Miracle-dz/UniFAR-FTUs huggingface dataset:
Does kynurenic acid act on nicotinic receptors? An assessment of the evidence

As a major metabolite of kynurenine in the oxidative metabolism of tryptophan, kynurenic acid is of considerable biological and clinical importance as an endogenous antagonist of glutamate in the central nervous system. It is most active as an antagonist at receptors sensitive to N‐methyl‐D‐aspartate (NMDA) which regulate neuronal excitability and plasticity, brain development and behaviour. It is also thought to play a causative role in hypo‐glutamatergic conditions such as schizophrenia, and a protective role in several neurodegenerative disorders, notably Huntington’s disease. An additional hypothesis, that kynurenic acid could block nicotinic receptors for acetylcholine in the central nervous system has been proposed as an alternative mechanism of action of kynurenate. However, the evidence for this alternative mechanism is highly controversial, partly because at least eight earlier studies concluded that kynurenic acid blocked NMDA receptors but not nicotinic receptors and five subsequent, independent studies designed to repeat the results have failed to do so. Many studies considered to support the alternative ‘nicotinic’ hypothesis have been based on the use of analogs of kynurenate such as 7‐chloro‐kynurenic acid, or putatively nicotinic modulators such as galantamine, but a detailed analysis of the pharmacology of these compounds suggests that the results have often been misinterpreted, especially since the pharmacology of galantamine itself has been disputed. This review examines the evidence in detail, with the conclusion that there is no confirmed, reliable evidence for an antagonist activity of kynurenic acid at nicotinic receptors. Therefore, since there is overwhelming evidence for kynurenate acting at ionotropic glutamate receptors, especially NMDAR glutamate and glycine sites, with some activity at GPR35 sites and Aryl Hydrocarbon Receptors, results with kynurenic acid should be interpreted only in terms of these confirmed sites of action.
Ten-Year Follow-Up of Clinical Governance Implementation in Primary Care: Improving Screening, Diagnosis and Control of Cardiovascular Risk Factors

Current improvement strategies for the control of cardiovascular risk factors (CRFs) in Europe are based on quality management policies. With the aim of understanding the effect of interventions delivered by primary healthcare systems, we evaluated the impact of clinical governance on cardiovascular health after ten years of implementation in Catalonia. A cohort study that included 1878 patients was conducted in 19 primary care centres (PCCs). Audits that comprised 13 cardiovascular health indicators were performed and general practitioners received periodic (annual, biannual or monthly) feedback about their clinical practice. We evaluated improvement in screening, diagnosis and control of the main CRFs and the effects of the feedback on cardiovascular risk (CR), incidence of cardiovascular disease (CVD) and mortality, comparing baseline data with data at the end of the study (after a 10-year follow-up). The impact of the intervention was assessed globally and with respect to feedback frequency. General improvement was observed in screening, percentage of diagnoses and control of CRFs. At the end of the study, few clinically significant differences in CRFs were observed between groups. However, the reduction in CR was greater in the group receiving high frequency feedback, specifically in relation to smoking and control of diabetes and cholesterol (Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL)). A protective effect of having a cardiovascular event (hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.44–0.94) or death (HR = 0.55, 95% CI = 0.35–0.88) was observed in patients from centres where general practitioners received high frequency feedback. Additionally, these PCCs presented improved cardiovascular health indicators and lower incidence and mortality by CVD, illustrating the impact of this intervention.
Proteinuria and Everolimus. The Relevance of Knowing Urinary Sodium Excretion in a Kidney Transplant Patient

A sixty-four year old male with a seven-year history of kidney transplantation started with increasing amounts of proteinuria. His maintenance immunosuppression consisted on meprednisone 4 mg/day, sodium mycophenolate 720 mg/day and everolimus 1.5 mg/day for the last three years. Two years after being on this regime, he started to display increasing amounts of proteinuria and no hematuria, while his kidney function remained steady and his blood pressure was normal. A Doppler sonogram was normal; antiHLA antibodies were negative and a kidney biopsy revealed mild mesangial expansion and 15% of interstitial fibrosis and tubular atrophy; C4d stain was negative. Twenty four urinary sodium was 385mEq/day. He was started on a 3 g sodium/day diet. Two months later urinary sodium excretion dropped to77 mEq/day and proteinuria decreased from a maximum of 3.85 g/day to 0.7 g/day. At first glance, the initial approach to reduce proteinuria would have been to withdraw everolimus, as it is a well-known cause of proteinuria. This case report underscores the relevance sodium tubular reabsorption plays on proteinuria and on glomerular filtration, showing that urinary ionograms are mandatory when the assessment of proteinuria is undertaken. It also calls the attention of nephrologists to pursue proteinuria and to treat it accordingly in the transplant population, as it is a cardiovascular risk factor and a surrogate of chronic kidney disease and of kidney disease progression.
Current and future perspectives on intracytoplasmic sperm injection: a critical

Intracytoplasmic sperm injection (ICSI) is an increasingly popular means of treating infertility in couples who wish to conceive. However, there are many potential complications that can be faced by the clinician while performing ICSI. These complications and other related issues are discussed, with an emphasis on understanding how these issues are being resolved, or how they can be resolved in the future. Matters of sperm selection and injection are discussed, as well as the effect of ICSI on fertilization, embryonic growth and development, and the health of ICSI-conceived children. These aspects are viewed from various perspectives, including genetic, mechanistic, developmental and clinical. Since new studies on ICSI are published regularly, it is important that the established protocol is revised often, and that the role of ICSI in infertility therapy is continually re-evaluated.
Interferon-?reduces Ia4 dendriticcell trafficto the lung

MHC class II' lung dendritic cells (DC) increase in number following treatment of animals with interferon-y (IFN-y) (Kradin et a! . (1991) Am. J, Resp. Mol. Biol. 4,210; Gonget al. (1992)J. Exp. Med. 175, 797). To test whether this is due to increased sequestration and/or trafficking of DC to the lung, bone marrow DC from BALB/c mice were obtained by culturing bone marrow with granulo- cyte-macrophage colony-stimulating factor (GM- CSF). Recipient BALB/c mice were injected intraperitoneally (i.p.) for 4 days with one of the following: IFN-'y, dexamethasone (Dex), or phos- phate-buffered saline (PBS). Twenty-four hours af- ter the last dose, they were injected intravenously (i.v.) with carboxyfluorescein (Fl) -labeled DC (1 x 106/mouse) and killed 4 h later. DC, double immu- nostained for La and Fl, were quantified by mor- phometry in frozen sections of lung. The number of injected dual-labeled DC/cm2 was reduced by 90% in IFN. 'y-treated mice. By contrast, there- was no significant difference between Dex- and PBS-treated animals in the number of double-labeled DC retained in pulmonary capillaries. Biodistribution and imag- ing studies were conducted on IFN-T- and PBS- treated mice using 1111n-labeled DC. Reduced radioactivity in the lung was accounted for by an equivalent increase in the liver of IFN-y-treated mice; imaging studies confirmed these observations. Removal of >80% of alveolar macrophages (AM) by pretreatment with intratracheally administered chlo- dronate-loaded liposomes did not change the biodis- tribution of DC in IFN-y- and PBS-injected mice. Serum levels of tumor necrosis factor-a (TNF-a) and nitrite/nitrate in IFN-'y-treated mice were similar to those of controls. Inununostaining for inducible m- tric oxide synthase (iNOS), however, revealed a 1.5- and 6-fold increase in the number of positively stained cells in the lung and liver, respectively, of IFN-'y-treated mice; the number of iNOS-expressing cells was markedly reduced in Dex-treated animals relative to controls. To test whether the systemic treatment with IFN-y stimulated the cytotoxic activity of Kupifer cells, mice were injected with chiodronate liposomes 5 days before death. After treating the mice in the ensuing 4 days with IFN-y or PBS, biodistribution and imaging studies with mInla. beled DC were conducted on the 5th day. After administration of chlodronate liposomes, there was a significant increase in the radioactivity detected in the lungs of IFN-y-injected mice but not in those of PBS- injected controls, a finding confirmed by im- aging studies. We conclude that IFN-'y treatment augmented Kupffer cell cytotoxic activity, which, in turn, effectively reduced the number of injected DC in circulation, with the result that fewer of these cells were retained in the lung vasculature. We further conclude that IFN-yincreases the number of Ialung DC by up-regulating La expression of resident Ia DC precursors and not by promoting the migration of circulating DC to the lung. J. Leukoc. Biol. 60: 519-527; 1996.
Individual cognitive remediation therapy benefits for patients with anorexia nervosa and high autistic features

Abstract Cognitive remediation therapy (CRT) is an increasingly implemented intervention in psychiatric conditions. The majority of randomized treatment trials in psychiatry reports cognitive improvements resulting in better functional outcomes in CRT groups. This brief report from the national inpatient treatment programme for eating disorders demonstrates cognitive performance task–based improvements in patients with high and low autistic characteristics. This preliminary study shows feasibility and benefits of individual CRT in patients who have autism spectrum disorder features.
Double spleen in Baladi goat in Beni-Suef governorate -Egypt: case report

The report of the occurrence of accessory spleen in domestic animals is rare in the literatures. We report a case of an accessory spleen in Baladi goat. Accessory spleen was present near the cranial groove of the rumen on the ventral ruminal sac. It was supplied by accessory splenic artery which originated from the splenic artery after giving off the epiploic branch.
Influence of Genetics and Gender in Takotsubo Syndrome: Unexplored Areas of an Incompletely Understood Disease

Stress cardiomyopathy, also known as “Takotsubo syndrome” (TS), is a complex disease that typically affects postmenopausal women. The pathophysiology is still largely unknown, but evidence of a frequent association between TS and stressful events has evoked the hypothesis of a pathophysiologic role of sympathetic overdrive in the myocardial dysfunction. However, despite several studies, the role gender plays in TS onset remains unclear because stress cardiomyopathy also has been described in young women and in men. Moreover, although several cases of a familial cluster of TS have been reported, no responsible gene mutations or polymorphisms have been clearly identified so far, and neither the modality of transmission or the true impact of genetic background. In this review, we discuss the role of gender in the onset, course, and outcomes of TS and we report the available data about polymorphisms and gene mutations so far investigated, trying to critically analyze the evidence reported in the literature.
Sweat Loss and Fluid Intake of Female Varsity Ice Hockey Players During On-Ice Practices and Games.

Bigg, JL, Gamble, ASD, Vermeulen, TF, Bigg, LM, and Spriet, LL. Sweat loss and fluid intake of female varsity ice hockey players during on-ice practices and games. J Strength Cond Res XX(X): 000-000, 2019-Sweat losses of ∼1.5-2% body mass (BM) during exercise impairs athletic performance in stop and go sports such as ice hockey. The study examined the pre-exercise hydration status, sweat loss, fluid and carbohydrate (CHO) intake, and sodium balance of female hockey players. Twenty-four female varsity hockey players were tested during 2 practices and 4 games. Data analyses were performed using a level of significance of p ≤ 0.05. Over 70% of players arrived at the practices and ∼50% of players arrived at the game mildly dehydrated. Before the high- (P1) and low-intensity (P2) practices, players consumed an average of 0.19 ± 0.14 and 0.15 ± 0.13 L. Before the games, mean fluid intake was 0.39 ± 0.19 L. The sweat rate during P1 was significantly greater than P2 (p = 0.006), but there was no significant difference in total fluid intake between practices (p = 0.279). Consequently, the average BM loss for P1 was significantly greater than that for P2 (p = 0.016). Sweat loss during games was 1.01 ± 0.29 L and fluid intake was 0.70 ± 0.43 L, resulting in minimal BM losses (<1% BM for all players). CHO intake during games was 39.2 ± 22.8 g, with 19/20 players consuming CHO before or during the intermissions of the game. Sweat sodium losses were 0.64 ± 0.34 and 0.32 ± 0.18 g·h for P1 and P2, and 0.83 ± 0.38 g during the game. In conclusion, female ice hockey players replaced the fluid they lost through sweat during practices and games and maintained adequate hydration. Players also consumed adequate CHO during games from the CHO containing food and drinks provided.
Daytime and nighttime correlates of fatigue and lack of energy in adults living with HIV

Objective To describe correlates of fatigue and lack of energy symptoms in adults living with HIV. Methods Adults living with HIV were recruited if they were ≥45 years old, unemployed, and reported either fatigue or lack of energy in the past week. HIV-associated correlates included CD4 cell count, viral load, and hemoglobin. Daytime correlates included physical activity, daytime sleepiness, napping behavior, and symptoms of anxiety and depression. Nighttime correlates included use of sleep medication, sleep duration, and sleep quality. Outcomes included physical and cognitive function. Results Most (70%) of the 53 participants were male. The mean age was 56.7 ± 6.7 years and participants had been living with HIV for a mean of 22 ± 6.4 years. Controlling for all other factors, African Americans reported less fatigue and more energy than other racial/ethnic groups. Lack of energy was associated with daytime napping and cognitive function. Fatigue was associated with shorter nighttime sleep duration, anxiety, and both physical and cognitive function. Discussion Findings highlight potential differences between lack of energy and fatigue that could influence intervention outcomes. Avoiding daytime naps and encouraging longer nighttime sleep may improve fatigue as well as physical and cognitive function in this chronic illness population.
PREVALENCE OF SICKLE CELL DISORDER IN RURAL PIPALWADA, GUJARAT

Sickle cell disorder has remained a neglected field of research in our country. The present study was started in rural population of Gujarat to find out the magnitude of sickle cell disorders. 395 subjects were studied. The prevalence of sickle cell trait was found to be 7.86 %. Through this study, we created awareness among people about the disorders. The villagers were explained about its’ hereditary nature and that no curative treatment is available, although it can be prevented through marriage counseling. It is necessary to continue with such activities since prevention appears to be the only solution in present circumstances.
The relationship between tyramine levels and inflammation in metabolic syndrome

Abstract Background Metabolic syndrome (MetS) is an important contributor to both type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Although MetS affects one third of American adults, its pathogenesis remains to be elucidated. Tyramine, a derivative of tyrosine, has been shown to act as a catecholamine releasing agent in the human body. The aim of this study is to investigate the role of tyramine as an early biomarker for nascent MetS without the confounding of T2DM, ASCVD or smoking. Patients and methods This was an exploratory study of 28 patients with nascent MetS and 20 matched controls carried out in 2018. Metabolites were evaluated from patient’s frozen early morning urine samples and were correlated with biomarkers of inflammation and adipokines. They were assayed by the National Institutes of Health (NIH) Western Metabolomics Center using liquid chromatography/mass spectrometry (LC/MS) and standardized to urinary creatinine. All patients had normal hepatic and renal function. Results Tyramine concentrations were significantly reduced in patients with MetS compared to controls, p = 0.0009. In addition, tyramine was significantly inversely correlated with multiple biomarkers of inflammation and cardiometabolic risk factors such as RBP4, monocyte TLR-4 abundance and P38MAPKinase activity, body mass index (BMI) and blood pressure (BP) (both systolic and diastolic). Conclusion In conclusion, low levels of tyramine could contribute to the proinflammatorty state of MetS.
Test–retest characteristic of [18F]MK-6240 quantitative outcomes in cognitively normal adults and subjects with Alzheimer’s disease

[18F]MK-6240 is a selective, high-affinity PET radiotracer for imaging neurofibrillary tangles (NFT) in Alzheimer’s disease (AD). Herein, we report test–retest (T–RT) reproducibility of [18F]MK-6240 in AD and healthy volunteers (HV). Twelve subjects with AD and three cognitively normal HV were enrolled in the study and dynamically scanned for 150 min with [18F]MK-6240 under a T–RT protocol. Two radioactivity doses were investigated: 165 ± 3 MBq (n = 6) and 300 ± 40 MBq (n = 9). Serial arterial blood samples were taken for each scan to obtain metabolite-corrected input functions. Following intravenous administration of [18F]MK-6240, the tracer rapidly partitioned into the brain and its heterogenous distribution pattern was consistent with known NFT pathology in AD. In contrast, uptake in HV was low and uniform across the brain parenchyma. Across all subjects, average T–RT variabilities in NFT-rich regions were ∼21%, ∼14% and ∼6% for various quantitative metrics: total distribution volume (VT), binding potential (BPND), and standardized uptake ratio (SUVR90–120), respectively. No significant differences in SUVR T–RT variability were observed between the high and low injected radioactivity groups (5.6% and 6.1%, respectively). This work suggests [18F]MK-6240 has adequate SUVR T–RT characteristics supporting the use of this outcome in future studies.
Ultrasound‐guided fine‐needle aspiration of a rectal submucosal nodule

Although endoscopic biopsy of a rectal submucosal nodule may be nondiagnostic, endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) can be an important tool to make diagnosis. We report a case of a female patient who had an EUS‐FNA of a submucosal nodule after a nondiagnostic rectal biopsy. The original diagnosis was erroneously rendered as concerning for necrotic neoplasm. The correct diagnosis of Solesta‐induced foreign body reaction was made on reviewing the slides once the history of remote Solesta injection was made available. This case illustrates the pathognomonic features of Solesta‐induced rectal nodule and underscores the importance of detailed history as well as inclusion of iatrogenic diseases in the differential to prevent erroneous diagnosis and management. Potential pitfalls in cytopathological diagnosis are discussed.
Comment on Ågren et al. Increased Incorporation of Antiplasmin Into the Fibrin Network in Patients With Type 1 Diabetes. Diabetes Care 2014;37:2007–2014

Antiplasmin (α2-antiplasmin or plasmin inhibitor) is the main physiological inhibitor of plasmin and efficiently attenuates fibrin clot lysis after being cross-linked to fibrin by the action of activated factor XIII (FXIIIa). Agren et al. (1) recently demonstrated that the fibrin network of plasma clots from patients with type 1 diabetes contains more antiplasmin than the fibrin network of plasma clots from control subjects. This is an interesting finding, as increased clot resistance to fibrinolysis might contribute to cardiovascular disease frequently associated with diabetes. The authors used a new, still unpublished method for the determination of the incorporation of antiplasmin …
CLINICO-MYCOLOGICAL PROFILE OF DERMATOPHYTIC INFECTIONS

The common cause of skin infections are dermatophytes and opportunistic fungi. The prevalence of dermatophyte infection varies with different geographic area and climatic conditions. This study was undertaken to study the clinical pattern and the etiological agents of dermatophyte infections. Clinical samples from 100 patients were subjected to microscopic examination and culture on various media. In total 100 specimens collected, 54 were skin scrapings, 39 were hair samples and 7 were nail clippings. Direct microscopy revealed fungal elements in 65% of the cases, of these 50(77%) were culture positive and 15(23%) was culture negative. No fungal elements were observed in KOH mount in 35% of the cases, of these 5 (14%) yielded growth of fungi and 30(86%) were culture negative. Among the 55 fungal isolates, 49 were dermatophytes.The predominant isolate from all samples were Trichophyton mentagrophytes (33%). The study signifies the importance of mycological examination in the diagnosis of various mycoses for their effective management.
Interlimb coupling in poststroke rehabilitation: a pilot randomized controlled trial

ABSTRACT Background: The interlimb coupling, coordination between the limbs, gets hampered in post-stroke hemiparesis. Most of the poststroke motor regimes primarily focus on the more affected limb. Objectives: To develop an interlimb coupling protocol and assess its feasibility and effect on motor recovery, gait and disability among post-stroke subjects. Design: A pilot randomized controlled, doubled blinded trial Setting: A rehabilitation institute Methods: 50 post-stroke (> 6 months) hemiparetic subjects (Brunnstrom recovery stage ≥ 3) were randomly divided into experimental (n=26) and control (n=24) groups. The 8-week experimental intervention (3 sessions of 1 hour each, per week) comprised activities demanding coordinated, alternate, and rhythmic use of the affected as well as the less-affected limbs. The outcome measures were feasibility of activities, Fugl-Meyer assessment (FMA), Rivermead visual gait assessment (RVGA), Functional ambulation category (FAC) and modified Rankin scale (mRS). Results: The experimental protocol was found to be feasible by the participants. Post intervention, the experimental group exhibited highly significant difference for FMA (mean difference = 7.12, 95% CI = 5.71 – 8.53, p < 0.001), RVGA reduction (mean difference = - 6.32, 95% CI = 7.51 – 5.13, p < 0.001), and median FAC enhancement (p < 0.001) in comparison to the controls. However, the median mRS level of experimental group did not change significantly (p = 0.056) when compared with the controls. Conclusions: The interlimb coupling training, a feasible program may enhance recovery of the upper and lower limbs and gait in stroke. Further definitive randomized trials are warranted to validate the present findings.