Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) Study, 1990–2006

Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized to be, in part, explanatory. We evaluated the association between glycated hemoglobin, a time‐integrated glycemia measure, and cancer incidence and mortality in nondiabetic and diabetic men and women. We conducted a prospective study of 12,792 cancer‐free participants attending the second visit (1990–1992) of the Atherosclerosis Risk in Communities (ARIC) Study. We measured glycated hemoglobin in whole‐blood samples using HPLC. Incident cancers were ascertained from registries and hospital records through 2006. We estimated multivariable‐adjusted hazard ratios (HR) of cancer incidence and mortality for nondiabetic participants with values ≥5.7% (elevated), nondiabetic participants with <5.0% (low) and diabetic participants all compared with nondiabetic participants with 5.0–5.6% (normal). We ascertained 2,349 incident cancer cases and 887 cancer deaths. Compared with nondiabetic women with normal glycated hemoglobin, nondiabetic women with elevated values had an increased risk of cancer incidence (HR:1.24; 95% CI:1.07,1.44) and mortality (HR:1.58; 95% CI:1.23,2.05) as did diabetic women (incidence, HR:1.30; 95% CI:1.06,1.60, mortality, HR:1.96; 95% CI:1.40,2.76). Nondiabetic women with low values also had increased risk. Diabetic women with good glycemic control (<7.0%) had a lower cancer risk than those with higher values. Glycated hemoglobin in nondiabetic and diabetic men, and diabetes were not statistically significantly associated with total cancer risk. Our findings support the hypothesis that chronic hyperglycemia, even in the nondiabetic range, increases cancer risk in women. Maintaining normal glycated hemoglobin overall, and good glycemic control among diabetic adults, may reduce the burden of cancer, especially in women.
Effects of treatment of hyperthyroidism on glucose homeostasis, insulin secretion, and markers of bone turnover.

OBJECTIVE To study glucose and bone metabolism in hyperthyroidism, assess their changes after treatment, and investigate their interrelationships. METHODS Thirty patients with hyperthyroidism matched with 32 normal control subjects were studied. After a 10- to 12-hour overnight fast, blood samples were collected for measurement of glucose, insulin, C-peptide, and intact proinsulin levels as well as for measurement of bone markers: serum alkaline phosphatase (ALP), osteocalcin, and procollagen type I C-terminal peptide (PICP) as markers of bone formation and serum C-terminal cross-linked telopeptide of type I collagen (ICTP) as a marker of bone resorption. A 3-hour 75-g oral glucose tolerance test was then performed, with measurement of glucose, insulin, and C-peptide levels every 30 minutes. Patients were studied at baseline and after treatment with an antithyroid drug (carbimazole) for 1 month and 6 months. RESULTS Pretreatment fasting glucose, insulin, C-peptide, and intact proinsulin levels were significantly higher in patients with hyperthyroidism than in control subjects. During the 3-hour oral glucose tolerance test, the area under the curve of glucose was significantly elevated in the patients, whereas the 3-hour areas under the curve of insulin and C-peptide were not significantly different between patients and control subjects. Fasting glucose, insulin, C-peptide, and intact proinsulin levels decreased significantly to levels similar to those of the control subjects after 1 month of antithyroid therapy and remained so at 6 months. Pretreatment ALP, osteocalcin, PICP, and ICTP were significantly higher in the patients than in the control subjects. After treatment, all markers of bone turnover decreased significantly to levels similar to those of the control subjects at 1 month (except ALP) and 6 months. Within the study group of patients, baseline PICP, osteocalcin, and ICTP demonstrated positive correlation trends with free triiodothyronine and free thyroxine. CONCLUSION Abnormal glucose metabolism and increased bone turnover are hallmarks of untreated hyperthyroidism. These factors normalize as early as 4 weeks after initiation of antithyroid therapy. Changes in bone markers, particularly those of resorption, are related to the degree of thyroid hyperactivity.
Modified Stoppa Approach versus Ilioinguinal Approach for Anterior Acetabular Fractures; A Systematic Review and Meta-Analysis.

INTRODUCTION Modified Stoppa approach was introduced as an alternative to ilioinguinal approach for management of anterior fractures of acetabulum in order to reduce complications of the latter. However, the efficacy of either approach over other is not well established. The aim of this meta-analysis is to compare the efficacy of modified stoppa and ilioinguinal approach in the management of acetabular fractures in terms of a) quality of reduction achieved b) complication rates c) functional outcomes d) operative time e) intra-operative blood loss. METHODS Databases of PubMed, EMBASE and Cochrane registry of controlled trials were taken into consideration for studies on modified Stoppa approach versus Ilioinguinal approach group for the treatment of anterior acetabular fractures. Dichotomous variables were presented as risk ratios (RRs) /Odds Ratio (OR) with 95% confidence intervals (CIs), and continuous data was measured as mean differences, with 95% CIs. RESULT Four studies involving 375 patients were included in this meta-analysis. Out of those 375 patients, 192 were managed with ilioinguinal approach and 183 were managed with modified Stoppa approach. Anatomical reduction was significantly higher in Stoppa group (p=0.052, RR=1. 19 (1.02, 1.37), p=0. 90, I2=0%). The complication rate was significantly higher in the Ilioinguinal approach as compared with the Stoppa approach (p=0.01, RR 0.63 (0.44 to 0.91), p=0.73 (I2= 0%). The operative time was significantly shorter with modified Stoppa approach (MD = -48.79 (-80.29 to -17.30), p=0.002). No significant differences were found between the two groups in terms of their functional outcomes (p=0.63, RR 0.96 (-0.80 to 1.15), p=0. 56, I2=0%) and blood loss (MD= -212.89 (-476.27 to 50.49) p=0. 06, I2=71%). CONCLUSION Anterior acetabular fractures, if operated with the modified Stoppa approach were found to have better reduction and lower complication rates with less operative time, when compared to ilioinguinal approach. No significant difference in terms of blood loss was found in both the groups. Further higher quality randomized controlled trials are needed to verify our results.
SOCS3 Deficiency Promotes M1 Macrophage Polarization and Inflammation

Macrophages participate in both the amplification of inflammation at the time of injury and downregulation of the inflammatory response to avoid excess tissue damage. These divergent functions of macrophages are dictated by their microenvironment, especially cytokines, which promote a spectrum of macrophage phenotypes. The M1 proinflammatory phenotype is induced by LPS, IFN-γ, and GM-CSF, and IL-4, IL-13, and M-CSF induce anti-inflammatory M2 macrophages. Suppressors of cytokine signaling (SOCS) proteins function as feedback inhibitors of the JAK/STAT signaling pathway, and they can terminate innate and adaptive immune responses. In this study, we have evaluated the influence of SOCS3 on macrophage polarization and function. Macrophages obtained from LysMCre-SOCS3fl/fl mice, which lack SOCS3 in myeloid lineage cells, exhibit enhanced and prolonged activation of the JAK/STAT pathway compared with macrophages from SOCS3fl/fl mice. Furthermore, SOCS3-deficient macrophages have higher levels of the M1 genes IL-1β, IL-6, IL-12, IL-23, and inducible NO synthase owing to enhanced transcriptional activation and chromatin modifications. SOCS3-deficient M1 macrophages also have a stronger capacity to induce Th1 and Th17 cell differentiation than M1 macrophages from SOCS3fl/fl mice. Lastly, LPS-induced sepsis is exacerbated in LysMCre-SOCS3fl/fl mice and is associated with enhanced STAT1/3 activation and increased plasma levels of M1 cytokines/chemokines such as IL-1β, TNF-α, IL-6, CCL3, CCL4, and CXCL11. These findings collectively indicate that SOCS3 is involved in repressing the M1 proinflammatory phenotype, thereby deactivating inflammatory responses in macrophages.
Clinical Significance of Late Phase of Lung Perfusion Blood Volume (Lung Perfusion Blood Volume) Quantified by Dual-Energy Computed Tomography in Patients With Pulmonary Thromboembolism

Purpose: Using dual-energy computed tomography (DECT), we quantified the lung perfusion blood volume (PBV) in the late phase, which may reflect both the pulmonary artery and systemic collateral flow. We then investigated the clinical significance of late-phase lung PBV values. Materials and Methods: We retrospectively studied 206 patients (266 scans) who underwent early-phase and late-phase DECT. The patients were divided into 2 groups depending on whether or not they had pulmonary thromboembolism (PTE) (n=94 and 112). Patients with PTE were further divided into 2 subgroups, depending on whether they had acute PTE or chronic PTE (n=66 and 28). Pulmonary artery enhancement (PAenh) was measured on DECT. We then calculated the [lung PBV/PAenh] ratio in all patients during both the early and late phases for adjustment of timing. Results: The [late-phase lung PBV/PAenh] ratio was 0.092±0.029 in the group with PTE and 0.108±0.030 in the group without PTE, showing a significant difference between the 2 groups (P<0.0001). The [early-phase lung PBV values/PAenh]/[late-phase lung PBV values/PAenh] ratio was 0.68±0.19 and 0.84±0.20, respectively, also showing a significant difference between the 2 groups (P<0.0001). Finally, the [early-phase lung PBV/PAenh]/[late-phase lung PBV/PAenh] ratio was 0.71±0.19 in patients with acute PTE and 0.56±0.16 in patients with chronic PTE, and there was a significant difference between these 2 subgroups (P=0.0004). Conclusions: It may be useful to determine late-phase lung PBV values in patients with PTE, because this parameter may reflect the systemic collateral flow, which is increased in chronic PTE.
Validation of Actigraphy in Middle Childhood.

STUDY OBJECTIVES Few studies have examined the validity of actigraphy in school-aged children. The objective of this study was to examine the validity of a commonly used actigraph compared to polysomnography (PSG) in a sample of children age 5 to 12 y born prematurely, sleeping in their natural home environment. METHODS 148 children born preterm (85 boys and 63 girls), ages 5-12 y (mean = 9.3 y, standard deviation = 2.0) wore the Philips Respironics Actiwatch-2 for 1 night concurrently with comprehensive, ambulatory PSG in the child's home. Sleep outcome variables were sleep onset latency, total sleep time (TST), and sleep efficiency. Epoch-by-epoch comparisons were used to determine sensitivity, specificity, and accuracy. Secondary analyses examined differences between children with no sleep issues, obstructive sleep apnea syndrome, and periodic limb movements in sleep (PLMS). RESULTS Actigraphy significantly underestimated TST (30 min) and sleep efficiency (5%). Actigraphy underestimated or overestimated sleep onset latency by at least 10 min for a third of the children. Sensitivity and accuracy were good at 0.88 and 0.84, respectively, whereas specificity was lower at 0.46. Differences between actigraphy and PSG for TST and sleep efficiency were greatest for children with PLMS. CONCLUSIONS This study adds to the small existing literature demonstrating the validity of actigraphy in middle childhood. Although actigraphy shows good sensitivity (ability to detect sleep), specificity (ability to detect wake) is poor in this age group. Further, the results highlight the importance of considering whether a child has PLMS when interpreting actigraphic data, as well as the difficulties in accurately capturing sleep onset latency with actigraphy.
Effect of Long-Acting Somatostatin Analog (Somatulin) on Renal Hyperfiltration in Patients With IDDM

OBJECTIVE To investigate whether long-acting somatostatin (SMS) can suppress renal hyperfiltration in patients with IDDM. RESEARCH DESIGN AND METHODS A double-blind, randomized treatment of nine patients with IDDM was used. Selection criteria were renal hyperfiltration (glomerular filtration rate [GFR] ≥ 129 ml · min−1 · 1.73 m2) and absence of hypertension and macroalbuminuria. Treatment was either with a long-acting SMS analog (Somatulin, 30 mg) or with placebo, given by intramuscular injections every 10 days for 9 months. GFR, effective renal plasma flow (ERPF), IGF-I, and 24-h growth hormone (GH) profiles were used as evaluation parameters. RESULTS Five patients were randomized to Somatulin, four patients to placebo. One of the patients treated with Somatulin stopped after 3 months because of persistent abdominal discomfort after the injections. Somatulin treatment for 3 months lowered GFR and ERPF compared with placebo (P < 0.05). After 9 months, the differences were no longer significant. After 3 months, IGF-I concentrations were decreased in all Somatulin-treated patients. GH secretion tended to increase in the placebo group. CONCLUSIONS The administration of long-acting Somatulin to patients with IDDM and renal hyperfiltration leads to only a temporary reduction of ERPF/GFR.
Characterization of Monocarboxylate Transporter 6: Expression in Human Intestine and Transport of the Antidiabetic Drug Nateglinide

Monocarboxylate transporter (MCT) 6, encoded by SLC16A5, is a member of the monocarboxylate transporter family. Nateglinide, an oral hypoglycemic agent, quickly reaches the maximal serum concentration after its premeal administration. Although the functional existence of uptake systems for nateglinide in the intestine has been demonstrated, these transport systems have not yet been identified at the molecular level. The aim of this study was to demonstrate the localization of MCT6 in the human small intestine and characterize the transport properties of nateglinide via MCT6. Immunohistochemical analysis of the human small intestine revealed that anti-MCT6 antiserum stained the luminal side of the epithelial cells. When expressed in Xenopus laevis oocytes, MCT6-mediated uptake of [14C]nateglinide was sensitive to extracellular pH and membrane potential. Furthermore, the Kt value of nateglinide (45.9 μM) for MCT6 was lower than those previously reported in Caco-2 cells and rat intestinal brush-border membrane vesicles. In addition, probenecid, fluorescein, valproic acid, and salicylic acid, which are inhibitors of nateglinide uptake in Caco-2 cells and rat intestine, did not inhibit the uptake of nateglinide via MCT6. These results suggest that MCT6 may play a role in the intestinal absorption of nateglinide, although other transporters are also likely involved.
Association between interferon gamma receptor 1 ‐56C/T gene polymorphism and tuberculosis susceptibility: a meta‐analysis

Background Genetic variations in the interferon‐gamma (IFN‐&ggr;) receptor 1 gene (IFNGR1) may contribute to tuberculosis (TB) risk in different populations. Many studies have investigated the relationship between IFNGR1 56C/T polymorphism and the susceptibility to TB, but have yielded conflicting results. A comprehensive meta‐analysis is needed to provide a more accurate estimation of the relationship between them. Methods A literature search based on a combination of manual and computer‐based methods was conducted on four English databases (PubMed, Science Direct, SpringerLink, and EBSCO) and three Chinese databases (Wanfang, CQVIP, and Chinese National Knowledge Infrastructure databases). Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using either the fixed‐effects model or the random‐effects model for different genetic models based on the heterogeneity examination. Results A total of six studies comprising 1 497 confirmed TB cases and 1 802 controls were included in this meta‐analysis. Overall, no significant association was observed between IFNGR1 ‐56C/T polymorphism and TB susceptibility (C vs. T, OR=0.90, 95% CI 0.69–1.17; CC vs. TT, OR=0.87, 95% CI 0.65–1.18; TC vs. TT, OR=1.031, 95% CI 0.872–1.219; CC+TC vs. TT, OR=0.89, 95% CI 0.64–1.26; CC vs. TC+TT, OR=0.92, 95% CI 0.66–1.29). In subgroup analysis, a significant association was found in the dominant model (CC+TC vs. TT, OR=1.24, 95% CI 1.02–1.51) in Africans, but not in Asians or Caucasians. Conclusions Our meta‐analysis did not provide enough powerful evidence to identify a significant association between IFNGR1 ‐56C/T polymorphism and TB susceptibility in the overall population. In subgroup analysis, it indicates that IFNGR1 ‐56C/T is possibly associated with increased TB risk in Africans, but not in Asians or Caucasians. However, larger sample size and better‐designed case‐control studies are needed to validate these findings.
Efficacy of topical combination of benzoyl peroxide 5% and clindamycin 1% for the treatment of progressive macular hypomelanosis: a randomized, doubleblind, placebo-controlled trial.

BACKGROUND Progressive macular hypomelanosis is a dermatosis without definite etiology. There is no consensus or first-line therapy in the treatment of progressive macular hypomelanosis, and the treatment options used are very little effective. OBJECTIVE To evaluate the therapeutic efficacy of the topical combination of benzoyl peroxide 5% and clindamycin 1% associated with sun exposure for the treatment of progressive macular hypomelanosis. MATERIALS AND METHODS This is a randomized, double-blind, placebo-controlled study in which patients were divided into two groups. Group A used the topical combination of benzoyl peroxide 5% and clindamycin 1% and Group B used gel cream as a placebo. Patients were advised to expose themselves to the sun on a daily basis and were systematically evaluated and photographed. The collected data were entered and analyzed using Epi Info. A p value < 0.05 was considered statistically significant. RESULTS Out of the 23 patients included in the study, 13 were in group A and 10 in group B. Eleven patients (85%) in group A had significant clinical improvement and only two patients (20%) in group B showed an equivalent clinical improvement (p = 0.003). Side effects were more frequent in group A (p = 0.003). CONCLUSION The topical combination of benzoyl peroxide 5% and clindamycin 1% is effective in the treatment of progressive macular hypomelanosis.
Bioactivation of Nitroglycerin by Purified Mitochondrial and Cytosolic Aldehyde Dehydrogenases*

Metabolism of nitroglycerin (GTN) to 1,2-glycerol dinitrate (GDN) and nitrite by mitochondrial aldehyde dehydrogenase (ALDH2) is essentially involved in GTN bioactivation resulting in cyclic GMP-mediated vascular relaxation. The link between nitrite formation and activation of soluble guanylate cyclase (sGC) is still unclear. To test the hypothesis that the ALDH2 reaction is sufficient for GTN bioactivation, we measured GTN-induced formation of cGMP by purified sGC in the presence of purified ALDH2 and used a Clark-type electrode to probe for nitric oxide (NO) formation. In addition, we studied whether GTN bioactivation is a specific feature of ALDH2 or is also catalyzed by the cytosolic isoform (ALDH1). Purified ALDH1 and ALDH2 metabolized GTN to 1,2- and 1,3-GDN with predominant formation of the 1,2-isomer that was inhibited by chloral hydrate (ALDH1 and ALDH2) and daidzin (ALDH2). GTN had no effect on sGC activity in the presence of bovine serum albumin but caused pronounced cGMP accumulation in the presence of ALDH1 or ALDH2. The effects of the ALDH isoforms were dependent on the amount of added protein and, like 1,2-GDN formation, were sensitive to ALDH inhibitors. GTN caused biphasic sGC activation with apparent EC50 values of 42 ± 2.9 and 3.1 ± 0.4 μm in the presence of ALDH1 and ALDH2, respectively. Incubation of ALDH1 or ALDH2 with GTN resulted in sustained, chloral hydrate-sensitive formation of NO. These data may explain the coupling of ALDH2-catalyzed GTN metabolism to sGC activation in vascular smooth muscle.
Small hepatocellular carcinomas and associated nodular lesions of the liver: pathology, pathogenesis, and imaging findings.

Hepatocellular carcinomas frequently occur in association with liver cirrhosis, as chronic liver disease is one of the most important factors in carcinogenesis. In addition to small hepatocellular carcinomas (less than 3 cm in diameter), recent reports of pathologic studies of resected specimens from cirrhotic liver describe associated small nodular lesions (i.e., regenerating nodule, adenomatous hyperplasia, and early hepatocellular carcinoma). In hepatocarcinogenesis of the cirrhotic liver, a regenerating nodule might be the first step in the development of hepatocellular carcinoma, going through phases of adenomatous hyperplasia and early hepatocellular carcinoma in a multistep fashion. We describe the pathologic characteristics of small hepatocellular carcinomas and associated nodular hepatic lesions and review the current concepts of the role of these associated lesions in carcinogenesis. We also discuss the imaging findings of these abnormalities, the efficacy of various imaging techniques for diagnosing them, and the importance of imaging in treatment planning.
On the origin of HIV-1 subtype C in South America

Objective:Our aim was to investigate the monophyletic status of the HIV-1C that circulates in South America and its phylogenetic relationships with other HIV-1C populations around the world in order to shed light on its the geographic origins as well as the place of introduction in the continent. Methods:Fifty-one sequences from South America and 46 from non-South American countries, including samples from Africa and Asia, were obtained from the Los Alamos National Laboratory. The data analyzed corresponded to the entire protease and two-thirds of the polymerase domain from the reverse transcriptase. Phylogenetic analyses using maximum likelihood and Bayesian inference were performed in Phylogenetic Analysis Using Parsymony, PHYlogenetic inferences using Maximum Likelihood, and MrBayes. Results:Samples from South America formed a monophyletic group independent of the method used. The bootstrap support of South American HIV-1C was higher than 60% in maximum likelihood trees and its posterior probability was 99% in the Bayesian analysis. These results indicate the monophyletic nature of the South American HIV-1C. Moreover, in all trees estimated, a sequence from Kenya was the most closely related to the South American clade, followed by two from Ethiopia. All South American sequences from countries other than Brazil showed closer phylogenetic relatedness to Brazilian samples, indicating that HIV-1C was introduced in South America in Brazil. Conclusion:Our results indicate that the entry of HIV-1C in South America occurred in a single episode or in multiples episodes of genetically related viruses, possibly from an eastern African country. HIV-1C was then disseminated to the remaining South American countries from Brazil.