Pre-frontal cortex guides dimension-reducing transformations in the occipito-ventral pathway for categorization behaviors.

To interpret our surroundings, the brain uses a visual categorization process. Current theories and models suggest that this process comprises a hierarchy of different computations that transforms complex, high-dimensional inputs into lower-dimensional representations (i.e., manifolds) in support of multiple categorization behaviors. Here, we tested this hypothesis by analyzing these transformations reflected in dynamic MEG source activity while individual participants actively categorized the same stimuli according to different tasks: face expression, face gender, pedestrian gender, and vehicle type. Results reveal three transformation stages guided by the pre-frontal cortex. At stage 1 (high-dimensional, 50-120 ms), occipital sources represent both task-relevant and task-irrelevant stimulus features; task-relevant features advance into higher ventral/dorsal regions, whereas task-irrelevant features halt at the occipital-temporal junction. At stage 2 (121-150 ms), stimulus feature representations reduce to lower-dimensional manifolds, which then transform into the task-relevant features underlying categorization behavior over stage 3 (161-350 ms). Our findings shed light on how the brain's network mechanisms transform high-dimensional inputs into specific feature manifolds that support multiple categorization behaviors.

A Pediatric Case of Fusobacterium necrophorum Mastoiditis and Meningitis Case Report in a Healthy Child and Review of the Literature.

In infants and children, bacterial meningitis caused by anaerobic bacteria is rare. However, a serious infection with the anaerobe Fusobacterium necrophorum can occur in previously healthy children with a peak incidence in preschool children and in adolescents. As the clinical presentation can be very similar to meningitis caused by aerobic bacteria, one should consider Fusobacterium necrophorum as the causative agent when preceded by or associated with otitis media with purulent otorrhea or mastoiditis, in combination with minimal or no improvement on empiric antibiotic treatment. As this pathogen can be difficult to culture, anaerobic cultures should be obtained. Prompt treatment with a third-generation cephalosporin and metronidazole should be initiated once suspected or confirmed. Surgical source control is often necessary, but even with adequate and prompt treatment, the morbidity and mortality in children with a Fusobacterium necrophorum meningitis remains high. In this report, we describe a case of Fusobacterium necrophorum meningitis in a previously healthy child and review the available literature.

COVID-19 in three waves in a tertiary referral hospital in Belgium: a comparison of patient characteristics, management, and outcome.

PURPOSE: Few studies have compared patient characteristics, clinical management, and outcome of patients with COVID-19 between the different epidemic waves. In this study, we describe patient characteristics, treatment, and outcome of patients admitted for COVID-19 in the Antwerp University Hospital over the first three epidemic waves of 2020-2021. METHODS: Retrospective observational study of COVID-19 patients in a Belgian tertiary referral hospital. All adult patients with COVID-19, hospitalized between February 29, 2020, and June 30, 2021, were included. Standardized routine medical data was collected from patient records. Risk factors were assessed with multivariable logistic regression. RESULTS: We included 722 patients, during the first (n = 179), second (n = 347) and third (n = 194) wave. We observed the lowest disease severity at admission during the first wave, and more elderly and comorbid patients during the second wave. Throughout the subsequent waves we observed an increasing use of corticosteroids and high-flow oxygen therapy. In spite of increasing number of complications throughout the subsequent waves, mortality decreased each wave (16.6%,15.6% 11.9% in 1st, 2nd and 3rd wave respectively). C-reactive protein above 150 mg/L was predictive for the need for intensive care unit admission (odds ratio (OR) 3.77, 95% confidence interval (CI) 2.32-6.15). A Charlson comorbidity index ≥ 5 (OR 5.68, 95% CI 2.54-12.70) and interhospital transfers (OR 3.78, 95% CI 2.05-6.98) were associated with a higher mortality. CONCLUSIONS: We observed a reduction in mortality each wave, despite increasing comorbidity. Evolutions in patient management such as high-flow oxygen therapy on regular wards and corticosteroid use may explain this favorable evolution.

Ongoing exposure to endocrine disrupting phthalates and alternative plasticizers in neonatal intensive care unit patients.

Due to endocrine disrupting effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices, was restricted in the EU Medical Devices Regulation (EU MDR 2017/745) and gradually replaced by alternative plasticizers. Neonates hospitalized in the neonatal intensive care unit (NICU) are vulnerable to toxic effects of plasticizers. From June 2020 to August 2022, urine samples (n = 1070) were repeatedly collected from premature neonates (n = 132, 4-10 samples per patient) born at <31 weeks gestational age and/or <1500 g birth weight in the Antwerp University Hospital, Belgium. Term control neonates (n = 21, 1 sample per patient) were included from the maternity ward. Phthalate and alternative plasticizers' metabolites were analyzed using liquid-chromatography coupled to tandem mass spectrometry. Phthalate metabolites were detected in almost all urine samples. Metabolites of alternative plasticizers, di-(2-ethylhexyl)-adipate (DEHA), di-(2-ethylhexyl)-terephthalate (DEHT) and cyclohexane-1,2-dicarboxylic-di-isononyl-ester (DINCH), had detection frequencies ranging 30-95 %. Urinary phthalate metabolite concentrations were significantly higher in premature compared to control neonates (p = 0.023). NICU exposure to respiratory support devices and blood products showed increased phthalate metabolite concentrations (p < 0.001). Phthalate exposure increased from birth until four weeks postnatally. The estimated phthalate intake exceeded animal-derived no-effect-levels (DNEL) in 10 % of samples, with maximum values reaching 24 times the DNEL. 29 % of premature neonates had at least once an estimated phthalate intake above the DNEL. Preterm neonates are still exposed to phthalates during NICU stay, despite the EU Medical Devices Regulation. NICU exposure to alternative plasticizers is increasing, though currently not regulated, with insufficient knowledge on their hazard profile.

Clinical and molecular epidemiological features of critically ill patients with invasive group A Streptococcus infections: a Belgian multicenter case-series.

BACKGROUND: Recent alerts have highlighted an increase in group A streptococcal (GAS) infections since 2022 in Europe and the United States. Streptococcus pyogenes can cause limited skin or mucosal disease, but can also present as severe invasive disease necessitating critical care. We performed a multicenter retrospective study of patients with GAS infections recently admitted to Belgian intensive care units (ICUs) since January 2022. We describe patient characteristics and investigate the molecular epidemiology of the S. pyogenes strains involved. RESULTS: Between January 2022 and May 2023, a total of 86 cases (56 adults, 30 children) with GAS disease were admitted to critical care in the university hospitals of Leuven, Antwerp and Liège. We noted a strikingly high incidence of severe community-acquired pneumonia (sCAP) (45% of adults, 77% of children) complicated with empyema in 45% and 83% of adult and pediatric cases, respectively. Two-thirds of patients with S. pyogenes pneumonia had viral co-infection, with influenza (13 adults, 5 children) predominating. Other disease presentations included necrotizing fasciitis (23% of adults), other severe skin/soft tissue infections (16% of adults, 13% of children) and ear/nose/throat infections (13% of adults, 13% of children). Cardiogenic shock was frequent (36% of adults, 20% of children). Fifty-six patients (65%) had toxic shock syndrome. Organ support requirements were high and included invasive mechanical ventilation (77% of adults, 50% of children), renal replacement therapy (29% of adults, 3% of children) and extracorporeal membrane oxygenation (20% of adults, 7% of children). Mortality was 21% in adults and 3% in children. Genomic analysis of S. pyogenes strains from 55 out of 86 patients showed a predominance of emm1 strains (73%), with a replacement of the M1global lineage by the toxigenic M1UK lineage (83% of emm1 strains were M1UK). CONCLUSIONS: The recent rise of severe GAS infections (2022-23) is associated with introduction of the M1UK lineage in Belgium, but other factors may be at play-including intense circulation of respiratory viruses and potentially an immune debt after the COVID pandemic. Importantly, critical care physicians should include S. pyogenes as causative pathogen in the differential diagnosis of sCAP.

Social class perception is driven by stereotype-related facial features.

Social class is a powerful hierarchy that determines many privileges and disadvantages. People form impressions of others' social class (like other important social attributes) from facial appearance, and these impressions correlate with stereotype judgments. However, what drives these related subjective judgments remains unknown. That is, what makes someone look like they are of higher or lower social class standing (e.g., rich or poor), and how does this relate to harmful or advantageous stereotypes? We addressed these questions using a perception-based data-driven method to model the specific three-dimensional facial features that drive social class judgments and compared them to those of stereotype-related judgments (competence, warmth, dominance, and trustworthiness), based on White Western culture participants and face stimuli. Using a complementary data-reduction analysis and machine learning approach, we show that social class judgments are driven by a unique constellation of facial features that reflect multiple embedded stereotypes: poor-looking (vs. rich-looking) faces are wider, shorter, and flatter with downturned mouths and darker, cooler complexions, mirroring features of incompetent, cold, and untrustworthy-looking (vs. competent, warm, and trustworthy-looking) faces. Our results reveal the specific facial features that underlie the connection between impressions of social class and stereotype-related social traits, with implications for central social perception theories, including understanding the causal links between stereotype knowledge and social class judgments. We anticipate that our results will inform future interventions designed to interrupt biased perception and social inequalities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cultural facial expressions dynamically convey emotion category and intensity information.

Communicating emotional intensity plays a vital ecological role because it provides valuable information about the nature and likelihood of the sender's behavior.1,2,3 For example, attack often follows signals of intense aggression if receivers fail to retreat.4,5 Humans regularly use facial expressions to communicate such information.6,7,8,9,10,11 Yet how this complex signaling task is achieved remains unknown. We addressed this question using a perception-based, data-driven method to mathematically model the specific facial movements that receivers use to classify the six basic emotions-"happy," "surprise," "fear," "disgust," "anger," and "sad"-and judge their intensity in two distinct cultures (East Asian, Western European; total n = 120). In both cultures, receivers expected facial expressions to dynamically represent emotion category and intensity information over time, using a multi-component compositional signaling structure. Specifically, emotion intensifiers peaked earlier or later than emotion classifiers and represented intensity using amplitude variations. Emotion intensifiers are also more similar across emotions than classifiers are, suggesting a latent broad-plus-specific signaling structure. Cross-cultural analysis further revealed similarities and differences in expectations that could impact cross-cultural communication. Specifically, East Asian and Western European receivers have similar expectations about which facial movements represent high intensity for threat-related emotions, such as "anger," "disgust," and "fear," but differ on those that represent low threat emotions, such as happiness and sadness. Together, our results provide new insights into the intricate processes by which facial expressions can achieve complex dynamic signaling tasks by revealing the rich information embedded in facial expressions.

Strength of predicted information content in the brain biases decision behavior.

Prediction-for-perception theories suggest that the brain predicts incoming stimuli to facilitate their categorization.1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17 However, it remains unknown what the information contents of these predictions are, which hinders mechanistic explanations. This is because typical approaches cast predictions as an underconstrained contrast between two categories18,19,20,21,22,23,24-e.g., faces versus cars, which could lead to predictions of features specific to faces or cars, or features from both categories. Here, to pinpoint the information contents of predictions and thus their mechanistic processing in the brain, we identified the features that enable two different categorical perceptions of the same stimuli. We then trained multivariate classifiers to discern, from dynamic MEG brain responses, the features tied to each perception. With an auditory cueing design, we reveal where, when, and how the brain reactivates visual category features (versus the typical category contrast) before the stimulus is shown. We demonstrate that the predictions of category features have a more direct influence (bias) on subsequent decision behavior in participants than the typical category contrast. Specifically, these predictions are more precisely localized in the brain (lateralized), are more specifically driven by the auditory cues, and their reactivation strength before a stimulus presentation exerts a greater bias on how the individual participant later categorizes this stimulus. By characterizing the specific information contents that the brain predicts and then processes, our findings provide new insights into the brain's mechanisms of prediction for perception.

Myopia management algorithm. Annexe to the article titled Update and guidance on management of myopia. European Society of Ophthalmology in cooperation with International Myopia Institute.

Myopia is becoming increasingly common in young generations all over the world, and it is predicted to become the most common cause of blindness and visual impairment in later life in the near future. Because myopia can cause serious complications and vision loss, it is critical to create and prescribe effective myopia treatment solutions that can help prevent or delay the onset and progression of myopia. The scientific understanding of myopia's causes, genetic background, environmental conditions, and various management techniques, including therapies to prevent or postpone its development and slow its progression, is rapidly expanding. However, some significant information gaps exist on this subject, making it difficult to develop an effective intervention plan. As with the creation of this present algorithm, a compromise is to work on best practices and reach consensus among a wide number of specialists. The quick rise in information regarding myopia management may be difficult for the busy eye care provider, but it necessitates a continuing need to evaluate new research and implement it into daily practice. To assist eye care providers in developing these strategies, an algorithm has been proposed that covers all aspects of myopia mitigation and management. The algorithm aims to provide practical assistance in choosing and developing an effective myopia management strategy tailored to the individual child. It incorporates the latest research findings and covers a wide range of modalities, from primary, secondary, and tertiary myopia prevention to interventions that reduce the progression of myopia.

Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients.

BACKGROUND: Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS: In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS: A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS: The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).

Evaluation of community pharmacist follow-up supported by the use of healthcare technology for type 2 diabetes patients.

Background: Prevalence of type 2 diabetes is high in Belgium (estimated at over 10%, 1 patient out of 3 being unaware of their diagnosis). Management based on a change of lifestyle and the adoption of health-promoting behaviors, supplemented when needed with drug treatment, prevents complications, improves the patient's quality of life and reduces mortality. Multidisciplinary patient support is essential. In this, pharmacists have a key role, e.g. through therapeutic patient education activities, in which they are increasingly involved. Moreover, research suggests that the use of mobile technologies can be a useful tool for helping patients with their daily life and disease management. Objectives: This study aims at exploring the benefits of community pharmacist follow-up supported by the use of mobile technologies in the monitoring of individuals with type 2 diabetes. The presented intervention aimed to reinforce the patients' willingness to actively participate in the management of their disease and to adopt favorable health behaviors, in order to increase their level of medication adherence. Methods: A quantitative quasi-experimental study was conducted in community pharmacies throughout Belgium over a 6-month period with 3 data collection periods (before, during and after the intervention). Primary outcomes, related to the level of medication adherence, and secondary outcomes, considered as markers of the patient's overall health, were analyzed. In addition, qualitative data concerning participants' opinions on their experience were collected. Results: 66 patients participated in the study, with 50 remaining after 3 months and 46 completing the entire study. Statistical analyses did not show an improvement in the level of medication adherence. This parameter was high from the beginning, reflecting patients with controlled diabetes. However, statistically significant results were observed for systolic blood pressure and waist circumference (both improved), while other outcomes showed a positive trend or remained stable. Patient follow-up by the pharmacist was a positive experience for both parties which noted their interest and satisfaction for the project. Conclusions: Although clinical results are not conclusive, patients were motivated and the attrition rate was low. Participants showed their interest in participating in this kind of project, opening up opportunities for further studies in the community pharmacy setting. As front-line health professionals, community pharmacists certainly have a key-role to play in therapeutic patient education and mobile technologies could be additional tools in this process.

The impact of a summative national prescribing assessment and curriculum type on the development of the prescribing competence of junior doctors.

PURPOSE: The primary aim of this study was to investigate the effect of including the Dutch National Pharmacotherapy Assessment (DNPA) in the medical curriculum on the level and development of prescribing knowledge and skills of junior doctors. The secondary aim was to evaluate the relationship between the curriculum type and the prescribing competence of junior doctors. METHODS: We re-analysed the data of a longitudinal study conducted in 2016 involving recently graduated junior doctors from 11 medical schools across the Netherlands and Belgium. Participants completed three assessments during the first year after graduation (around graduation (+ / - 4 weeks), and 6 months, and 1 year after graduation), each of which contained 35 multiple choice questions (MCQs) assessing knowledge and three clinical case scenarios assessing skills. Only one medical school used the DNPA in its medical curriculum; the other medical schools used conventional means to assess prescribing knowledge and skills. Five medical schools were classified as providing solely theoretical clinical pharmacology and therapeutics (CPT) education; the others provided both theoretical and practical CPT education (mixed curriculum). RESULTS: Of the 1584 invited junior doctors, 556 (35.1%) participated, 326 (58.6%) completed the MCQs and 325 (58.5%) the clinical case scenarios in all three assessments. Junior doctors whose medical curriculum included the DNPA had higher knowledge scores than other junior doctors (76.7% [SD 12.5] vs. 67.8% [SD 12.6], 81.8% [SD 11.1] vs. 76.1% [SD 11.1], 77.0% [12.1] vs. 70.6% [SD 14.0], p < 0.05 for all three assessments, respectively). There was no difference in skills scores at the moment of graduation (p = 0.110), but after 6 and 12 months junior doctors whose medical curriculum included the DNPA had higher skills scores (both p < 0.001). Junior doctors educated with a mixed curriculum had significantly higher scores for both knowledge and skills than did junior doctors educated with a theoretical curriculum (p < 0.05 in all assessments). CONCLUSION: Our findings suggest that the inclusion of the knowledge focused DNPA in the medical curriculum improves the prescribing knowledge, but not the skills, of junior doctors at the moment of graduation. However, after 6 and 12 months, both the knowledge and skills were higher in the junior doctors whose medical curriculum included the DNPA. A curriculum that provides both theoretical and practical education seems to improve both prescribing knowledge and skills relative to a solely theoretical curriculum.

Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.

Ferroptosis and pyroptosis signatures in critical COVID-19 patients.

Critical COVID-19 patients admitted to the intensive care unit (ICU) frequently suffer from severe multiple organ dysfunction with underlying widespread cell death. Ferroptosis and pyroptosis are two detrimental forms of regulated cell death that could constitute new therapeutic targets. We enrolled 120 critical COVID-19 patients in a two-center prospective cohort study to monitor systemic markers of ferroptosis, iron dyshomeostasis, pyroptosis, pneumocyte cell death and cell damage on the first three consecutive days after ICU admission. Plasma of 20 post-operative ICU patients (PO) and 39 healthy controls (HC) without organ failure served as controls. Subsets of COVID-19 patients displayed increases in individual biomarkers compared to controls. Unsupervised clustering was used to discern latent clusters of COVID-19 patients based on biomarker profiles. Pyroptosis-related interleukin-18 accompanied by high pneumocyte cell death was independently associated with higher odds at mechanical ventilation, while the subgroup with high interleuking-1 beta (but limited pneumocyte cell death) displayed reduced odds at mechanical ventilation and lower mortality hazard. Meanwhile, iron dyshomeostasis with a tendency towards higher ferroptosis marker malondialdehyde had no association with outcome, except for the small subset of patients with very high catalytic iron independently associated with reduced survival. Forty percent of patients did not have a clear signature of the cell death mechanisms studied in this cohort. Moreover, repeated moderate levels of soluble receptor of advanced glycation end products and growth differentiation factor 15 during the first three days after ICU admission are independently associated with adverse clinical outcome compared to sustained lower levels. Altogether, the data point towards distinct subgroups in this cohort of critical COVID-19 patients with different systemic signatures of pyroptosis, iron dyshomeostasis, ferroptosis or pneumocyte cell death markers that have different outcomes in ICU. The distinct groups may allow 'personalized' treatment allocation in critical COVID-19 based on systemic biomarker profiles.

Hair as an alternative matrix to assess exposure of premature neonates to phthalate and alternative plasticizers in the neonatal intensive care unit.

Due to adverse health effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices (PMDs), was restricted, and gradually replaced by alternative plasticizers (APs). Up to this date, urine was the sole matrix studied for plasticizer exposure in neonates hospitalized in the neonatal intensive care unit (NICU), a population highly vulnerable to toxic effects of plasticizers. The primary aim of this study was to assess simultaneous measurement of phthalate and AP metabolites in neonatal scalp hair. In addition, we aimed to use this matrix to investigate exposure of premature neonates to plasticizers during their stay in the NICU. Hair samples in this study were collected from premature neonates and their mothers included in a prospective birth cohort study in a tertiary NICU at the Antwerp University Hospital (UZA), Belgium. Samples from premature neonates (n = 45) and their mothers (n = 107) as well as from control neonates (n = 24) and mothers (n = 29) were analyzed using liquid-chromatography coupled to tandem mass spectrometry. This is the first study reporting metabolites of phthalate and alternative plasticizers in neonatal hair samples as biomarkers for exposure to these plasticizers. Results showed that hair sampled from premature neonates after a NICU stay contained significantly higher metabolite concentrations of both phthalates (DEHP, DiBP, and DnBP; 9.0-2500, 9.3-2200, and 24.7-5300 ng/g), and alternative plasticizers (DEHA, DEHT, and TOTM; 38.8-3400, 127.5-5700, and 10.8-8700 ng/g) - when compared to healthy control neonates. Besides, DEHP and DEHT metabolite concentrations were significantly higher than in hair sampled from adult populations. In addition, prolonged NICU exposure to non-invasive respiratory support devices and gastric tubes was correlated with increased concentrations in hair samples, indicating accumulation of plasticizers in this alternative matrix. In conclusion, our data indicate that preterm neonates are still highly exposed to phthalate and alternative plasticizers during NICU stay, despite the EU Medical Devices Regulation.

Decrease in the Ratio proBDNF/BDNF in the Urine of Aging Female Patients with OAB.

Imbalance in the levels of neurotrophins, growth factors crucial in the development, function, and survival of neurons is commonly observed in many pathological states. Concentrations of brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) were measured in the urine of a cohort of aging female patients with overactive bladder disease (OAB). When reported to creatinine, levels were similar between OAB patients and healthy controls. However, the ratio proBDNF/BDNF was significantly decreased in the OAB group. Receiver operating characteristic (ROC) curve analysis of the ratio proBDNF/BDNF displayed a good diagnostic value for OAB (AUC = 0.729). Clinical questionnaires of symptom severity (OABSS and IIQ-7) were negatively correlated with this ratio. On the other hand, microRNAs (miRNA) involved in proBDNF gene translation were expressed at comparable levels between groups. However, urinary enzymatic activity of matrix metalloproteinase-9 (MMP-9), the enzyme that cleaves proBDNF into BDNF, was increased in OAB compared to controls. Levels of miR-491-5p, the main miRNA that downregulates MMP-9 synthesis, were greatly decreased in urine from OAB patients. These results suggest that the ratio proBDNF/BDNF could be useful in the phenotyping of OAB in an aging population, and the difference could originate from enhanced MMP-9 enzymatic activity rather than translational control.

Network Communications Flexibly Predict Visual Contents That Enhance Representations for Faster Visual Categorization.

Models of visual cognition generally assume that brain networks predict the contents of a stimulus to facilitate its subsequent categorization. However, understanding prediction and categorization at a network level has remained challenging, partly because we need to reverse engineer their information processing mechanisms from the dynamic neural signals. Here, we used connectivity measures that can isolate the communications of a specific content to reconstruct these network mechanisms in each individual participant (N = 11, both sexes). Each was cued to the spatial location (left vs right) and contents [low spatial frequency (LSF) vs high spatial frequency (HSF)] of a predicted Gabor stimulus that they then categorized. Using each participant's concurrently measured MEG, we reconstructed networks that predict and categorize LSF versus HSF contents for behavior. We found that predicted contents flexibly propagate top down from temporal to lateralized occipital cortex, depending on task demands, under supervisory control of prefrontal cortex. When they reach lateralized occipital cortex, predictions enhance the bottom-up LSF versus HSF representations of the stimulus, all the way from occipital-ventral-parietal to premotor cortex, in turn producing faster categorization behavior. Importantly, content communications are subsets (i.e., 55-75%) of the signal-to-signal communications typically measured between brain regions. Hence, our study isolates functional networks that process the information of cognitive functions.SIGNIFICANCE STATEMENT An enduring cognitive hypothesis states that our perception is partly influenced by the bottom-up sensory input but also by top-down expectations. However, cognitive explanations of the dynamic brain networks mechanisms that flexibly predict and categorize the visual input according to task-demands remain elusive. We addressed them in a predictive experimental design by isolating the network communications of cognitive contents from all other communications. Our methods revealed a Prediction Network that flexibly communicates contents from temporal to lateralized occipital cortex, with explicit frontal control, and an occipital-ventral-parietal-frontal Categorization Network that represents more sharply the predicted contents from the shown stimulus, leading to faster behavior. Our framework and results therefore shed a new light of cognitive information processing on dynamic brain activity.

Is cholesterol a risk factor for breast cancer incidence and outcome?

Cholesterol plays important roles in many physiological processes, including cell membrane structure and function, hormone synthesis, and the regulation of cellular homeostasis. The role of cholesterol in breast cancer is complex, and some studies have suggested that elevated cholesterol levels may be associated with an increased risk of developing breast cancer, while others have found no significant association. On the other hand, other studies have shown that, for total cholesterol and plasma HDL-associated cholesterol levels, there was inverse association with breast cancer risk. One possible mechanism by which cholesterol may contribute to breast cancer risk is as a key precursor of estrogen. Other potential mechanisms by which cholesterol may contribute to breast cancer risk include its role in inflammation and oxidative stress, which have been linked to cancer progression. Cholesterol has also been shown to play a role in signaling pathways regulating the growth and proliferation of cancer cells. In addition, recent studies have shown that cholesterol metabolism can generate tumor promoters such as cholesteryl esters, oncosterone, 27-hydroxycholesterol but also tumor suppressor metabolites such as dendrogenin A. This review summarizes some of the most important clinical studies that have evaluated the role of cholesterol or its derivatives in breast cancer. It also addresses the role of cholesterol and its derivatives at the cellular level.

Risk Factors Associated with Severe RSV Infection in Infants: What Is the Role of Viral Co-Infections?

The respiratory syncytial virus (RSV) represents the leading cause of viral lower respiratory tract infections (LRTI) in children worldwide and is associated with significant morbidity and mortality rates. The clinical picture of an RSV infection differs substantially between patients, and the role of viral co-infections is poorly investigated. During two consecutive winter seasons from October 2018 until February 2020, we prospectively included children up to 2 years old presenting with an acute LRTI, both ambulatory and hospitalized. We collected clinical data and tested nasopharyngeal secretions for a panel of 16 different respiratory viruses with multiplex RT-qPCR. Disease severity was assessed with traditional clinical parameters and scoring systems. A total of 120 patients were included, of which 91.7% were RSV positive; 42.5% of RSV-positive patients had a co-infection with at least one other respiratory virus. We found that patients suffering from a single RSV infection had higher pediatric intensive care unit (PICU) admission rates (OR = 5.9, 95% CI = 1.53 to 22.74), longer duration of hospitalization (IRR = 1.25, 95% CI = 1.03 to 1.52), and a higher Bronchiolitis Risk of Admission Score (BRAS) (IRR = 1.31, 95% CI = 1.02 to 1.70) compared to patients with RSV co-infections. No significant difference was found in saturation on admission, O2 need, or ReSViNET-score. In our cohort, patients with a single RSV infection had increased disease severity compared to patients with RSV co-infections. This suggests that the presence of viral co-infections might influence the course of RSV bronchiolitis, but heterogeneity and small sample size in our study prevents us from drawing strong conclusions. IMPORTANCE RSV is worldwide the leading cause of serious airway infections. Up to 90% of children will be infected by the age of 2. RSV symptoms are mostly mild and typically mimic a common cold in older children and adolescents, but younger children can develop severe lower respiratory tract disease, and currently it is unclear why certain children develop severe disease while others do not. In this study, we found that children with a single RSV infection had a higher disease severity compared to patients with viral co-infections, suggesting that the presence of a viral co-infection could influence the course of an RSV bronchiolitis. As preventive and therapeutic options for RSV-associated disease are currently limited, this finding could potentially guide physicians to decide which patients might benefit from current or future treatment options early in the course of disease, and therefore, warrants further investigation.