Auditory steady-state evoked potentials (ASSEPs): a study of optimal stimulation parameters for frequency-specific threshold measurement in dogs.

OBJECTIVE: To define the optimal stimulation parameters (AM/FM vs AM alone and modulation rate) for frequency-specific threshold measurements using ASSEPs in dogs. Dependent variables were thresholds and recording times needed to obtain a response at threshold. To compare the ASSEP threshold results obtained with the optimal stimulation parameters to those obtained with the Tone-Burst/Auditory Brainstem Response (TB/ABR) combination. METHODS: Thirty-two sedated Beagle puppies were tested at 5 audiometric frequencies (0.5-8 kHz) and 6 ASSEP modulation rates (21-199 Hz). RESULTS: The ASSEP threshold-modulation rate functions had a high-pass profile with corner frequencies of 101 Hz for 0.5, 1 and 2 kHz carriers and of 151 Hz for 4 and 8 kHz carriers. AM stimuli did not yield higher thresholds than the AM/FM ones except at 1 kHz. Modulation type had no effect on testing duration. Audiometric profiles were obtained much more rapidly with ASSEPs than with TB/ABRs (mean: 50 vs 135 min). Both ASSEP and TB/ABR provided thresholds estimates characterized by low intersubject variability. CONCLUSIONS: ASSEPs are a valid and rapid method for audiometric assessment in sedated dogs. SIGNIFICANCE: ASSEPs offer a new, competitive tool for frequency-specific assessment of hearing in the canine species.     

Depression,sleeping pattern,and suicidal ideation among medical students in Bangladesh: a cross-sectional pilot study

Journal of Public Health - Depression is a major morbidity and the most common mental disorder among the medical students in medical schools globally. Undergraduate students suffer stress more due...     

Seminal cell-free DNA and sperm characteristic’s: An added biomarker for male infertility investigation

Cell-free DNA (Cf-DNA) fragments may constitute an easy-to-measure molecular tool for guiding the choice of care provided to infertile couples who benefit assisted reproductive technology (ART) programmes. Data on Cf-DNA levels in the seminal plasma of men with sperm alterations are scarce. The objective of the present study was to quantify the presence of Cf-DNA in semen by using a quantitative real-time PCR. We compared men with abnormal sperm characteristics (n = 21) with normospermic controls (n = 21). The PCR assay evidenced significantly higher mean Cf-DNA levels in patients with sperm abnormalities than in controls (2.09 versus 1.18 µg/ml, respectively; p = .0003). The Cf-DNA levels were notably higher in men with azoospermia (3.65 µg/ml, versus 1.34 µg/ml in matched controls; p = .03) and men with teratozoospermia (1.80 µg/ml, versus 1.29 µg/ml in matched controls; p = .008). Our data report a significant association between elevated Cf-DNA levels and sperm abnormalities. These results may open up new diagnostic and prognostic perspectives in male infertility.     

Development and characterization of naproxen-chitosan solid systems with improved drug dissolution properties.

The solubilizing and amorphizing properties toward naproxen (a poorly water-soluble antiinflammatory drug) of chitosan, an emerging pharmaceutical biopolymer, have been investigated. Solid binary systems at different drug/polymer ratios have been prepared according to different techniques (mixing, cogrinding, kneading, coevaporation) using chitosan at low (CS-L(w)) and medium (CS-M(w)) molecular weight, and tested for dissolution properties. Drug-carrier interactions were investigated in both the liquid and solid state, by phase solubility analysis, differential scanning calorimetry, X-ray powder diffractometry, FT-IR spectroscopy, and scanning electron microscopy. Drug dissolution parameters improved with increasing the polymer amount in the mixture, reaching the highest values at the 1:9 (w/w) drug/polymer ratio, and CS-L(w) was more efficacious than CS-M(w). Cogrinding was the most effective technique, showing the strongest amorphizing effect toward the drug and enabling an increase of more than ten times its relative dissolution rate. Coground mixtures at 3:7 (w/w) drug/polymer ratio were able to give directly compressed tablets which maintained unchanged the improved drug dissolution properties. Enhancer dissolution properties combined with its direct compression feasibility and antiulcerogenic action make CS-L(w) an optimal carrier for developing fast-release oral solid dosage forms of naproxen.     

Physiological and Psychosocial Factors that Predict HIV-Related Fatigue

Fatigue is one of the most common and debilitating symptoms experienced by HIV-infected people. We report the results of our longitudinal analysis of physiological and psychosocial factors that were thought to predict changes in HIV-related fatigue in 128 participants over a 1-year period, in an effort to sort out the complex interplay among a comprehensive set of physiological and psychosocial variables. Physiological measures included hepatic function (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, total bilirubin, hepatitis C status), thyroid function (thyroid stimulating hormone, thyroxine), HIV viral load, immunologic function (CD4, CD8, CD4/CD8 ratio, CD16, CD8CD38), gonadal function (testosterone, dehydroepiandrosterone), hematologic function (hemoglobin, hematocrit, serum erythropoietin), and cellular injury (lactic acid). Psychosocial measures included childhood and adult trauma, anxiety, depression, social support, stressful life events, and post-traumatic stress disorder (PTSD). Unemployment, not being on antiretroviral therapy, having fewer years since HIV diagnosis, more childhood trauma, more stressful life events, less social support, and more psychological distress (e.g., PTSD, anxiety and depression) put HIV-infected persons at risk for greater fatigue intensity and fatigue-related impairment in functioning during 1-year follow-up. Physiological variables did not predict greater fatigue. Stressful life events had both direct and indirect effects on fatigue.     

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow’s milk

Background

Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. However, its pathogenesis remains poorly understood and biomarkers are lacking. We aimed to perform in-depth characterization of humoral and cellular immune responses in children with cow’s milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature.

Methods

Children with CM-FPIES and control subjects with an IgE-mediated CM allergy (IgE-CMA), both avoiding CM, were recruited on the day of an oral food challenge. Blood samples were collected before the challenge. Total and specific levels of IgE, IgG1-4, IgA, IgM and IgD to various whey and casein allergens and to their gastroduodenal digestion products were measured in plasma, using plasma from CM-tolerant peanut allergic patients (IgE-PA, not avoiding CM) as additional controls. Cytokine secretion and cellular proliferation were analyzed after stimulation of PBMC with different CM allergens. Metabolomic profiles were obtained for plasma samples using liquid chromatography coupled to high-resolution mass spectrometry.

Results

Nine children with CM-FPIES and 12 control subjects (6 IgE-CMA and 6 IgE-PA) were included. In children with CM-FPIES, total Ig concentrations were lower than in control subjects, specific Ig against CM components were weak to undetectable, and no specific IgE against CM digestion products were detected. Moreover, in CM-FPIES patients, we did not find any Th cell proliferation or associated cytokine secretion after allergen reactivation, whereas such responses were clearly found in children with IgE-CMA. Plasma metabolic profiles were different between CM allergic patients, with significantly lower concentrations of various fatty acids and higher concentrations of primary metabolites such as amino acids in CM-FPIES compared to IgE-CMA patients.

Conclusions

In CM-FPIES, both humoral and cellular specific immune responses are weak or absent, and this is not related to CM avoidance. A metabolomic signature was identified in patients with CM-FPIES that may be useful for the diagnosis and management of this disease.

     

Effects on human heart valve immunogenicity in vitro by high concentration cryoprotectant treatment

It has been shown previously that cryopreservation, using an ice‐free cryopreservation method with the cryoprotectant formulation VS83, beneficially modulated immune reactions in vivo and in vitro when compared with conventionally frozen tissues. In this study, we assessed the impact of a VS83 post‐treatment of previously conventionally frozen human tissue on responses of human immune cells in vitro. Tissue punches of treated and non‐treated (control) aortic heart valve tissue (leaflets and associated aortic root) were co‐cultured for 7 days with peripheral blood mononuclear cells or enriched CD14⁺ monocytes. Effects on cellular activation markers, cytokine secretion and immune cell proliferation were analysed by flow cytometry. Flow cytometry studies showed that VS83 treatment of aortic root tissue promoted activation and differentiation of CD14⁺ monocytes, inducing both up‐regulation of CD16 and down‐regulation of CD14. Significantly enhanced expression levels for the C‐C chemokine receptor (CCR)7 and the human leukocyte antigen (HLA)‐DR on monocytes co‐cultured with VS83‐treated aortic root tissue were measured, while the interleukin (IL)‐6 and monocyte chemoattractant protein (MCP)‐1 release was suppressed. However, the levels of interferon (IFN)γ and tumour necrosis factor (TNF)α remained undetectable, indicating that complete activation into pro‐inflammatory macrophages did not occur. Similar, but non‐significant, changes occurred with VS83‐treated leaflets. Additionally, in co‐cultures with T cells, proliferation and cytokine secretion responses were minimal. In conclusion, post‐treatment of conventionally cryopreserved human heart valve tissue with the VS83 formulation induces changes in the activation and differentiation characteristics of human monocytes, and thereby may influence long‐term performance following implantation. Copyright © 2017 John Wiley & Sons, Ltd.