Miracle-dz/UniFAR-FTUs huggingface dataset:
Rate of cognitive decline in relation to sex after 60 years‐of‐age: A systematic review

Some studies have shown differences in specific cognitive ability domains between the sexes at 60 years‐of‐age. However is important to analyze whether the rate of cognitive decline is also similar between the sexes after this age. The present study examined previously published literature to investigate whether cognitive decline is distinct between men and women after the age of 60 years. A systematic review was carried out with the PubMed, LILACS and PsycINFO databases (2001–2011) using the following search terms: aging, aged, cognitive function, mild cognitive impairment, mental health and cognition. We analyzed longitudinal research that used neuropsychological tests for evaluating cognitive function, showed results separated by sex and that excluded participants with dementia. Elderly women showed better performance in tests of episodic memory, whereas elderly men had a better visuospatial ability. Only one study detected distinct rates of cognitive decline in specific tests between the sexes. Despite differences observed in some domains, most of the studies showed that this rate is similar between the sexes until the age of 80 years. It is unclear whether sex influences the rate of cognitive decline after the age of 80 years. The present review observed that sex does not determine the rate of cognitive decline between 60 and 80 years‐of‐age. The contextual and cultural factors that involve men and women might determine a distinct decline between them, rather than sex alone. Geriatr Gerontol Int 2014; 14: 23–31.
Anti-tubercular screening of natural products from Colombian plants: 3-methoxynordomesticine, an inhibitor of MurE ligase of Mycobacterium tuberculosis.

OBJECTIVES New anti-mycobacterial entities with novel mechanisms of action are clinically needed for treating resistant forms of tuberculosis. The purpose of this study was to evaluate anti-tubercular activity and selectivity of seven recently isolated natural products from Colombian plants. METHODS MICs were determined using a liquid medium growth inhibition assay for Mycobacterium tuberculosis H(37)Rv and both solid and liquid media growth inhibition assays for Mycobacterium bovis BCG. Escherichia coli growth inhibition and mammalian macrophage cell toxicity were evaluated to establish the degree of selectivity of the natural product against whole cell organisms. Enzymatic inhibition of ATP-dependent MurE ligase from M. tuberculosis was assayed using a colorimetric phosphate detection method. The most active compound, 3-methoxynordomesticine hydrochloride, was further investigated on M. bovis BCG for its inhibition of sigmoidal growth, acid-fast staining and viability counting analysis. RESULTS Aporphine alkaloids were found to be potent inhibitors of slow-growing mycobacterial pathogens showing favourable selectivity and cytotoxicity. In terms of their endogenous action, the aporphine alkaloids were found inhibitory to M. tuberculosis ATP-dependent MurE ligase at micromolar concentrations. A significantly low MIC was detected for 3-methoxynordomesticine hydrochloride against both M. bovis BCG and M. tuberculosis H(37)Rv. CONCLUSIONS Considering all the data, 3-methoxynordomesticine hydrochloride was found to be a potent anti-tubercular compound with a favourable specificity profile. The alkaloid showed MurE inhibition and is considered an initial hit for exploring related chemical space.
Prevalence of Escherichia coli carrying extended-spectrum β-lactamases (CTX-M and TEM-52) from broiler chickens and turkeys in Great Britain between 2006 and 2009.

OBJECTIVES to determine the prevalence of extended-spectrum β-lactamases (ESBLs) in Escherichia coli from poultry in Great Britain (GB). METHODS E. coli was isolated from 388 broiler chicken caecal samples from 22 abattoirs and from boot swabs from 442 turkey flocks over successive 1 year periods. CHROMagar ECC with and without cephalosporin antibiotics was used as isolation medium and the chicken study also used CHROMagar CTX. ESBL phenotype isolates were tested for the presence of bla(CTX-M,) bla(OXA), bla(SHV), bla(TEM) and ampC genes(.) CTX-M isolates were tested for O25 serogroup, replicon, CTX-M sequence, multilocus sequence type (MLST), PFGE type, plasmid transfer and qnrA, qnrB, qnrS, qepA and aac(6')-Ib genes. RESULTS CTX-M-carrying E. coli were isolated from 54.5% of the broiler abattoirs and from 3.6% of individual broiler caecal samples and were CTX-M sequence types 1 (mainly), 3 and 15 with replicon types I1-γ, A/C and P/F, and I1-γ, respectively. CTX-M-carrying E. coli were isolated from 5.2% of turkey meat production farms and 6.9% of turkey breeder farms and were CTX-M sequence types 1, 14 (mainly), 15 and 55 with mainly replicon types F, FIA, K and I1-γ, respectively. None of the CTX-M isolates was serogroup O25. PFGE/MLST showed the CTX-M isolates to be clonally diverse, although MLST 156 with CTX-M-15 was isolated from both chickens and turkeys and has been previously reported in gulls. CTX-M-negative, ESBL- and bla(TEM)-positive strains were mainly TEM-52C. CONCLUSIONS poultry-derived CTX-M E. coli in GB are different from major CTX-M sequence types causing disease in humans.
ffects of environmental enrichment and voluntary exercise on neurogenesis , earning and memory , and pattern separation : BDNF as a critical variable ?

Adult-generated neurons in the dentate gyrus of the hippocampus have been the focus of many studies concerned with learning and memory (L&M). It has been shown that procedures like environmental enrichment (EE) or voluntary physical exercise (Vex) can increase neurogenesis (NG) and also enhance L&M. It is tempting to conclude that improvements in L&M are due to the increased NG; that is, a causal relationship exists between enhancement of NG and enhancement of L&M. However, it remains unclear whether the L&M enhancement observed after these treatments is causally dependent on the increase in newborn neurons in the dentate gyrus. It remains a possibility that some unspecified change – a “third variable” – brought about by EE and/or Vex could be a causal determinant of both NG and L&M. We suggest that this third variable could be neurotrophic and/or plasticity-related factors such as BDNF. Indeed, both EE and Vex can induce expression of such proteins, and BDNF in particular has long been linked with L&M. In addition, we argue that a very likely source of variation in previous experiments was the load on “pattern separation”, a process that keeps similar memories distinct, and in which NG has been shown to be critically involved. To attempt to bring these ideas together, we present preliminary evidence that BDNF is also required for pattern separation, which strengthens the case for BDNF as a candidate third variable. Other ways in which BDNF might be involved are also discussed. © 2011 Elsevier Ltd. All rights reserved.
Therapy of atrial arrhythmias by temperature-controlled radiofrequency ablation

Summary form only received: Atrial fibrillation is the most prevalent arrhythmia in the world occurring in 0.4% of the general population and 2 to 5% of the patients over the age of 60. Although generally not considered dangerous arrhythmia, atrial fibrillation can cause significant morbidity due to its associated symptoms of palpitations and its thrombo-embolic complications, including stroke. For that reason, a variety of strategies have been pursued to suppress or eliminate atrial fibrillation. It has been demonstrated surgically that long linear regions of block (in these cases created with surgeon's scalpel) can prevent the "critical mass" of atrium required for re-entrant rhythms to occur. It has been the goal of this investigator to try and emulate the surgical maze operation by creating long linear lesions in the atria.
In vitro trypanocidal activity of DB745B and other novel arylimidamides against Trypanosoma cruzi.

OBJECTIVES As part of a search for new therapeutic opportunities to treat chagasic patients, in vitro efficacy studies were performed to characterize the activity of five novel arylimidamides (AIAs) against Trypanosoma cruzi. METHODS The trypanocidal effect against T. cruzi was evaluated by light microscopy through the determination of IC₅₀ values. Cytotoxicity was determined by MTT assays against mouse cardiomyocytes. RESULTS Our data demonstrated the trypanocidal efficacy of these new compounds against bloodstream trypomastigotes and intracellular amastigotes, exhibiting IC₅₀ values ranging from 0.015 to 2.5 and 0.02 to0.2 μM, respectively. One of the compounds, DB745B, was also highly active against a broad panel of isolates, including those naturally resistant to benznidazole. DB745B showed higher in vitro efficacy than the reference drugs used to treat patients (benznidazole IC₅₀= 12.94 μM) and to prevent blood bank infection (gentian violet IC₅₀= 30.6 μM). CONCLUSIONS AIAs represent promising new chemical entities against T. cruzi and are also potential trypanocidal agents to prevent transfusion-associated Chagas' disease.
Self-Efficacy as a Measure of Confidence.

Self-Efficacy as a Measure of Confidence To the Editor I enjoyed reading Dr Elfenbein’s review on confidence among surgery residents.1 Elfenbein summarizes the currently available data and describes the limitations to interpreting these data. Specifically, she notes that there are a number of varying definitions of confidence that make the data difficult to interpret. She also suggests that perhaps confidence is not the appropriate construct to measure; rather, she proposes studying self-efficacy. The only data I know of on surgery residents’ selfefficacy are our own. General self-efficacy data (144 surgical residents from 1 institution, across 9 subspecialties) using the New General Self-Efficacy Scale2 suggest that, contrary to reported confidence data, residents have a reasonably high sense of general self-efficacy (mean score of 4.23 on a 5-point scale, with a validation sample of undergraduates having a mean score of 3.87 [t = 5.73, P < .001]). These data support Elfenbein’s idea that there may not be a true confidence crisis. The lack of previous self-efficacy data prohibits us, unfortunately, from making comparisons between residents’ selfefficacy now and that of those in the past. Surprisingly, Elfenbein only briefly touches on the widely noted discrepancy between confidence and competence among women.3-5 Many studies outside of medicine, and 2 of the 15 articles selected for review by Elfenbein,1 have replicated this finding and make it worthy of discussion. In our data, there was no difference in self-efficacy by gender, suggesting that measuring confidence may be associated with gender bias. Interestingly, in our data, residents’ general self-efficacy is strongly correlated with their sense of belonging (r = 0.26, P < .01) and their psychological well-being (r = 0.23, P < .01). This highlights, perhaps, Elfenbein’s suggestion that social factors are important to take into account when discussing confidence. It may be that those who find themselves in a psychologically safe environment have higher self-efficacy; it could also be that those with higher self-efficacy have better well-being and feel more like they belong. It is important to point out that domain-specific selfefficacy and general self-efficacy are different constructs. Identifying what long-term end points (related to patient care or related to physician wellness) are of interest may help determine which of these constructs is most appropriate to measure in the future. I applaud Elfenbein for casting a shadow over the idea of a confidence crisis among surgery residents. I particularly appreciate the discussion of the effect of faculty members’ nostalgia on trainees’ confidence. Hopefully, her work inspires others to further investigate the perceived, and perhaps manufactured, problem of confidence.
Regulation of peritoneal and systemic neutrophil-derived tumor necrosis factor-α release in patients with severe peritonitis: Role of tumor necrosis factor-α converting enzyme cleavage*

Objective:Polymorphonuclear neutrophil (PMN) influx and peritoneal tumor necrosis factor (TNF)-α production are key host defense mechanisms during peritonitis. The aim of this study was to explore the potential interactions between TNF-α production and TNF-α converting enzyme (TACE) expression by PMN in the blood and peritoneum of patients with severe peritonitis. Design:A prospective study. Setting:A surgical adult intensive care unit in a university hospital. Patients:A total of 29 consecutive immunocompetent patients with severe sepsis within 48 hrs of onset were enrolled and underwent laparotomy for a diffuse secondary peritonitis. Thirteen volunteers served as controls. Measurements:Blood and peritoneal fluid recovered during laparotomy were analyzed and compared for 1) soluble TNF-α, soluble L-selectin, and type I and II TNF-α receptor levels; 2) PMN membrane TNF-α, membrane L-selectin, and TACE expression (flow cytometry); and 3) TNF-α production by cultured PMN. Correlations between these forms of PMN-derived TNF-α and the severity of the peritonitis and patient’s outcome were investigated. Main Results:Elevated soluble TNF-α levels in both plasma and peritoneal fluid from the patients were found, together with decreased expression of membrane TNF-α and TACE up-regulation at the PMN surface. Soluble L-selectin and type I and II TNF receptors were highly released, suggesting also the role of TACE. In contrast, the capacity of both blood and peritoneal PMN to synthesize TNF-α in vitro, in optimal conditions of stimulation (lipopolysaccharide + interferon-γ), was impaired as compared with controls’ blood PMN. Regulation of PMN-derived TNF-α was similar in the two compartments, but responses were more pronounced in the peritoneum. TACE up-regulation at the surface of blood-derived PMN correlated with the Sequential Organ Failure Assessment score and vital outcome. Conclusion:These human data demonstrate that mTACE is up-regulated at the PMN surface during severe peritonitis. This finding could be related to a paracrine regulatory loop involving some TACE substrates such as TNF-α, L-selectin, and TNF receptors.
Structure-function relationships of CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii.

OBJECTIVES In the context of the increasing worldwide occurrence of imipenem-resistant Acinetobacter baumannii strains, we investigated a possible porin-mediated mechanism relating to the carbapenem resistance-associated outer membrane protein, CarO. The aim of this study was to determine whether this porin may be a diffusion pathway for carbapenems in A. baumannii. METHODS By analysing and comparing the sequences of CarO with protein databanks, we identified two major groups of sequences that we named CarOa and CarOb. We overproduced in Escherichia coli, extracted, purified by affinity chromatography and refolded in Triton X-100 rCarO from both groups. Their functional properties were investigated and compared by reconstitution in planar lipid bilayers. RESULTS This functional study showed that rCarOa and rCarOb exhibit identical single-channel conductances (i.e. 20 pS in 1 M KCl) and similar poor cationic selectivity. Both channels were not specific towards meropenem and glutamic acid and poorly specific towards arginine, but they presented a marked specificity towards imipenem. From the calculated binding constants, we highlight that the CarOb channel was twice as specific as the CarOa channel for this antibiotic. Moreover, the CarOa channel could facilitate ornithine diffusion when the CarOb channel would not. CONCLUSIONS We provide here the first evidence that CarO channels possess an imipenem (but not meropenem) binding site, and that their specificities depend on their primary structure. Any decrease in CarO expression would thus reduce the susceptibility of A. baumannii to this antibiotic.
Transfer of an Escherichia coli ST131 multiresistance cassette has created a Klebsiella pneumoniae-specific plasmid associated with a major nosocomial outbreak.

OBJECTIVES To characterize the complete sequence, horizontal spread and stability of the CTX-M-15-encoding multiresistance plasmid of a Klebsiella pneumoniae strain involved in a large nosocomial outbreak. METHODS The 220 kbp plasmid pUUH239.2 was completely sequenced using 454 technology. The conjugational host range, conjugation frequencies, plasmid stability and fitness cost of plasmid carriage were studied in vitro. Conjugational spread during the outbreak was assessed retrospectively by multiplex PCR screening, restriction fragment length polymorphism and PFGE. RESULTS Plasmid pUUH239.2 encodes resistance to β-lactams (bla(CTX-M-15), bla(TEM-1) and bla(OXA-1)), aminoglycosides [aac-(6')-1b-cr and aadA2], tetracyclines [tet(A) and tetR], trimethoprim (dhfrXII), sulphonamides (sul1), quaternary ammonium compounds (qacEΔ1), macrolides [mph(A)-mxr-mphR(A)] and heavy metal ions (silver, copper and arsenic). The plasmid consists of a backbone, highly similar to the K. pneumoniae plasmid pKPN3, and a 41 kbp resistance region, highly similar to the resistance regions of plasmids pEK499 and pC15-1a previously isolated from Escherichia coli strains belonging to the outbreak lineage ST131 (where ST stands for sequence type). The pUUH239.2 plasmid is stable in K. pneumoniae but unstable in E. coli and confers a fitness cost when introduced into a naive host cell. Transfer of pUUH239.2 from the outbreak K. pneumoniae clone to the E. coli of the patients' intestinal floras has occurred on multiple occasions during the outbreak. CONCLUSIONS The plasmid pUUH239.2 is a composite of the pKPN3 K. pneumoniae plasmid backbone and the bla(CTX-M-15)-encoding multiresistance cassette associated with the internationally recognized outbreak strain E. coli ST131. The resulting plasmid differs in stability between K. pneumoniae and E. coli, and this has probably limited the spread of this plasmid during the outbreak.
Medical Malpractice Lawsuits Involving Surgical Residents

Importance Medical malpractice litigation against surgical residents is rarely discussed owing to assumed legal doctrine of respondeat superior, or “let the master answer. ” Objective To better understand lawsuits targeting surgical trainees to prevent future litigation. Design, Setting, and Participants Westlaw, an online legal research database containing legal records from across the United States, was retrospectively reviewed for malpractice cases involving surgical interns, residents, or fellows from January 1, 2005, to January 1, 2015. Infant-related obstetric and ophthalmologic procedures were excluded. Exposures Involvement in a medical malpractice case. Main Outcomes and Measures Data were collected on patient demographics, case characteristics, and outcomes and were analyzed using descriptive statistics. Results During a 10-year period, 87 malpractice cases involving surgical trainees were identified. A total of 50 patients were female (57%), and 79 were 18 years of age or older (91%), with a median patient age of 44.5 years (interquartile range, 45-56 years). A total of 67 cases (77%) resulted in death or permanent disability. Most cases involved elective surgery (61 [70%]) and named a junior resident as a defendant (24 of 35 [69%]). Cases more often questioned the perioperative medical knowledge, decision making errors, and injuries (53 [61%]: preoperative, 19 of 53 [36%]) and postoperative, 34 of 53 [64%]) than intraoperative errors and injuries (43 [49%]). Junior residents were involved primarily with lawsuits related to medical decision making (21 of 24 [87%]). Residents’ failure to evaluate the patient was cited in 10 cases (12%) and lack of direct supervision by attending physicians was cited in 48 cases (55%). A total of 42 cases (48%) resulted in a jury verdict or settlement in favor of the plaintiff, with a median payout of $900 000 (range, $1852 to $32 million). Conclusions and Relevance This review of malpractice cases involving surgical residents highlights the importance of perioperative management, particularly among junior residents, and the importance of appropriate supervision by attending physicians as targets for education on litigation prevention.
Antimicrobial effect of diallyl sulphide on Campylobacter jejuni biofilms.

OBJECTIVES Bacterial biofilms pose significant food safety risks because of their attachment to fomites and food surfaces, including fresh produce surfaces. The purpose of this study was to systematically investigate the activity of selected antimicrobials on Campylobacter jejuni biofilms. METHODS C. jejuni biofilms and planktonic cells were treated with ciprofloxacin, erythromycin and diallyl sulphide and examined using infrared and Raman spectroscopies coupled with imaging analysis. RESULTS Diallyl sulphide eliminated planktonic cells and sessile cells in biofilms at a concentration that was at least 100-fold less than used for either ciprofloxacin or erythromycin on the basis of molarity. Distinct cell lysis was observed in diallyl sulphide-treated planktonic cells using immunoblot analysis and was confirmed by a rapid decrease in cellular ATP. Two phases of C. jejuni biofilm recalcitrance modes against ciprofloxacin and erythromycin were validated using vibrational spectroscopies: (i) an initial hindered adsorption into biofilm extracellular polymeric substance (EPS) and delivery of antibiotics to sessile cells within biofilms; and (ii) a different interaction between sessile cells in a biofilm compared with their planktonic counterparts. Diallyl sulphide destroyed the EPS structure of the C. jejuni biofilm, after which the sessile cells were killed in a similar manner as planktonic cells. Spectroscopic models can predict the survival of sessile cells within biofilms. CONCLUSIONS Diallyl sulphide elicits strong antimicrobial activity against planktonic and sessile C. jejuni and may have applications for reducing the prevalence of this microbe in foods, biofilm reduction and, potentially, as an alternative chemotherapeutic agent for multidrug-resistant bacterial strains.
Epidemiology of niddm in Indians

Epidemiology is the study of the distribution and determinants of disease frequency in man. The application of epidemiology to the study of non-insulin dependent diabetes mellitus (NIDDM) has provided valuable information on several aspects of this disease such as its natural history, prevalence, incidence, morbidity and mortality in diverse populations around the world. In addition, it has led to the identification of the cause of the disease and the possible preventive measures that could be instituted to arrest or delay the onset of this disease which has reached epidemic proportions in both, the developed and the developing nations [1].
High‐Throughput Assays for Assessing Mitochondrial Dysfunction Caused by Compounds that Impair mtDNA‐Encoded Protein Levels in Eukaryotic Cells

Compounds that impair the synthesis of either mitochondrial DNA (mtNDA) or mtDNA‐encoded proteins reduce the levels of 13 proteins essential for oxidative phosphorylation, leading to a decrease in mitochondrial ATP production. Toxicity caused by these compounds is seldom identified in 24 to 72 hr cytotoxicity assays due to the low turnover rates of both mtDNA and mtDNA‐encoded proteins. Here, we describe three high‐throughput screening assays that detect compounds that affect mtDNA‐encoded protein levels. All three assays measure the levels of two proteins, one a mtDNA‐encoded protein synthesized on mitochondrial ribosomes and the other, a nuclear DNA‐encoded protein synthesized on cytosolic ribosomes. The first assay measures the levels of these two proteins by quantitative image analysis and requires a high‐content imaging system. The second assay is an in‐cell immunoassay that utilizes infrared dyes for detection of the two proteins and, thus, requires a LI‐COR Odyssey system. The third assay is an in‐cell immunoassay that utilizes colorimetric detection of the two proteins and requires an absorbance microplate reader. Curr. Protoc. Toxicol. 48:3.11. 1‐3.11. 17. © 2011 by John Wiley & Sons, Inc.