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Objective: The Impella 5.5 (Abiomed, Inc), a surgically implanted endovascular microaxial left ventricular assist device, is increasingly used worldwide and there have been more than 10,000 implants. The purpose of this study is to describe a large-volume, single-center experience with the use of the Impella 5.5. Methods: Data were obtained retrospectively from patients supported with the Impella 5.5 implanted at our institution from May 1, 2020, to December 31, 2022. Demographic, operative, and postoperative outcomes for each group are described. Results are reported in median (interquartile range) or n (%). The entire cohort was divided into 5 main groups based on the intention to treat at the time of the Impella 5.5 implantation: (1) patients who had a planned Impella 5.5 implanted at the time of high-risk cardiac surgery; (2) patients with cardiogenic shock; (3) patients bridged to a durable left ventricular assist device; (4) patients bridged to transplant; and (5) patients with postcardiotomy shock who received an unplanned Impella 5.5 implant. Results: A total of 126 patients were supported with the Impella 5.5. Overall survival to device explant was 76.2%, with 67.5% surviving to discharge. Midterm survival was assessed with a median follow-up time of 318 days and demonstrated an overall survival of 60.3% and a median of 650 days (549-752). Conclusions: Outcomes after using the Impella 5.5 are variable depending on the indication of use. Patient selection may be of utmost importance and requires further experience with this device to determine who will benefit from insertion.
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The alfalfa weevil (Hypera postica Gyllenhal (Coleoptera: Curculionidae)), a key pest of alfalfa (Medicago sativa L. (Fabales: Fabacae)) across the US, has developed resistance to pyrethroids lambda-cyhalothrin and zeta-cypermethrin in at least 6 western US states. Unfortunately, 6 pyrethroid active ingredients represent most commercial insecticides registered for alfalfa weevil control in forage alfalfa systems. Thus, the loss of efficacy of this mode of action group due to multiple resistance represents a significant agricultural challenge because of a limited registered alternative mode of actions. To evaluate the extent and severity of resistance among pyrethroids around the United States, laboratory bioassays using larvae from Arizona, California, Montana, Oregon, Washington, and Wyoming, including both the Egyptian and western strains, were conducted. Results indicated that similar degrees of resistance among type II pyrethroids as determined by both laboratory bioassays and field trials exist. The LC50 values of alpha-cypermethrin, beta-cyfluthrin and zeta-cypermethrin produced significant correlations with the LC50 values of lambda-cyhalothrin. In contrast, resistance did not include type I pyrethroid, bifenthrin (registered for seed alfalfa production), whose LC50 values yielded a slope not significantly different from zero when correlated with lambda-cyhalothrin. Field trials conducted in Arizona, Montana, and Washington corroborated laboratory results, as commercial formulations with type II pyrethroid active ingredients failed to adequately control alfalfa weevils resistant to lambda-cyhalothrin. Integrated resistance management recommendations are discussed.
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Escarabajos , Insecticidas , Nitrilos , Piretrinas , Gorgojos , Animales , Insecticidas/farmacología , Medicago sativa , Arizona , Resistencia a los InsecticidasRESUMEN
Objective: Even though severe tricuspid regurgitation is not uncommon after cardiac transplantation, primary severe tricuspid regurgitation is rare. We present such a case with additional complexities. Methods: The patient was 44-year-old man with a HeartWare durable left ventricular assist device (Heartware Inc) who received a temporary right ventricular assist device (RVAD) with a ProtekDuo cannula (LivaNova Inc USA) for refractory ventricular fibrillation and underwent a heart transplant as United Network for Organ Sharing Status 1, in the presence of partially compensated cardiogenic shock, renal failure. Given complex re-operative surgery in a volume-overloaded patient with unknown pulmonary vascular resistance, an RVAD cannula was preserved and re- inserted during cardiac transplant. Postoperatively he required hemodialysis, had severe primary tricuspid regurgitation discovered after RVAD removal and developed Enterobacter mediastinitis. He underwent complex tricuspid valve repair for flail tricuspid leaflet due to ruptured papillary muscle likely due to RVAD cannula injury, after multiple mediastinal washouts and was followed by delayed chest reconstruction. Results: The patient is doing well, 6 months after discharge to home, asymptomatic, without re-admissions, on renal recovery path, with no tricuspid regurgitation and good biventricular function. Conclusions: Replacing the tricuspid valve in presence of hemodialysis catheter, immunosuppression and mediastinitis could be high risk for endocarditis. Even though we have short-term follow-up, tricuspid valve repair can be an effective way of managing primary severe regurgitation especially when there is a desire or need to avoid valve replacement.
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PURPOSE: This systematic review explored dental complications associated with metal ion release from oral piercings using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. METHODS: Item retrieval from October 2022 to December 2022 from databases, such as Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, Scopus and Web of Science, using predefined search terms was undertaken by two independent reviewers. Data were extracted and risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. From 1509 identified studies, 25 were included for analysis. RESULTS: Of the 25 studies, 20 included both clinical examination and questionnaire-based data. The remaining five studies were deemed low quality based on the Joanna Briggs Institute criteria. The average time piercings were worn ranged between 5 and 48 months. Most studies did not investigate complications from metal ion release. Only two studies examined the direct effects of metal ion release and showed that metal ions may cause hypersensitivity reactions and mucosal changes. Other soft tissue complications were reported, with gingival recession noted in 16 out of 25 studies, especially due to lip piercings. Studies reporting other complications were as follows: swelling (9), pain (8), infection (6), bleeding (6), inflammation (5), alterations to speech, eating and/or swallowing (5), changes to taste or metallic taste (5), and mucosal changes (4). Ten studies reported tooth chipping from tongue piercings. CONCLUSION: Oral piercings leach metal ions into surrounding tissues which may cause local mucosal changes. Furthermore, oral piercings cause damage to both soft and hard oral tissues, particularly gingival recession for lip piercings and tooth chipping for tongue piercings. Thus, to prevent such adverse injuries, dental professionals should discourage patients against oral piercings.
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Recesión Gingival , Humanos , Recesión Gingival/etiología , Lengua/lesiones , Labio/lesiones , IonesRESUMEN
OBJECTIVES: This laboratory-based study measured ion release from metallic piercings when exposed to organic acids (lactic, citric) and inorganic acids (phosphoric, hydrochloric) that could be encountered in the oral cavity. METHODS: Barbell and ring oral piercings composed of stainless steel, titanium or gold-plated titanium were submerged in 2 mL volumes of 0.1% lactic acid, 10% citric acid, 0.2% phosphoric acid, and 0.1% hydrochloric acid for 7 and 34 days. Ion release into the liquid was measured using inductively coupled plasma optical emission spectroscopy (ICPOES) and expressed in relationship to surface area. Surface changes from baseline were assessed using light and backscatter scanning electron microscopy (SEM). RESULTS: ICPOES results showed that hydrochloric and phosphoric acid caused the greatest release of material per surface area. Released elements included (ranked highest to lowest): Fe, P, Ti, Na, Cr, S, Ni, Ca, Mg, K, Si, Al, V, Mn, Ba, and Co. SEM imaging identified qualitative surface changes consistent with corrosion, for most piercing types examined. CONCLUSIONS: Under the exposure conditions used, inorganic acids cause greater metal dissolution than organic acids. Inorganic acids could therefore pose a risk of corrosion and leaching of ions from metallic oral piercings.
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Acero Inoxidable , Titanio , Humanos , Titanio/química , Microscopía Electrónica de Rastreo , Acero Inoxidable/química , Iones , Ácidos Fosfóricos , Corrosión , Propiedades de Superficie , Ensayo de MaterialesRESUMEN
OBJECTIVES: To determine the prevalence of antibiotic use by pregnant women in Najran, Saudi Arabia. METHODS: A total of 125 women aged 18 to 45 with a full-term pregnancy participated from October to December 2019. Age, order of current pregnancy, body mass index (BMI), history of miscarriage, and comorbidity were used to estimate antibiotic use. RESULTS: The majority were Saudis (67.2%), aged 30-35 (39.2%) years, with no history of miscarriage (53.6%), second order of pregnancy (26.4%), and going through weeks 20-25 of pregnancy (21.6%). A total of 26.4% of pregnant women had antibiotic prescriptions in the study population. Pregnant women under 30 years were less likely to receive antibiotics. CONCLUSION: The results found an association between maternal age, order of pregnancy and antibiotic use during pregnancy. An association was observed between maternal BMI and the occurrence of adverse drug reactions after antibiotic use. In addition, a history of miscarriage was negatively associated with the use of antibiotics during pregnancy. These predictors of antibiotic administration have the potential to serve as general health indicators and to direct preventative strategies aimed at increasing the rational use of antibiotics.
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Aborto Espontáneo , Mujeres Embarazadas , Femenino , Embarazo , Humanos , Antibacterianos/efectos adversos , Arabia Saudita/epidemiología , Aborto Espontáneo/epidemiología , HospitalesRESUMEN
Background: Vaccines have been widely exploited to prevent tick-borne infections in cattle. Most vaccines have faced failure in the field because of inconsistency in an immune response. It is presumed that the cement-cone proteins of ticks that participate in the acquisition of blood meal for ticks possess strong immune-stimulating properties and, hence, could be a useful candidate in vaccine development. Aims: We evaluated cement-cone proteins of tick Hyalomma anatolicum as a vaccine candidate against infestations of H. anatolicum and H. aegyptium in cattle. Methods: The cement-cone proteins were extracted from H. anatolicum to develop stage-reactive and immunogenic cross-reactive vaccine against the infestation of two species of ticks H. anatolicum and H. aegyptium. The immune response of the vaccine was tested against cement-cone proteins starved, partially fed, and richly fed ticks. Results: The findings of the present study demonstrated the cross-reactivity among the two species of ticks that belonged to the same genus (Hyalomma). The antigenic similarity between the two ticks species suggests that a common antigen may possibly be suitable for a vaccine against the two different species of ticks. The results have also indicated that the 23 kDa cement-cone protein of H. anatolicum and H. aegyptium may be responsible for the induction, or elicitation of immunogenic, common stage reactive, and cross-reactive host immune responses with consistent intensity throughout the life stages of ticks. Conclusion: The vaccine based upon cement-cone proteins of ticks may be a useful deterrent against tick-borne infections in cattle in countries like Pakistan.
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BACKGROUND: Single balloon enteroscopy (SBE) allows ease of access for small bowel visualization and has multiple diagnostic and therapeutic indications. It provides the advantage of performing various therapeutic interventions alongside the diagnostic procedure. SBE has also been considered a relatively safe procedure with no major complications. AIM: To investigate the indications, safety, and clinical yield of SBE, and determine its effect on disease outcome. METHODS: A retrospective, descriptive study was conducted at a tertiary care hospital in Karachi, Pakistan. Medical records of 56 adult patients (≥ 18 years) who underwent SBE between July 2013 and December 2021 were reviewed and data were collected using a structured proforma. A descriptive analysis of the variables was performed using Statistical Package of Social Sciences Version 19. Results are reported as the mean ± SD for quantitative variables and numbers and percentages for qualitative variables. Missing data are reported as unknown. RESULTS: A total of 56 patients who underwent 61 SBE procedures were included. The mean age was 50.93 ± 16.16 years, with 53.6% of them being males. Hypertension (39.3%) and diabetes mellitus (25.0%) were the most common pre-existing comorbidities. Obscure gastrointestinal bleed (39.3%) was the most common indication for enteroscopy, followed by chronic diarrhea (19.7%) and unexplained anemia (16.4%). The majority of procedures were performed in the endoscopy suite (90.2%) under monitored anaesthesia care (93.4%). Most procedures were diagnostic (91.8%) and completed without complications (95.1%). The depth of examination ranged from 95 cm to 500 cm with a mean of 282.05 ± 90.04 cm. The most common findings were inflammation and ulcerations (29.5%), followed by masses (19.7%) and vascular malformations (14.8%). As a result of the findings, a new diagnosis was made in 47.5% of the cases and a previous one was ruled out in 24.6% of them; 65.6% of the cases had a change in management. CONCLUSION: SBE is a suitable modality for investigating diseases in the small bowel. It is shown to be technically efficient and reasonably safe and is associated with high diagnostic and therapeutic yield.
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BACKGROUND: Surgical mechanical ventricular assistance and cardiac replacement therapies, although life-saving in many heart failure (HF) patients, remain high-risk. Despite this, the difficulty in timely identification of medical therapy nonresponders and the dire consequences of nonresponse have fueled early, less selective surgical referral. Patients who would have ultimately responded to medical therapy are therefore subjected to the risk and life disruption of surgical therapy. OBJECTIVES: The purpose of this study was to develop deep learning models based upon commonly-available electronic health record (EHR) variables to assist clinicians in the timely and accurate identification of HF medical therapy nonresponders. METHODS: The study cohort consisted of all patients (age 18 to 90 years) admitted to a single tertiary care institution from January 2009 through December 2018, with International Classification of Disease HF diagnostic coding. Ensemble deep learning models employing time-series and densely-connected networks were developed from standard EHR data. The positive class included all observations resulting in severe progression (death from any cause or referral for HF surgical intervention) within 1 year. RESULTS: A total of 79,850 distinct admissions from 52,265 HF patients met observation criteria and contributed >350 million EHR datapoints for model training, validation, and testing. A total of 20% of model observations fit positive class criteria. The model C-statistic was 0.91. CONCLUSIONS: The demonstrated accuracy of EHR-based deep learning model prediction of 1-year all-cause death or referral for HF surgical therapy supports clinical relevance. EHR-based deep learning models have considerable potential to assist HF clinicians in improving the application of advanced HF surgical therapy in medical therapy nonresponders.
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Aprendizaje Profundo , Insuficiencia Cardíaca , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Registros Electrónicos de Salud , Insuficiencia Cardíaca/diagnóstico , Hospitalización , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Background The COVID-19 pandemic continues to devastate communities all over the world. The aim of this study was to evaluate the efficacy and safety of the test agent as a prophylaxis against SARS-CoV-2 infection in a population of high-risk healthcare workers. Methods The study was a multi-centre, prospective, double blind, randomized, placebo-controlled trial. Key eligibility criteria included absence of significant co-morbidity and no previous SARS-CoV-2 infection or vaccination. Participants were randomised to either the active agent nasal spray or placebo using computer generated random number tables. The nasal spray was administered 3 times daily over a 45 day course. The primary end point was the percentage of subjects who tested positive for IgGS (anti-spike, immunoglobulin G specific to the spike protein of SARS-CoV-2) at day 45. Results Between 16th April 2021 and 26th July 2021, 556 participants were analysed for the primary endpoint (275 Test; 281 Placebo). The test agent significantly reduced SARS-CoV-2 infection compared to placebo [36 cases (13.1%) Vs 97 cases (34.5%); OR 0.29 (95% CI; 0.18-0.45), p < 0.0001]. Fewer clinical symptoms were also seen in the test group [57 cases (17.6%) vs 112 cases (34.6%); OR 0.40, (95% CI; 0.27-0.59), p < 0.0001]. No harmful effects were associated with taking the test agent. Conclusion The test agent significantly reduced SARS-CoV-2 infection in healthcare workers, with 62% fewer infections when compared to placebo. It was found to be safe and well tolerated and offers a novel treatment option for prophylaxis against SARS-CoV-2 infection.
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COVID-19 , COVID-19/prevención & control , Humanos , Rociadores Nasales , Pandemias/prevención & control , Estudios Prospectivos , SARS-CoV-2RESUMEN
Androgens are endogenous hormones that play a crucial role in the paracrine and intracrine hormone system to perform and maintain vital physiological functions. Altered levels of androgens are implicated in many diseases such as sexual dysregulation, breast cancer, prostate cancer, and heart diseases etc. In this manuscript we describe a liquid chromatography-mass spectrometry (LC-MS) method using multiple reaction monitoring (MRM) for quantitatively measuring specific androgens such as dehydroepiandrosterone, testosterone, androsterone sulphate, androstenedione, and dihydrotestosterone in serum and urine samples. Serum acquired from nine different subjects (three pre-menopausal women, three postmenopausal women, and three healthy males) were used to evaluate the developed methods. In the sample preparation methods for serum either protein precipitation or liquid-liquid extraction (LLE) was used while the analysis of urinary androgens used LLE. The extracted androgens were quantitatively measured using LC-MRM-MS to which known amounts of stable isotope labeled standards were added. This manuscript also presents a LC-MRM-MS method mode for the analysis of oxime derivatized androgens potentially to enhance the sensitivity of the assay if required, from urine and venous-drawn serum samples.
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Andrógenos , Espectrometría de Masas en Tándem , Androstenodiona , Cromatografía Liquida/métodos , Femenino , Humanos , Masculino , Posmenopausia , Espectrometría de Masas en Tándem/métodos , TestosteronaRESUMEN
Colorectal cancer (CRC) is the third leading type of adult cancer in both genders with high morbidity and mortality worldwide. Even though the discovery of many antineoplastic drugs for CRC, the current therapy is not adequately efficient.This study was designed to investigate the effect and mechanism of Piclamilast (PIC), a selective PDE4 inhibitor, on a DMH-induced colorectal cancer (CRC) rat model. The rats were grouped (n = 10) into group 1 (control), group 2 (PIC 3 mg/kg, p.o.), groups 3-5 received DMH (20 mg/kg/week, S.C.), and groups 4 and 5 received PIC (1 and 3 mg/kg/day, p.o.) for 15 weeks. The DMH treatment increased aberrant crypt foci (ACF), Proliferating cell nuclear antigen (PCNA), and TBARS levels, along with decreased antioxidant defenses (GSH, GSH-Px, and catalase). Increased NF-κß expression and inflammatory cytokines were also evident. PIC dose-dependently reduced ACF and restored oxidative stress and inflammatory markers favorably. Moreover, PIC in its large, tested dose only significantly increased the intracellular level of cAMP and suppressed the activation of Ras and PI3K and its downstream Akt/mTOR signaling. Furthermore, PIC promoted CRC apoptosis, and increased the gene expression of the apoptotic factors, caspase-3 and Bax, and decreased the anti-apoptotic factor Bcl-2. The results of this study show that PIC may be a promising therapeutic agent for the treatment of CRC. PIC might inhibit the proliferation of CRC cells and induce apoptosis via multiple mechanisms that involve its antioxidant effect and inhibition of NF-κß and Ras/PI3K/Akt/mTOR signaling.
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1,2-Dimetilhidrazina/antagonistas & inhibidores , 1,2-Dimetilhidrazina/toxicidad , Benzamidas/farmacología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Inhibidores de Fosfodiesterasa 4/farmacología , Piridinas/farmacología , Focos de Criptas Aberrantes/tratamiento farmacológico , Focos de Criptas Aberrantes/metabolismo , Focos de Criptas Aberrantes/patología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/inducido químicamente , Modelos Animales de Enfermedad , Masculino , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas ras/metabolismoRESUMEN
Urine drug testing (UDT) is an important analytical/bio-analytical technique that has inevitably become an integral and vital part of a testing programme for diagnostic purposes. This manuscript presents a tailor-made LC-MS/MS quantitative assay method development and validation for a custom group of 33 pain panel drugs and their metabolites belonging to different classes (opiates, opioids, benzodiazepines, illicit, amphetamines, etc.) that are prescribed in pain management and depressant therapies. The LC-MS/MS method incorporates two experiments to enhance the sensitivity of the assay and has a run time of about 7 minutes with no prior purification of the samples required and a flow rate of 0.7 mL/min. The method also includes the second-stage metabolites for some drugs that belong to different classes but have first-stage similar metabolic pathways that will enable to correctly identify the right drug or to flag the drug that might be due to specimen tampering. Some real case examples and difficulties in peak picking were provided with some of the analytes in subject samples. Finally, the method was deliberated with some randomly selected de-identified clinical subject samples, and the data evaluated from "direct dilute and shoot analysis" and after "glucuronide hydrolysis" were compared. This method is now used to run routinely more than 100 clinical subject samples on a daily basis.
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Analgésicos/orina , Antidepresivos/orina , Cromatografía Liquida , Monitoreo de Drogas , Espectrometría de Masa por Ionización de Electrospray , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem , Humanos , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , UrinálisisRESUMEN
Background: Increased interarm systolic blood pressure difference (IASBPD) is one of the major predictors of cardiovascular disease. An IASBPD of >10 mmHg is of clinical significance. However, studies have reported a high number of patients visiting the emergency department (ED) with high IASBPD and varying correlation of IASBPD to age, ethnic background, and comorbidities such as hypertension and diabetes. Objective: The CALIBRATE study aimed to measure the IABPDs in the multiethnic patient population presenting to the ED in Qatar and to assess the distribution of IASBPD in this population. Methods: In a sitting position, two consecutive blood pressure (BP) measurements were recorded from the right and left arms for each participant using a calibrated automated machine and appropriate cuff sizes. The data were recorded using predefined data fields, including patient demographics, past medical, and social and family history. The continuous variables were reported as mean or median based on the distribution of data. The data were analyzed using Stata MP 14.0. Results: A total of 1800 patients, with a mean age of 34 (10) years, were prospectively recruited from the ED. The median absolute systolic BP difference (ΔSBP) between the right and left arms was 6 (3-10) mmHg, and it was the same for the first (ΔSBP1) and the second readings (ΔSBP2). The absolute average of ΔSBP1 and ΔSBP2 was 7 (4-10) mmHg. The difference in systolic BP difference (SBP) of < 20 mmHg for interarm blood pressure was seen in the 95th percentile of the population. No meaningful association could be detected between the IABPD and the study variables such as age, demographics, regions of interest, and risk factors. Conclusion: In population presenting to the ED, the IASBPD of at least 20 mmHg reached at the 95th percentile, validating the known significant difference. The utility of SBP difference can be improved further by taking the average of two individual readings.
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This study was designed to investigate the effect of prenatal exposure to synthetic sex steroid on sperm quantity and quality, relative testicular and epididymal weights, and reproductive hormones level in adult Wistar rats. Forty male Wistar rats were divided into two groups: a test group (n = 20) that included mature rats that were born to dams exposed to gestational treatment with hydroxyprogesterone and a control group (n = 20) that included mature rats born to untreated dams. Compared to the control group, the test group showed a significant reduction in the sperm count, viability and motility, relative testicular and epididymal weights together with increased abnormal spermatozoa (p < 0.001). The reproductive hormonal assay revealed significantly lower serum testosterone and higher levels of FSH and LH among the test groups compared to the control (p < 0.05 for all). Prenatal exposure to synthetic progesterone negatively affected sperm production and function, relative testicular and epididymal weights, and reproductive hormone levels.
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AIMS: To evaluate whether and what combinations of diabetes quality metrics were achieved in a multicentre trial in South Asia evaluating a multicomponent quality improvement intervention that included non-physician care coordinators to promote adherence and clinical decision-support software to enhance physician practices, in comparision with usual care. METHODS: Using data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, we evaluated the proportions of trial participants achieving specific and combinations of five diabetes care targets (HbA1c <53 mmol/mol [7%], blood pressure <130/80 mmHg, LDL cholesterol <2.6 mmol/L, non-smoking status, and aspirin use). Additionally, we examined the proportions of participants achieving the following risk factor improvements from baseline: ≥11-mmol/mol (1%) reduction in HbA1c , ≥10-mmHg reduction in systolic blood pressure, and/or ≥0.26-mmol/l reduction in LDL cholesterol. RESULTS: Baseline characteristics were similar in the intervention and usual care arms. Overall, 12.3%, 29.4%, 36.5%, 19.5% and 2.2% of participants in the intervention group and 16.2%, 38.3%, 31.6%, 11.3% and 0.8% of participants in the usual care group achieved any one, two, three, four or five targets, respectively. We noted sizeable improvements in HbA1c , blood pressure and cholesterol, and found that participants in the intervention group were twice as likely to achieve improvements in all three indices at 12 months that were sustained over 28 months of the study [relative risk 2.1 (95% CI 1.5,2.8) and 1.8 (95% CI 1.5,2.3), respectively]. CONCLUSIONS: The intervention was associated with significantly higher achievement of and greater improvements in composite diabetes quality care goals. However, among these higher-risk participants, very small proportions achieved the complete group of targets, which suggests that achievement of multiple quality-of-care goals is challenging and that other methods may be needed in closing care gaps.
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Sistemas de Apoyo a Decisiones Clínicas , Diabetes Mellitus Tipo 2/terapia , Mejoramiento de la Calidad , Indicadores de Calidad de la Atención de Salud , Aspirina/uso terapéutico , Presión Sanguínea , LDL-Colesterol/metabolismo , Atención a la Salud/organización & administración , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobina Glucada/metabolismo , Humanos , India , Pakistán , Inhibidores de Agregación Plaquetaria/uso terapéutico , Calidad de la Atención de Salud , Fumar/epidemiologíaRESUMEN
Tyrosinase plays an important role in melanin biosynthesis and protects skin against ultraviolet radiations. Functional deficiency of tyrosinase results in serious dermatological diseases. Tyrosinase also participates in neuromelanin formation in the human brain, which leads to neurodegeneration resulting in Parkinson's disease. In fruits and vegetables, tyrosinase plays a critical role in senescence, causing undesired browning that results in faster deterioration and shorter shelf lines. The only commercially available tyrosinase is mushroom tyrosinase and it shows the highest homology to the mammalian tyrosinase. Although kojic acid is currently used as a tyrosinase inhibitor, they have serious side effects such as dermatitis, carcinogenesis and hepatotoxicity. Therefore, in order to develop a more active and safer tyrosinase inhibitor, 3D QSAR pharmacophore models were generated based on experimentally known inhibitors. The pharmacophore model, Hypo1, was developed with a large cost difference, high correlation coefficient and low RMS deviation. Hypo1 showed a good spatial arrangement; consisting of five-point features including two hydrogen bond acceptor, one hydrogen bond donor and two hydrophobic features. Hypo1 was further validated by cost analysis, test set and Fisher's randomisation method. Hypo1 was used as a 3D query for screening the in-house drug-like databases, and the hits were further selected by applying ADMET, Lipinski's rule of five and fit value criteria. To identify binding conformations, the obtained hits were subjected to molecular docking. Finally, molecular dynamics simulations revealed the appropriate binding modes of hit compounds. To conclude, we propose the final three hit compounds with new structural scaffolds as a virtual candidate as tyrosinase inhibitors.Communicated by Ramaswamy H. Sarma.
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Monofenol Monooxigenasa , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad Cuantitativa , Humanos , Enlace de Hidrógeno , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Monofenol Monooxigenasa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Perception of self-motion is difficult for patients to describe. In addition, the relationship between perceived rotation and eye movements is poorly understood, because most studies of patients have investigated only static orientation. OBJECTIVE: First, to determine whether patients with benign paroxysmal positional vertigo (BPPV) can use visual images to report perceived rotation elicited by the Dix-Hallpike maneuver. Second, to determine if the direction of patients' perceptions align with data on classical nystagmus direction. METHODS: After the Dix-Hallpike maneuver, BPPV patients viewed images - sketches or video animations - representing possible perceived motions. They selected one or more images representing perception. RESULTS: All subjects could select images. The directions of the videos were most often backward pitch and/ or ipsilateral roll and yaw relative to body orientation in the supine Dix-Hallpike position, generally consistent with the canal stimulus. Perceived direction of rotation was statistically significantly different from the direction of eye movements as published previously, suggesting a difference in mechanisms for perception and eye movements. CONCLUSION: Patients can easily learn to use a video language to describe their experiences. Perception is generally aligned with canal stimulus and nystagmus, but not exactly.