Miracle-dz/UniFAR-FTUs huggingface dataset:
Intensive Insulin Therapy in Hospitalized Patients: A Systematic Review

BACKGROUND The benefits and harms of intensive insulin therapy (IIT) titrated to strict glycemic targets in hospitalized patients remain uncertain. PURPOSE To evaluate the benefits and harms of IIT in hospitalized patients. DATA SOURCES MEDLINE and Cochrane Database of Systematic Reviews from 1950 to January 2010, reference lists, experts, and unpublished sources. STUDY SELECTION English-language randomized, controlled trials comparing protocols titrated to strict or less strict glycemic targets. DATA EXTRACTION Two reviewers independently abstracted data from each study on sample, setting, glycemic control interventions, glycemic targets, mean glucose levels achieved, and outcomes. Results were grouped by patient population or setting. A random-effects model was used to combine trial data on short-term mortality (≤28 days), long-term mortality (90 or 180 days), infection, length of stay, and hypoglycemia. The Grading of Recommendations Assessment, Development, and Evaluation system was used to rate the overall body of evidence for each outcome. DATA SYNTHESIS In a meta-analysis of 21 trials in intensive care unit, perioperative care, myocardial infarction, and stroke or brain injury settings, IIT did not affect short-term mortality (relative risk, 1.00 [95% CI, 0.94 to 1.07]). No consistent evidence showed that IIT reduced long-term mortality, infection rates, length of stay, or the need for renal replacement therapy. No evidence of benefit from IIT was reported in any hospital setting, although the best evidence for lack of benefit was in intensive care unit settings. Data combined from 10 trials showed that IIT was associated with a high risk for severe hypoglycemia (relative risk, 6.00 [CI, 4.06 to 8.87]; P < 0.001). Risk for IIT-associated hypoglycemia was increased in all hospital settings. LIMITATIONS Methodological shortcomings and inconsistencies limit the data in perioperative care, myocardial infarction, and stroke or brain injury settings. Differences in insulin protocols and patient and hospital characteristics may affect generalizability across treatment settings. CONCLUSION No consistent evidence demonstrates that IIT targeted to strict glycemic control compared with less strict glycemic control improves health outcomes in hospitalized patients. Furthermore, IIT is associated with an increased risk for severe hypoglycemia. PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs Health Services Research and Development Service.
Anthropometric measurements of femur and tibia on the byzantine skeletons of nicea remains (13th century A.D.)

Skeletal anthropometric measurements to reveal regional diversity between different populations or within the same one are beneficial for understanding temporary evolutionary and developmental progress relevant to our species. Our material consisted of 26 femurs (13 left, 13 right) and 60 tibias (30 left, 30 right) of male Byzantine skeletons (13th century) excavated at Nicea in Turkey, between 1981 and 1985. Twelve osteometric parameters for femurs and five for tibias were taken into account. Indices of platymeria and platycnemia were derived and compared with other studies. Non-paired t-tests were used to compare left and right. No noticeable difference was found for femurs. Anteroposterior diameter at the nutrient foramen of tibias showed minimal difference between the left and right. The platymeric index was eumeric (mean = 86). Our material indicates the existence of eurycnemia with respect to tibial flattening (mean = 74).
The operating surgeon is an independent predictor of chest tube drainage following cardiac surgery.

OBJECTIVES Bleeding into the chest is a major cause of blood transfusion and adverse outcomes following cardiac surgery. The authors investigated predictors of bleeding following cardiac surgery to identify potentially correctable factors. DESIGN Data were retrieved from the medical records of patients undergoing cardiac surgery over the period of 2002 to 2008. Multivariate analysis was used to identify the independent predictors of chest tube drainage. SETTING Tertiary hospital. PARTICIPANTS Two thousand five hundred seventy-five patients. INTERVENTIONS Cardiac surgery. RESULTS The individual operating surgeon was independently associated with the extent of chest tube drainage. Other independent factors included internal mammary artery grafting, cardiopulmonary bypass time, urgency of surgery, tricuspid valve surgery, redo surgery, left ventricular impairment, male gender, lower body mass index and higher preoperative hemoglobin levels. Both a history of diabetes and administration of aprotinin were associated with reduced levels of chest tube drainage. CONCLUSIONS The individual operating surgeon was an independent predictor of the extent of chest tube drainage. Attention to surgeon-specific factors offers the possibility of reduced bleeding, fewer transfusions, and improved patient outcomes.
Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases

Probiotics are defined as nonpathogenic living microorganisms, including some commensal bacterial flora, which have beneficial effects on host health and disease prevention and/or treatment. Clinical trials have shown beneficial effects of probiotics on several human diseases, such as inflammatory bowel diseases (IBDs), which are among the most‐studied diseases testing probiotics as a potential therapy. However, a significant question regarding clinical use of probiotics is the mechanism underlying the wide range of actions. Studies discussed in this review suggest 3 distinct cellular and molecular mechanisms for probiotic regulation in IBD therapy: 1) Probiotics block pathogenic bacterial effects by producing bactericidal substances and competing with pathogens and toxins for adherence to the intestinal epithelium; 2) Probiotics regulate immune responses by enhancing the innate immunity and modulating pathogen‐induced inflammation via toll‐like receptor‐regulated signaling pathways; and 3) Probiotics regulate intestinal epithelial homeostasis by promoting intestinal epithelial cell survival, enhancing barrier function, and stimulating protective responses. Probiotics modulate host cell signaling pathways, including Akt, mitogen‐activated protein kinases, and nuclear factor‐&kgr;B to mediate these intestinal epithelial functions. It is hoped that developing a mechanistic understanding of probiotic action will provide the rationale to support the development of new hypothesis‐driven studies to define the clinical efficacy in preventive, adjunctive, or alternative treatments for IBD.
Effects of 28 days of dairy or soy ingestion on skeletal markers of inflammation and proteolysis in post-menopausal women

Background: Aging is associated with increased local inflammation and resultant proteolysis in skeletal muscle. In animal models, soy supplementation is a beneficial countermeasure against muscle inflammation and proteolysis; however, the effect on aging humans is not clear. Methods: A single-blinded, randomized, controlled trial was conducted on 31 post-menopausal women. Volunteers were randomly assigned to consume three servings of soy (n=16) or dairy (n=15) milk each day for 28 days. The expression of inflammation-responsive (TNF-α, IL-1β, IL-6) and proteolytic (calpain 1, calpain 2, ubiquitin, E2, atrogin-1, muRF-1) genes in skeletal muscle was determined using real-time polymerase chain reaction before and after supplementation, and then after a downhill run performed to elicit muscle damage. Results: While no group by time interactions were observed, significant main effects for time were observed for IL-1β, IL-6, calpain 2, and atrogin-1 mRNA post exercise. Further analysis revealed that, compared with post-supplementation values, calpain 2 and atrogin-1 mRNA significantly increased at 4 h post exercise (p=0.01 and p<0.01, respectively), whereas IL-1β and IL-6 mRNA significantly decreased at 4 h post exercise (both p<0.01). Conclusions: Soy or dairy milk supplementation at the amount ingested for 28 days does not appear to preferentially inhibit the expression of inflammation-responsive and proteolytic genes that were assessed, and does not attenuate the eccentric exercise-induced up-regulation in the proteolytic genes.
Treatment of Focal Status Epilepticus plus Epileptic Spasms with Leukotomy in an Infant with TSC 1 Mutation: A Case Study

ABSTRACT Background: Focal status epilepticus and catastrophic epilepsy are not rare in infants. Epilepsy surgery can be safely done in selected infants to cure epilepsy. Patient description: We report on an infant who began having drug-resistant status epilepticus at 2 weeks of age and developed epileptic spasms. We discuss in detail how the clinical and electroencephalographic data were used to reach a consensus for epilepsy surgery and why a particular surgical approach was preferred over other alternatives. Method: Presurgical evaluation consisted of 32-channel scalp video EEG using the standard 10–20 system of electrodes, 3-Tesla brain magnetic resonance imaging, and 18 F-fluorodeoxyglucose positron emission tomography. The surgery consisted of resection of the extensive epileptogenic lesion, in addition to disconnection of the left frontal lobe anterior to the motor strip. Result: The infant underwent epilepsy surgery at three months of age. At two-year follow up, she remained seizure free, with no focal motor deficit and the epileptic encephalopathy resolved. The disconnected left frontal lobe shows epileptiform discharges restricted to the disconnected tissue. Conclusion: We highlight the importance of epilepsy surgery in selected infants to achieve seizure freedom and to reverse epileptic encephalopathy. In the process, we demonstrate how epileptic spasms, although clinically and electrographically generalized, resolved after disconnecting the epileptogenic zone.
Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology

The Iroquois homeobox (Irx) homeodomain transcription factors are important for several aspects of embryonic development. In the developing heart, individual Irx genes are important for certain postnatal cardiac functions, including cardiac repolarization (Irx5) and rapid ventricular conduction (Irx3). Irx genes are expressed in dynamic and partially overlapping patterns in the developing heart. Here we show in mice that Irx3 and Irx5 have redundant function in the endocardium to regulate atrioventricular canal morphogenesis and outflow tract formation. Our data suggest that direct transcriptional repression of Bmp10 by Irx3 and Irx5 in the endocardium is required for ventricular septation. A postnatal deletion of Irx3 and Irx5 in the myocardium leads to prolongation of atrioventricular conduction, due in part to activation of expression of the Na+ channel protein Nav1.5. Surprisingly, combined postnatal loss of Irx3 and Irx5 results in a restoration of the repolarization gradient that is altered in Irx5 mutant hearts, suggesting that postnatal Irx3 activity can be repressed by Irx5. Our results have uncovered complex genetic interactions between Irx3 and Irx5 in embryonic cardiac development and postnatal physiology.
Effectiveness of hepatic resection for early-stage hepatocellular carcinoma in cirrhotic patients: subgroup analysis according to Milan criteria.

BACKGROUND The aim of this study was to determine the long-term post-resection outcomes for cirrhotic patients with early-stage hepatocellular carcinoma (HCC). METHODS A total of 217 < or = 65-year-old cirrhotic patients who underwent hepatic resection were divided into four groups in accordance with the Milan criteria: Group 1, those who met the Milan criteria (n = 130); Group 2A, those with a solitary tumor > 5 cm in size (n = 12); Group 2B, those with 2 or 3 tumors > 3 cm in size (n = 35); and Group 2C, those with > or = 4 tumors (n = 33). Overall and recurrence-free survival were compared between the groups. RESULTS At 1, 3, 5 and 10 years, overall survival rates were 91, 67, 45 and 12%, and recurrence-free survival rates were 62, 26, 16 and 0%, respectively. Independent prognostic factors for overall survival were age, blood transfusion, tumor number, tumor size and microscopic vascular invasion; and for recurrence they were hepatitis C infection, tumor number, tumor size, microscopic vascular invasion and histological tumor grade. Group 1 patients had significantly better survival (5-year survival rate, 56%) than those of other groups (5-year survival rate, around 30%). The median tumor-free survival time was significantly shorter in Groups 2B and 2C (0.7 years and 0.6 years, respectively) than in Groups 1 and 2A. CONCLUSIONS Hepatic resection can confer a considerable overall survival benefit for cirrhotic patients with HCC who meet the Milan criteria. For patients with HCC who do not meet the criteria, however, hepatic resection has limited efficacy. We suggest that application of non-surgical therapy or expansion of the indications for liver transplantation may be warranted for such patient subsets.
Peritonitis caused by Aeromonas species at a hospital in southern Taiwan.

OBJECTIVE This study was conducted to investigate the clinical characteristics of patients with Aeromonas peritonitis, particularly secondary peritonitis. METHODS Patients with Aeromonas peritonitis treated between July 2004 and December 2011 were identified from the computerized database of a regional hospital in southern Taiwan. The medical records of these patients were retrospectively reviewed. RESULTS A total of 50 patients with Aeromonas peritonitis were identified. Nine cases were classified as spontaneous bacterial peritonitis, and 41 cases were classified as secondary peritonitis. The most common etiology of secondary peritonitis was acute appendicitis (n=26), followed by small bowel perforation (n=7) and colon perforation (n=6). The patients with spontaneous bacterial peritonitis were more likely to be immunocompromised (p=0.0013) and more frequently had an initial presentation of shock (p=0.0129), an abnormal liver function (p<0.05) and concomitant bacteremia (p=0.0024) than the patients with secondary peritonitis. Although the patients with secondary peritonitis had higher levels of inflammatory parameters, including leukocytes and C-reactive protein, and more frequent polymicrobial infections, their survival outcome rates, such as in-hospital mortality, were significantly lower (p=0.0007). The overall in-hospital mortality rate was 20%, and initial shock was the only independent prognostic factor for mortality (p=0.012). CONCLUSION The clinical characteristics, including outcomes, of patients with spontaneous and secondary Aeromonas peritonitis differ. In-hospital mortality is significantly associated with the initial presentation of shock.
Exploring patient demographic and clinical characteristics associated with lipid-lowering pharmacotherapy use in primary care.

BACKGROUND Lipid-lowering therapeutics, particularly HMG Co-A reductase inhibitors, can be beneficial in primary and secondary cardiovascular prevention. The Canadian population frequently uses these medications but the manner in which they are used in community-based practice is unknown. OBJECTIVES To assess the patient characteristics associated with lipid lowering drug use in community-based clinical practice across four geographic regions in Canada. To assess amongst lipid-lowering drugs users the proportion of patients that would meet accepted dyslipidemia management guidelines. To assess the community-based effectiveness of anti-hyperlipidemic drugs. METHODS Patients filling a prescription for any anti-hyperlipidemia therapy in selected pharmacies in Ontario (ON), Quebec (PQ), British Columbia (BC) and Nova Scotia (NS). All eligible patients were interviewed over the telephone. Physicians who were providing healthcare to the participating patients were requested to provide information from the patient's medical record. RESULTS The mean patient age was > 60 yr in all four provinces. There were some differences amongst the four provinces pertaining to patient characteristics, prescription patterns and therapeutic indicators, but not to outcomes. Anti-hyperlipidemia therapy was associated with a 1.81 mmol/L decrease in LDL-Cholesterol (P < 0.001); however only 73% of patients achieved target LDL-Cholesterol concentrations. A lag time of 1.96 yr (P < 0.0001) was observed from the diagnosis of dyslipidemia until the drug treatment was initiated. Patients had an average of 2.8 cardiovascular (CV) risk factors and 86% of patients had at two or more CV risk factors. Thirty-nine percent (95% CI, 36% - 42%) of the patients were being treated for secondary prevention. Thirteen percent (11-16%) of patients who were being treated for primary prevention had diabetes. Metabolic syndrome was observed in 32% (29-35%) of patients. CONCLUSION Almost all patients fulfilled guideline requirements for the use of anti-hyperlipidemic therapy. Although the use of pharmacotherapy was associated with a lowering of LDL cholesterol more aggressive management is required to attain target LDL cholesterol concentrations.
Cost Analysis of Commonly used Combination of Drugs in Primary Open Angle Glaucoma.

BACKGROUND Glaucoma is second cause of blindness in the world. The financial burden on the patient during long-term treatment is immense and affects the compliance to medications, thus visual morbidity. OBJECTIVE To analyse economic impact of three commonly used drug combinations (Dorzolamide + Timolol = DT; Brimonidine + Timolol = BT; Latanoprost+Timolol = LT) in primary open angle glaucoma. MATERIALS AND METHODS This observational, prospective study was undertaken at M & J Institute of Ophthalmology, Civil Hospital, Ahmedabad, a western regional institute of Ophthalmology. A total of 257 patients were included in the study. Only101 patients could complete the 6 month follow-up, of which 35, 34 and 32 patients belonged to DT, BT and LT group respectively. Cost of drug, details of the transportation were noted at every visit. Total cost incurred per patient/eye was calculated. Cost effectiveness was calculated by cost per mm Hg IOP (Intra-Ocular Pressure) reduction. RESULTS Treatment with DT, BT & LT group consumed 8.6%, 4.6% and 7.7% of the per annum income of the family, respectively. Cost of medications per annum (in INR)/eye for DT, BT & LT group were 2562 ± 15.74, 1544 ± 32.06, 3876 ± 73.68 (Mean±SEM) respectively. Additional cost of travelling was different for patients coming from Ahmedabad (Locals) and outsiders (patients coming outside Ahmedabad, India). Outsiders has to bear the brunt of higher transport charges, where they spent an average of Rs. 914, 856 & 933 per annum (5 follow-ups), whereas, Locals spent an average of Rs. 104, 112, 100 for DT, BT & LT group respectively. CONCLUSION Treatment with BT was found to be most cost-effective among three groups. Drug therapy takes substantial amount from per annum income of family and was an important compliance factor in the treatment of POAG.
Posttranscriptional Upregulation by MicroRNAs

MicroRNAs are small non‐coding RNA guide molecules that regulate gene expression via association with effector complexes and sequence‐specific recognition of target sites on other RNAs; misregulated microRNA expression and functions are linked to a variety of tumors, developmental disorders, and immune disease. MicroRNAs have primarily been demonstrated to mediate posttranscriptional downregulation of expression; translational repression, and deadenylation‐dependent decay of messages through partially complementary microRNA target sites in mRNA untranslated regions (UTRs). However, an emerging assortment of studies, discussed in this review, reveal that microRNAs and their associated protein complexes (microribonucleoproteins or microRNPs) can additionally function to posttranscriptionally stimulate gene expression by direct and indirect mechanisms. These reports indicate that microRNA‐mediated effects can be selective, regulated by the RNA sequence context, and associated with RNP factors and cellular conditions. Like repression, translation upregulation by microRNAs has been observed to range from fine‐tuning effects to significant alterations in expression. These studies uncover remarkable, new abilities of microRNAs and associated microRNPs in gene expression control and underscore the importance of regulation, in cis and trans, in directing appropriate microRNP responses. WIREs RNA 2012, 3:311–330. doi: 10.1002/wrna.121
Distinct changes in HIV type 1 RNA versus p24 antigen levels in serum during short-term zidovudine therapy in asymptomatic individuals with and without progression to AIDS.

Serum HIV-1 RNA and p24 antigen levels were examined in 28 seropositive asymptomatic individuals participating in a trial on the efficacy of zidovudine. Sixteen individuals remained asymptomatic until 4 years after the onset of the trial, whereas 12 individuals were diagnosed with an AIDS-defining event. The serum HIV-1 RNA load and p24 antigen levels were determined before the onset of therapy and during the first 8 weeks of therapy to establish whether the patterns of change were predictive of clinical outcome. Among the 28 participants 43% had measurable pretreatment concentrations of p24 antigen. Initiation of zidovudine therapy was followed by a similar decline of p24 antigen levels in nonprogressors as well as progressors and, therefore, these groups could not be distinguished on the basis of this parameter. HIV-1 RNA was detected in the pretreatment samples of 82% of the individuals and could be detected in p24 antigen-positive as well as p24 antigen-negative individuals. Similar changes in HIV-1 RNA load during zidovudine therapy were observed in p24 antigen-positive and -negative individuals. Analysis of the HIV-1 RNA response according to clinical outcome demonstrated that HIV-1 RNA copy numbers had declined significantly after 4 weeks of therapy in both nonprogressors and progressors, but the decline in RNA load was much stronger in the nonprogressors. Our data show that the HIV-1 RNA load in serum can be used to monitor the response to antiviral therapy in p24 antigen-positive as well as -negative individuals. Posttreatment changes in p24 antigen levels are not indicative for clinical outcome, whereas RNA copy numbers are. (ABSTRACT TRUNCATED AT 250 WORDS)
A new male hypogonadism mutant rat (hgn/hgn): concentrations of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the serum and the responsiveness of accessory sex organs to exogenous T, FSH, human chorionic gonadotropin, and luteinizing hormone-releasing hormone.

To determine the etiology of male hypogonadism in a newly found mutant rat (hgn/hgn, with a single autosomal recessive trait), concentrations of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured, and the responsiveness of the urogenital organs, hypothalamus, and pituitary gland to testosterone (1 mg/kg s.c. for 7 days), FSH (0.3 AU/kg s.c. for 7 days), human chorionic gonadotropin (hCG) (40 IU/kg s.c. for 7 days), and luteinizing hormone-releasing hormone (LHRH) (0.5 or 5.0 micrograms/kg s.c. for 7 days) were tested. Treatment with testosterone only increased the weights of all of the accessory sex organs, whereas treatment with FSH, hCG, or LHRH did not. Levels of serum FSH and LH were extremely higher and testosterone was lower in hgn/hgn males than in normal males. Serum FSH and LH decreased to levels found in intact animals after treatment with testosterone, suggesting that hypothalamic responsiveness to exogenous testosterone is present in the hgn/hgn males. Thus, the status of the hgn/hgn males was indicated to be due to primary Leydig cell dysfunction.