Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimal management of type 2 diabetes in patients with increased risk of hypoglycemia

With the number of individuals diagnosed with type 2 diabetes on the rise, it has become more important to ensure these patients are effectively treated. The Centers for Disease Control and Prevention estimated that 8.3% of all Americans were diagnosed with diabetes in 2011 and this number will likely continue to rise. With lifestyle interventions, such as proper diet and exercise, continuing to be an essential component of diabetes treatment, more patients are requiring medication therapy to help them reach their therapeutic goals. It is important for the clinician, when determining the treatment strategy for these individuals, to find a balance between reaching treatment goals and limiting the adverse effects of the treatments themselves. Of all the adverse events associated with treatment of diabetes, the risk of hypoglycemia is one that most therapies have in common. This risk is often a limiting factor when attempting to aggressively treat diabetic patients. This manuscript will review how hypoglycemia is defined and categorized, as well as discuss the prevalence of hypoglycemia among the many different treatment options.
Inhibition of mTOR-Dependent Autophagy Sensitizes Leukemic Cells to Cytarabine-Induced Apoptotic Death

The present study investigated the role of autophagy, a cellular self-digestion process, in the cytotoxicity of antileukemic drug cytarabine towards human leukemic cell lines (REH, HL-60, MOLT-4) and peripheral blood mononuclear cells from leukemic patients. The induction of autophagy was confirmed by acridine orange staining of intracellular acidic vesicles, electron microscopy visualization of autophagic vacuoles, as well as by the increase in autophagic proteolysis and autophagic flux, demonstrated by immunoblot analysis of p62 downregulation and LC3-I conversion to autophagosome-associated LC3-II in the presence of proteolysis inhibitors, respectively. Moreover, the expression of autophagy-related genes Atg4, Atg5 and Atg7 was stimulated by cytarabine in REH cells. Cytarabine reduced the phosphorylation of the major negative regulator of autophagy, mammalian target of rapamycin (mTOR), and its downstream target p70S6 kinase in REH cells, which was associated with downregulation of mTOR activator Akt and activation of extracellular signal- regulated kinase. Cytarabine had no effect on the activation of mTOR inhibitor AMP-activated protein kinase. Leucine, an mTOR activator, reduced both cytarabine-induced autophagy and cytotoxicity. Accordingly, pharmacological downregulation of autophagy with bafilomycin A1 and chloroquine, or RNA interference-mediated knockdown of LC3β or p62, markedly increased oxidative stress, mitochondrial depolarization, caspase activation and subsequent DNA fragmentation and apoptotic death in cytarabine-treated REH cells. Cytarabine also induced mTOR-dependent cytoprotective autophagy in HL-60 and MOLT-4 leukemic cell lines, as well as primary leukemic cells, but not normal leukocytes. These data suggest that the therapeutic efficiency of cytarabine in leukemic patients could be increased by the inhibition of the mTOR-dependent autophagic response.
Performance of Channel Prediction Using 3D Ray-tracing Scheme Compared to Conventional 2D Scheme

Channel prediction tools using ray-tracing scheme can be used to get information of communication channel instead of channel measurement. Three dimensional (3D) ray-tracing technique is known for the better accuracy compared to two dimensional (2D) ray-tracing. But it requires a lot of calculations, thus 2D simulation has been generally performed. This paper shows how precious 3D ray-tracing predicts the received power indoors compared to 2D one. For this work, wave propagation phenomena are analyzed using finite difference time domain (FDTD) method and the channel measurement data also will be offered as a standard of comparison
Metabolic syndrome, inflammation and atherothrombosis

Summary Extensive research of the past decades altered our traditional concept about the genesis of atherosclerosis fundamentally. Today, the crucial role of inflammation in the formation and progression of atherosclerotic plaques is indisputable. Patients at high risk for developing cardiovascular disease, owing to poor diet, obesity and low physical activity have been shown to exhibit a particular inflammatory pattern. Therefore, the present review highlights the crosslink between the metabolic syndrome (MetS), adipose tissue, adipokines and selected inflammatory cytokines in the context of atherothrombosis and cardiovascular disease.
Effect of Obesity on Outcome of Hallux Valgus Surgery

Background: Obesity is a global epidemic, but its effect on foot and ankle surgeries is not well defined. This study aimed to investigate the influence of obesity on functional outcome scores, incidence of postoperative surgical site infection (SSI), and repeat surgery after hallux valgus (HV) corrective surgery. Methods: Between January 2007 and December 2011, 452 patients who underwent HV corrective surgery at a tertiary hospital were evaluated. They were categorized into 2 groups based on their body mass index (BMI): (1) BMI less than 30 kg/m2 (control); (2) BMI 30 kg/m2 or more (obese). The patients were prospectively followed for 2 years. Results: Patients in the obese group were significantly older by 4 years (95% CI, 1-7 years) (P = .043). The preoperative American Orthopaedic Foot & Ankle Society Hallux Metatarsophalangeal-Interphalangeal (AOFAS Hallux MTP-IP) Scale and Physical Component Score were 6 points (95% CI, 1-11 points) and 3 points (95% CI, 1-6 points) poorer, respectively, in the obese group (P = .014 and P = .032, respectively). However, the Visual Analog Scale, AOFAS Hallux MTP-IP Scale, Physical Component Score, and Mental Component Score were comparable between the 2 groups at 6 months and 2 years of follow-up (all P > .05). Eleven patients (3%) in the control group and 1 patient in the obese group (2%) developed postoperative SSI (P = .777). Nine patients (2%) in the control group and 7 patients in the obese group (14%) required repeat surgery for complications (P < .001). Conclusion: The authors conclude that while it is important to warn obese patients of the significantly higher risk of repeat surgery, these patients should not be excluded from undergoing HV surgery. Level of Evidence: Level III, retrospective comparative series.
Moderate obesity and endothelial dysfunction in humans: influence of gender and systemic inflammation

Our objective was to determine whether moderate obesity (Body Mass Index [BMI] ≥ 30 kg/m²) is associated with impaired conduit and microvascular endothelial function, and whether men or women are more susceptible to impairment of endothelial function related to moderate obesity. Forty‐one middle aged, nondiabetic moderately obese (BMI 34.7 ± 4.0 kg/m2) and nonobese (BMI 24.3 ± 2.6 kg/m2) subjects of both sexes underwent noninvasive studies of endothelial function (brachial reactivity) and measurements of endothelial‐dependent vasodilation of gluteal subcutaneous arterioles to acetylcholine (Ach). Endothelium‐dependent vasodilation to Ach was decreased in the moderately obese compared with the nonobese (P < 0.001). Stratified analysis based on sex showed impairment of arteriolar endothelial function in women BMI ≥ 30 kg/m2 (P = 0.02), but not men. There was no difference between in vivo endothelial function flow‐mediated dilation (FMD%) by BMI category. Sex‐specific analysis showed FMD% was lower in women with BMI ≥ 30 kg/m2 compared to those with BMI < 30 kg/m2 (P = 0.02). No differences were seen in men based on BMI category (P = 0.18). In women, high sensitivity C‐reactive protein (hsCRP) correlated with BMI (ρ = 0.68, P = 0.006). Moderate obesity is associated with impaired resistance arteriolar endothelial function. This is more prominent in women than men and is associated with systemic inflammation.
Transthoracic Surgical Treatment for Centrally Located Thoracic Disc Herniations Presenting With Myelopathy: A 5-year Institutional Experience

Study Design Retrospective review. Objective Review clinical outcomes for myelopathic patients undergoing transthoracic discectomies for central calcified herniations. Summary of Backround Data Ideal surgical treatment for thoracic disc herniation is controversial due to variations in patient presentation, pathology, and possible surgical approach. Although discectomy may lead to improvements in neurologic function, it can be complicated by approach-related morbidity, especially for ventral calcified disc herniations. Review of clinical outcomes for myelopathic patients undergoing transthoracic discectomies for central calcified herniations was completed, paying special attention to neurologic status and procedure-related complications. Methods Between 2002 and 2007, 27 myelopathic patients were treated with 28 transthoracic surgeries for centrally located symptomatic calcified thoracic disc herniations over the last 5 years at a single institution. Demographic data, details of surgery, preoperative and postoperative Nurick and American Spinal Injury Association scores, length of stay, complications, and follow-up data were collected in all patients. Results A total of 27 patients, 8 male (30%) and 19 female (70%) with an average age of 52.3 years (range: 19 to 72) underwent 28 thoracotomies. All had myelopathy whereas 6/27 also had radicular pain syndromes. Fourteen patients had anterior instrumentation alone, 3 had anterior and posterior instrumentation, and 1 had posterior instrumentation alone. Average Nurick grade was 2.5 preoperatively and 1.4 postoperatively. Of note, American Spinal Injury Association scores improved postoperatively in 12/27 patients (10D to 10E; 2C to 2D), remained unchanged in 13/27 (11E to 11E, 2D to 2D), and worsened in 2/27 (2D to 2C). Average length of stay was 7 days (range: 3 to 15). All patients required chest tube placement with average duration of 4 days (range: 1 to 7). Major complications occurred in 6 cases (21.4%) over an average follow-up of 12 months (range: 1 to 40 mo). Conclusions Thoracotomy for treatment of centrally located thoracic disc herniations is associated with improvement in or stabilization of myelopathic symptoms in the majority of patients with an acceptable rate of complications. Interestingly, most patients with weakness improved in strength (12/16, 75%), no patients with normal strength developed new weakness (10/10, 100%), and only 2 patients had new weakness noted postoperatively (7.4%).
Relationship Between Maternal and Fetal Fuels and Placental Glucose Transfer in Rats with Maternal Diabetes of Varying Severity

Gestational diabetes mellitus (GDM) is a nonhomogenous entity known to affect fetal development in different ways in both rats and human beings. The degree of severity of diabetes could affect the maternal-fetal transfer of metabolic fuels and consequently influence fetal development. To study this hypothesis, pregnant rats were made diabetic by streptozocin (STZ) treatment (45 mg/kg) at day 7 of gestation and were treated with different daily doses of insulin until the 20th day of gestation, when-they were killed and examined. Differences in plasma glucose levels in the groups studied were not accompanied by differences in plasma glycerol, β-hydroxybutyrate (β-OHB), or total amino acid levels in mothers or their fetuses. Fetal/maternal ratios of these circulating fuels were not modified by maternal diabetes, whereas the glucose level was enhanced in diabetic rats not treated with insulin. Placental glucose transfer was studied directly with a recently reported in situ experimental design and was found to increase linearly with maternal glycemia, independently of whether this was modified by insulin treatment or by acute intravenous (i.v.) infusion of glucose in normal animals. Lactate production by the fetal/placental unit decreased in proportion to the glucose level in the maternal circulation. The present data indicate that the diabetic condition of the mother rat does not modify the mechanisms of placental transfer of metabolic fuels to the fetus, and that the actual transfer is mainly dependent on the concentrations of these fuels in the maternal circulation. The limited capacity of the fetus to handle the great influx of glucose through the placenta of a highly hyperglycemic mother may aggravate the diabetic condition of the fetus, affecting its subsequent development.
Postpartum glucose tolerance status 6 to 12 weeks after gestational diabetes mellitus: a Brazilian cohort.

OBJECTIVES The aims of this study were to estimate the local rate of postpartum diabetes screening after gestational diabetes mellitus (GDM) pregnancies, and to identify clinical variables associated with retesting rates and with the persistence of decreased glucose tolerance. SUBJECTS AND METHODS Prospective cohort of GDM women with prenatal delivery at a specialized center, from November 2009 to May 2012. All women were advised to schedule a 6 weeks postpartum 75-g oral glucose tolerance test (OGTT). RESULTS Of the 209 women included, 108 (51.7%) returned to be tested with fasting plasma glucose (n=14), OGTT (n=93) or random glucose (n=1). Return was associated with lower parity rate (2 vs. 3, p<0.001) and higher pregnancy 2-h OGTT (165 vs. 155 mg/dL, p=0.034), but not with socio-demographic characteristics. Four women (3.7%) had diabetes, 22 (20.4%) had impaired fasting glucose or impaired glucose tolerance. Persistent hyperglycemia was associated with a positive family history of diabetes (relative risk-RR 2.41, p=0.050), diagnostic 2-h OGTT in pregnancy (RR 1.01, p=0.045), insulin use during pregnancy (RR 2.37, p=0.014), and cesarean section (RR 2.61, p=0.015). CONCLUSIONS Even though postpartum abnormalities were frequent in GDM, rates of postpartum diabetes screening were undesirably low. As no specific clinical profile defines who will adhere to postpartum testing, it is essential to encourage all women to reevaluate their glucose status, particularly those with a family history of diabetes and more severe hyperglycemia.
Psychopathology and social competencies of adolescents who were extremely low birth weight.

BACKGROUND We have previously shown that infants who were extremely low birth weight (ELBW) are particularly vulnerable to problems related to inattention and hyperactivity at school age. It is not known whether these problems persist to adolescence. OBJECTIVE To explore and compare the levels of psychopathology in a regional cohort of ELBW infants and sociodemographically matched term controls as reported by teens and their parents. DESIGN/METHODS Cross-sectional cohort study/geographically defined region. PARTICIPANTS TEENS: ELBW 141/169 (83%) and control 122/145 (84%), aged 12 to 16 years. PARENTS: ELBW 143/169 (85%) and control 123/145 (85%). Both cohorts and their parents completed the Ontario Child Health Study-Revised questionnaire with 6 behavioral subsca1es: conduct disorder, oppositional defiant disorder, attention-deficit/hyperactivity disorder (ADHD), overanxious, separation anxiety, and depression. RESULTS By teen self-report, there were no significant differences between ELBW and control teens on any of the 6 subscale scores. However, parents of ELBW teens reported significantly higher scores than parents of control for depression and ADHD based on 2-way analysis of variance (group x gender). Comparison within teen/parent dyads showed that both cohorts of teens reported significantly higher scores than their parents. Multivariable analyses on behavioral subscale scores demonstrated a number of variables that were significant predictors by parent report: group (ELBW vs control), gender, family function, developmental quotient, maternal mood, and socioeconomic status; no predictors were significant by teen report. There were no statistically significant interaction effects for any of the models. These models explained a greater percent of the variance in behavioral scores for parents than for teens (12.5%-22.0% vs 3.4%-8.2%). Results were similar when teens with neurosensory impairment were excluded. CONCLUSIONS This study is unique in the inclusion of both parent and teen self-report of behaviors. Significant differences were apparent only by parent report for ADHD and depression among ELBW teens. Significant predictors of behavioral scores for parents include group, gender, family function, developmental quotient, maternal mood, and socioeconomic status.
MicroRNA Loss Enhances Learning and Memory in Mice

Dicer-dependent noncoding RNAs, including microRNAs (miRNAs), play an important role in a modulation of translation of mRNA transcripts necessary for differentiation in many cell types. In vivo experiments using cell type-specific Dicer1 gene inactivation in neurons showed its essential role for neuronal development and survival. However, little is known about the consequences of a loss of miRNAs in adult, fully differentiated neurons. To address this question, we used an inducible variant of the Cre recombinase (tamoxifen-inducible CreERT2) under control of Camk2a gene regulatory elements. After induction of Dicer1 gene deletion in adult mouse forebrain, we observed a progressive loss of a whole set of brain-specific miRNAs. Animals were tested in a battery of both aversively and appetitively motivated cognitive tasks, such as Morris water maze, IntelliCage system, or trace fear conditioning. Compatible with rather long half-life of miRNAs in hippocampal neurons, we observed an enhancement of memory strength of mutant mice 12 weeks after the Dicer1 gene mutation, before the onset of neurodegenerative process. In acute brain slices, immediately after high-frequency stimulation of the Schaffer collaterals, the efficacy at CA3-to-CA1 synapses was higher in mutant than in control mice, whereas long-term potentiation was comparable between genotypes. This phenotype was reflected at the subcellular and molecular level by the elongated filopodia-like shaped dendritic spines and an increased translation of synaptic plasticity-related proteins, such as BDNF and MMP-9 in mutant animals. The presented work shows miRNAs as key players in the learning and memory process of mammals.
Intranasal Immunization with Recombinant HA and Mast Cell Activator C48/80 Elicits Protective Immunity against 2009 Pandemic H1N1 Influenza in Mice

Background Pandemic influenza represents a major threat to global health. Vaccination is the most economic and effective strategy to control influenza pandemic. Conventional vaccine approach, despite being effective, has a number of major deficiencies including limited range of protection, total dependence on embryonated eggs for production, and time consuming for vaccine production. There is an urgent need to develop novel vaccine strategies to overcome these deficiencies. Methodology/Principal Findings The major objective of this work was to develop a novel vaccine strategy combining recombinant haemagglutinin (HA) protein and a master cell (MC) activator C48/80 for intranasal immunization. We demonstrated in BALB/c mice that MC activator C48/80 had strong adjuvant activity when co-administered with recombinant HA protein intranasally. Vaccination with C48/80 significantly increased the serum IgG and mucosal surface IgA antibody responses against HA protein. Such increases correlated with stronger and durable neutralizing antibody activities, offering protection to vaccinated animals from disease progression after challenge with lethal dose of A/California/04/2009 live virus. Furthermore, protected animals demonstrated significant reduction in lung virus titers, minimal structural alteration in lung tissues as well as higher and balanced production of Th1 and Th2 cytokines in the stimulated splenocytes when compared to those without C48/80. Conclusions/Significance The present study demonstrates that the novel vaccine approach of combining recombinant HA and mucosal adjuvant C48/80 is safe and effective in eliciting protective immunity in mice. Future studies on the mechanism of action of C48/80 and potential combination with other vaccine strategies such as prime and boost approach may help to induce even more potent and broad immune responses against viruses from various clades.
Immunological Markers for PML Prediction in MS Patients Treated with Natalizumab

Natalizumab (NTZ), a monoclonal antibody recognizing the alpha4 integrin chain, has been approved for the treatment of active multiple sclerosis, but expose to the onset of a rare side effect, progressive multifocal leukoencephalopathy (PML). Estimating the individual risk of PML in NTZ-treated patients is a major challenge, and therapeutic strategies are mainly guided by the overall PML risk assessed by identified risk factors: JC virus (JCV) seropositivity, treatment duration (with peak incidence after 24 months), and the previous use of immunosuppressive therapies. Given that this stratification does not yet allow a precise individual prediction of PML, other predictive markers are needed, and several immunological biomarkers have been described. Quantification of anti-JCV antibody levels may improve individual predictive value, with higher baseline titers indicating increased risk. Other immunological biomarkers such as leukocyte cell membrane markers (CD49d, CD11a, and CD62L), detection of circulating JCV-specific activated T effector memory cells (TEM) or genetic screening have been proposed. In this review, we discuss how recent progress in immunology has paved the way for «new combined monitoring», which will include immunological screening, in NTZ-treated patients.
Minimal Head Trauma in Children Revisited: Is Routine Hospitalization Required?

Objective. Children with a question of occult head injury are routinely hospitalized despite having both normal central nervous system (CNS) and computed tomographic (CT) scan examinations. We determined the incidence of significant CNS morbidity after occult head injury to determine whether or not hospital admission was necessary in children after minimal head trauma. Methods. We reviewed the records of children admitted to a level I trauma center with a question of closed head injury, an initial Glasgow Coma Scale equal to 15, a normal neurologic exam, and a normal head CT scan. Children with associated injuries requiring admission were excluded. The endpoints were deterioration in CNS exam, new CT findings, and the need for a prolonged hospital stay. Results. Sixty-two patients were studied with a mean age of 7 years (range, 1 month to 15 years), and 65% were male. The primary mechanisms of injury were fall (45%) and vehicular crash (23%). The mean injury severity score was 4 ± 2. The mean length of stay was 1.2 days (range, 1 to 3 days). Prolonged hospitalization occurred in 9 patients (15%). No child developed significant CNS sequelae warranting hospital admission. Total charges for these hospitalizations were $177 874. Conclusions. Children undergoing emergency department work-up of occult head injury, who have a normal CNS exam and a normal head CT scan, do not seem to be at risk for significant CNS sequelae. These patients can be discharged home with parental supervision and avoid unnecessary and costly hospitalization.