Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined strength and aerobic training increases transforming growth factor-β1 in patients with type 2 diabetes

OBJECTIVE: The aim of the present study was to examine the effects of a combined strength and aerobic training program on pro- and anti-inflammatory cytokines and transforming growth factor-β1 in patients with type 2 diabetes. DESIGN: Ten patients with type 2 diabetes, aged 55.5 (5) years [median (IQR)] participated in a supervised systematic exercise training program which included aerobic exercise and strength training, undertaken four days per week for eight weeks. RESULTS: The training program increased transforming growth factor-β1 concentration (+50.4%) and reduced high sensitivity C reactive protein levels (−24.1%) without altering the levels of interleukin-6, interleukin-10, interferon-γ and tumor necrosis factor-α. Additional improvements were also achieved in anthropometric characteristics, glycated hemoglobin (HbA1c: −11.8%), homeostasis model assessment of insulin resistance index (HOMA-IR: −15%) and physical fitness parameters (stress test: +26.6%, upper muscle strength: +32.4% and lower muscle strength: +48.9%). CONCLUSION: A combined strength and aerobic exercise program has a potential anti-atherogenic and anti-inflammatory impact which most likely reduces the risk of cardiovascular disease and improves the health status in patients with type 2 diabetes.
Establishment and Validation of RNA-Based Predictive Models for Understanding Survival of Vibrio parahaemolyticus in Oysters Stored at Low Temperatures

ABSTRACT This study developed RNA-based predictive models describing the survival of Vibrio parahaemolyticus in Eastern oysters (Crassostrea virginica) during storage at 0, 4, and 10°C. Postharvested oysters were inoculated with a cocktail of five V. parahaemolyticus strains and were then stored at 0, 4, and 10°C for 21 or 11 days. A real-time reverse transcription-PCR (RT-PCR) assay targeting expression of the tlh gene was used to evaluate the number of surviving V. parahaemolyticus cells, which was then used to establish primary molecular models (MMs). Before construction of the MMs, consistent expression levels of the tlh gene at 0, 4, and 10°C were confirmed, and this gene was used to monitor the survival of the total V. parahaemolyticus cells. In addition, the tdh and trh genes were used for monitoring the survival of virulent V. parahaemolyticus. Traditional models (TMs) were built based on data collected using a plate counting method. From the MMs, V. parahaemolyticus populations had decreased 0.493, 0.362, and 0.238 log10 CFU/g by the end of storage at 0, 4, and 10°C, respectively. Rates of reduction of V. parahaemolyticus shown in the TMs were 2.109, 1.579, and 0.894 log10 CFU/g for storage at 0, 4, and 10°C, respectively. Bacterial inactivation rates (IRs) estimated with the TMs (−0.245, −0.152, and −0.121 log10 CFU/day, respectively) were higher than those estimated with the MMs (−0.134, −0.0887, and −0.0732 log10 CFU/day, respectively) for storage at 0, 4, and 10°C. Higher viable V. parahaemolyticus numbers were predicted using the MMs than using the TMs. On the basis of this study, RNA-based predictive MMs are the more accurate and reliable models and can prevent false-negative results compared to TMs. IMPORTANCE One important method for validating postharvest techniques and for monitoring the behavior of V. parahaemolyticus is to establish predictive models. Unfortunately, previous predictive models established based on plate counting methods or on DNA-based PCR can underestimate or overestimate the number of surviving cells. This study developed and validated RNA-based molecular predictive models to describe the survival of V. parahaemolyticus in oysters during low-temperature storage (0, 4, and 10°C). The RNA-based predictive models show the advantage of being able to count all of the culturable, nonculturable, and stressed cells. By using primers targeting the tlh gene and pathogenesis-associated genes (tdh and trh), real-time RT-PCR can evaluate the total surviving V. parahaemolyticus population as well as differentiate the pathogenic ones from the total population. Reliable and accurate predictive models are very important for conducting risk assessment and management of pathogens in food.
Plasma Neutrophil Elastase and Elafin as Prognostic Biomarker for Acute Respiratory Distress Syndrome: A Multicenter Survival and Longitudinal Prospective Observation Study

Background: Neutrophil elastase (HNE) is a destructive enzyme and plays crucial roles in the pathophysiology of acute respiratory distress syndrome (ARDS). Endogenous proteinase inhibitors elafin (PI3) is important to protect against lung tissue destruction. We proposed to examine whether HNE and PI3 serve as prognostic biomarkers for ARDS. Methods: This study is a survival and longitudinal analysis of plasma profiles of HNE and PI3 in ARDS patients from a multicenter prospective observational cohort in Beijing, China. Plasma samples were collected on day-1, day-3, and day-7 of study enrollment. Results: HNE levels were higher in ARDS non-survivors than survivors, whereas PI3 showed opposite direction for all three measurements (P < 0.01 for all). Patients with HNE level above median and PI3 level below median values had the lowest survival probability and died the fastest. There was a significant longitudinal effect of HNE levels and PI3 level on mortality. Receiver-operating characteristic analysis demonstrated combination of HNE and PI3 had the discrimination ability for 28-day mortality (area under the receiver-operating characteristic curve [AUC]: 0.76), better than the combination of Berlin categories and APACHE II (AUC: 0.63). The addition of HNE and PI3 to Berlin categories and APACHE II has significantly improved the prognostic discrimination ability (AUC: 0.81, P < 0.0001). Conclusions: Imbalance between HNE and PI3 levels in ARDS patients was associated with ARDS mortality. By combining these biomarkers with Berlin categories and APACHE II, prognostic power of ARDS was greatly improved. Circulation levels of HNE and PI3 may have the potential to predict ARDS mortality and better inform clinicians about ARDS mortality risk.
Effects of Short-Term Acclimatization at the Summit of Mt. Fuji (3776 m) on Sleep Efficacy, Cardiovascular Responses, and Ventilatory Responses.

Horiuchi, Masahiro, Shiro Oda, Tadashi Uno, Junko Endo, Yoko Handa, and Yoshiyuki Fukuoka. Effects of short-term acclimatization at the summit of Mt. Fuji (3776 m) on sleep efficacy, cardiovascular responses, and ventilatory responses. High Alt Med Biol. 18:171-178, 2017. -We investigated the effects of a short period of acclimatization, at 3776 m on Mt. Fuji, on sleep parameters and related physiological responses. Physiological responses were assessed in seven healthy lowlander men during both daytime and sleep while at sea level (SL), as well as for three consecutive nights at high altitude (HA; 3776 m, day 1 [D1], D2, D3, and morning only of D4). Blood pressure variables, heart rate (HR), pulmonary ventilation (VE), and breathing frequency (Bf) progressively increased each day, with significant differences between SL and HA (p < 0.05, respectively). In contrast, end-tidal PCO2 (PETCO2) progressively decreased each day with statistical differences between SL and D3 at HA (p < 0.05). During sleep at HA, mean arterial pressure (MAP) was stable, whereas it decreased during sleep at SL. Sleep efficacy, which was assessed by actigraphy, was linearly impaired with statistical differences between SL and D3 (p < 0.05). These impairments in sleep efficacy at HA were associated with higher MAP and HR, as well as lower Bf and PETCO2 during the daytime (pooled data, p < 0.05, respectively). These results suggest that hypoxia-induced cardiovascular and ventilatory responses may be crucial contributors to changes in sleep efficacy at HA.
The impact of iron overload in patients with acute leukemia and myelodysplastic syndrome on hepatic and endocrine functions

Patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusion usually have an elevated serum ferritin. These findings have led to the suggestion that iron overload is common and may have deleterious effects in these patients. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. Therefore, we measured the liver iron content (LIC) by the FerriScan® method and investigated the liver function and some endocrine tests in 27 patients with acute leukemia (AL) or myelodysplastic syndromes (MDS). Using FerriScan® method, the normal mean LIC levels are: 4.3±2.9 mg Fe/g dry weight (d.w.). In our patients, the mean serum ferritin level was 1965±2428 ng/mL. In our patients, the mean total iron in the blood received by them was 7177±5009 mg. In 6 out of 27 patients LIC was >7 mg Fe/g d.w. and in 11/27 serum ferritin was >1000 ng/ml. Measuring fasting blood glucose revealed 3/27 with diabetes mellitus and 4/27 with impaired fasting glucose (IFG). All patients had normal serum concentrations of calcium, parathormone (PTH), free thyroxine (FT4) and thyrotropin (TSH). Four patients had elevated serum alanine transferase (ALT). LIC was correlated significantly with ferritin level (r=0.5666; P<0.001) and the cumulative amount of iron in the transfused blood (r=0.523; P<0.001). LIC was correlated significantly with ALT (r=0.277; P = 0.04) and fasting blood glucose (FBG) was correlated significantly with the amount of iron transfused (r=0.52, p<0.01) and ALT level (r=0.44; P<0.01). The age of patients did not correlate with LIC, FBG or ALT. In conclusions, these results contribute to our understanding of the prevalence of dysglycemia and hepatic dysfunction in relation to parenchymal iron overload in patients with hematologic malignancies undergoing chemotherapy and requiring blood transfusions. (www.actabiomedica.it)
The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation

Significant racial disparity remains in the incidence of unfavorable outcomes following heart transplantation. We sought to determine which pediatric posttransplantation outcomes differ by race and whether these can be explained by recipient demographic, clinical, and genetic attributes. Data were collected for 80 black and 450 nonblack pediatric recipients transplanted at 1 of 6 centers between 1993 and 2008. Genotyping was performed for 20 candidate genes. Average follow‐up was 6.25 years. Unadjusted 5‐year rates for death (p = 0.001), graft loss (p = 0.015), acute rejection with severe hemodynamic compromise (p = 0.001), late rejection (p = 0.005), and late rejection with hemodynamic compromise (p = 0.004) were significantly higher among blacks compared with nonblacks. Black recipients were more likely to be older at the time of transplantation (p < 0.001), suffer from cardiomyopathy (p = 0.004), and have public insurance (p < 0.001), and were less likely to undergo induction therapy (p = 0.0039). In multivariate regression models adjusting for age, sex, cardiac diagnosis, insurance status, and genetic variations, black race remained a significant risk factor for all the above outcomes. These clinical and genetic variables explained only 8–19% of the excess risk observed for black recipients. We have confirmed racial differences in survival, graft loss, and several rejection outcomes following heart transplantation in children, which could not be fully explained by differences in recipient attributes.
The Challenges of Caring for Long-Stay Patients in the PICU*

Objective: Compared to shorter-stay patients, caring for long-stay patients in the ICU entails a disproportionate burden for staff. Our objective was to gain a deeper understanding of the impact on staff of caring for children who have a prolonged stay on the PICU. Design: Qualitative study based on semi-structured interviews. Data were analyzed using the Framework approach. Setting: Children’s tertiary hospital. Participants: Seventeen members of staff (7 psychosocial staff, 7 nurses, 3 consultants) working in the PICU, neonatal ICU, or cardiac ICU (PICU will be used to encompass neonatal ICU, cardiac ICU, and PICU for the remainder of this article). Interventions: Semi-structured, tape-recorded interviews. Measurements and Main Results: Staff reported both positive and challenging aspects of caring for long-stay patients in the PICU. Five key areas relating to the challenges of caring for long-stay patients were identified: staff expectations about their work, characteristics of the patient group, the impact on staff, the impact on the wider unit, and the availability of support. Staff views were often compounded by individual cases they had been involved with or had heard about which fell at either end of the spectrum of “good” and “bad”. Conclusions: Whilst there are reported benefits associated with caring for long-stay patients, there are a number of challenges reported that may have implications for staff and the wider unit. When caring for a particular sub-group of long-stay patients, staff may be more likely to experience negative impacts. A key priority for the PICU is to ensure that support mechanisms are timely, accessible, and allow staff to explore their own reactions to their work.
Active Estrogen Receptor-alpha Signaling in Ovarian Cancer Models and Clinical Specimens

Purpose: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha (ERα) in approximately 80% of HGSOC and some small but promising clinical trials of endocrine therapy, ERα has been understudied as a target in this disease. We sought to identify hormone-responsive, ERα-dependent HGSOC. Experimental Design: We characterized endocrine response in HGSOC cells across culture conditions [ two-dimensional (2D), three-dimensional (3D), forced suspension] and in patient-derived xenograft (PDX) explants, assessing proliferation and gene expression. Estrogen-regulated transcriptome data were overlapped with public datasets to develop a comprehensive panel of ERα target genes. Expression of this panel and ERα H-score were assessed in HGSOC samples from patients who received endocrine therapy. Time on endocrine therapy was used as a surrogate for clinical response. Results: Proliferation is ERα-regulated in HGSOC cells in vitro and in vivo, and is partly dependent on 3D context. Transcriptomic studies identified genes shared by cell lines and PDX explants as ERα targets. The selective ERα downregulator (SERD) fulvestrant is more effective than tamoxifen in blocking ERα action. ERα H-score is predictive of efficacy of endocrine therapy, and this prediction is further improved by inclusion of target gene expression, particularly IGFBP3. Conclusions: Laboratory models corroborate intertumor heterogeneity of endocrine response in HGSOC but identify features associated with functional ERα and endocrine responsiveness. Assessing ERα function (e.g., IGFBP3 expression) in conjunction with H-score may help select patients who would benefit from endocrine therapy. Preclinical data suggest that SERDs might be more effective than tamoxifen. Clin Cancer Res; 23(14); 3802–12. ©2017 AACR.
Molecular and morphological variation of Paragonimus westermani in Vietnam with records of new second intermediate crab hosts and a new locality in a northern province

SUMMARY Paragonimus westermani is one of the most medically important lung flukes and is widely distributed in Asia. It exhibits considerable variation in morphological, genetic and biological features. In central provinces of Vietnam, a high prevalence of metacercariae of this species has been reported from the crab intermediate host, Vietopotamon aluoiense. In this study, we detected P. westermani metacercariae in two additional crab hosts, Donopotamon haii in Quang Tri Province, central Vietnam and Indochinamon tannanti in Yen Bai Province in the north. The latter is a new locality for P. westermani in a northern region of Vietnam where P. heterotremus is the only species currently known to cause human paragonimiasis. Paragonimus westermani metacercariae found in Vietnam showed considerable morphological variation but slight genetic variation based on DNA sequences from the nuclear ribosomal ITS2 region and the mitochondrial 16S gene. Co-infection of the same individual crabs with P. westermani and P. heterotremus and/or some other Paragonimus species was found frequently, suggesting potential for co-infection in humans. The findings of the present study emphasize the need for highly specific molecular and immunodiagnostic methods to differentially diagnose between P. westermani and P. heterotremus infections.
EFFECT OF SOME POLYMERS USED IN PREPARATION OF TABLETS ON ABSORPTION OF ACTIVE INGREDIENTS Research Article

In this study, the effect of long term use of tablets containing hydrophilic polymer hydroxypropylmethylcellulose (HPMC) and plastic polymers (ethylcellulose and Eudragit RL PO) on absorption of Diltiazem hydrochloride was evaluated by using non-everted intestinal gut sac model and by giving rabbits these polymers for a month to evaluate the intestinal histological changes that may be caused by these polymers. For this purpose, Diltiazem HCl was used with various amounts of these polymers. Permeability of Diltiazem HCl was measured by taking samples at specific intervals for 4 hours, and determining the concentrations by UV-visible spectrophotometer at wave length of 237nm. In vivo study was applied by dividing rabbits into four groups (six animals in each group). Rabbits in the first group were served as normal and received water and food only. Rabbits in the second group received hydroxypropylmethylcellulose (20 mg/kg of body weight) for a month. Rabbits in the third group received eudragit RL PO (20 mg/kg of body weight) for a month. Rabbits in the fourth group received ethylcellulose (15 mg/kg of body weight) for a month also. Then the intestine was examined histologically. Results showed that the cumulative concentrations of these polymers decreased the absorption of Diltiazem HCl through the intestine by this sequence: ethylcellulose> Eudragit RL PO> HPMC due to histological alterations that were evaluated after in vivo study which indicated that ethylcellulose caused marked morphological changes on tissues. Eudragit RL PO caused morphological changes ranged from moderate to marked changes, and hydroxypropylmethylcellulose caused mild to marked morphological changes on intestinal tissues.
Identification of Transcriptional and Receptor Networks That Control Root Responses to Ethylene1[OPEN]

The kinetics of changes in the ethylene transcriptome in light-grown roots combined with mutant analyses reveal a central role of the ETR1 receptor and a limited role of EIN3 in root development. Transcriptomic analyses with high temporal resolution provide substantial new insight into hormonal response networks. This study identified the kinetics of genome-wide transcript abundance changes in response to elevated levels of the plant hormone ethylene in roots from light-grown Arabidopsis (Arabidopsis thaliana) seedlings, which were overlaid on time-matched developmental changes. Functional annotation of clusters of transcripts with similar temporal patterns revealed rapidly induced clusters with known ethylene function and more slowly regulated clusters with novel predicted functions linked to root development. In contrast to studies with dark-grown seedlings, where the canonical ethylene response transcription factor, EIN3, is central to ethylene-mediated development, the roots of ein3 and eil1 single and double mutants still respond to ethylene in light-grown seedlings. Additionally, a subset of these clusters of ethylene-responsive transcripts were enriched in targets of EIN3 and ERFs. These results are consistent with EIN3-independent developmental and transcriptional changes in light-grown roots. Examination of single and multiple gain-of-function and loss-of-function receptor mutants revealed that, of the five ethylene receptors, ETR1 controls lateral root and root hair initiation and elongation and the synthesis of other receptors. These results provide new insight into the transcriptional and developmental responses to ethylene in light-grown seedlings.
Patient-independent variables affecting the assessment of aspirin responsiveness by serum thromboxane measurement

Summary The serum TXB2 (sTXB2) assay reflects the pharmacodynamics of platelet inhibition by low-dose aspirin. However, different studies reported variable sTXB2 values. sTXB2 assay requires whole blood incubation at 37 °C as a condition for optimal thrombin generation, arachidonic acid release and its metabolism by platelet cyclooxygenase-1 to form TXA2. Access to 37 °C incubation may be variably delayed, and different methods to quantitate sTXB2 may contribute to variable results between different Centers. We investigated whether delaying 37 °C incubation and/or analytical issues affect sTXB2 concentrations, biasing the assessment of aspirin responsiveness. Sixty-eight samples from 54 volunteers, on- and off-aspirin, were incubated at 37 °C immediately after sampling (reference sample) or after 5, 10, 15, 20, 30 or 60 minutes at room temperature (RT); 8 samples remained at RT 60 minutes, without subsequent incubation; 314 sera were measured by enzyme immunoassay (EIA) and liquid chromatography-tandem mass-spectrometry (LC/MS-MS) methods. sTXB2 concentrations decreased exponentially as a function of the delay before 37 °C incubation, ranging from 94 ± 11 % at 5 minutes to 23 ± 22 % of the reference sample after 60 minutes at RT. There was high agreement between EIA and LC/MS-MS. Moreover, we simulated the influence of a 15– or 30-minute delayed incubation on 300 sTXB2 measurements from previously-studied, aspirin-treated patients. Delayed incubation reduced the percentage of aspirin ‘non-responders’ by 22 % to 52 %, depending on the response threshold. In conclusion, a variable delay in the 37 °C incubation of blood samples may affect the assessment of platelet cyclooxygenase-1 inhibition by aspirin and confound the characterization of the determinants of aspirin responsiveness.
Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection

As a noninvasive marker, serum alanine aminotransferase (ALT) has limitations, because a large proportion of patients chronically infected with hepatitis B virus (HBV) suffer from severe hepatic necroinflammation, but have normal or mildly elevated ALT. In the present study, we aimed to investigate the potential value of serum Golgi protein 73 (GP73) in predicting significant hepatic necroinflamation among chronic HBV infected patients. A cohort of 497 chronic HBV infected patients was retrospectively recruited. Liver biopsy was performed in all patients and serum GP73 levels were measured by enzyme‐linked immunosorbent assay. Serum GP73 increased in parallel with the increase in hepatic necroinflammatory activity grade (r = 0.682) and the stage of liver fibrosis (r = 0.539). The positive correlation of serum GP73 with the degree of hepatic necroinflammatory activity was statistically significant, while serum GP73 with the stage of liver fibrosis was weaker than that with hepatic necroinflammation. Furthermore, serum GP73 levels were significantly greater in patients with normal or mildly elevated ALT and significant hepatic necroinflammation (≥G2) than in patients with minimal to mild hepatic necroinflammation. The sensitivity and specificity of GP73 for the diagnosis of G2 hepatic necroinflammation was 42.35% and 95.0%, respectively, at a cut‐off value of 88.38 ng/mL. When the cut‐off value was set at 124.76 ng/mL, the sensitivity and specificity of GP73 for the diagnosis of G3 hepatic necroinflammation was 55.56% and 97.29%, respectively. These findings indicate that GP73 holds promise as an important candidate for diagnosing significant hepatic necroinflammation.