Evaluation of a commercial ELISA for measurement of feline urinary alpha1-microglobulin

Urinary alpha1-microglobulin (a1M) in people is a biomarker of renal tubular damage (Bazzi, 2001), butit has not yet been used in cats with chronic kidney disease (CKD).The aim of this study was to validate an ELISA test marketed for the measurement of feline a1M.Thirty-four urine supernatants collected from cats affected by or at risk for CKD were assayed by SDSAGE,to classify patients according to presence or absence of low molecular weight proteinuriasuggestive of tubular damage.Two samples with and one without tubular bands were used to evaluate intra-assay variability, linearityunder dilution (LUD) and spiking recovery test (SRT) of the ELISA. Then, a1M concentration wasmeasured in samples with (n°=10) or without (n°=25) tubular bands. The standard solution included inthe kit was also assayed by SDS-AGE.The intra-assay CVs was >20%. LUD and SRT showed that the test is not accurate. No significantdifference was found between a1M concentration in samples with and without tubular bands (medianvalues: 35.19 and 40.83 μg/mL respectively). SDS-AGE on the standard solution failed to identify bandswith molecular weight consistent with a1M but showed the presence of albumin.Results of this investigation did not support the use of this test to measure a1M in cats likely due to theabsence of a1M in the standard solution provided with the kit

Medical Students Knowledge and Attitude Towards Direct-To-Consumer Genetic Tests

Aims: This study reports on the attitudes of 179 Italian Medical Students to direct-to-consumer genetic test and to participation in research practices. Methods: Data were collected using a self-completion online questionnaire sent to 380 medical students at the faculty of Medicine of the Università Cattolica del Sacro Cuore in Rome, Italy. Questions pertained issues related to awareness and attitudes towards genetic testing, reactions to hypothetical results, and views about contributing to scientific research. Results: The response rate was 47.1%. Less than 50% of students were aware of DTC genetic test. Seventy-four percent of the sample were interested in undergoing DTC genetic test, and the main reason was being aware on genetic predisposition to diseases. Among those who were not willing to undergo a genetic test, the main reason was the lack of confidence in the results. In the hypothetical situations of an increased disease risk after undergoing DTC genetic testing, respondents would take actions to reduce that risk, while in the opposite scenario they would feel unaffected because of the probabilistic nature of the test. Conclusions: We reported a good level of awareness about DTC genetic test and a high interest in undergoing DTC genetic test in our sample. Nevertheless, opinions and reactions are strongly dependent by the hypothetical good or bad result that the test could provide and by the context whereby a genetic test could be performed. Respondents seem to be exposed to the risk of psychological harms, and a strong regulation regarding their use is required

No Untoward Effect of Long-Term Ketoconazole Administration on Electrocardiographic QT Interval in Patients with Cushing's Disease.

Ketoconazole is listed among drugs that prolong QT interval and may increase the risk of torsade de pointes, a severe ventricular arrhythmia. This compound has recently been approved for treatment of Cushing's syndrome, a severe endocrine disorder. These patients harbour several risk factors for prolonged QT interval, for example hypokalaemia and left ventricular hypertrophy, but no study has evaluated whether administration of ketoconazole affects their QT interval. The aim of this study was to assess the QT interval in patients with Cushing's disease during long-term administration of ketoconazole. Electrocardiograms from 15 patients with Cushing's disease (12 women, 3 men, age: 37.8 ± 2.66 years) on ketoconazole treatment (100 mg-800 mg qd) for 1 month to 12 years were reviewed retrospectively. QT interval was measured and corrected for heart rate (QTc). Measurements before and during ketoconazole treatment were compared and any abnormal QTc value recorded. Concurrent medical therapies were also documented. On average, QTc was superimposable before and during ketoconazole treatment (393.2 ± 7.17 versus 403.3 ± 6.05 msec. in women; 424.3 ± 23.54 versus 398.0 ± 14.93 msec. in men, N.S.). QTc normalized on ketoconazole in one man with prolonged QTc prior to treatment; no abnormal QTc was observed in any other patient during the entire observation period, even during concurrent treatment with other QT-prolonging drugs. In conclusion, long-term ketoconazole administration does not appear to be associated with significant prolongation of QT interval in patients with Cushing's disease. ECG monitoring can follow recommendations drawn for other low-risk QT-prolonging drugs with attention to specific risk factors, for example hypokalaemia and drug interactions

reduction in heart rate variability in autosomal dominant polycystic kidney disease

Introduction: Cardiovascular disease is one of the main causes of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Autonomic dysfunction is associated with an increased risk for all cardiovascular events in the general population and can be evaluated with heart rate variability (HRV). Objective: To evaluate HRV in ADPKD patients with mild hypertension versus hypertensive patients with organ damage and healthy controls (HC). Materials and Methods: We have enrolled 65 patients: 21 ADPKD patients (10 males), 20 patients with hypertension (14 males), and 24 HC (10 males). Biochemical analysis, clinical evaluation, anthropometric data, intima-media thickness, 24-h ECG Holter recording, and echocardiography were investigated at the time of enrollment. Results: No significant differences in HRV parameters were found between ADPKD with mild hypertension and hypertensive patients with organ damage. The median of HRV variables in time domain as SDNN (global autonomic activity) was significantly lower in ADPKD and hypertensive patients than HC (p < 0.05). In the frequency domain analysis, low frequency (LF), which mainly reflects the sympathetic component, showed higher values in ADPKD and hypertensive patients than HC during the night (p < 0.01). During the night, the sympathovagal balance, LF/high frequency (HF), showed higher values in ADPKD and hypertensive patients than HC (p < 0.0001). Conversely, LF day was lower in ADPKD and hypertensive patients than HC (p < 0.01). HF, which mainly reflects the parasympathetic component, was lower in ADPKD and hypertensive patients during the night than HC (p < 0.0001). Conclusions: HRV reduction is present in ADPKD patients with mild hypertension in the absence of organ damage. The evaluation of sympathovagal balance can provide novel information on the cardiovascular risk in ADPKD patients in addition to classical risk factors

Ice‐binding proteins and the ‘domain of unknown function’ 3494 family

Ice‐binding proteins (IBPs) control the growth and shape of ice crystals to cope with subzero temperatures in psychrophilic and freeze‐tolerant organisms. Recently, numerous proteins containing the domain of unknown function (DUF) 3494 were found to bind ice crystals and, hence, are classified as IBPs. DUF3494 IBPs constitute today the most widespread of the known IBP families. They can be found in different organisms including bacteria, yeasts and microalgae, supporting the hypothesis of horizontal transfer of its gene. Although the 3D structure is always a discontinuous β‐solenoid with a triangular cross‐section and an adjacent alpha‐helix, DUF3494 IBPs present very diverse activities in terms of the magnitude of their thermal hysteresis and inhibition of ice recrystallization. The proteins are secreted into the environments around the host cells or are anchored on their cell membranes. This review covers several aspects of this new class of IBPs, which promise to leave their mark on several research fields including structural biology, protein biochemistry and cryobiology

On driver behavior recognition for increased safety:A roadmap

Advanced Driver-Assistance Systems (ADASs) are used for increasing safety in the automotive domain, yet current ADASs notably operate without taking into account drivers’ states, e.g., whether she/he is emotionally apt to drive. In this paper, we first review the state-of-the-art of emotional and cognitive analysis for ADAS: we consider psychological models, the sensors needed for capturing physiological signals, and the typical algorithms used for human emotion classification. Our investigation highlights a lack of advanced Driver Monitoring Systems (DMSs) for ADASs, which could increase driving quality and security for both drivers and passengers. We then provide our view on a novel perception architecture for driver monitoring, built around the concept of Driver Complex State (DCS). DCS relies on multiple non-obtrusive sensors and Artificial Intelligence (AI) for uncovering the driver state and uses it to implement innovative Human–Machine Interface (HMI) functionalities. This concept will be implemented and validated in the recently EU-funded NextPerception project, which is briefly introduced

Correlação entre perda auditiva e controle glicêmico em pacientes diabéticos atendidos em um serviço de otorrinolaringologia

Introduction: Hearing loss is the fourth leading cause of disability in the world, with more than a billion people with some degree of loss, resulting in high annual costs. The auditive deficit can be a consequence of infections, genetic and environmental factors and comorbidities such as hypertension and diabetes mellitus (DM). Although the role of DM in hearing loss is still uncertain, studies suggest that diabetic microangiopathy and neuropathy are involved. Objective: Evaluate the audiometric profile of patients with DM treated at an outpatient clinic in Curitiba-PR. Methods: Cross-sectional observational study evaluating 41 diabetic patients between April 2020 and March 2021 regarding hearing complaints, presence of comorbidities and degree and type of hearing loss. Results: The mean age was 66.3 years, being 63.4% female and the mean value of glycated hemoglobin (HbA1c) was 7.67%. 82.9% of patients had tinnitus and 68.3% had hearing loss. 36.6% had hypertension, while 80.5% had dyslipidemia. As for the diabetes control, 65.9% had a HbA1c ≥ 7%. Conclusions: DM may be associated with hearing loss, however, it is not possible to verify a clear correlation between cause and effect. Thus, further studies with more extensive and detailed data are necessary.Introdução: Perdas auditivas correspondem à quarta maior causa de incapacitação no mundo, com mais de um bilhão de pessoas com algum grau de perda, acarretando elevados gastos anuais. O déficit auditivo pode ser consequência de infecções, fatores genéticos, ambientais e comorbidades como hipertensão e diabetes mellitus (DM). Apesar de ainda o papel da DM na perda auditiva ser incerto, estudos sugerem que a microangiopatia e neuropatia diabéticas estejam envolvidas. Objetivo: Avaliar o perfil audiométrico de pacientes com DM atendidos em um ambulatório em Curitiba-PR. Métodos: Estudo observacional transversal com avaliação de 41 pacientes diabéticos entre abril de 2020 e março de 2021 quanto a queixa auditiva, presença de comorbidades e grau e tipo de perda auditiva. Resultados: A média de idade foi de 66,3 anos, sendo 63,4% do sexo feminino e o valor médio da hemoglobina glicada (HbA1c) foi de 7,67%. 82,9% dos pacientes apresentaram tinnitus e 68,3% apresentaram hipoacusia. 36,6% apresentaram hipertensão, enquanto 80,5% tinham dislipidemia. Quanto ao controle de glicemia, 65,9% tinham HbA1c ≥ 7%. Conclusões: A DM pode estar associada com perda auditiva, não sendo, contudo, possível constatar uma clara correlação de causa e efeito. Assim, novos estudos, mais aprofundados e com um N maior, são necessários

Nutritional status and quality of life in adults undergoing allogeneic hematopoietic stem cell transplantation

Although the effects of malnutrition on morbidity and mortality in adult patients undergoing allogeneic hematopoietic stem cell transplantation are clear, the relationship with quality of life (QOL) is less clear. The purpose of this study was to assess the relationship between malnutrition and QOL. A prospective observational study was conducted in 36 adult patients undergoing allogeneic hematopoietic stem cell transplantation. Adapted criteria of the Global Leadership Initiative on malnutrition have been used for the diagnosis of malnutrition in clinical settings. A cancer linear analog scale was used to assess QOL. Overall QOL at 14 days after allogeneic hematopoietic stem cell transplantation was 37.1 (95% CI 2.9–45.39) in patients without severe malnutrition, versus 16.0 (95% CI − 6.6 to 38.6) in patients with severe malnutrition (p = 0.05). At discharge, it was 48.0 (95% CI 38.4–57.6) versus 34.0 (95% CI 4.1–63.9) (p = 0.27). The results of our study suggest that patients with severe malnutrition at discharge tend to have worse QOL. A larger cohort of patients is required to confirm this hypothesis

Etest® versus broth microdilution for ceftaroline MIC determination with Staphylococcus aureus: results from PREMIUM, a European multicentre study

Objectives: To compare the concordance of ceftaroline MIC values 24 by reference broth microdilution (BMD) and Etest (BioMérieux, France) for MSSA and MRSA isolates, respectively, in isolates from PREMIUM (D372SL00001), a European multi-centre study.  Methods: Ceftaroline MICs were determined by reference BMD and by Etest for 1,242 MSSA and MRSA from adult patients with community-acquired pneumonia or complicated skin and soft tissue infections collected between February and May 2012; tests were performed across six European laboratories. Selected isolates with ceftaroline resistance in broth (MIC >1 mg/L) were retested in three central laboratories to confirm their behaviour.  Results: Overall concordance between BMD and Etest was good, with >97% essential agreement and >95% categorical agreement. Nevertheless, 12 of the 26 MRSA isolates found resistant by BMD scored as susceptible by Etest, with MICs ≤1 mg/L, thus counting as very major errors, whereas only five of 380 MRSA found ceftaroline susceptible in BMD were mis-categorised as resistant by Etest. Twenty-one of the 26 isolates with MICs of 2 mg/L by BMD were then re-tested twice by each of three central laboratories: BMD MICs of 2 mg/L were consistently found for 19 of the 21 isolates. Among 147 Etest results for these 21 isolates (original plus six repeats per isolate) 112 were >1 mg/L.  Conclusions: BMD and Etest have good overall agreement for ceftaroline against Staphylococcus aureus; nevertheless, reliable Etest-based discrimination of the minority of ceftaroline-resistant (MIC 2 mg/L) MRSA is extremely challenging, requiring careful reading of strips, ideally with duplicate testing