.6 ± 9.0 kg to 55.3 ± 9.4 kg; p 0.001) and fat mass (14.3 ± 6.9 kg to 16.8 ± 6.5 kg; p = 0.005). There was a reduction in resting energy expenditure corrected for weight (28.7 ± 4.0 kcal/kg to 21.5 ± 4.1 kcal/kg; p 0.001) and an increase in respiratory quotient (0.76 to 0.81; p = 0.037). Resting energy expenditure increased significantly with increasing free triiodothyronine levels (p = 0.007). Significant increases in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were noted. There was no significant change in leptin levels, but adiponectin levels increased significantly (p = 0.018). Significant reductions in fasting C2, medium-chain, long-chain, and total acylcarnitines were observed, but no changes in the fat-free mass, branched chain amino acid levels, or insulin sensitivity during recovery from hyperthyroidism were noted.Serum metabolomics profile changes complemented the physiological changes observed during the transition from hyperthyroidism to euthyroidism. This study provides a comprehensive and integrated view of the changes in fuel metabolism and energy balance that occur following the treatment of hyperthyroidism.

Objective This study was aimed to identify the potential indications for simultaneous resection of abdominal cancer and synchronous pancreaticoduodenal metastasis (SRAPM) and improve the efficacy of SRAPM. Methods The data of 34 patients who underwent SRAPM were retrospectively reviewed. The intraoperative findings, morbidity and mortality, patterns of tumor invasion in the pancreas and duodenum, lymph node metastases, long-term outcomes and causes of death were evaluated. Results Fourteen patients (41.2%) developed complications, and 2 died of pancreatic fistulas with abdominal bleeding. The in-hospital mortality was 5.9%. The overall 1-year, 2-year and 3-year survival rates were 52.9%, 32.3% and 21.8%, respectively. The survival rates depended on the primary tumor, the invasion pattern, the presence of metastatic lymph nodes at the paraaortic site and the presence of residual tumor. The follow-up outcomes revealed that the main causes of death were as follows: systemic metastasis (n = 7), peritoneal metastasis (n = 6) and intrahepatic metastasis (n = 6). Conclusions SRAPM is indicated for low-grade malignant tumors and in cases with direct invasion of the pancreaticoduodenum. The presence of metastatic lymph nodes at the paraaortic site, intrahepatic metastasis, micro-peritoneal metastasis, and distinct metastasis should be contraindications for the surgical procedure.

Weight loss, early after Roux-en-Y gastric bypass (GB) surgery, is associated with reduced concentrations of plasma branched-chain amino acids (BCAAs) and improved insulin sensitivity. Herein, we evaluated whether changes in BCAAs and insulin sensitivity persist with weight stabilization (1 year) after GB or sleeve gastrectomy (SG). We prospectively examined 22 severely obese patients (mean age 40.6 ± 2.1 years, BMI 38.8 ± 1.3 kg/m2, and 59.1 % female) who underwent SG (n = 12) or GB (n = 10) for morbid obesity. Body fat composition was measured with dual X-Ray absorptiometry and abdominal fat volume with computed tomography. BCAAs and acylcarnitines were profiled using liquid chromatography with tandem mass spectrometry. Insulin resistance was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. At 1-year follow-up, the decrease in BMI, body weight, total fat mass (TFM), fat free mass, and visceral adipose tissue (VAT) was similar between SG and GB. HOMA-IR was associated with BCAA concentrations, and both were decreased equally in both surgical groups. In multivariate analysis with BCAAs, TFM, and VAT as independent factors, only VAT remained significantly associated with insulin resistance. The metabolic benefits from bariatric surgery, including the changes in BCAA profile, are comparable between SG and GB. The reduction in BCAAs and improvement in the AC profiles after bariatric surgery persists up to 12 months after surgery and may not be surgical related but is influenced primarily by the amount of weight loss, in particular the reduction in visceral adiposity.

It is known that age is an important factor for postoperative cognitive dysfunction (POCD) and the patients with POCD suffer from the impairment of multiple brain regions and multiple brain functions. However currently animal studies of POCD mainly focus on hippocampus region, therefore in this study we performed partial hepatectomy in young adult and aged rats to test the questions (1) whether POCD in animals involves other brain areas besides hippocampus; (2) how age influences POCD of young adult and aged animals. We found that (1) in young adult rats, the memory was not significantly affected (P>0.05) 1d, 3d and 7d after partial hepatectomy, but was significantly impaired (p0.05, respectively) 1d and 3d post-surgery, but the spine densities at CA1 and DG of aged rats were significant reduced 1d and 3d post-surgery (p0.05); (3) In young adult rats, surgery didn't affect the activation of microglia and levels of TNF-α and IL-1β at hippocampus (P>0.05), but significantly activated microglia and increased levels of TNF-α and IL-1β at hippocampus of aged rats (P

Consumptive hypothyroidism (CH) is a rare form of hypothyroidism due to increased catabolic activity of type 3 iodothyronine deiodinase (DIO3) that can occur in large tumors. PATIENTs with CH typically present with markedly increased requirements for exogenous thyroid hormone and resolution after removal of the source of ectopic DIO3. DIO3 is encoded by DIO3, an imprinted gene expressed on the paternal allele that is located in a DIO3/delta-like 1 homolog (DLK1) gene locus regulated by a common control region, intergenic differentially methylated region (IGDMR). Because DIO3 is an imprinted gene, loss of imprinting at the IGDMR is thought to play a role in its increased expression; however, the molecular mechanism for DIO3 in CH currently is not known.The aim of the study was to determine the molecular mechanism for CH in an adult patient.The study was conducted in the Department of Endocrinology of a tertiary care center in Singapore.We report the case of an adult Asian female patient with a large intrathoracic fibrous tumor and severe hypothyroidism that resolved after tumor resection.The patient's tumor expressed increased levels of DIO3 and DLK1 mRNA and protein levels. Methylation-specific PCR of the IGDMR showed similar hypomethylation in placenta, thyroid, leukocytes, and tumor. Western blotting showed activation of sonic hedgehog (SHH) and MAPK signaling pathways that can increase DIO3 and DLK1 expression.Loss of imprinting did not account for overexpression of DIO3 in the patient's tumor. Instead SHH and MAPK/ERK pathway activation was associated with systemic thyroid hormone catabolism and growth of the tumor. These findings raise the possibility that other tumors that have increased SHH and MAPK/ERK signaling also may have intratumor or systemic effects on thyroid hormone function.