Incidence of myopia in Swedish schoolchildren: A longitudinal study.

PURPOSE: The prevalence of myopia in Scandinavia tends to be lower than in other parts of the world. This study aimed to investigate the incidence of myopia and its predictors in Swedish children to characterise this trend. METHODS: A 2-year longitudinal study was conducted following a cohort of schoolchildren aged 8-16 years. Myopia was defined as a spherical equivalent refraction (SER) ≤ -0.50 D. The study enrolled 128 participants, 70 (55%) females with a mean age of 12.0 years (SD = 2.4). RESULTS: The cumulative incidence of myopia during the follow-up period was 5.5%, and the incidence rate of myopia was 3.2 cases per 100 person-years. Participants with myopia at baseline exhibited a faster increase in refractive error during the follow-up period. Likewise, participants with two myopic parents exhibited a more marked change towards myopia, regardless of their initial refractive error. CONCLUSION: In the current study, similar to prevalence, the incidence of myopia was low when compared with other parts of the world. These results lead us to formulate a new hypothesis that the normal emmetropisation process may be protected by low educational pressure practised in Sweden during early childhood. Further research is necessary to test this new hypothesis.

Comparing algorithms to approximate accuracies for single-step genomic best linear unbiased predictor.

The exact accuracy of estimated breeding values can be calculated based on the prediction error variances obtained from the diagonal of the inverse of the left-hand side (LHS) of the mixed model equations (MME). However, inverting the LHS is not computationally feasible for large datasets, especially if genomic information is available. Thus, different algorithms have been proposed to approximate accuracies. This study aimed to: 1) compare the approximated accuracies from 2 algorithms implemented in the BLUPF90 suite of programs, 2) compare the approximated accuracies from the 2 algorithms against the exact accuracy based on the inversion of the LHS of MME, and 3) evaluate the impact of adding genotyped animals with and without phenotypes on the exact and approximated accuracies. Algorithm 1 approximates accuracies based on the diagonal of the genomic relationship matrix (G). In turn, algorithm 2 combines accuracies with and without genomic information through effective record contributions. The data were provided by the American Angus Association and included 3 datasets of growth, carcass, and marbling traits. The genotype file contained 1,235,930 animals, and the pedigree file contained 12,492,581 animals. For the genomic evaluation, a multi-trait model was applied to the datasets. To ensure the feasibility of inverting the LHS of the MME, a subset of data under single-trait models was used to compare approximated and exact accuracies. The correlations between exact and approximated accuracies from algorithms 1 and 2 of genotyped animals ranged from 0.87 to 0.90 and 0.98 to 0.99, respectively. The intercept and slope of the regression of exact on approximated accuracies from algorithm 2 ranged from 0.00 to 0.01 and 0.82 to 0.87, respectively. However, the intercept and the slope for algorithm 1 ranged from -0.10 to 0.05 and 0.98 to 1.10, respectively. In more than 80% of the traits, algorithm 2 exhibited a smaller mean square error than algorithm 1. The correlation between the approximated accuracies obtained from algorithms 1 and 2 ranged from 0.56 to 0.74, 0.38 to 0.71, and 0.71 to 0.97 in the groups of genotyped animals, genotyped animals without phenotype, and proven genotyped sires, respectively. The approximated accuracy from algorithm 2 showed a closer behavior to the exact accuracy when including genotyped animals in the analysis. According to the results, algorithm 2 is recommended for genetic evaluations since it proved more precise.

The genomic estimated breeding value (GEBV) represents an animal's genetic merit calculated using a combination of phenotypes, pedigree, and genomic information through a procedure known as single-step genomic best linear unbiased prediction (ssGBLUP). The accuracy of a GEBV reflects how closely it correlates with the true breeding value. However, calculating accuracies is not computationally feasible for large datasets with genomic information. In this context, methods for approximating accuracies have been proposed and implemented into genetic evaluations. This study aimed to compare 2 algorithms to approximate accuracies for ssGBLUP. In algorithm 1, genomic contributions are based on the diagonal of the genomic relationship matrix (G), combined with contributions from animal records and pedigrees. In turn, algorithm 2 combines accuracies with and without genomic information through effective record contributions. The data for this study were provided by the American Angus Association and included datasets of growth, carcass, and marbling traits. Genotypes were available for 1,235,930 animals, and the pedigree had 12,492,581 animals. We showed that algorithm 2 is better suited for approximating accuracies, as its approximations closely matched the exact accuracy values obtained from the inverse of the mixed model equations.

Strategies to address diabetic kidney disease burden in Mexico: a narrative review by the Mexican College of Nephrologists.

Chronic kidney disease (CKD) is a growing global public health challenge worldwide. In Mexico, CKD prevalence is alarmingly high and remains a leading cause of morbidity and mortality. Diabetic kidney disease (DKD), a severe complication of diabetes, is a leading determinant of CKD. The escalating diabetes prevalence and the complex regional landscape in Mexico underscore the pressing need for tailored strategies to reduce the burden of CKD. This narrative review, endorsed by the Mexican College of Nephrologists, aims to provide a brief overview and specific strategies for healthcare providers regarding preventing, screening, and treating CKD in patients living with diabetes in all care settings. The key topics covered in this review include the main cardiometabolic contributors of DKD (overweight/obesity, hyperglycemia, arterial hypertension, and dyslipidemia), the identification of kidney-related damage markers, and the benefit of novel pharmacological approaches based on Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA). We also address the potential use of novel therapies based on Mineralocorticoid Receptor Antagonists (MRAs) and their future implications. Emphasizing the importance of multidisciplinary treatment, this narrative review aims to promote strategies that may be useful to alleviate the burden of DKD and its associated complications. It underscores the critical role of healthcare providers and advocates for collaborative efforts to enhance the quality of life for millions of patients affected by DKD.

Effects of the Use of Neuronavigation in Patients with Supratentorial Brain Gliomas: A Cohort Study.

OBJECTIVE: Despite the growing acceptance of neuronavigation in the field of neurosurgery, there is limited comparative research with contradictory results. This study aimed to compare the effectiveness (tumor resection rate and survival) and safety (frequency of neurological complications) of surgery for brain gliomas with or without neuronavigation. METHODS: This retrospective cohort study evaluated data obtained from electronic records of patients who underwent surgery for gliomas at Dr. Alejandro Dávila Bolaños Military Hospital and the Clinic Hospital of Barcelona between July 2016 and September 2022. The preoperative and postoperative clinical and radiologic characteristics were analyzed and compared according to the use of neuronavigation. RESULTS: This study included 110 patients, of whom 79 underwent surgery with neuronavigation. Neuronavigation increased gross total resection by 57% in patients in whom it was used; gross total resection was performed in 56% of patients who underwent surgery with neuronavigation as compared with 35.5% in those who underwent surgery without neuronavigation (risk ratio [RR], 1.57; P=0.056). The incidence of postoperative neurologic deficits (transient and permanent) decreased by 79% with the use of neuronavigation, (12% vs. 33.3%; RR, 0.21; P=0.0003). Neuronavigation improved survival in patients with grade IV gliomas (15 months vs. 13.8 months), but it was not statistically significant (odds ratio (OR), 0.19; P=0.13). CONCLUSIONS: Neuronavigation improved the effectiveness (greater gross total resection of tumors) and safety (fewer neurological deficits) of brain glioma surgery. However, neuronavigation does not significantly influence the survival of patients with grade IV gliomas.

Pixel-wise programmability enables dynamic high-SNR cameras for high-speed microscopy.

High-speed wide-field fluorescence microscopy has the potential to capture biological processes with exceptional spatiotemporal resolution. However, conventional cameras suffer from low signal-to-noise ratio at high frame rates, limiting their ability to detect faint fluorescent events. Here, we introduce an image sensor where each pixel has individually programmable sampling speed and phase, so that pixels can be arranged to simultaneously sample at high speed with a high signal-to-noise ratio. In high-speed voltage imaging experiments, our image sensor significantly increases the output signal-to-noise ratio compared to a low-noise scientific CMOS camera (~2-3 folds). This signal-to-noise ratio gain enables the detection of weak neuronal action potentials and subthreshold activities missed by the standard scientific CMOS cameras. Our camera with flexible pixel exposure configurations offers versatile sampling strategies to improve signal quality in various experimental conditions.

Reducing delivery insurance costs through risk score model for food delivery company.

In this paper, we propose a novel pricing model for delivery insurance in a food delivery company in Latin America, with the aim of reducing the high costs associated with the premium paid to the insurer. To achieve this goal, a thorough analysis was conducted to estimate the probability of losses based on delivery routes, transportation modes, and delivery drivers' profiles. A large amount of data was collected and used as a database, and various statistical models and machine learning techniques were employed to construct a comprehensive risk profile and perform risk classification. Based on the risk classification and the estimated probability associated with it, a new pricing model for delivery insurance was developed using advanced mathematical algorithms and machine learning techniques. This new pricing model took into account the pattern of loss occurrence and high and low-risk behaviors, resulting in a significant reduction of insurance costs for both the contracting company and the insurer. The proposed pricing model also allowed for greater flexibility in insurance contracting, making it more accessible and appealing to delivery drivers. The use of estimated loss probabilities and a risk score for the pricing of delivery insurance proved to be a highly effective and efficient alternative for reducing the high costs associated with insurance, while also improving the profitability and competitiveness of the food delivery company in Latin America.

Blood Phytosterol Concentration and Genetic Variant Associations in a Sample Population.

The main objective of this study was to determine plasma levels of PS and to study SNVs rs41360247, rs4245791, rs4148217, and rs11887534 of ABCG8 and the r657152 SNV at the ABO blood group locus in a sample of a population treated at our hospital, and to determine whether these SNVs are related to plasma PS concentrations. The secondary objective was to establish the variables associated with plasma PS concentrations in adults. Participants completed a dietary habit questionnaire and a blood sample was collected to obtain the following variables: campesterol, sitosterol, sitostanol, lanosterol, stigmasterol, biochemical parameters, and the SNVs. In addition, biometric and demographic variables were also recorded. In the generalized linear model, cholesterol and age were positively associated with total PS levels, while BMI was negatively related. For rs4245791, homozygous T allele individuals showed a significantly lower campesterol concentration compared with C homozygotes, and the GG alleles of rs657152 had the lowest levels of campesterol compared with the other alleles of the SNV. Conclusions: The screening of certain SNVs could help prevent the increase in plasma PS and maybe PNALD in some patients. However, further studies on the determinants of plasma phytosterol concentrations are needed.

Effects of a home care community-dwelling intervention on cognition, mental health, loneliness and quality of life in elder people: The VERA study.

BACKGROUND: New technologies can provide practical solutions that respond to the needs of the elderly, improving their quality of life and well-being. The aim of this research was to validate a multimodal approach based on a video call system, by comparing the scores of different clinically validated tests at baseline and at the end of the intervention. METHODS: A longitudinal study was conducted with 7 healthy participants aged 61 to 92 years over a 6-month period. To measure the effectiveness of the intervention, five variables were assessed: cognitive impairment, quality of life, general health, perceived loneliness, and depression. The following inventories were used as instruments to measure the aforementioned variables at baseline, mid intervention and after intervention: MEC-35 scale, Fototest, FUMAT scale, WHOQOL-BREF scale, Yesavage Geriatric Depression Scale, the Spanish adaptation of the Hamilton Scale, the revised ESTE scale and the Goldberg's GHQ28 Mental Health scale. RESULT: The obtained results confirmed our hypothesis and the participants showed significant improvements after intervention in all the assessed domains except the cognitive domain, as expected. Results in FUMAT, WHOQOL-BREF, Yesavage Geriatric Depression, revised ESTE and the Goldberg's GHQ28 Mental Health scales were statistically significant (p < 0.05) and the effect sizes were large after intervention compare to baseline. CONCLUSIONS: We have shown that the intervention has been effective in providing the participants with psychological and social benefits in the variables of quality of life, general health, perceived loneliness and depression. The high clinical relevance achieved from the results obtained makes the system a very suitable tool to promote the independence and well-being of people who receive community-dwelling home care.

Virulent systemic feline calicivirus infection: a case report and first description in Ireland.

BACKGROUND: Virulent systemic feline calicivirus (VS-FCV) infection is an emerging disease. It is distinct from classic oronasal calicivirus infection as it manifests with unique systemic signs including severe cutaneous ulcerations, limb oedema, and high mortality, even in adequately vaccinated cats. Devastating epizootic outbreaks with hospital-acquired infections have been described in the United States, the United Kingdom, continental Europe and Australia with up to 54 cats affected in one outbreak and a mortality rate of up to 86%. This highly contagious and potentially fatal disease has not yet been reported in Ireland. CASE PRESENTATION: An 11-month-old male neutered vaccinated domestic shorthair cat was presented with a 10-day history of lethargy, decreased appetite and progressively worsening pitting oedema in all four limbs. The signs were first noted after another kitten from a high-density cat shelter was introduced in to the household. Additional physical examination findings included marked pyrexia, and lingual and cutaneous ulcers. Virulent systemic feline calicivirus was diagnosed based on compatible history and clinical signs, exclusion of other causes, and calicivirus isolation by RT-PCR both in blood and oropharyngeal samples. Negative calicivirus RT-PCR in blood following resolution of the clinical signs further supported the diagnosis. CONCLUSION: This case represents the first known case of VS-FCV infection in Ireland. Given the severity of the clinical signs, and the high risk for epizootic outbreaks, Irish veterinarians should be aware of the disease to ensure prompt diagnosis and implementation of adequate preventive measures, in order to limit the threat that this disease represents for the wider cat population and particularly given the risk of hospital-acquired VS-FCV infection. Virulent systemic calicivirus should be suspected in cats with pyrexia of unknown origin, oedema or ulceration affecting the limbs or the face, and exposure to rescue cats from high-density households.

Home-based exercise interventions' impact on breast cancer survivors' functional performance: a systematic review.

INTRODUCTION: Home-based exercise (HBE) programs can be a feasible strategy to enhance functional performance and promote physical activity (PA) in breast cancer survivors. A deeper analysis of the effects of HBE interventions, structured by HBE program type and treatment phase, is needed. This systematic review aimed to synthesize the evidence on HBE interventions' impact on breast cancer survivors' functional performance, PA levels, and program adherence rates, according to HBE intervention type and treatment phase. METHODS: A comprehensive search of peer-reviewed articles reporting HBE interventions' effects on the outcomes of interest was performed in Pubmed, Google Scholar, EBSCO, Web of Science, Science Direct, and B-ON until January 15th, 2024. Data were synthesized according to Denton's domains to classify HBE interventions (prescription: structured vs. unstructured; Delivery method: supervised vs. facilitated vs. unsupervised) and treatment phase. Methodological quality appraisal was performed using the Effective Public Health Practice Project tool. RESULTS: Twenty-six studies were included. Most studies conducted structured/facilitated interventions and reported positive effects on functional performance (particularly aerobic capacity), increases in PA levels, and high adherence rates (> 70%) during and post-treatment. CONCLUSION: HBE interventions may be feasible to improve functional performance and promote physical activity among breast cancer survivors. Further studies are needed to confirm which HBE intervention type is more appropriate for each treatment phase. More evidence applying HBE interventions with different designs is required to allow the drawing of more solid conclusions. Studies exploring the effects of HBE interventions on the pre-treatment phase are needed.

Genomic analysis of feed efficiency traits in beef cattle using random regression models.

Feed efficiency plays a major role in the overall profitability and sustainability of the beef cattle industry, as it is directly related to the reduction of the animal demand for input and methane emissions. Traditionally, the average daily feed intake and weight gain are used to calculate feed efficiency traits. However, feed efficiency traits can be analysed longitudinally using random regression models (RRMs), which allow fitting random genetic and environmental effects over time by considering the covariance pattern between the daily records. Therefore, the objectives of this study were to: (1) propose genomic evaluations for dry matter intake (DMI), body weight gain (BWG), residual feed intake (RFI) and residual weight gain (RWG) data collected during an 84-day feedlot test period via RRMs; (2) compare the goodness-of-fit of RRM using Legendre polynomials (LP) and B-spline functions; (3) evaluate the genetic parameters behaviour for feed efficiency traits and their implication for new selection strategies. The datasets were provided by the EMBRAPA-GENEPLUS beef cattle breeding program and included 2920 records for DMI, 2696 records for BWG and 4675 genotyped animals. Genetic parameters and genomic breeding values (GEBVs) were estimated by RRMs under ssGBLUP for Nellore cattle using orthogonal LPs and B-spline. Models were compared based on the deviance information criterion (DIC). The ranking of the average GEBV of each test week and the overall GEBV average were compared by the percentage of individuals in common and the Spearman correlation coefficient (top 1%, 5%, 10% and 100%). The highest goodness-of-fit was obtained with linear B-Spline function considering heterogeneous residual variance. The heritability estimates across the test period for DMI, BWG, RFI and RWG ranged from 0.06 to 0.21, 0.11 to 0.30, 0.03 to 0.26 and 0.07 to 0.27, respectively. DMI and RFI presented within-trait genetic correlations ranging from low to high magnitude across different performance test-day. In contrast, BWG and RWG presented negative genetic correlations between the first 3 weeks and the other days of performance tests. DMI and RFI presented a high-ranking similarity between the GEBV average of week eight and the overall GEBV average, with Spearman correlations and percentages of individuals selected in common ranging from 0.95 to 1.00 and 93 to 100, respectively. Week 11 presented the highest Spearman correlations (ranging from 0.94 to 0.98) and percentages of individuals selected in common (ranging from 85 to 94) of BWG and RWG with the average GEBV of the entire period of the test. In conclusion, the RRM using linear B-splines is a feasible alternative for the genomic evaluation of feed efficiency. Heritability estimates of DMI, RFI, BWG and RWG indicate enough additive genetic variance to achieve a moderate response to selection. A new selection strategy can be adopted by reducing the performance test to 56 days for DMI and RFI selection and 77 days for BWG and RWG selection.

Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Sabatolimab is an immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), an immuno-myeloid regulator expressed on immune cells and leukaemic stem cells. In this trial, we compared the efficacy and safety of sabatolimab plus hypomethylating agent with placebo plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes. METHODS: STIMULUS-MDS1 was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study done at 54 investigational sites in 17 countries. Adult patients (aged ≥18 years) with intermediate-risk, high-risk, and very high-risk myelodysplastic syndromes (according to Revised International Prognostic Scoring System criteria) who had not received previous treatment were included. Patients were randomly assigned (1:1) to intravenous sabatolimab (400 mg on day 8 and 22) or placebo plus a hypomethylating agent (intravenous decitabine 20 mg/m2 on day 1-5 or intravenous or subcutaneous azacitidine 75 mg/m2 on day 1-7 or day 1-5 and day 8 and 9) every 28 days until treatment discontinuation. The two primary endpoints were complete response rate and progression-free survival, assessed in the full analysis set, which included all randomly assigned patients. Complete response was analysed, as prespecified, 7 months after the last patient was randomly assigned. All other analyses presented, including progression-free survival, were done at the final data cutoff prespecified via a protocol amendment on Sept 2, 2021. Safety was assessed in in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03946670, and is ongoing. FINDINGS: Between July 29, 2019, and Aug 10, 2020, 127 patients were randomly assigned to sabatolimab plus a hypomethylating agent group (sabatolimab group; n=65) or placebo plus a hypomethylating agent (placebo group; n=62). The median age of participants was 73 years (IQR 69-77), of whom 86 (68%) of 127 patients were male and 77 (61%) were White. The primary endpoints were not met. Complete response (cutoff date of March 10, 2021) was achieved in 14 (22%; 95% CI 12·3-33·5) of 65 patients in the sabatolimab group vs 11 (18%; 9·2-29·5) of 62 patients in the placebo group (p=0·77). At the cutoff date of the final analysis (March 1, 2022), median follow-up for progression-free survival was 17·8 months (IQR 16·6-19·4) in the sabatolimab group and 19·2 months (17·7-22·3) in the placebo group, and the median progression-free survival was 11·1 months (95% CI 7·6-17·6) in the sabatolimab group vs 8·5 months (6·9-11·3) in the placebo group (hazard ratio 0·75 [95% CI 0·48-1·17]; p=0·1022). The most common adverse events of any grade were neutropenia (35 [56%] of 62 patients in the sabatolimab group vs 43 [68%] of 63 patients in the placebo group), thrombocytopenia (30 [48%] vs 32 [51%]), constipation (29 [47%] vs 24 [38%]), diarrhoea (27 [44%] vs 14 [22%]), anaemia (22 [35%] vs 34 [54%]), febrile neutropenia (22 [35%] vs 15 [24%]), and leukopenia (15 [24%] vs 20 [32%]). One patient developed a serious potential treatment-related immune-mediated adverse event in the sabatolimab group. There was one treatment-related death in the sabatolimab group due to pneumonitis. INTERPRETATION: The addition of sabatolimab to hypomethylating agents in this study did not result in a significant improvement in complete response rates or progression-free survival. Sabatolimab had a manageable safety in most patients with higher-risk myelodysplastic syndromes. A randomised phase 3 trial is ongoing to assess the potential benefit of sabatolimab plus azacitidine on overall survival in this setting. FUNDING: Novartis Pharmaceuticals.

The Influence of Perceived Security in Childhood on Adult Self-Concept: The Mediating Role of Resilience and Self-Esteem.

Secure attachment, developed through consistent relationships with attachment figures in childhood, is a crucial factor in fostering healthy interpersonal relationships and a positive self-perception. Part of the positive parenting approach and the theory of affect is taken as a basis to assess how perceived security, as an indicator of secure attachment, predicts adult self-concept through the mediating effects of resilience and positive self-esteem. A quantitative, cross-sectional, and nonprobabilistic study was conducted with 383 participants. We unveiled significant positive associations between perceived security, self-concept, resilience, and positive self-esteem. Path analysis demonstrated that resilience and positive self-esteem sequentially mediate the relationship between perceived security during childhood and adult self-concept. Findings suggest that the ability to cope with adversity and personal acceptance underlie the impact of perceived security on self-concept. It is recommended to promote family intervention programs framed within positive parenting that focus on fostering secure attachment given its influence on adult life. It is also deemed essential to incorporate the promotion of resilience and self-esteem into programs aimed at youths, and adult role models can enhance their self-perception and resilience in the face of potential effects stemming from insecure parenting practices.

Impact of vaccination against COVID-19 on patients with cancer in ACHOC-C19 study: Real world evidence from one Latin American country.

Introduction: During the pandemic, it has been recommended that vaccination against COVID-19 be a priority for patients with cancer; however, these patients were not included in the initial studies evaluating the available vaccines. Objective: To define the impact of vaccination against COVID-19 in preventing the risk of complications associated with the infection in a cohort of patients with cancer in Colombia. Methods: An analytical observational cohort study, based on national registry of patients with cancer and COVID 19 infection ACHOC-C19, was done. The data was collected from June 2021, until October 2021. Inclusion criteria were: Patients older than 18 years with cancer diagnosis and confirmed COVID-19 infection. Data from the unvaccinated and vaccinated cohorts were compared. Outcomes evaluated included all-cause mortality within 30 days of COVID-19 diagnosis, hospitalization, and need for mechanical ventilation. The estimation of the effect was made through the relative risk (RR), the absolute risk reduction (ARR) and the number needed to treat (NNT). Multivariate analysis was performed using generalized linear models. Results: 896 patients were included, of whom 470 were older than 60 years (52.4%) and 59% were women (n=530). 172 patients were recruited in the vaccinated cohort and 724 in the non-vaccinated cohort (ratio: 1 to 4.2). The cumulative incidence of clinical outcomes among the unvaccinated vs vaccinated patients were: for hospitalization 42% (95% CI: 38.7%-46.1%) vs 29%; (95% CI: 22.4%-36.5%); for invasive mechanical ventilation requirement 8.4% (n=61) vs 4.6% (n=8) and for mortality from all causes 17% (n=123) vs 4.65% (n=8). Conclusion: In our population, unvaccinated patients with cancer have an increased risk of complications for COVID -19 infection, as hospitalization, mechanical ventilation, and mortality. It is highly recommended to actively promote the vaccination among this population.

Hippocampal memory reactivation during sleep is correlated with specific cortical states of the retrosplenial and prefrontal cortices.

Episodic memories are thought to be stabilized through the coordination of cortico-hippocampal activity during sleep. However, the timing and mechanism of this coordination remain unknown. To investigate this, we studied the relationship between hippocampal reactivation and slow-wave sleep up and down states of the retrosplenial cortex (RTC) and prefrontal cortex (PFC). We found that hippocampal reactivations are strongly correlated with specific cortical states. Reactivation occurred during sustained cortical Up states or during the transition from up to down state. Interestingly, the most prevalent interaction with memory reactivation in the hippocampus occurred during sustained up states of the PFC and RTC, while hippocampal reactivation and cortical up-to-down state transition in the RTC showed the strongest coordination. Reactivation usually occurred within 150-200 msec of a cortical Up state onset, indicating that a buildup of excitation during cortical Up state activity influences the probability of memory reactivation in CA1. Conversely, CA1 reactivation occurred 30-50 msec before the onset of a cortical down state, suggesting that memory reactivation affects down state initiation in the RTC and PFC, but the effect in the RTC was more robust. Our findings provide evidence that supports and highlights the complexity of bidirectional communication between cortical regions and the hippocampus during sleep.

Next-generation sequencing of baseline genetic mutations and outcomes of eltrombopag and azacitidine therapy in patients with myelodysplastic syndromes and thrombocytopenia: Data from the SUPPORT clinical trial.

Eltrombopag has been previously shown to be effective in reversing azacitidine-mediated thrombocytopenia. This was further investigated in the SUPPORT trial, a phase III study assessing the efficacy/safety of eltrombopag plus azacitidine in patients with intermediate- to high-risk myelodysplastic syndromes and thrombocytopenia. The results did not support a clinical benefit for the addition of eltrombopag to azacitidine. We investigated if the somatic mutational profiles in the patient cohort were associated with treatment outcomes. Based on the available data, we observed no imbalance in the mutational profiles between treatment arms or a clear association between identified somatic mutations and clinical outcomes.

Synergistic depolymerisation of alginate and chitosan by high hydrostatic pressure (HHP) and pulsed electric fields (PEF) treatment in the presence of H2O2.

Physically-induced depolymerisation procedures are often preferred for obtaining alginate and chitosan oligosaccharides as they either do not use or make minimal use of additional chemicals; therefore, separation of the final products is facile. In this work, solutions of three types of alginate with different mannuronic and guluronic acid residues ratio (M/G ratio) and molecular weights (Mw) and one type of chitosan were non-thermally processed by applying high hydrostatic pressures (HHP) up to 500 MPa (20 min) or pulsed electric fields (PEF) up to 25 kV cm-1 (4000 µm) in the absence or presence of 3 % hydrogen peroxide (H2O2). The impact on the physicochemical properties of alginate and chitosan was investigated by rheology, GPC, XRD, FTIR, and 1H NMR. In the rheological investigations, the apparent viscosities of all samples decreased with increasing shear rate, indicating a non-Newtonian shear-thinning behaviour. GPC results reported Mw reductions that ranged between 8 and 96 % for all treatments. NMR results revealed that HHP and PEF treatment predominantly reduced the M/G ratio of alginate and the degree of deacetylation (DDA) of chitosan, whilst H2O2 promoted an increase in the M/G ratio in alginate and DDA of chitosan. Overall, the present investigation has demonstrated the feasibility of HHP and PEF for rapidly producing alginate and chitosan oligosaccharides.

Salivary Cortisol in Guide Dogs.

Guide dogs work for extended periods and are exposed to multiple environmental stimuli that could lead to higher stress compared with companion dogs. Cortisol is the main hormone associated with stress in most mammals. This study included seven guide dogs and seven same-breed dogs that were trained as guide dogs but became companion dogs to compare their salivary cortisol levels before, during, and after a period of social isolation and exposure to a 110-decibel gunshot sound. Each dog was left alone in an empty room for 60 min. After 15 min, the dogs were exposed to the sound. We collected four saliva samples from each dog. The first one was taken 5 min before starting the social isolation period, and the following ones at 15, 30, and 45 min after the test started. A two-way ANOVA was used to compare the group effect and the time effect during isolation and noise exposure. The results showed higher levels of cortisol in the guide dogs compared with the companion dogs throughout the test. No differences were found in time or in the interaction between time and group. This suggests that being a guide dog increases levels of basal cortisol when compared with dogs that live as companion animals and family members.