In Vitro Study on the Influence of the Buccal Surface Convexity of the Tooth upon Enamel Loss after Bracket Removal.

Polishing after the removal of brackets is the final step in orthodontic treatment. It is simple to perform, though some studies have reported that polishing causes damage to the enamel surface. An in vitro study was made of the influence of the buccal surface convexity of the tooth upon possible enamel loss when the remaining resin and adhesive are removed after bracket decementing using two different polishing modes: a tungsten carbide bur at low and high speeds. The convexity of the buccal surface was quantified in 30 incisors and 30 premolars. A stereoscopic microscope was used to obtain photographs of the profile of the crown, and Image J software was used to calculate convexity by dividing the length of a line from the cementoenamel junction to the incisal margin by another line from the mentioned junction to the maximum convexity of the buccal surface. Brackets were cemented on all the teeth and were decemented 24 h later. In both groups, the residual composite was removed with a tungsten carbide bur at a low speed in one-half of the teeth and at a high speed in the other half. The buccal surface of each tooth was then photographed again, and the convexity was calculated and compared against the baseline value. The difference between the two values were taken to represent the enamel loss. The convexity of the premolars was significantly greater than that of the incisors, but this did not result in greater enamel loss when the same polishing mode was used. However, the tungsten carbide bur at a high speed proved more aggressive, causing significantly greater enamel loss than when used at a low speed.

Glycosaminoglycan dermatan sulfate supplementation decreases diet-induced obesity and metabolic dysfunction in mice.

Glycosaminoglycans are complex carbohydrates used as nutraceuticals for diverse applications. We studied the potential of the glycosaminoglycan dermatan sulfate (DS) to counteract the development of diet-induced obesity (DIO) using obesity-prone mice fed a high-fat diet (HFD) as a model. Oral DS supplementation protected the animals against HFD-induced increases in whole-body adiposity, visceral fat mass, adipocyte size, blood glucose levels, insulin resistance, and pro-inflammatory lipids levels in brown adipose tissue (BAT) and the liver, where it largely counteracted the HFD-induced changes in the nonpolar metabolome. Protection against DIO in the DS-supplemented mice occurred despite higher energy intake and appeared to be associated with increased energy expenditure, higher uncoupling protein 1 expression in BAT, decreased BAT "whitening," and an enhanced channeling of fuel substrates toward skeletal muscle. This work is the first preclinical study to examine the anti-obesity activity of DS tested individually in vivo. The results support possible uses of DS as an active component in functional foods/supplements to manage obesity and associated metabolic diseases.

Taurine and N-acetylcysteine treatments prevent memory impairment and metabolite profile alterations in the hippocampus of high-fat diet-fed female mice.

Background: Obesity constitutes a risk factor for cognitive impairment. In rodent models, long-term exposure to obesogenic diets leads to hippocampal taurine accumulation. Since taurine has putative cyto-protective effects, hippocampal taurine accumulation in obese and diabetic models might constitute a counteracting response to metabolic stress. Objective: We tested the hypothesis that treatment with taurine or with N-acetylcysteine (NAC), which provides cysteine for the synthesis of taurine and glutathione, prevent high-fat diet (HFD)-associated hippocampal alterations and memory impairment. Methods: Female mice were fed either a regular diet or HFD. Some mice had access to 3%(w/v) taurine or 3%(w/v) NAC in the drinking water. After 2 months, magnetic resonance spectroscopy (MRS) was used to measure metabolite profiles. Memory was assessed in novel object and novel location recognition tests. Results: HFD feeding caused memory impairment in both tests, and reduced concentration of lactate, phosphocreatine-to-creatine ratio, and the neuronal marker N-acetylaspartate in the hippocampus. Taurine and NAC prevented HFD-induced memory impairment and N-acetylaspartate reduction. NAC, but not taurine, prevented the reduction of lactate and phosphocreatine-to-creatine ratio. MRS revealed NAC/taurine-induced increase of hippocampal glutamate and GABA levels. Conclusion: NAC and taurine can prevent memory impairment, while only NAC prevents alterations of metabolite concentrations in HFD-exposed female mice.

Measuring Inflammation in the Vitreous and Retina: A Narrative Review.

Uveitis consists of a group of syndromes characterised by intraocular inflammation, accounting for up to 15% of visual loss in the western world and 10% worldwide. Assessment of intraocular inflammation has been limited to clinician-dependent, subjective grading. Developments in imaging technology, such as optical coherence tomography (OCT), have enabled the development of objective, quantitative measures of inflammatory activity. Important quantitative metrics including central macular thickness and vitreous signal intensity allow longitudinal monitoring of disease activity and can be used in conjunction with other imaging modalities enabling holistic assessment of ocular inflammation. Ongoing work into the validation of instrument-based measures alongside development of core outcome sets is crucial for standardisation of clinical trial endpoints and developing guidance for quantitative multi-modal imaging approaches. This review outlines methods of grading inflammation in the vitreous and retina, with a focus on the use of OCT as an objective measure of disease activity.

Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood.

Nicotinamide riboside, an NAD+ precursor, has been attracting a lot of attention in recent years due to its potential benefits against multiple metabolic complications and age-related disorders related to NAD+ decline in tissues. The metabolic programming activity of NR supplementation in early-life stages is much less known. Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. Suckling male mice received a daily oral dose of NR or vehicle (water) from day 2 to 20 of age, were weaned at day 21 onto a chow diet, and at day 90 were distributed to either a high-fat diet (HFD) or a normal-fat diet for 10 weeks. Compared to controls, NR-treated mice were protected against HFD-induced triacylglycerol accumulation in skeletal muscle and displayed lower triacylglycerol levels and steatosis degree in the liver and distinct capacities for fat oxidation and decreased lipogenesis in both tissues, paralleling signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling. These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.

Taurine Supplementation as a Neuroprotective Strategy upon Brain Dysfunction in Metabolic Syndrome and Diabetes.

Obesity, type 2 diabetes, and their associated comorbidities impact brain metabolism and function and constitute risk factors for cognitive impairment. Alterations to taurine homeostasis can impact a number of biological processes, such as osmolarity control, calcium homeostasis, and inhibitory neurotransmission, and have been reported in both metabolic and neurodegenerative disorders. Models of neurodegenerative disorders show reduced brain taurine concentrations. On the other hand, models of insulin-dependent diabetes, insulin resistance, and diet-induced obesity display taurine accumulation in the hippocampus. Given the possible cytoprotective actions of taurine, such cerebral accumulation of taurine might constitute a compensatory mechanism that attempts to prevent neurodegeneration. The present article provides an overview of brain taurine homeostasis and reviews the mechanisms by which taurine can afford neuroprotection in individuals with obesity and diabetes. We conclude that further research is needed for understanding taurine homeostasis in metabolic disorders with an impact on brain function.

Cognitive Impairment and Metabolite Profile Alterations in the Hippocampus and Cortex of Male and Female Mice Exposed to a Fat and Sugar-Rich Diet are Normalized by Diet Reversal.

Diabetes impacts on brain metabolism, structure, and function. Alterations in brain metabolism have been observed in obesity and diabetes models induced by exposure to diets rich in saturated fat and/or sugar and have been linked to memory impairment. However, it remains to be determined whether brain dysfunction induced by obesogenic diets results from permanent brain alterations. We tested the hypothesis that an obesogenic diet (high-fat and high-sucrose diet; HFHSD) causes reversible changes in hippocampus and cortex metabolism and alterations in behavior. Mice were exposed to HFHSD for 24 weeks or for 16 weeks followed by 8 weeks of diet normalization. Development of the metabolic syndrome, changes in behavior, and brain metabolite profiles by magnetic resonance spectroscopy (MRS) were assessed longitudinally. Control mice were fed an ingredient-matched low-fat and low-sugar diet. Mice fed the HFHSD developed obesity, glucose intolerance and insulin resistance, with a more severe phenotype in male than female mice. Relative to controls, both male and female HFHSD-fed mice showed increased anxiety-like behavior, impaired memory in object recognition tasks, but preserved working spatial memory as evaluated by spontaneous alternation in a Y-maze. Alterations in the metabolite profiles were observed both in the hippocampus and cortex but were more distinct in the hippocampus. HFHSD-induced metabolic changes included altered levels of lactate, glutamate, GABA, glutathione, taurine, N-acetylaspartate, total creatine and total choline. Notably, HFHSD-induced metabolic syndrome, anxiety, memory impairment, and brain metabolic alterations recovered upon diet normalization for 8 weeks. In conclusion, cortical and hippocampal derangements induced by long-term HFHSD consumption are reversible rather than being the result of permanent tissue damage.

Adherence to supportive periodontal treatment in relation to patient awareness.

BACKGROUND: To evaluate the risk profile of noncompliant patients in relation to adherence to supportive periodontal therapy in order to identify factors associated with this profile, and be able to prevent the abandonment of periodontal therapy. MATERIAL AND METHODS: This cross-sectional observational and comparative study was carried out on the patients who attended the Periodontics department of a University in Valencia (by a questionnaire and followed-up the periodontal supportive therapy through the medical history.) 220 patients were interviewed and gave their informed consent and data release permission before taking part in the study, which was approved by the Ethics Committee (UCV/2019-2020/048). RESULTS: 48.84% of self-reported patients were regular compliers, in contrast with 10.62% of referred patients. Those with acute symptoms were greater adherent than those patients who didn´t present symptoms. Regarding patients undergoing surgical procedures, significant results were obtained: 69.70% showed adherence, in contrast with 18.67% patients with basic treatment. Results between men and women were similar. However, the age of the non-compliant patients was slightly older. CONCLUSIONS: Self-reported patients presented a significantly higher degree of adherence to periodontal supportive therapy than the referred patients. Patients with acute symptoms presented higher adherence than those without them. Patients who underwent surgery presented a significantly higher degree of adherence than patients who received basic periodontal treatment. No conclusive data have been found regarding sex and age. Key words:Awareness, periodontal disease, compliance, SPT.

Prevention of Emotional Disorders and Symptoms Under Health Conditions: A Pilot Study using the Unified Protocol in a Fertility Unit

Los trastornos emocionales (TE) son frecuentes durante los tratamientos de fertilidad. El Protocolo Unificado (PU) es una intervención transdiagnóstica que ha demostrado su eficacia en la prevención de TE en condiciones médicas. El objetivo de este estudio piloto es:1) mejorar la disregulación emocional para prevenir síntomas ansiosos y depresivos en mujeres en tratamiento de inseminación artificial (IA); 2) evaluar la acepta-bilidad (satisfacción y adherencia). Método: 5 mujeres en tratamiento de IA, sin diagnóstico clínico, respondieron a medidas de estado de ánimo (ansiedad y depresión),afecto,calidad de vida y regulación emocional en el pre-y post-evaluación, y en los seguimientos a los 1, 3 y 6 meses. La adap-tación preventiva del PU se basó en la aplicación de 6 sesiones presenciales grupales de 2 horas de duración. La situación generada por la COVID-19 provocó el cambio al formato online para finalizar el programa. Resultados: las mujeres no desarrollaron TE, no se encontraron diferencias pre-post y pre-seguimientos estadísticamente significativas en ansiedad, depresión, ca-lidad de vida y disregulación emocional (p>.050). Se observa una tenden-cia a la mejoría en la evaluación post-programa. Conclusiones: Parece que programas como el PU, centrado en factores terapéuticos compartidos, ha tenido un efecto emocional preventivo durante IA.(AU)

Emotional Disorders (EDs) are common in women who under-go fertility treatments. The Unified Protocol (UP) is a transdiagnostic in-tervention that has demonstrated efficacy in preventing EDs under differ-ent health conditions. The aim of this pilot study is to: 1) improve emo-tional dysregulation for the prevention of anxiety and depressive symp-toms in women undergoing intrauterine inseminations (IUI); 2) assess their acceptability (e.g., satisfaction and adherence rates). Method: Five women undergoing IUI, with no clinical diagnoses, responded to measures of mood (anxiety and depression), affect, quality of life and emotional dysregulation in the pre-and post-assessments, and at the 1-, 3-and 6-month follow-ups. The UP was adapted to be applied during six face-to-face group sessions lasting 2 h. The COVID-19 pandemic situation im-plied changing to an online format to end the program. Results: The re-sults showed that women did not develop EDs, and no statistically signifi-cant pre-post and pre-follow-up differences werefound for anxiety, de-pression,quality of life and emotional dysregulation (all p>.050). A ten-dency towards improvement in the post-assessment evaluation was noted. Satisfaction with the format and UP program was high. Conclusions: It would seem that programs focusing on therapeutic common factors like the UP could have an emotional preventive effect during IUI.(AU)

Alterations to Cerebral Perfusion, Metabolite Profiles, and Neuronal Morphology in the Hippocampus and Cortex of Male and Female Mice during Chronic Exposure to a High-Salt Diet.

Excess dietary salt reduces resting cerebral blood flow (CBF) and vascular reactivity, which can limit the fueling of neuronal metabolism. It is hitherto unknown whether metabolic derangements induced by high-salt-diet (HSD) exposure during adulthood are reversed by reducing salt intake. In this study, male and female mice were fed an HSD from 9 to 16 months of age, followed by a normal-salt diet (ND) thereafter until 23 months of age. Controls were continuously fed either ND or HSD. CBF and metabolite profiles were determined longitudinally by arterial spin labeling magnetic resonance imaging and magnetic resonance spectroscopy, respectively. HSD reduced cortical and hippocampal CBF, which recovered after dietary salt normalization, and affected hippocampal but not cortical metabolite profiles. Compared to ND, HSD increased hippocampal glutamine and phosphocreatine levels and decreased creatine and choline levels. Dietary reversal only allowed recovery of glutamine levels. Histology analyses revealed that HSD reduced the dendritic arborization and spine density of cortical and hippocampal neurons, which were not recovered after dietary salt normalization. We conclude that sustained HSD exposure throughout adulthood causes permanent structural and metabolic alterations to the mouse brain that are not fully normalized by lowering dietary salt during aging.

Protective Effects of Individual and Combined Low Dose Beta-Carotene and Metformin Treatments against High-Fat Diet-Induced Responses in Mice.

Anti-obesity activity has been reported for beta-carotene (BC) supplementation at high doses and metformin (MET). We studied whether BC treatment at a closer to dietary dose and MET treatment at a lower than therapeutic dose are effective in ameliorating unwanted effects of an obesogenic diet and whether their combination is advantageous. Obesity-prone mice were challenged with a high-fat diet (HFD, 45% energy as fat) for 4 weeks while receiving a placebo or being treated orally with BC (3 mg/kg/day), MET (100 mg/kg/day), or their combination (BC+MET); a fifth group received a placebo and was kept on a normal-fat diet (10% energy as fat). HFD-induced increases in body weight gain and inguinal white adipose tissue (WAT) adipocyte size were attenuated maximally or selectively in the BC+MET group, in which a redistribution towards smaller adipocytes was noted. Cumulative energy intake was unaffected, yet results suggested increased systemic energy expenditure and brown adipose tissue activation in the treated groups. Unwanted effects of HFD on glucose control and insulin sensitivity were attenuated in the treated groups, especially BC and BC+MET, in which hepatic lipid content was also decreased. Transcriptional analyses suggested effects on skeletal muscle and WAT metabolism could contribute to better responses to the HFD, especially in the MET and BC+MET groups. The results support the benefits of the BC+MET cotreatment.

Assessment of Oxygen Expansion during Internal Bleaching with Enamel and Dentin: A Comparative In Vitro Study.

Internal bleaching is a conservative, non-invasive, and simple treatment that is frequently performed in daily clinical practice. The present in vitro study analyzes the oxygen expansion of different bleaching agents resulting from the oxidation reaction when interacting with enamel and dentin. Enamel and dentin were crushed separately until obtaining a fine powder with particles of an approximate size between 0.06 and 0.2 mm. Each enamel and dentin sample were mixed with 37% carbamide peroxide (CP 37%), 30% hydrogen peroxide (HP 30%), sodium perborate (SP) combined with HP 30% (HP 30% + SP) and SP with distilled water (SP). A total of 280 1 mm diameter glass tubes were used with 70 for each bleaching agent (30 for powdered enamel evaluation, 30 for powdered dentin evaluation, and 10 controls). The bleaching agents were placed in the prepared tubes immediately after mixing the components. As expansion occurred, the oil inside the tube was displaced, through which the resulting expansion was evaluated and measured for 10 days. A significant expansion was observed that varied in magnitude according to the bleaching agent and the tooth structure used. Student's t test and Welch's ANOVA were used to analyze the data obtained. The highest mean expansion of both enamel and dentin was observed with 30% HP (66.6 mm for enamel, 94.5 mm for dentin) followed by HP 30% + SP (48.6 mm for enamel, 52.7 mm for dentin), CP 37% (38.4 mm for enamel, 52.6 mm for dentin) and finally SP with water (12.7 mm for enamel, 4.4 mm for dentin). It was observed that the expansion in the SP group with enamel was significantly lower than in the rest of the groups, while that registered for HP 30% was significantly higher. (p < 0.001). The results with dentin were similar, with a significantly lower expansion for SP and higher for HP 30% (p < 0.001). The oxygen expansion observed as a result of the interaction between bleaching agents and dental tissues could contribute to improving our understanding of bleaching and its results. These results suggest that bleaching agents react with the organic component of the tooth structure.

Baricitinib reduces 30-day mortality in older adults with moderate-to-severe COVID-19 pneumonia.

BACKGROUND: Older adults are at the highest risk of severe disease and death due to COVID-19. Randomized data have shown that baricitinib improves outcomes in these patients, but focused stratified analyses of geriatric cohorts are lacking. Our objective was to analyze the efficacy of baricitinib in older adults with COVID-19 moderate-to-severe pneumonia. METHODS: This is a propensity score [PS]-matched retrospective cohort study. Patients from the COVID-AGE and Alba-Score cohorts, hospitalized for moderate-to-severe COVID-19 pneumonia, were categorized in two age brackets of age <70 years old (86 with baricitinib and 86 PS-matched controls) or ≥70 years old (78 on baricitinib and 78 PS-matched controls). Thirty-day mortality rates were analyzed with Kaplan-Meier and Cox proportional hazard models. RESULTS: Mean age was 79.1 for those ≥70 years and 58.9 for those <70. Exactly 29.6% were female. Treatment with baricitinib resulted in a significant reduction in death from any cause by 48% in patients aged 70 or older, an 18.5% reduction in 30-day absolute mortality risk (n/N: 16/78 [20.5%] baricitinib, 30/78 [38.5%] in PS-matched controls, p < 0.001) and a lower 30-day adjusted fatality rate (HR 0.21; 95% CI 0.09-0.47; p < 0.001). Beneficial effects on mortality were also observed in the age group <70 (8.1% reduction in 30-day absolute mortality risk; HR 0.14; 95% CI 0.03-0.64; p = 0.011). CONCLUSIONS: Baricitinib is associated with an absolute mortality risk reduction of 18.5% in adults older than 70 years hospitalized with COVID-19 pneumonia.

Long-term programming of skeletal muscle and liver lipid and energy metabolism by resveratrol supplementation to suckling mice.

Metabolic programming by dietary chemicals consumed in early life stages is receiving increasing attention. We here studied long-term effects of mild resveratrol (RSV) supplementation during lactation on muscular and hepatic lipid metabolism in adulthood. Newborn male mice received RSV or vehicle from day 2-20 of age, were weaned onto a chow diet on day 21, and were assigned to either a high-fat diet (HFD) or a normal-fat diet on day 90 of age for 10 weeks. RSV-treated mice showed in adulthood protection against HFD-induced triacylglycerol accumulation in skeletal muscle, enhanced muscular capacities for fat oxidation and mitochondria activity, signs of enhanced sirtuin 1 and AMP-dependent protein kinase signaling in muscle, and increased fat oxidation capacities and a decreased capacity for lipogenesis in liver compared with controls. Thus, RSV supplementation in early postnatal life may help preventing later diet-related disorders linked to ectopic lipid accumulation in muscle and liver tissues.

High-Temperature Short-Time and Holder Pasteurization of Donor Milk: Impact on Milk Composition.

Holder pasteurization (HoP; 62.5 °C, 30 min) is commonly used to ensure the microbiological safety of donor human milk (DHM) but diminishes its nutritional properties. A high-temperature short-time (HTST) system was designed as an alternative for human milk banks. The objective of this study was to evaluate the effect of this HTST system on different nutrients and the bile salt stimulated lipase (BSSL) activity of DHM. DHM was processed in the HTST system and by standard HoP. Macronutrients were measured with a mid-infrared analyzer. Lactose, glucose, myo-inositol, vitamins and lipids were assayed using chromatographic techniques. BSSL activity was determined using a kit. The duration of HTST treatment had a greater influence on the nutrient composition of DHM than did the tested temperature. The lactose concentration and the percentage of phospholipids and PUFAs were higher in HTST-treated than in raw DHM, while the fat concentration and the percentage of monoacylglycerides and SFAs were lower. Other nutrients did not change after HTST processing. The retained BSSL activity was higher after short HTST treatment than that following HoP. Overall, HTST treatment resulted in better preservation of the nutritional quality of DHM than HoP because relevant thermosensitive components (phospholipids, PUFAs, and BSSL) were less affected.

Swept-source optical coherence tomography objective composite activity score for uveitis.

PURPOSE: To develop an objective intraocular inflammation composite score. METHODS: Cross-sectional study. Non-invasive image acquisition and processing were conducted from April 2017 to April 2019. Inflammation-grade stratified eyes from patients with active, inactive uveitis and healthy controls were recruited. After clinical assessment, four anterior and posterior segment image acquisition protocols per eye, using swept-source optical coherence tomography (SS-OCT), were performed at inclusion. Eight imaging biomarkers in three domains: anterior, intermediate and posterior were studied. They were ranked and selected by discriminatory power and correlation with clinical scores. A final SS-OCT-derived composite uveitis activity score (SS-UAS) was developed through multiple linear regression. RESULTS: We studied 224 eyes with uveitis (165 active and 59 inactive) from 165 patients (mean age 46.6 SD 15.5 years; 55.3% women) and 38 eyes from 19 healthy controls (mean age 43.6 SD 17.1; 47% women). The selected SS-OCT-derived biomarkers to build the final score were anterior chamber hyper-reflective dots (anterior), high-definition relative vitreous intensity (intermediate) and the averaged thickened retinal index (posterior). Swept-source (SS)-UAS was highly discriminant between active and inactive, and between active and healthy eyes (means 2.06 SD 1.86, 0.93 SD 0.44, and 0.96 SD 0.38, respectively, both p -, Mann-Whitney U). Construct validity (Cronbach's alpha = 0.7), internal consistency, criterion validity and reliability (concordance correlation coefficient intra-rater = 0.99, 95% CI: 0.98-0.99; inter-rater = 0.98, 95% CI: 0.96-0.99) were favourable. CONCLUSIONS: Global intraocular inflammation can potentially be staged and scored objectively, continuously, consistently and in a valid manner through the combined processing of SS-OCT scans.

A glucose-stimulated BOLD fMRI study of hypothalamic dysfunction in mice fed a high-fat and high-sucrose diet.

The hypothalamus is the central regulator of energy homeostasis. Hypothalamic neuronal circuits are disrupted upon overfeeding, and play a role in the development of metabolic disorders. While mouse models have been extensively employed for understanding the mechanisms of hypothalamic dysfunction, functional magnetic resonance imaging (fMRI) on hypothalamic nuclei has been challenging. We implemented a robust glucose-induced fMRI paradigm that allows to repeatedly investigate hypothalamic responses to glucose. This approach was used to test the hypothesis that hypothalamic nuclei functioning is impaired in mice exposed to a high-fat and high-sucrose diet (HFHSD) for seven days. The blood oxygen level-dependent (BOLD) fMRI signal was measured from brains of mice under light isoflurane anaesthesia, during which a 2.6 g/kg glucose load was administered. The mouse hypothalamus responded to glucose but not saline administration with a biphasic BOLD fMRI signal reduction. Relative to controls, HFHSD-fed mice showed attenuated or blunted responses in arcuate nucleus, lateral hypothalamus, ventromedial nucleus and dorsomedial nucleus, but not in paraventricular nucleus. In sum, we have developed an fMRI paradigm that is able to determine dysfunction of glucose-sensing neuronal circuits within the mouse hypothalamus in a non-invasive manner.

Improving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice.

A cohort of 128 patients from 118 families diagnosed with non-syndromic or syndromic hearing loss (HL) underwent an exhaustive clinical evaluation. Molecular analysis was performed using targeted next-generation sequencing (NGS) with a custom panel that included 59 genes associated with non-syndromic HL or syndromic HL. Variants were prioritized according to the minimum allele frequency and classified according to the American College of Medical Genetics and Genomics guidelines. Variant(s) responsible for the disease were detected in a 40% of families including autosomal recessive (AR), autosomal dominant (AD) and X-linked patterns of inheritance. We identified pathogenic or likely pathogenic variants in 26 different genes, 15 with AR inheritance pattern, 9 with AD and 2 that are X-linked. Fourteen of the found variants are novel. This study highlights the clinical utility of targeted NGS for sensorineural hearing loss. The optimal panel for HL must be designed according to the spectrum of the most represented genes in a given population and the laboratory capabilities considering the pressure on healthcare.

Brain Metabolism Alterations in Type 2 Diabetes: What Did We Learn From Diet-Induced Diabetes Models?

Type 2 diabetes (T2D) is a metabolic disease with impact on brain function through mechanisms that include glucose toxicity, vascular damage and blood-brain barrier (BBB) impairments, mitochondrial dysfunction, oxidative stress, brain insulin resistance, synaptic failure, neuroinflammation, and gliosis. Rodent models have been developed for investigating T2D, and have contributed to our understanding of mechanisms involved in T2D-induced brain dysfunction. Namely, mice or rats exposed to diabetogenic diets that are rich in fat and/or sugar have been widely used since they develop memory impairment, especially in tasks that depend on hippocampal processing. Here we summarize main findings on brain energy metabolism alterations underlying dysfunction of neuronal and glial cells promoted by diet-induced metabolic syndrome that progresses to a T2D phenotype.

Concentrates of buttermilk and krill oil improve cognition in aged rats.

Cognitive decline is one of the hallmarks of aging and can vary from mild cognitive impairment to dementia to Alzheimer's disease. In addition to some lifestyle interventions, there is room for the use of nutraceuticals/functional foods as pharma-nutritional tools to lessen the burden of cognitive decline before it worsens. We previously reported the promising molecular actions of milk fat globule membranes and krill oil concentrates in a rat model of aging. In this study, we concentrated on the activities on cognition, using an array of validated tests. We also performed lipidomic analyses of plasma, erythrocytes, and different brain areas. We report lower emotional memory (contextual fear conditioning) in aged rats supplemented with concentrates of polar lipids from buttermilk or krill oil at doses that approximate human consumption. No other behavioral parameter was significantly influenced by the supplements, calling for further research to confirm or not the purported salubrious activities of polar lipids, namely those rich in ω3 long-chain polyunsaturated fatty acids, on cognitive decline.