Persistence and generalization of adaptive changes in auditory localization behavior following unilateral conductive hearing loss

Introduction: Sound localization relies on the neural processing of binaural and monaural spatial cues generated by the physical properties of the head and body. Hearing loss in one ear compromises binaural computations, impairing the ability to localize sounds in the horizontal plane. With appropriate training, adult individuals can adapt to this binaural imbalance and largely recover their localization accuracy. However, it remains unclear how long this learning is retained or whether it generalizes to other stimuli. Methods: We trained ferrets to localize broadband noise bursts in quiet conditions and measured their initial head orienting responses and approach-to-target behavior. To evaluate the persistence of auditory spatial learning, we tested the sound localization performance of the animals over repeated periods of monaural earplugging that were interleaved with short or long periods of normal binaural hearing. To explore learning generalization to other stimulus types, we measured the localization accuracy before and after adaptation using different bandwidth stimuli presented against constant or amplitude-modulated background noise. Results: Retention of learning resulted in a smaller initial deficit when the same ear was occluded on subsequent occasions. Each time, the animals’ performance recovered with training to near pre-plug levels of localization accuracy. By contrast, switching the earplug to the contralateral ear resulted in less adaptation, indicating that the capacity to learn a new strategy for localizing sound is more limited if the animals have previously adapted to conductive hearing loss in the opposite ear. Moreover, the degree of adaptation to the training stimulus for individual animals was significantly correlated with the extent to which learning extended to untrained octave band target sounds presented in silence and to broadband targets presented in background noise, suggesting that adaptation and generalization go hand in hand. Conclusions: Together, these findings provide further evidence for plasticity in the weighting of monaural and binaural cues during adaptation to unilateral conductive hearing loss, and show that the training-dependent recovery in spatial hearing can generalize to more naturalistic listening conditions, so long as the target sounds provide sufficient spatial information

Protein-energy wasting syndrome in advanced chronic kidney disease: Prevalence and specific clinical characteristics

Introduction: Protein-energy wasting (PEW) is associated with increased mortality and differs depending on the chronic kidney disease (CKD) stage and the dialysis technique. The prevalence in non-dialysis patients is understudied and ranges from 0 to 40.8%. Objective: To evaluate the nutritional status of a group of Spanish advanced CKD patients by PEW criteria and subjective global assessment (SGA). Patients and methods: Cross-sectional study of 186 patients (101 men) with a mean age of 66.1 ± 16 years. The nutritional assessment consisted of: SGA, PEW criteria, 3-day dietary records, anthropometric parameters and bioelectrical impedance vector analysis. Results: The prevalence of PEW was 30.1%, with significant differences between men and women (22.8 vs. 33.8%, p &lt; 0.005), while 27.9% of SGA values were within the range of malnutrition. No differences were found between the 2 methods. Men had higher proteinuria, percentage of muscle mass and nutrient intake. Women had higher levels of total cholesterol, HDL and a higher body fat percentage. The characteristics of patients with PEW were low albumin levels and a low total lymphocyte count, high proteinuria, low fat and muscle mass and a high Na/K ratio. The multivariate analysis found PEW to be associated with: proteinuria (OR: 1.257; 95% CI: 1.084–1.457, p = 0.002), percentage of fat intake (OR: 0.903; 95% CI: 0.893–0.983, p = 0.008), total lymphocyte count (OR: 0.999; 95% CI: 0.998–0.999, p = 0.001) and cell mass index (OR: 0.995; 95% CI: 0.992–0.998). Conclusion: Malnutrition was identified in Spanish advanced CKD patients measured by different tools. We consider it appropriate to adapt new diagnostic elements to PEW criteria.Introducción: El desgaste proteico energético (DPE) se asocia a mayor mortalidad y difieredependiendo del estadio de la enfermedad renal y de la técnica de diálisis. Su prevalenciaen pacientes sin diálisis se encuentra poco estudiada y oscila entre el 0 y el 40,8%.Objetivo: Evaluar el estado nutricional según criterios de DPE y por valoración global subje-tiva (VGS) de un colectivo de pacientes espa˜noles con enfermedad renal crónica avanzada(ERCA).Pacientes y métodos: Estudio transversal de 186 pacientes (101 hombres) con edad media de66,1 ± 16 a˜nos. Se realizó evaluación nutricional mediante: VGS, criterios de DPE, registrodietético de 3 días, parámetros antropométricos y bioimpedancia vectorial.Resultados: Un 30,1% presentaba DPE, con diferencias significativas entre hombres y mujeres(22,8 vs. 33,8%; p < 0,005) y un 27,9% tenía valores de VGS en rangos de desnutrición. Sindiferencia entre los 2 métodos estudiados. Los hombres presentaron mayores niveles deproteinuria, porcentaje de masa muscular e ingesta de nutrientes. Las mujeres tuvieronmayores niveles de colesterol total, HDL y porcentaje de masa grasa. Las característicasde los pacientes con DPE fueron: bajos valores de albúmina y recuento total de linfocitos,elevada proteinuria, baja masa grasa, baja masa muscular y cociente Na/K elevado.El análisis multivariante mostró asociación de DPE con proteinuria (OR: 1,257; IC 95%:1,084-1,457; p = 0,002), porcentaje de ingesta lipídica (OR: 0,903; IC 95%: 0,893-0,983; p = 0,008),recuento total de linfocitos (OR: 0,999; IC 95%: 0,998-0,999; p = 0,001) y el índice de masacelular (OR: 0,995; IC 95%: 0,992-0,998)

Environmental heat stress on maternal physiology and fetal blood flow in pregnant subsistence farmers in The Gambia, west Africa: an observational cohort study.

BACKGROUND: Anthropogenic climate change has caused extreme temperatures worldwide, with data showing that sub-Saharan Africa is especially vulnerable to these changes. In sub-Saharan Africa, women comprise 50% of the agricultural workforce, often working throughout pregnancy despite heat exposure increasing the risk of adverse birth outcomes. In this study, we aimed to improve understanding of the pathophysiological mechanisms responsible for the adverse health outcomes resulting from environmental heat stress in pregnant subsistence farmers. We also aimed to provide data to establish whether environmental heat stress also has physiological effects on the fetus. METHODS: We conducted an observational cohort study in West Kiang, The Gambia, at the field station for the Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine (named the MRC Keneba field station). Pregnant women who were aged 16 years or older and who were at 160 beats per min [bpm] or <115 bpm, or increase in umbilical artery resistance index) were measured at rest and during the working period. Multivariable repeated measure models (linear regression for FHR, and logistic regression for fetal strain) were used to evaluate the association of heat stress and heat strain with acute fetal strain. FINDINGS: Between Aug 26, 2019, and March 27, 2020, 92 eligible participants were recruited to the study. Extreme heat exposure was frequent, with average exposures of WBGT of 27·2°C (SD 3·6°C) and UTCI equivalent temperature of 34·0°C (SD 3·7°C). The total effect of UTCI on fetal strain resulted in an odds ratio (OR) of 1·17 (95% CI 1·09-1·29; p<0·0001), with an adjusted direct effect of OR of 1·12 (1·03-1·21; p=0·010) with each 1°C increase in UTCI. The adjusted OR of maternal heat strain on fetal strain was 1·20 (1·01-1·43; p=0·038), using the UTCI model, with each unit increase. INTERPRETATION: Data from our study show that decreasing maternal exposure to heat stress and heat strain is likely to reduce fetal strain, with the potential to reduce adverse birth outcomes. Further work that explores the association between heat stress and pregnancy outcomes in a variety of settings and populations is urgently needed to develop effective interventions. FUNDING: The Wellcome Trust

Cognitive reserve benefits brain efficiency in healthy aging

The concept of cognitive reserve (CR) describes the mind’s resistance to the progressive damage of the brain and probably this can be reflected as the ability to recruit brain networks in an effective way. It is as- sociated with the abilityto copewith the deleterious effects of brain damage,brain degeneration, or age-related changes on cognitive performance

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Event versus activity-based cues and motivation in school-related prospective memory tasks.

Prospective memory (PM), the ability to remember an intention in the future, is essential to children's everyday lives. We explored age differences (6- to 7- vs. 10- to 11-year-olds) in PM depending on the nature of the task and the children's motivation. Children performed event-based PM tasks (in which the cue was presented during the ongoing activity) and activity-based PM tasks (in which the cue consisted of finishing the ongoing activity). Additionally, the children were assigned to either a reward condition or a no-reward condition. The results showed better performance in event than in activity based tasks, with older children outperforming younger children in both. There was a marginal effect of reward for PM accuracy. These patterns suggest that the cue detection process and children's motivation play a role in PM performance during development

Targeted doxorubicin-containing luteinizing hormone-releasing hormone analogue AN-152 inhibits the growth of doxorubicin-resistant MX-1 human breast cancers.

Purpose: The receptors for luteinizing hormone-releasing hormone receptor (LHRH-R) are found in >50% of human breast cancers. Doxorubicin (DOX) was linked to [D-Lys 6 ]LHRH to form a cytotoxic conjugate, AN-152, which can be targeted to tumor cells expressing LHRH-R. We evaluated the effects of AN-152 on the estrogen-independent, DOX-resistant human mammary carcinoma line MX-1, xenografted into nude mice. Experimental Design: Nude mice bearing MX-1 tumors were administered five i.v. injections of AN-152 or DOX at doses equivalent to 3 mg/kg DOX. Tumor growth was followed, and changes in the expression of LHRH-R on tumors were evaluated by radioreceptor assays, reverse transcription-PCR, and Western blotting. The effects of AN-152 on the expression of human epidermal growth factor receptor (HER)-2 were investigated. Because LHRH-R are coupled to various G proteins, which are involved in mitogenic signaling, we determined the outcome of treatment with AN-152 on the levels of mRNA for different G proteins. Results: Treatment with AN-152 significantly ( P 3 , compared with the control tumors, which measured 2837.38 ± 515.38 mm 3 . Tumor doubling time was likewise significantly ( P i2 , and Gα 11 and the levels of HER-2 and HER-3 proteins were also significantly reduced by AN-152. Conclusions: Cytotoxic LHRH analogue AN-152 could be considered for targeted chemotherapy of DOX-resistant breast cancers expressing LHRH-R