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Enterolith in the Roux limb of hepaticojejunostomy causing jaundice is a rare occurrence. A 40-year-old woman had an extrahepatic biliary obstruction and cholangitis 13 years after the Roux-en-Y repair of postcholecystectomy benign biliary stricture. On evaluation, an enterolith was obstructing the Roux limb, which was successfully managed surgically.

BACKGROUND: The association between obesity (body mass index (BMI) ≥ 30 kg/m(2)) and pattern of medication use during pregnancy in the United States is not well-studied. Higher prepregnancy BMI may be associated with increases or decreases in medication use across pregnancy as symptoms (e.g. reflux) or comorbidities (e.g. gestational diabetes) requiring treatment that may be associated with higher BMI could also change with advancing gestation. OBJECTIVES: To determine whether prenatal medication use, by the number and types of medications, varies by pre-pregnancy obesity status. METHODS: In a secondary data analysis of a racially/ethnically diverse prospective cohort of pregnant women with low risk for fetal abnormalities enrolled in the first trimester of pregnancy and followed to delivery (singleton, 12 United States clinical sites), free text medication data were obtained at enrollment and up to five follow-up visits and abstracted from medical records at delivery. RESULTS: In 436 women with obesity and 1750 women without obesity (pre-pregnancy BMI, 19–29.9 kg/m(2)), more than 70% of pregnant women (77% of women with and 73% of women without obesity) reported taking at least one medication during pregnancy, respectively (adjusted risk ratio (aRR)=1.10, 95% confidence interval (CI)=1.01, 1.20), with 81% reporting two and 69% reporting three or more. A total of 17 classes of medications were identified. Among medication classes consumed by at least 5% of all women, the only class that differed between women with and without obesity was hormones and synthetic substitutes (including steroids, progesterone, diabetes, and thyroid medications) in which women with obesity took more medications (11 vs. 5%, aRR = 1.9, 95% CI = 1.38, 2.61) compared to women without obesity. Within this class, a higher percentage of women with obesity took diabetes medications (2.3 vs. 0.7%) and progesterone (3.4 vs. 1.3%) than their non-obese counterparts. Similar percentages of women with and without obesity reported consuming medications in the remaining medication classes including central nervous system agents (50 and 46%), gastrointestinal drugs (43 and 40%), anti-infective agents (23 and 21%), antihistamines (20 and 17%), autonomic drugs (10 and 9%), and respiratory tract agents (7 and 6%), respectively (p > 0.05 for all adjusted comparisons). There were no differences in medication use by obesity status across gestation. Since the study exclusion criteria limited the non-obese group to women without thyroid disease, in a sensitivity analysis we excluded all women who reported thyroid medication intake and still a higher proportion of women with obesity took the hormones and synthetic substitutes class compared to women without obesity. CONCLUSION: Our findings suggest that pre-pregnancy obesity in otherwise healthy women is associated with a higher use of only selected medications (such as diabetes medications and progesterone) during pregnancy, while the intake of other more common medication types such as analgesics, antibiotics, and antacids does not vary by pre-pregnancy obesity status. As medication safety information for prenatal consumption is insufficient for many medications, these findings highlight the need for a more in-depth examination of factors associated with prenatal medication use.

BACKGROUND Environmental and genetic factors are suggested to exhibit factor-based association with HDL-cholesterol (HDL-C) levels. However, the population-based effects of environmental and genetic factors have not been compared clearly. We conducted a cross-sectional study using data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study to evaluate the population-based impact of smoking, drinking, and genetic factors on low HDL-C. METHODS Data from 11,498 men and women aged 35-69 years were collected for a genome-wide association study (GWAS). Sixty-five HDL-C-related SNPs with genome-wide significance (P < 5 × 10-8) were selected from the GWAS catalog, and seven representative SNPs were defined, and the population-based impact was estimated using population attributable fraction (PAF). RESULTS We found that smoking, drinking, daily activity, habitual exercise, egg intake, BMI, age, sex and the SNPs CETP rs3764261, APOA5 rs662799, LIPC rs1800588, LPL rs328, ABCA1 rs2575876, LIPG rs3786247, and APOE rs429358 were associated with HDL-C levels. The gene-environmental interactions on smoking and drinking were not statistically significant. The PAF for low HDL-C was the highest in men (63.2%) and in rs3764261 (31.5%) of the genetic factors, and the PAFs of smoking and drinking were 23.1% and 41.8%, respectively. CONCLUSIONS The present study showed that the population-based impact of genomic factor CETP rs3764261 for low HDL-C was higher than that of smoking and lower than that of drinking.

Does Subjective Evaluation of Probability Impact Asset Prices? The Nobel Prize–winning capital asset pricing model (CAPM) predicts that expected excess return of any asset is positively proportional to its exposure to the overall market: the beta, leading to an upward-sloping security market line. However, this prediction is contradicted by empirical studies that the return–beta slope is often flat or even downward-sloping, a puzzle called the “beta anomaly.” The CAPM is premised upon the notion that market participants are all rational, including that they are able to objectively evaluate probabilities. However, evidence abounds that individuals are often unable to do so, examples being purchase of lottery tickets and insurance products, in which the extremely small probabilities of winning or losing big are exaggerated. This phenomenon of distorting probabilities at both tails is called “probability weighting” (PW), which is a key component of modern behavioral finance. The paper “Beta and Coskewness Pricing: Perspective from Probability Weighting” approaches the beta anomaly through PW. It offers an explanation of the beta anomaly via a new theoretical CAPM involving PW and an extensive empirical study.

Objectives: Identification of the high risk alleles, genotypes and haplotypes of the human leukocyte antigens (HLA) in different populations is beneficial for understanding their roles in type 1 diabetes (T1D) pathogenesis and intervention practices. This study aimed to identify T1D-associated HLA gene alleles in the Omani population. Methods: The present case-control study included 73 diabetic seropositive children (mean age 9.08 ± 3.27 years) attending the paediatric clinic at Sultan Qaboos University Hospital in Muscat, Oman, and 110 healthy controls. HLA–A, -B, -C, -DRB1 and -DQB1 genes were genotyped using a sequence-specific primer polymerase chain reaction (SSP-PCR). Results: Two HLA class I alleles (B*08, B*58) and three class II alleles (DQB1*02, DRB1*03 and DRB1*04) were associated with T1D susceptibility, while one class I (B*51) and three class II (DQB1*05, DQB1*06 and DRB1*16) alleles were associated with T1D protection. HLA-DRB1*03 and DQB1*02 alleles showed the strongest risk association among all alleles. Six DRB1 residues (E9, S11, S13, Y30, V70 and K71) were significantly associated with T1D susceptibility. Heterozygous genotypes, HLA-DRB1*03/*04 and DQB1*02/*03 were significantly associated with T1D susceptibility (P

Using the combined application of L-arginine with HMG-Co-A reductase inhibitors simvastatin, atorvastatin, rosuvastatin and nanoparticulated rosuvastatin on the background of modeling of sepsis-induced disease through the introduction of strain 603 Staphylococcus aureus shows endotelio- and cardioprotective effects, manifesting itself in preventing the proliferation of endothelial dysfunction coefficient (CED), adrenoreactivity, maintenance of myocardial reserve and the normalization of biochemical markers values (Total NO, eNOS expression, C-reactive protein, IL-6, TNF). In this case, the combined therapy was so effective that the values obtained thereunder did not differ from those obtained from control animals.

Objectives: The purpose of this study was to investigate the surgical efficacy and risk factors of cervical spondylotic myelopathy (CSM) patients with increased signal intensity (ISI) on T2-weighted magnetic resonance imaging (MRI-T2WI). Methods: We compared the surgical outcomes of CSM patients with and without ISI. In addition, we compared the efficacy of anterior and posterior cervical decompression in CSM patients with ISI. We also analyzed the risk factors of MRI-T2WI ISI in CSM patients. Results: The incidence of ISI among 153 CSM patients was 71.89 %. The JOA score and JOA remission rate were better in the ISI-free than in the ISI group. The postoperative JOA score and JOA remission rate were better in the posterior than the anterior approach surgery group. The disease duration and vertebral canal volume were found to be risk factors for ISI in CSM patients. Conclusion: Among patients with CSM, the prognosis is worse for those with ISI than those without ISI. Posterior cervical decompression surgery produces a better curative effect than anterior cervical decompression surgery in CSM patients with ISI. CSM patients with longer disease duration and small vertebral canal volume should undergo surgical treatment as early as possible.

Background. Hypercholesterolemia and inflammation both contribute to the pathogenesis of atherosclerosis and its clinical manifestations. Statins, possessing both lipid-lowering and anti-inflammatory properties, are currently recommended in all ischemic syndromes. Purpose. To compare the effects of atorvastatin and rosuvastatin on lipid and inflammatory markers in patients with acute coronary syndromes (ACS). Methods. Two hundred thirty-nine consecutive patients with ACS, without familial hypercholesterolaemia and no statin treatment in the preceding 4 weeks, were randomly assigned within 24 hours after hospital admission to either atorvastatin 80 mg (119 patients) or rosuvastatin 20 mg (120 patients). Lipid and inflammatory markers were assessed before randomization and after 4 and 12 weeks of treatment. Results. Both statins similarly reduced total cholesterol and LDL-cholesterol at 4 weeks, with substantial stability at 12 weeks. At 4 weeks, LDL-cholesterol decreased from 129 mg/dL to 71 mg/dL in atorvastatin group and from 126 mg/dL to 71 mg/dL in rosuvastatin group. Apolipoprotein B significantly decreased in both groups. Otherwise, apolipoprotein A1 increased in rosuvastatin group only. As a consequence, ApoB/ApoA1 ratio decreased more in rosuvastatin group. No significant differences were seen in triglycerides, HDL-cholesterol and Lipoprotein (a) levels. Among inflammatory markers, hs-CRP, interleukin-6, interleukin 1-RA, TGF-β1, and MMP-9 significantly and similarly decreased at 4 and 12 weeks in both groups. Interleukin-10 levels decreased only in patients randomized to atorvastatin. Conclusions. A moderate dose of rosuvastatin provided similar effects, as compared to a high dose of atorvastatin, on a large series of lipid and inflammatory markers. Rosuvastatin was more effective than atorvastatin in reducing ApoB/ApoA1. Considering these findings, rosuvastatin 20 mg daily may be an alternative to atorvastatin 80 mg in acute coronary syndromes.

Retinoic acid (RA), a bioactive metabolite of vitamin A, has shown therapeutic effects in liver disease, and its effect in improving non-alcoholic fatty liver disease (NAFLD) is associated with the inhibition of adipogenesis in the white adipose tissue (WAT) and fatty acid oxidation induction in the liver. However, the major target organ of RA is unknown. We performed chronic administration of RA in high-fat diet (HFD)-induced NAFLD mice. Further, hepatic and adipose cells were used to study the direct effect of RA on lipid metabolism. In addition, qRT-PCR was performed to examine differential gene expression in mouse adipose tissue. RA administration ameliorated NAFLD in HFD-induced obese mice and increased mouse energy expenditure. Although RA had therapeutic effects on liver histology and lipid accumulation, it did not directly affect lipid metabolism in HepG2 cells. In contrast, RA reduced the weight of several adipose tissues and improved lipid accumulation in OP9 cells. In addition, RA upregulated genes responsible for fatty acid oxidation and thermogenesis in three different WATs. Our work suggests that the liver may not be the main target organ of RA during NAFLD treatment. WAT browning induced by RA may be the primary contributor towards the amelioration of NAFLD in HFD-induced obese mice.

Naturally fermented filed water-dropwort (Oenanthe javanica) extracts by steeping with oligosaccharides (FDE) show a hepatoprotective activity against the liver injury induced by carbon tetrachloride (CCl4) and ethanol. However, the role of FDE in non-alcoholic steatohepatitis (NASH) has not yet been reported. In the present study, we investigated the effect of FDE on NASH using a mouse model with a methionine/choline-deficient diet (MCD). C57BL/6 male mice (9 weeks old) were fed on an MCD diet for 6 weeks with parallel water or FDE orally administration each day. FDE administered mice showed decreasing MCD diet-induced triglyceride (TG) levels, oxidative stress, infiltrating macrophages and elevating inflammatory cytokines in the liver. Our results suggest that FDE suppressed MCD diet-induced liver injury by inhibiting TG synthesis, the blocking of oxidative stress and hepatic inflammation, highlighting FDE as a potential therapeutic agent for the prevention and treatment of NASH.

Objective: The study aimed at identifying the influence of socio-demographic factors on perceived stress during the first and the second “waves” of the COVID-19 pandemic among patients with depression and anxiety in remission compared to controls. Method: The study was designed as case-control, cross-sectional and non-interventional, and included 60 outpatients with depressive and anxiety disorders in remission and 60 controls with or without family history of affective disorder. A self-assessment scale (Perceived Stress Scale, PSS-10) was used to evaluate perceived stress. The remission was objectified by the Clinical Global Impression scale (CGI-S ≤ 2) and a questionnaire about the socio-demographic features and clinical characteristics of the disorders was completed. Results: By using multiple logistic regression, it was found that the diagnostic category and/or the relevant family history did not predict higher levels of perceived stress during the COVID-19 pandemic (p > 0.05). Females were associated with higher risk of moderate or high stress (OR = 2.613, p = 0.017), as well as those working from home during the pandemic (OR = 4.00, p = 0.026). Conclusions: Addressing the COVID-19 effects on mental health in a biopsychosocial manner, the study shows the impact of socio-demographic factors such as gender and work environment in times of a psychosocial crisis. The lack of differences in stress perception by the patients in remission and healthy controls implicates the importance of adequate maintenance treatment and easy access to mental health services in times of crisis.

Background:This study measured the outer media thickness (OMT) at the false lumen by using microscopic images of specimens collected intraoperatively and assessed the impact of OMT on secondary dilatation of the downstream aorta., Methods:Of 238 patients undergoing surgical procedures for acute type A dissection between 2007 and 2016, 129 patients fulfilled the inclusion criteria for this study: DeBakey type I dissection with a patent false lumen, histopathologic examination of full-thickness aortic wall, and at least 1 follow-up computed tomographic scan at more than 3 months after surgical procedures. On average, 5.1 scans were obtained per patient, and median follow-up was 4.3 years., Results:Considerable variation was observed in OMT (median, 0.21 mm; range, 0.04-0.51 mm). The aortic diameter growth rate was inversely correlated with the OMT, and in the lowest tertile of OMT the aortic diameter dilated significantly faster in the first year than later and faster than in the other tertiles. Multivariable Fine-Gray analysis, with death as the competing risk, identified OMT as an independent variable for aortic-related events. Patients with OMT of 0.04 to 0.15 mm had a 3.54-fold higher risk of aortic-related events and those with 0.16 to 0.31 mm had a 1.56-fold higher risk of aortic-related events than did patients with OMT of 0.32 to 0.51 mm. Multivariable Cox regression analyses revealed OMT of 0.04 to 0.15 mm as an independent variable for all-cause mortality., Conclusions:In patients with DeBakey type I aortic dissection with a patent false lumen, the growth rate of the distal residual dissecting aorta was inversely correlated with the OMT. The risk of aortic-related events was significantly higher in patients with OMT of 0.04 to 0.15 mm.

Fast-acting insulin aspart (faster aspart) is an ultra-rapid-acting formulation of insulin aspart developed to more closely match the prandial endogenous insulin profile, and its accelerated absorption kinetics are expected to provide clinical benefits for patients using insulin pump therapy. A head-to-head trial versus the original insulin aspart formulation in pump therapy did not demonstrate superiority of faster aspart in terms of A1C reduction, but pump settings were not optimized for the pharmacokinetic/pharmacodynamic profile of faster aspart. Nevertheless, meal test and continuous glucose monitoring data suggest that faster aspart is beneficial for postprandial glucose control, and a case study is presented illustrating excellent results using this insulin in pump therapy. Frequent blood glucose monitoring and appropriate patient education are vital for success.

Introduction We have previously shown that some patients present thrombocytopenia (less than 100 × 109/L platelets) in non-alcoholic fatty liver disease (NAFLD). To further explore the nature of this association, we have now analyzed the association of thrombocytopenia with neutropenia (less than 0.5 × 109/L granulocytes) in NAFLD. Material and methods Persons with NAFLD were prospectively accrued in the study after February 2018. The presence of NAFLD was defined by both serologic determinations (Fibromax ®) and liver transient elastography (TE/Fibroscan ®). Results In 123 consecutive patients with NAFLD without cirrhosis, thrombocytopenia was identified in 20 (16%), whereas neutropenia was identified in 9 (7%). In the subset of 20 patients with NAFLD and thrombocytopenia, granulocytopenia was identified in 5 (25%), whereas in the subset of 9 patients with granulocytopenia, thrombocytopenia was identified in 5 (55%). We found a significant association between thrombocytopenia and both leukopenia and granulocytopenia (OR 8.25, 95% CI 1.9–34.2, p = 0.004). Conclusions Both thrombocytopenia and neutropenia were identified in persons with NAFLD and, as there is a significant relationship between these two variables, we speculate that this finding may support the possibility of hypersplenism being involved in the cytopenias found in NAFLD without cirrhosis.

Uniportal video-assisted thoracoscopic surgery (U-VATS) can achieve traditional clinical outcomes comparable to those of multiportal video-assisted thoracoscopic surgery (M-VATS). This study aimed to compare patient-reported outcomes between U-VATS and M-VATS for lung cancer lobectomy in the early postoperative period.This comparative analysis used data from a longitudinal prospective study (Perioperative Symptom Study of Lung Cancer [CN-PRO-Lung 1]). Symptom severity, functional status, and quality of life were compared between groups using generalized estimation equation models. Symptom severity and functional status were reported as proportion of patients with clinically meaningful severe scores on 0- to 10-point scales assessed using the MD Anderson Symptom Inventory-Lung Cancer module.Of the 174 patients included, 102 (58.6%) underwent U-VATS lobectomy and 72 (41.4%) underwent M-VATS lobectomy. After adjusting for confounders, patients in the U-VATS group reported less severe pain (P = .02), fatigue (P = .001), constipation (P = .01), coughing (P = .003), shortness of breath (P.001), and disturbed sleep (P = .007) during the 6-day postoperative hospitalization than did patients in the M-VATS group. Moreover, fewer patients reported severe impairment in walking (P = .033) or their capacity to enjoy life (P = .027) in the U-VATS group. Meanwhile, there were no significant between-group differences in the quality of life scores, operative time, chest tube duration, length of hospital stay, or early complication rate (grade II or higher) (all P.05).U-VATS may produce fewer severe symptoms and better functional status than M-VATS for lung cancer lobectomy in the early postoperative period.

Purpose: A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests. Patients and Methods: RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed. Results: Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed. Conclusion: TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk. Funding: This study was carried out with the support of Instituto de Salud Carlos III (ISCIII) (grant number PI0810119).

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) remain two of the most commonly encountered metabolic emergencies. They are both potentially life threatening when not managed correctly. DKA occurs most frequently (but not exclusively) in people with type 1 diabetes who are absolutely insulin deficient. HHS (formerly known as HONK – hyperosmolar non-ketotic state) occurs most frequently (but not exclusively) in more elderly people with type 2 diabetes, who have insufficient insulin concentration to lower blood glucose but enough to prevent ketone production. Diabetes may present for the first time as DKA or HHS, but these conditions occur more frequently in people known to have diabetes. The treatment of DKA and HHS differs because the conditions are biochemically different. In DKA the emphasis of treatment has changed; with increasing access to bedside plasma ketone monitors, β-hydroxybutyrate concentration rather than blood glucose is often used to guide therapy. In HHS, glucose lowering should be achieved predominantly using fluid rehydration, with insulin being introduced only when the rate of glucose lowering has stabilized.

Background: People with impaired awareness of hypoglycemia (IAH) are at elevated risk of severe, potentially hazardous, hypoglycemia and would benefit from a device alerting to hypoglycemia. Heart rate variability (HRV) changes with hypoglycemia due to sympathetic activity. Since IAH is associated with suppressed sympathetic activity, we investigated whether hypoglycemia elicits a measurable change in HRV in patients with T1D and IAH. Method: Eligible participants underwent a modified hyperinsulinemic euglycemic hypoglycemic clamp (glucose nadir, 43.1 ± 0.90 mg/dl), while HRV was measured by a VitalConnect HealthPatch. Measurements of HRV included Root Mean Square of the Successive Differences (RMSSD) and low to high frequency (LF:HF) ratio. Wilcoxon rank-sum test was used for testing within-subject HRV changes. Results: We included 12 participants (8 female, mean age 57 ± 12 years, mean HbA1c 57 ± 5 mmol/mol (7.4 ± 0.4%)). Symptoms increased from 4.0 (1.5-7.0) at euglycemia to 7.5 (5.0-11.0) during hypoglycemia ( P = .003). In response to hypoglycemia, the LF:HF ratio and RMSSD increased when normalized for data obtained during euglycemia (both P < .01). The LF:HF ratio increased in 6 participants (50%) and declined in one other participant (8%). The RMSSD decreased in 3 (25%) and increased in 4 (33%) participants. In 2 patients, no change in HRV could be detected in response to hypoglycemia. Conclusions: This study reveals that hypoglycemia-induced changes in HRV are retained in the majority of people with T1D and IAH, and that these changes can be detected by a wearable device. Real-time HRV seems usable for detection of hypoglycemia in patients with IAH.

Acanthosis Nigricans is considered to be a skin marker of insulin resistance and atherosclerosis. It is rarely reported in cases of insulinoma where there is marked hyperinsulinaemia. We report two cases of insulinoma with acanthosis nigricans which regressed, concomitant with significant weight loss and reduction in blood pressure following surgical resection. This strengthens the hypothesis that hyperinsulinaemia is responsible for Acanthosis nigricans and atherosclerotic risk factors.

Background and Aims: Nocturnal hypoglycemia is mainly a consequence of inappropriate basal insulin therapy in type 1 diabetes (T1D) and may compromise optimal glycemic control. Insulin degludec is associated with a lower risk of nocturnal hypoglycemia in T1D. As nocturnal hypoglycemia is often asymptomatic, we applied continuous glucose monitoring (CGM) to detect a more precise occurrence of nocturnal hypoglycemia in the HypoDeg trial, comparing insulin degludec with insulin glargine U100 in people with T1D and previous nocturnal severe hypoglycemia. Materials and Methods: In the HypoDeg trial, 149 people with T1D were included in an open-label randomized cross-over trial. Sixty-seven participants accepted optional participation in the predefined substudy of 4 × 6 days of blinded CGM requiring completion of at least one CGM period in each treatment arm. CGM data were reviewed for hypoglycemic events. Results: Treatment with insulin degludec resulted in a relative rate reduction (RRR) of 36% (95% confidence interval [CI]: 10%-54%; P

Abstract: Type 2 diabetes (T2D), which affects many people around the world, is one of the diseases that is on the rise. Various studies have revealed that insulin resistance and lessened insulin production have been associated with T2D, and they also show that this disease can have a genetic origin and is associated with different genes, such as KCNQ1, PPAR-γ, calpain-10, ADIPOR2, TCF7L2, which can be utilized as therapeutic targets. Different therapeutic approaches and strategies such as exercise and diet, pharmacological approaches, and utilization of nanoparticles in drug delivery and gene therapy can be effective in the treatment and control of T2D. Glucagon-like peptide 1 (GLP-1) and sodiumglucose cotransporter-2 (SGLT2) have both been considered as drug classes in the treatment of T2D and T2D-related diseases such as cardiovascular disease and renal disease, and have considerable influences such as diminished cardiovascular mortality in individuals with T2D, ameliorated postprandial glycaemia, ameliorated fasting glycaemia, and diminished bodyweight on disease treatment and improvement process. In the present review article, we have attempted to explore the risk factors, genes, and diseases associated with T2D, therapeutic approaches in T2D, the influences of drugs such as dapagliflozin, metformin, acarbose, Januvia (sitagliptin), and ertugliflozin on T2D in clinical trials and animal model studies. Research in clinical trials has promising results that support the role of these drug approaches in T2D prophylaxis and ameliorate safety even though additional clinical research is still obligatory.

Background Statins are the mainstay for the treatment of dyslipidemia. Recently, rosuvastatin has also been demonstrated to possess analgesic properties in animal studies. The present study has been planned to further confirm the analgesic activity of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline and study the interaction of rosuvastatin with the above-mentioned analgesics. The objective of the study was to confirm the analgesic activity of rosuvastatin and determine the minimum analgesic dose of rosuvastatin, etoricoxib, tramadol, amlodipine and amitriptyline and to study the analgesic effect of combination of subanalgesic doses of rosuvastatin with sub-analgesic doses of etoricoxib, tramadol, amlodipine, and amitriptyline. Method After IAEC approval, the study was carried out in albino mice in two phases. In phase I, the analgesic effect of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline was confirmed by using tail-flick and writhing methods. In phase II, analgesic effect of combinations of subanalgesic dose of rosuvastatin with subanalgesic dose of etoricoxib, tramadol, amlodipine, and amitriptyline was studied. Results Minimal analgesic dose of rosuvastatin, etoricoxib, tramadol, amlodipine, and amitriptyline was observed as 5, 20, 10, 5, and 10 mg/kg, respectively. In phase II, combination of subanalgesic dose of rosuvastatin 2.5 mg/kg with subanalgesic doses of etoricoxib (10 mg/kg), tramadol (5 mg/kg), amlodipine (2.5 mg/kg), and amitriptyline (5 mg/kg), demonstrated synergistic analgesic activity. Conclusion Rosuvastatin exerts dose-dependent analgesic activity that is synergistic to that of etoricoxib, tramadol, amlodipine, and amitriptyline. If established in clinical studies as well, this finding can lead to the reduction of analgesic dosing in patients already on statins.

Background Roux-en-Y gastric bypass (RYGB) is considered the gold standard procedure for bariatric surgery that leads to sustained weight loss and amelioration of obesity-related comorbidities. Objectives To verify long-term efficacy and safety and to investigate the influence of early weight loss on post-RYGB long-term weight maintenance in obese Chinese with body mass index (BMI) Methods All patients were followed up for evaluating the variations in their BMI, percentage of excess weight loss (%EWL), and total body percentage weight loss (%TWL). Linear regression models were applied to evaluate the effects of early weight loss on successful weight maintenance. Optimal cutoff values were analyzed via plotting the receiver operative characteristic (ROC) curve. Results In the current study, 143 patients were recruited. Preoperative BMI and weight were recorded as 32.24 (29.39-33.12) kg/m2, and 88.90 ± 9.52 kg, respectively. At 1, 3, and 5 years, successful weight loss i.e., greater than 25% TWL was attained by 46.85%, 37.76%, and 37.06% of patients, respectively. The obtained data revealed that %TWL at 0.5 years was considerably associated with %TWL for up to 5 years (P-value Conclusion RYGB is a safe and effective approach for weight loss and %TWL at 6 months might be used for predicting weight maintenance up to 5 years post-RYGB in obese Chinese with a BMI

Pre-eclampsia is a common pregnancy complication with many associated maternal and fetal risks, yet its pathophysiology remains poorly understood. Hyponatraemia is a rarely described finding in pre-eclampsia that has been associated with both maternal and fetal complications and medically indicated delivery. We present a case of hyponatraemia in a patient admitted for induction of labour for gestational hypertension, which developed into pre-eclampsia with severe features requiring magnesium sulfate therapy for seizure prophylaxis. The patient’s hyponatraemia resolved with delivery, fluid restriction and serial sodium monitoring. Adjustment to the components of the patient’s magnesium sulfate infusion was made to reduce free water intake and avoid further exacerbation of her hyponatraemia. While there is currently no recommendation to routinely monitor sodium levels in hypertensive disorders of pregnancy, careful consideration of this potential finding in cases of pre-eclampsia should be given due to the overlap between symptoms of hyponatraemia and cerebral symptoms of pre-eclampsia.

We present a case of hypoglycemia in a young patient without diabetes mellitus who presented initially with enlarging neck mass and weight loss, and was found to have aggressive melanoma with metastasis to multiple organs and diffuse lymphadenopathy. He had presented to the emergency room two times with neuroglycopenic symptoms that required admission and intravenous dextrose continuously. Evaluation of hypoglycemia included C-peptide, insulin levels, insulin-like growth factor (IGF) -I and -II, and ß- hydroxybutyrate. Insulin levels were suppressed appropriately during hypoglycemia, however, IGF-II:IGF-I ratio was high, suggesting non-islet tumour induced hypoglycemia. The presence of IGF-II produced by large tumors results in a low hepatic glucose output and increased uptake by skeletal muscle, resulting in hypoglycemia especially in a patient with extremely low appetite such as our patient. Treating the culprit malignancy leads to resolution of hypoglycemia, but corticosteroids have been used to suppress IGF-II levels and alleviate symptoms.

A 37-year-old woman presented with a few days’ history of lower abdominal pain and an incidental finding of hypercalcaemia. A thorough workup ensued, and the cause was found to be an exceptionally rare ovarian tumour—ovarian small cell carcinoma of the hypercalcaemic type. Acute treatment of hypercalcaemia consisted of aggressive intravenous fluids and bisphosphonates. She underwent surgery to remove the tumour and is currently receiving systemic platinum/etoposide chemotherapy combination to be followed by pelvic radiotherapy. This case highlights the wide range of differential diagnosis for hypercalcaemia and the importance of a stepwise and thorough approach during investigations. We discuss the pathophysiology of malignancy-related hypercalcaemia, focusing especially on parathyroid hormone-related peptide-associated hypercalcaemia.

We present a case of a 73-year-old woman who developed recurrent hypoglycaemia during a prolonged hospital stay following a mechanical fall. She had a complex history of insulin-treated diabetes mellitus, hypothyroidism, diffuse systemic cutaneous sclerosis, Raynaud’s disease, previous breast cancer, Barrett’s oesophagus and previous partial gastrectomy for a benign mass. Hypoglycaemia persisted despite weaning of insulin. She had no clinical features of adrenal or pituitary insufficiency with an acceptable cortisol on stopping prednisolone and had an optimal thyroid replacement. A 72-hour fast elicited hypoglycaemia with corresponding low insulin level. Although the C-peptide was detectable, there were no clinical, biochemical or radiological features suggestive of insulinoma. Reactive hypoglycaemia post partial gastrectomy was ruled out based on limited relation of the hypoglycaemia to meals and the low insulin levels. Hydroxychloroquine (HCQ)-induced hypoglycaemia was considered based on previous case reports and the recent literature, with a successful resolution of hypoglycaemia on discontinuation of HCQ.

Severe hypertriglyceridaemia can lead to acute pancreatitis, which is associated with maternal and perinatal mortality when it occurs in pregnancy. Rapid reduction of triglyceride levels is a primary goal in the management of severe hypertriglyceridaemia, however, there are limited safe option for treatment in pregnancy. We present a case of a woman without diabetes presenting with severe hypertriglyceridaemia in late gestation who was safely and successfully treated with insulin and review the literature surrounding the management of this important condition.

Simultaneous occurrences of diabetic ketoacidosis (DKA) and thyroid storm have long been known, but only a few cases have been reported to date. Both these endocrine emergencies demand timely diagnosis and management to prevent adverse outcomes. Due to the similarities in their clinical presentation, DKA can mask the diagnosis of thyroid storm and vice versa. This case report describes a patient with Graves’ disease who presented to the emergency department with nausea, vomiting and abdominal pain. He was found to have severe DKA without an explicit history of diabetes mellitus. Further evaluation revealed that the patient also had a concomitant thyroid storm that was the likely cause of his DKA. Early recognition and appropriate management of both conditions resulted in a favourable outcome. This paper emphasises that a simultaneous thyroid storm diagnosis should be considered in patients with DKA, especially those with a known history of thyroid disorders.

"False" foramina and fissures of the skull are described as openings formed between the adjacent edges of two or more bones and not conduits directly through a single bone. Trauma and metabolic disorders appear to affect these foramina and fissures differently when compared to the "true" foramina and fissures. Therefore, the aim of this paper is to provide a narrative review of the current literature about "false" foramina and fissures of the skull and skull base with a focus on their clinical significance.

Aim The safety concern of statins is still a major issue for Asians. The aim of this study is to compare the risk of statin-associated adverse events among potent statins. Methods We included patients from the Taiwan National Health Insurance Research Database who had been treated with atorvastatin, rosuvastatin, or pitavastatin and were without diabetes at baseline. They were classified into three groups: usual-dose statin (atorvastatin 10 mg/d or rosuvastatin 5-10 mg/d), high-dose statin (atorvastatin 20-40 mg/d and rosuvastatin 20 mg/d), and pitavastatin (2-4 mg/d). The primary endpoint is a composite of safety events, including hepatitis, myopathy, and new-onset diabetes mellitus (NODM). We matched age, sex, and year of recruitment among the three groups (n=50,935 in each group) and then used the multivariate Cox proportional hazards model to evaluate the relation between the safety endpoint and different statin groups. Results After a mean follow-up of 3.08±0.83 years, the safety events occurred in 9.84% in the pitavastatin group, 10.88% in the usual-dose statin group, and 10.49% in high-dose statin group. The multivariate Cox proportional hazards model indicated that usual-dose statin and high-dose statin were associated with a higher risk of the composite safety events compared with pitavastatin (adjusted hazard ratio [aHR]: 1.12, 95% confidence interval [CI]: 1.08-1.17 for usual-dose statin and aHR: 1.06, 95% CI: 1.02-1.10 for high-dose statin). The risks of hepatitis requiring hospitalization and NODM were especially lower in pitavastatin group. Conclusions Compared with atorvastatin and rosuvastatin, pitavastatin might be associated with a lower risk of safety events in Asians.

Microplastics (MPs) have attracted a significant concern due to persistence and their adverse effects on organisms. In this review, we summarize the recent literature regarding the natural and artificial aging process of MPs, also discuss the associated aging characteristics and mechanisms of MPs. The aged MPs showed different morphological and chemical properties from the pristine MPs. Furthermore, to evaluate associated aging effects, the corresponding release of aging process of MPs were systematically revealed, including the additives and intermediates. Different types of organic pollutants and heavy metals additives are listed. In addition, the release of MPs is affected by environmental factors (i.e., Illumination, salinity, temperature and pH). Aged MPs are more easily absorbed by organisms and have different toxic effects from the pristine MPs. The potential risks of aging MPs and the release of MPs during aging are discussed in detail. Based on the current deficiency of published literatures, the prospects are proposed. Therefore, this review provides a direction for further study on the behaviors and the toxic effects of MPs in the environment.

Nonalcoholic fatty liver disease (NAFLD) is a kind of metabolic stress-induced liver injury closely related to insulin resistance and genetic susceptibility, and there is no specific drug for its clinical treatment currently. In recent years, a large amount of literature has reported that many natural compounds extracted from traditional Chinese medicine (TCM) can improve NAFLD through various mechanisms. According to the latest reports, some emerging natural compounds have shown great potential to improve NAFLD but are seldom used clinically due to the lacking special research. : This paper aims to summarize the molecular mechanisms of the potential natural compounds on improving NAFLD, thus providing a direction and basis for further research on the pathogenesis of NAFLD and the development of effective drugs for the prevention and treatment of NAFLD. : By searching various online databases, such as Web of Science, SciFinder, PubMed, and CNKI, NAFLD and these natural compounds were used as the keywords for detailed literature retrieval. : The pathogenesis of NAFLD and the molecular mechanisms of the potential natural compounds on improving NAFLD have been reviewed. : Many natural compounds from traditional Chinese medicine have a good prospect in the treatment of NAFLD, which can serve as a direction for the development of anti-NAFLD drugs in the future.

The widespread presence of microplastics (MPs) in the environment has led to the rise of the study on the interaction between MPs and microorganisms. The variety and characteristics of MPs in the environment make their interaction with microorganisms more complex. Recent studies have found that MPs can also serve as an important carrier for microorganisms to form fully developed biofilms on the substrates. The emergence of new ecological sites will also affect the ecosystem of water and soil. We present the latest knowledge of MPs' interactions with microorganisms and summarize their respective potential impacts on the environment. It was found that the main factors affecting microbial colonization on MPs were the characteristics of MPs, exposure time and environmental factors. Furthermore, microbial colonization on MPs can affect the composition and distribution of the microbial community in the environment, as well as the migration and transformation of other contaminants which also occur in the animal guts. When it come to the toxicity of MPs to microorganisms, it has been found that the main effects of MPs on microorganisms are the effect on microbial growth, photosynthesis of microorganisms and some single cells. In addition, the combined effects of MPs with heavy metals and organic compounds on microorganisms can be divided into antagonistic effects, synergistic toxicity, promoting effects and non-effects. In turn, microbes will have impacts on MPs in terms of degradation, absorption, transfer and deposition. In practical application, MPs will affect the biological treatment stage of sewage treatment. This review discusses the interaction mechanism and influencing factors between microorganisms and MPs. It also called for active exploration of methods for treating MPs with microorganisms in the actual environment, providing a theoretical basis for the treatment of microorganisms, and a better understanding of the environmental behavior and ecological risk assessment of MPs.

Objective:\ud Normal pregnancy is characterized by significant changes in maternal hemodynamics that are associated with fetal growth. Pregnancies complicated by gestational diabetes mellitus (GDM) are associated with large-for-gestational age and macrosomia, but the relationship between maternal hemodynamic parameters and birth weight (BW) among women with GDM has not been established. Our objective was to investigate the influence of maternal hemodynamics on neonatal BW in healthy pregnancies and in those complicated by GDM.\ud \ud Methods:\ud This was a prospective, cross-sectional case–control study of women aged ≥ 16 years with a singleton viable pregnancy, recruited between January 2016 and February 2021 at Leicester Royal Infirmary, Leicester, UK. GDM was defined as a fasting glucose level ≥ 5.3 mmol/L and/or serum glucose level ≥ 7.8 mmol/L, 2 h following a 75-g oral glucose load. We collected data on maternal characteristics and pregnancy outcome, including body mass index (BMI) at booking and BW centile adjusted for gestational age at delivery. Maternal hemodynamic parameters were assessed at 34–42 weeks' gestation using the Arteriograph® and bioreactance techniques. Graphical causal inference methodology was used to identify causal effects of the measured variables on neonatal BW centile.\ud \ud Results:\ud Included in the analysis were 141 women with GDM and 136 normotensive non-diabetic pregnant controls. 62% of the women with GDM were managed pharmacologically, with metformin and/or insulin. Variables included in the final model were cardiac output (CO), mean arterial pressure (MAP), total peripheral resistance (TPR), aortic augmentation index (AIx), aortic pulse wave velocity (PWV) and BMI at booking. Among the controls, maternal BMI, CO and aortic PWV were significantly associated with neonatal BW. Each SD increase in booking BMI produced an increase of 8.4 BW centiles (P = 0.002), in CO produced an increase of 9.4 BW centiles (P = 0.008) and in aortic PWV produced an increase of 7.1 BW centiles (P = 0.017). We found no significant relationship between MAP, TPR or aortic AIx and neonatal BW. Maternal hemodynamics influenced neonatal BW among the women with GDM in a similar manner to that in the control group, but only the relationship between maternal BMI and neonatal BW reached statistical significance, with a 1-SD increase in BMI producing an increase of 6.1 BW centiles (P = 0.019).\ud \ud Conclusions:\ud Maternal BMI, CO and PWV were determinants of BW in our control group. The relationship between maternal hemodynamics and neonatal BW was similar between women with GDM and healthy controls. Our findings therefore suggest that fetal growth restriction in pregnancies complicated by GDM may indicate maternal cardiovascular dysfunction. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Microplastics (MPs) are major global environmental pollutants that have been extensively detected in agroecosystems. However, researches on their distribution and fates in farmland as well as their potential impacts on soil ecosystems are limited, especially studies on the influences of MPs on enzymes associated with carbon (C), nitrogen (N), and phosphorus (P) cycling and microbial nutrient limitations characterized by enzymatic stoichiometry are missing. In this study, we investigated the MPs characteristics under different continuous mulching management years (3, 6, 10, 15, and 20a) of tobacco fields in Enshi Prefecture, China, and identified the mechanisms of MPs pollution on soil microbial nutrient limitations. The results showed that the abundance of MPs varied from 647 to 2840 items/kg. Films, fibers and small-sized particles (0–1.0 mm) were the predominant types and size, respectively, and increased significantly with the increase of planting years. A vector analysis of enzyme activity suggested that microbial metabolism was limited both with C and P. The correlation analysis demonstrated that MPs pollution and soil properties were significantly linked to microbial nutrient limitations. Meanwhile, partial least squares path model (PLS-PM) revealed that MPs abundance exacerbated microbial limitation mainly by directly affecting soil microbial properties, followed by soil physical properties and soil nutrients, whereas MPs size and shapes indirectly exacerbated microbial nutrient limitation by significantly influencing MPs abundance. These results demonstrated that contamination of soil with MPs may have deleterious effects on soil key functions related to microbial metabolism, nutrient cycling, etc. Changes in soil properties and functions can damage plant growth and development, which may further affect crop yield and quality. This study provided a new theoretical basis for the response of soil microbial metabolism to MPs pollution and facilitated a better understanding and estimation of the environmental behavior and ecological risk of MPs in agricultural fields.

Objective To develop an insight scale for Prader-Willi Syndrome (PWS), a genetically determined neurodevelopmental disorder with different psychopathological and behavioural problems. Methodology A sample of 36 PWS patients (58.3% women) attended at the Endocrinological Department of the Corporacio Sanitaria Parc Tauli (Sabadell, Barcelona) was evaluated. Insight was assessed by means of an adapted version of the Scale of Unawareness of Mental Disorder (SUMD), including three general insight dimensions: awareness of having a PWS, awareness of the effects of psychopharmacological medication and awareness of the social consequences, as well as three items that assess awareness of each particular symptom of the disease (obesity/overweight, excessive appetite and excessive food intake). Results The final Scale included six items and demonstrated an adequate internal consistency (Cronbach Alfa of 0.857 for Caregivers and 0.798 for Clinicians) but a high inter-rate variability. External validation using an Analytical-Visual Insight Scale was adequate. Conclusions The Adapted version for Prader-Willi patients of the Scale of Unawareness of Mental Disorder (APW-SUD) showed adequate psychometric properties and it is an easy to administer means to assess insight in this population.

In recent years, microplastic (MP) pollution has been widely reported. Many studies have shown that MPs in the oceans not only exist in the water but also are eaten by plankton and may be transferred to other trophic levels via the plankton food web. This paper reviews the relationship between MPs and zooplankton, and discusses two aspects of the potential harm of MPs to zooplankton: the effects of MPs on zooplankton ingestion and the influence of MP toxicity on zooplankton. MPs are often eaten by zooplankton because they resemble prey in size, color, and buoyancy. Zooplankton ingest MPs directly or indirectly, resulting in intestinal damage, reduced ingestion, slow or delayed growth, reduced spawning, shortened lifespan, and abnormal or even fatal gene expression. MP ingestion by zooplankton also affects their behavior, reproduction, and offspring. MPs constitute an uncertain threat to zooplankton. Integration of MPs into the zooplankton community affects filtering organisms feeding. The mechanism of MP toxicity in zooplankton is not yet fully understood and more studies are needed.

PurposeThe clinical significance of body mass index (BMI) on long-term outcomes has not been extensively investigated in Asian patients with colorectal cancer (CRC). This study aims to describe the association between BMI and survival, plus providing BMI cut-off value for predicting prognosis in CRC patients.Materials and MethodsA total of 1,182 patients who had undergone surgery for stage I-III CRC from June 2004 to February 2014 were included. BMI was categorized into four groups based on the recommendation for Asian ethnicity. The optimal BMI cut-off value was determined to maximize overall survival (OS) difference. ResultsIn multivariable analysis, underweight BMI was significantly associated with poor OS (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.55 to 3.71; p < 0.001) and obese BMI was associated with better OS (HR, 0.72; 95% CI, 0.53 to 0.97; p=0.036) compared with the normal BMI. Overweight and obese BMI were associated with better recurrence-free survival (HR, 0.64; 95% CI, 0.42 to 0.99; p=0.046 and HR, 0.58; 95% CI, 0.38 to 0.89; p=0.014, respectively) compared with the normal BMI group. BMI cutoff value was 20.44 kg/m2. Adding the BMI cutoff value to cancer staging could increase discriminatory performance in terms of integrated area under the curve and Harrell’s concordance index. ConclusionCompared to normal BMI, underweight BMI was associated with poor survival whereas obese BMI was associated with better survival. BMI cut-off value of 20.44 kg/m2 is a useful discriminator in Asian patients with CRC.

The quality of care for patients admitted with a primary diagnosis of gout, both before and after admission, has not been systematically examined.To understand national trends in hospital admission for a primary diagnosis of gout in Aotearoa New Zealand over the past 10 years and the quality of care for gout received by these patients before and after the admission.Data from the Aotearoa New Zealand National Collections from 1 January 2007 to 31 December 2019 were analysed to determine rates of hospital admission for a primary diagnosis of gout. Admission data include cost-weight analysis, as well as quality of care data including gout-specific medication dispensing in the year prior and year after admission.There were 13 721 admissions with a primary diagnosis of gout over the analysis period, with an average cost per admission in 2019 of NZ$4301. The rate of admission per 100 000 population was highest in Pacific peoples followed by Māori. Although dispensing of any allopurinol increased in the year after admission, rates of regular allopurinol dispensing remained low; 38.1% for admissions in 2018. Patients who were younger (especially 20-44 years), not enrolled in a primary health organisation before admission and female had lower rate of regular allopurinol after admission.In this nationwide study, rates of admission for gout were highest in Pacific peoples and in Māori. Rates of regular allopurinol dispensing were low even after admission for a primary diagnosis of gout. These findings highlight the need for improvements in gout management in Aotearoa New Zealand, including in post-discharge planning from secondary care inpatient services.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder and is caused by G6PD gene mutations. To date, more than 400 variants in the G6PD gene have been discovered, and about 160 identified variants are associated with a significant decrease in the G6PD enzyme activity. However, the molecular characterization and epidemiological study of G6PD deficiency are still limited in Vietnam. Therefore, we conducted this study to determine the G6PD variants among the Vietnamese populations and evaluate their correlation to G6PD enzyme activity. A total of 339 patients (302 males and 37 females) were enrolled in this study. The G6PD variants were identified by Sanger sequencing. Our results indicate that males are more severely deficient in G6PD than females. This enzyme activity in males (1.27 ± 1.06 IU/g·Hb) is significantly lower than in females (2.98 ± 1.57 IU/g·Hb) ( p < 0.0001 ). The enzyme activity of the heterozygous-homozygous females and heterozygous females-hemizygous males was found to be significantly different ( p < 0.05 ), which is interpreted due to random X-inactivation. For G6PD molecular characteristics, Viangchan (c.871G>A), Canton (c.1376G>T) and Kaiping (c.1388G>A) variants were the most dominant, accounting for 24.48%, 17.70%, and 22.42%, respectively, whereas the highest frequency of complex variants was observed in Viangchan/Silent with 20.35%. In terms of G6PD activity, the Union variant presented the lowest mean value (1.03 IU/g·Hb) compared to the other variants ( p < 0.05 ). Computational analysis using Polyphen-2 tool investigated that all variants were relative to G6PD deficiency and separated the levels as benign and damaged. The result will establish effective methods to screen G6PD variants in Vietnam.

As the proportion of visceral (VAT) to subcutaneous adipose tissue (SAT) may contribute to type 2 diabetes (T2D) development, we examined this relation in a cross-sectional design within the Multiethnic Cohort that includes Japanese Americans known to have high VAT. The aim was to understand how ectopic fat accumulation differs by glycemic status across ethnic groups with disparate rates of obesity, T2D, and propensity to accumulate VAT.In 2013-2016, 1,746 participants aged 69.2 (standard deviation, 2.7) years from five ethnic groups completed questionnaires, blood collections, and whole-body dual X-ray absorptiometry and abdominal magnetic resonance imaging scans. Participants with self-reported T2D and/or medication were classified as T2D, those with fasting glucose125 and 100-125 mg/dL as undiagnosed cases (UT2D) and prediabetes (PT2D), respectively. Using linear regression, we estimated adjusted means of adiposity measures by T2D status.Overall, 315 (18%) participants were classified as T2D, 158 (9%) as UT2D, 518 (30%) as PT2D, and 755 (43%) as normoglycemic (NG), with significant ethnic differences (P0.0001). In fully adjusted models, VAT, VAT/SAT, and percent liver fat increased significantly from NG, PT2D, UT2D, to T2D (P0.001). Across ethnic groups, the VAT/SAT ratio was lowest for NG participants and highest for T2D cases. Positive trends were observed in all groups except African Americans, with highest VAT/SAT in Japanese Americans.These findings indicate that VAT plays an important role in T2D etiology, in particular among Japanese Americans with high levels of ectopic adipose tissue, which drives the development of T2D to a greater degree than in other ethnic groups.

Determination of plasma vitamin B12 (B12) is a frequently requested laboratory analysis, mainly employed to establish B12 deficiency. However, an increased level of B12 is a common unexpected finding that may be related to an increased concentration of one of the B12 binding proteins, haptocorrin or transcobalamin. This paper describes the extensive laboratory evaluation of a patient with an elevated level of plasma B12 with various well-established assays. Initial studies suggested the presence of a macromolecule consisting of haptocorrin bound B12. Specific determinations of the B12-binding proteins revealed normal amounts of haptocorrin but a markedly increase in both total and B12 saturated transcobalamin (holo-TC). The results are in accord with the presence of macro-transcobalamin. These experiments reveal that determination of the nature of the B12-macromolecules is troublesome due to differences in assays applied to measure these proteins. In addition, this publication creates awareness of macro-holo-TC as a cause of an unexplained increased B12 level.

Objective To examine whether patterns of body mass index (BMI) percentile gains across childhood predict BMI percentile, overweight and obesity, waist circumference, and elevated or prehypertensive blood pressure at age 15. Methods Trained technicians in the Study of Early Child Care and Youth Development assessed children's weight and height from birth to 15 years and waist circumference and blood pressure at age 15 (n = 1,132). Children's BMI percentile trajectories from age 2 to age 13 along with 28 demographic and social covariates were used to predict BMI percentile, waist circumference, overweight, obesity, and elevated or prehypertensive blood pressure. Linear and logistic regressions were used to predict BMI percentile, overweight, obesity, waist circumference, and elevated or prehypertensive blood pressure. Results Children were classified into one of four BMI percentile trajectories: "low stable" (28.4%), "low-to-high" (11.8%), "median stable" (29.0%), and "high rising" (30.7%). Children in trajectory classes characterized by persistent above average BMI percentile or by periods of rapid BMI percentile gains were more likely than their peers to experience poor weight and elevated or prehypertensive outcomes in adolescence. Trajectory class membership explained substantially more variance in adolescent health outcomes than demographic covariates alone. Estimated maternal BMI was a key independent predictor of adolescent outcomes. Conclusions Different patterns of BMI percentile gains, namely those with rapid gains or persistently above average BMI percentile, from ages 2-13 predicted weight, waist circumference, and elevated or prehypertensive blood pressure at age 15, above and beyond demographic and social characteristics.

Resumen Introduccion La infeccion por el coronavirus del sindrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) se asocia con frecuencia con hiponatremia (sodio plasmatico Material y metodo Estudio de cohorte observacional y retrospectivo. Se incluyeron pacientes que ingresaron con diagnostico de infeccion por COVID-19 e hiponatremia en el periodo marzo-mayo de 2020. Registramos variables epidemiologicas, demograficas, clinicas, analiticas y radiologicas de la infeccion por SARS-CoV-2 e hiponatremia en el momento del diagnostico y durante la hospitalizacion. El seguimiento clinico comprendio desde el ingreso hasta el exitus o el alta. Resultados Noventa y un pacientes (21,8%) de los 414 ingresados por infeccion del SARS-CoV-2 presentaron hiponatremia (81,32% hiponatremia leve, 9,89% moderada y 8,79% grave). La ausencia de correccion de la hiponatremia a las 72-96 horas del ingreso hospitalario estuvo asociado a mayor mortalidad en los pacientes con COVID-19 (odds ratio 0,165; 95% intervalo de confianza: 0,018-0,686; p = 0,011). Fallecieron 19 pacientes (20,9%). Se observo un aumento de la mortalidad en pacientes con hiponatremia grave en comparacion con hiponatremia moderada y leve durante el ingreso (37,5% versus 11,1% versus 8,1%, respectivamente; p = 0,041). Conclusiones La persistencia de la hiponatremia tras las primeras 72-96 horas del ingreso hospitalario se asocio a mayor mortalidad en los pacientes con SARS-CoV-2.

Prader-Willi syndrome (PWS) is characterized by hypotonia, distinctive facial features, hyperphagia, obesity, short stature, hypogonadism, intellectual disability, and behavior problems. Uncontrolled hyperphagia can lead to dangerous food-seeking behavior and with life-threatening obesity. Severe obesity is prone to obstructive sleep apnea (OSA) and can lead to cor pulmonale. This study reports on a case involving a 21-year-old man with PWS who developed OSA due to severe obesity, which led to cor pulmonale, a life-threatening complication. Multidisciplinary care provided in the intensive care unit included weight reduction, ventilation support, antipsychotics, sedative drugs, rehabilitation, and meticulous skin care. The patient did recover. To prevent severe obesity in adults with PWS, hyperphagia must be controlled, and the patient must also be managed by an endocrinologist throughout childhood.

Purpose Type 1 diabetes (T1D) is the most common type of diabetes in children, but the frequency of type 2 diabetes (T2D) is increasing rapidly. Classification of diabetes is based on a constellation of features that are typical of each type. We aimed to compare demographic, clinical and laboratory characteristics at diabetes diagnosis in pediatric T1D and T2D. Methods We studied children who attended a large academic hospital in Houston, Texas (USA) with a new diagnosis of T2D (n=753) or T1D (n=758). We compared age, sex, race/ethnicity, presence of obesity, glucose, hemoglobin A1c, islet autoantibody positivity, C-peptide, and presence of diabetic ketoacidosis (DKA) at diabetes diagnosis. Results At diagnosis of diabetes, children with T2D, compared with those with T1D, were older (13.6 vs 9.7 years old), more likely females (63.2% vs 47.8%), of racial/ethnic minority (91.1% versus 42.3%) and obese (90.9% vs 19.4%), and were less likely to have DKA (7.8% vs 35.0%) and diabetes autoantibodies (5.5% vs 95.4%). Children with T2D also had significantly less marked elevation of glucose and hemoglobin A1c, and lower C-peptide levels (all comparisons, p

Afamin is a member of the hepatokine that are strongly associated with various metabolic diseases. The relationship between afamin and nonalcoholic fatty liver disease (NAFLD) remains unclear. This study aimed to explore the correlation between serum afamin levels and NAFLD. We analyzed 88 NAFLD patients and 88 age- and sex-matched healthy controls who took their health examinations at the First Affiliated Hospital, Zhejiang University School of Medicine. The association was further confirmed in 22 biopsy-confirmed NAFLD patients and 36 healthy controls. Serum afamin levels were evaluated using an enzyme-linked immunosorbent assay (ELISA). NAFLD patients had significantly higher serum afamin levels than the healthy controls (14.79 ± 5.04 mg/L versus 10.83 ± 3.24 mg/L; P < 0.001 ). Serum afamin levels were positively correlated with metabolic parameters including the body mass index, waist circumference, systolic blood pressure, liver enzymes, and lipid profiles. A multiple regression analysis showed that serum afamin levels were independently related to the risk of NAFLD (OR: 1.289, 95% CI, 1.141–1.456; P < 0.001 ). The receiver operating characteristic (ROC) analysis showed that the area under curve (AUC) of serum afamin plus the BMI for detecting NAFLD was 0.878. In participants with liver biopsies, the serum afamin plus the BMI detected NAFLD with an AUC of 0.758. In conclusion, serum afamin levels were positively associated with prevalence and risk of NAFLD, and serum afamin plus the BMI had a high diagnostic performance for NAFLD. This study provides epidemiological evidence of afamin in NAFLD.

Thyroid cancer is considered to be one of the most common endocrine tumors worldwide. Cystathionine β-synthase (CBS) plays a crucial role in the occurrence of several types of malignancies. And yet, the mechanism of action of CBS in the growth of thyroid carcinoma cells is still unrevealed. We found that CBS level in thyroid carcinoma tissue was higher than that in adjacent normal tissue. The overexpression of CBS enhanced the proliferation, migration, and invasion of thyroid cancer cells, while the downregulation of CBS exerted reverse effects. CBS overexpression reduced the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase in thyroid cancer cells, whereas CBS knockdown showed reverse trends. CBS overexpression decreased reactive oxygen species (ROS) levels but increased the levels of Wnt3a and phosphorylations of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR), β-catenin, and glycogen synthase kinase-3 beta, while CBS knockdown exerted opposite effects. In addition, CBS overexpression promoted the growth of xenografted thyroid carcinoma, whereas CBS knockdown decreased the tumor growth by modulating angiogenesis, cell cycle, and apoptosis. Furthermore, aminooxyacetic acid (an inhibitor of CBS) dose-dependently inhibited thyroid carcinoma cell growth. CBS can regulate the proliferation, migration, and invasion of human thyroid cancer cells via ROS-mediated PI3K/AKT/mTOR and Wnt/β-catenin pathways. CBS can be a potential biomarker for diagnosing or prognosing thyroid carcinoma. Novel donors that inhibit the expression of CBS can be developed in the treatment of thyroid carcinoma.

The metabolic derangements that lead to Diabetic Ketoacidosis (DKA) are described. Understanding the pathogenesis is the key to rapid and accurate diagnosis and hence successful management. DKA may often be prevented by clear advice to patients about how to manage their type 1 or ketosis-prone type 2 diabetes during periods of intercurrent illness. DKA must be considered in the differential diagnosis of metabolic acidosis even where other diseases that may present similarly, such as malaria, are highly prevalent.