Dissection of a Down syndrome-associated trisomy to separate the gene dosage-dependent and -independent effects of an extra chromosome.

As an aneuploidy, trisomy is associated with mammalian embryonic and postnatal abnormalities. Understanding the underlying mechanisms involved in mutant phenotypes is broadly important and may lead to new strategies to treat clinical manifestations in individuals with trisomies, such as trisomy 21 [Down syndrome (DS)]. Although increased gene dosage effects because of a trisomy may account for the mutant phenotypes, there is also the possibility that phenotypic consequences of a trisomy can arise because of the presence of a freely segregating extra chromosome with its own centromere, i.e. a 'free trisomy' independent of gene dosage effects. Presently, there are no reports of attempts to functionally separate these two types of effects in mammals. To fill this gap, here we describe a strategy that employed two new mouse models of DS, Ts65Dn;Df(17)2Yey/+ and Dp(16)1Yey/Df(16)8Yey. Both models carry triplications of the same 103 human chromosome 21 gene orthologs; however, only Ts65Dn;Df(17)2Yey/+ mice carry a free trisomy. Comparison of these models revealed the gene dosage-independent impacts of an extra chromosome at the phenotypic and molecular levels for the first time. They are reflected by impairments of Ts65Dn;Df(17)2Yey/+ males in T-maze tests when compared with Dp(16)1Yey/Df(16)8Yey males. Results from the transcriptomic analysis suggest the extra chromosome plays a major role in trisomy-associated expression alterations of disomic genes beyond gene dosage effects. This model system can now be used to deepen our mechanistic understanding of this common human aneuploidy and obtain new insights into the effects of free trisomies in other human diseases such as cancers.

SARS-CoV-2's brain impact: revealing cortical and cerebellar differences via cluster analysis in COVID-19 recovered patients.

BACKGROUND: COVID-19 is a disease known for its neurological involvement. SARS-CoV-2 infection triggers neuroinflammation, which could significantly contribute to the development of long-term neurological symptoms and structural alterations in the gray matter. However, the existence of a consistent pattern of cerebral atrophy remains uncertain. OBJECTIVE: Our study aimed to identify patterns of brain involvement in recovered COVID-19 patients and explore potential relationships with clinical variables during hospitalization. METHODOLOGY: In this study, we included 39 recovered patients and 39 controls from a pre-pandemic database to ensure their non-exposure to the virus. We obtained clinical data of the patients during hospitalization, and 3 months later; in addition we obtained T1-weighted magnetic resonance images and performed standard screening cognitive tests. RESULTS: We identified two groups of recovered patients based on a cluster analysis of the significant cortical thickness differences between patients and controls. Group 1 displayed significant cortical thickness differences in specific cerebral regions, while Group 2 exhibited significant differences in the cerebellum, though neither group showed cognitive deterioration at the group level. Notably, Group 1 showed a tendency of higher D-dimer values during hospitalization compared to Group 2, prior to p-value correction. CONCLUSION: This data-driven division into two groups based on the brain structural differences, and the possible link to D-dimer values may provide insights into the underlying mechanisms of SARS-COV-2 neurological disruption and its impact on the brain during and after recovery from the disease.

Efficacy and Safety of Erenumab, Galcanezumab, and Fremanezumab in the Treatment of Drug-Resistant Chronic Migraine: Experience in Real Clinical Practice.

BACKGROUND: Due to the recent introduction of new biologic drugs for chronic migraine, a global evaluation in real clinical practice is necessary. OBJECTIVE: The objective was to evaluate the effectiveness and safety in real clinical practice of drugs targeting the calcitonin gene-related peptide receptor (CGRPr) in patients with chronic migraine. METHODS: Single-center, restrospective study (2019-2022), including patients with chronic migraine treated with erenumab, galcanezumab, or fremanezumab. Effectiveness variables were recorded, namely, number of migraine headache days per month (MHD), Migraine Disability Assessment Scale (MIDAS) score, and Headache Impact Test-6 (HIT-6) score, assessing changes at week 12, 24 from baseline. Toxicity was recorded following the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. RESULTS: In all, 104 patients were included (46.2% erenumab, 41.3% galcanezumab, 12.5% fremanezumab). A reduction in MHD, MIDAS, and HIT-6 was achieved at weeks 12 and 24 with erenumab (p75% at week 24 than those intensified; P = 0.041). There was no difference in efficacy (P = 0.154) or improvement in quality of life (P = 0.783, P = 0.150), but there was greater toxicity (P < 0.001) among nonresponders with erenumab 70 mg versus erenumab 140 mg. CONCLUSIONS: The results confirm the effectiveness and safety of anticalcitonin gene-related peptide (CGRP) drugs in real clinical practice. However, the study shows little benefit from erenumab intensification, with similar effectiveness and worse tolerability than the standard dose.

Association between prolonged corticosteroids use in COVID-19 and increased mortality in hospitalized patients: a retrospective study with inverse probability of treatment weighting analysis.

BACKGROUND: Previous studies have demonstrated a beneficial effect of early use of corticosteroids in patients with COVID-19. This study aimed to compare hospitalized patients with COVID-19 who received short-course corticosteroid treatment with those who received prolonged-course corticosteroid treatment to determine whether prolonged use of corticosteroids improves clinical outcomes, including mortality. METHODS: This is a retrospective cohort study including adult patients with positive testing for Sars-CoV-2 hospitalized for more than 10 days. Data were obtained from electronic medical records. Patients were divided into two groups, according to the duration of treatment with corticosteroids: a short-course (10 days) and a prolonged-course (longer than 10 days) group. Inverse probability treatment weighting (IPTW) analysis was used to evaluate whether prolonged use of corticosteroids improved outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were hospital infection and the association of different doses of corticosteroids with hospital mortality. Restricted cubic splines were used to assess the nonlinear association between mortality and dose and duration of corticosteroids use. RESULTS: We enrolled 1,539 patients with COVID-19. Among them, 1127 received corticosteroids for more than 10 days (prolonged-course group). The in-hospital mortality was higher in patients that received prolonged course corticosteroids (39.5% vs. 26%, p < 0.001). The IPTW revealed that prolonged use of corticosteroids significantly increased mortality [relative risk (RR) = 1.52, 95% confidence interval (95% CI): 1.24-1.89]. In comparison to short course treatment, the cubic spline analysis showed an inverted U-shaped curve for mortality, with the highest risk associated with the prolonged use at 30 days (RR = 1.50, 95% CI 1.21-1.78). CONCLUSIONS: Prolonged course of treatment with corticosteroids in hospitalized patients with COVID-19 was associated with higher mortality.

Mapping the Cerebellar Cognitive Affective Syndrome in Patients with Chronic Cerebellar Strokes.

The cerebellar cognitive affective syndrome (CCAS) has been consistently described in patients with acute/subacute cerebellar injuries. However, studies with chronic patients have had controversial findings that have not been explored with new cerebellar-target tests, such as the CCAS scale (CCAS-S). The objective of this research is to prove and contrast the usefulness of the CCAS-S and the Montreal Cognitive Assessment (MoCA) test to evaluate cognitive/affective impairments in patients with chronic acquired cerebellar lesions, and to map the cerebellar areas whose lesions correlated with dysfunctions in these tests. CCAS-S and MoCA were administrated to 22 patients with isolated chronic cerebellar strokes and a matched comparison group. The neural bases underpinning both tests were explored with multivariate lesion-symptom mapping (LSM) methods. MoCA and CCAS-S had an adequate test performance with efficient discrimination between patients and healthy volunteers. However, only impairments determined by the CCAS-S resulted in significant regional localization within the cerebellum. Specifically, patients with chronic cerebellar lesions in right-lateralized posterolateral regions manifested cognitive impairments inherent to CCAS. These findings concurred with the anterior-sensorimotor/posterior-cognitive dichotomy in the human cerebellum and revealed clinically intra- and cross-lobular significant regions (portions of right lobule VI, VII, Crus I-II) for verbal tasks that overlap with the "language" functional boundaries in the cerebellum. Our findings prove the usefulness of MoCA and CCAS-S to reveal cognitive impairments in patients with chronic acquired cerebellar lesions. This study extends the understanding of long-term CCAS and introduces multivariate LSM methods to identify clinically intra- and cross-lobular significant regions underpinning chronic CCAS.

Critical role of acute hypoxemia on the cognitive impairment after severe COVID-19 pneumonia: a multivariate causality model analysis.

BACKGROUND: A high proportion of coronavirus disease 2019 (COVID-19) survivors may develop long-term cognitive impairment. We aimed to develop a multivariate causal model exposing the links between COVID-19-associated biomarkers, illness-related variables, and their effects on cognitive performance. METHODS: In this prospective study, we assess the potential drivers for the development of cognitive impairment in patients with severe COVID-19 pneumonia aged ≥ 18 years at 6-month follow-up after hospital discharge, using the Montreal Cognitive Assessment (MoCA). Patients with pre-existing cognitive impairment were excluded. Laboratory results at hospital admission were clustered by principal component analysis (PCA) and included in a path analysis model evaluating the causal relationship between age, comorbidities, hypoxemia, invasive mechanical ventilation (IMV) requirement, in-hospital delirium, and cognitive performance. RESULTS: We studied 92 patients: 54 (58.7%) men and 38 (41.3%) women, with median age of 50 years (interquartile range 42-55), among whom 50 (54.4%) tested positive for cognitive impairment at 6-month follow-up. Path analysis revealed a direct link between the thrombo-inflammatory component of PCA (C-reactive protein, fibrinogen, and neutrophils) and hypoxemia severity at hospital admission. Our model showed that low PaO2/FiO2 ratio values, unlike the thrombo-inflammatory component, had a direct effect on cognitive performance, independent from age, in-hospital delirium, and invasive mechanical ventilation. CONCLUSION: In this study, biomarkers of thrombo-inflammation in COVID-19 and low PaO2/FiO2 had a negative effect on cognitive performance 6 months after hospital discharge. These results highlight the critical role of hypoxemia as a driver for impaired cognition in the mid-term.

Frontostriatal Circuits Alterations Associated with Cognitive Flexibility Deterioration in Huntington's Disease.

BACKGROUND: Recent resting-state functional magnetic resonance imaging studies have reported abnormal functional connectivity (FC) in the prefrontal cortex (PFC)-striatum circuit in patients with premanifest Huntington's disease (HD). However, there is a lack of evidence showing persistence of abnormal frontostriatal FC and its relation to cognitive flexibility performance in patients with clinically manifest HD. OBJECTIVE: The aim of this study was to evaluate the resting-state FC integrity of the frontostriatal circuit and its relation to cognitive flexibility in HD patients and healthy controls (HCs). METHOD: Eighteen patients with early clinical HD manifestation and 18 HCs matched for age, sex, and education participated in this study. Both groups performed the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional (IED) set-shift task, which measures cognitive flexibility. Resting-state functional magnetic resonance images were also acquired to examine the FC in specific frontostriatal circuits. Eight regions of interest were preselected based on regions previously associated with extradimensional (ED) shifting in patients with premanifest HD. RESULTS: Significant negative correlations between the number of attentional set-shifting errors and the ventral striatum-ventrolateral PFC FC were found in the HD group. This group also showed negative FC correlations between the total errors and the FC between right ventral striatum-right ventrolateral PFC, left ventral striatum-left ventrolateral PFC, and right ventral striatum-left ventrolateral PFC. Negative correlations between the ED errors and left ventral striatum-left ventrolateral PFC and right ventral striatum-right ventrolateral PFC FC were also found. Finally, a positive correlation between the number of stages completed and left ventral striatum-left ventrolateral PFC FC was found. CONCLUSIONS: Manifest HD patients show significant cognitive flexibility deficits in attentional set-shifting that are associated with FC alterations in the frontostriatal circuit. These results show that FC abnormalities found in the prodromal stage of the disease can also be associated with cognitive flexibility deficits at a later clinical stage, making them good candidates to be explored in longitudinal studies.

Cognitive Impairments in Spinocerebellar Ataxia Type 10 and Their Relation to Cortical Thickness.

BACKGROUND: Spinocerebellar ataxia type 10 is a neurodegenerative disorder caused by the expansion of an ATTCT pentanucleotide repeat. Its clinical features include ataxia and, in some cases, epileptic seizures. There is, however, a dearth of information about its cognitive deficits and the neural bases underpinning them. OBJECTIVES: The objectives of this study were to characterize the performance of spinocerebellar ataxia type 10 patients in 2 cognitive domains typically affected in spinocerebellar ataxias, memory and executive function, and to correlate the identified cognitive impairments with ataxia severity and cerebral/cerebellar cortical thickness, as quantified by MRI. METHODS: Memory and executive function tests were administered to 17 genetically confirmed Mexican spinocerebellar ataxia type 10 patients, and their results were compared with 17 healthy matched volunteers. MRI was performed in 16 patients. RESULTS: Patients showed deficits in visual and visuospatial short-term memory, reduced storage capacity for verbal memory, and impaired monitoring, planning, and cognitive flexibility, which were ataxia independent. Patients with seizures (n = 9) and without seizures (n = 8) did not differ significantly in cognitive performance. There were significant correlations between short-term visuospatial memory impairment and posterior cerebellar lobe cortical thickness (bilateral lobule VI, IX, and right X). Cognitive flexibility deficiencies correlated with cerebral cortical thickness in the left middle frontal, cingulate, opercular, and temporal gyri. Cerebellar cortical thickness in several bilateral regions was correlated with motor impairment. CONCLUSIONS: Patients with spinocerebellar ataxia type 10 show significant memory and executive dysfunction that can be correlated with deterioration in the posterior lobe of the cerebellum and prefrontal, cingulate, and middle temporal cortices. © 2021 International Parkinson and Movement Disorder Society.

National Estimates of Prevalence, Time-Trend, and Correlates of Smoking in US People Living with HIV (NHANES 1999-2016).

OBJECTIVE: Approximately one in four deaths among people living with HIV (PLWH) in the United States can be attributed to cigarette smoking. Using a nationally representative sample of PLWH, this study examines the prevalence, time-trends, and correlates of current cigarette smoking among PLWH compared to people without HIV. DESIGN: Secondary analysis of population-based cross-sectional biobehavioral survey. METHODS: Data were pooled from the 1999-2016 National Health and Nutrition Examination Survey (NHANES). All adults (20-59 years) who self-reported their smoking status and were tested for HIV (HIV+ = 152; HIV- = 26 305) were included in the analysis. Prevalence with 95% confidence interval (95% CI), trend analysis by year and group (HIV+/HIV-), and multivariable logistic regression analyses were performed with the complex survey design adjustments. RESULTS: Overall, 47.0% of PLWH were current smokers compared to 25.5% of those without HIV. From 1999 to 2016, the decline in smoking in PLWH was comparable to those without HIV (10.7% vs. 8.0%). PLWH smokers were more likely than PLWH nonsmokers to be substance users (adjusted odds ratio [aOR] = 17.52; 95% CI = 2.04 to 27.8). Compared to smokers without HIV, PLWH smokers were more likely to be older (1.10; 1.06 to 1.14), males (7.96; 2.50 to 25.40), non-Hispanic Black (10.45; 4.13 to 26.45), with depression (Patient Health Questionnaire-9 sum score ≥5) (3.79; 1.22 to 11.79), and less likely to be gay (0.02; 0.00 to 0.07). CONCLUSION: Cigarette smoking among PLWH is a major public health problem in the United States. Targeted and tailored smoking cessation interventions that incorporate assessment and treatment of depression and co-occurring substance use are critical for PLWH, especially among those who are disproportionately affected by smoking and HIV (sexual minority). IMPLICATIONS: This study offers important research implications in four areas:1. The decline in smoking among PLWH over 18 years has been modest, and half of PLWH are still smokers.2. More resources and efforts should be allocated to reduce cigarette smoking among PLWH.3. There is a critical need to develop and test culturally tailored smoking cessation interventions for minority subgroups who are most impacted by HIV infection and smoking (non-Hispanic Blacks and men who have sex with men)4. Smoking cessation interventions designed for PLWH should incorporate assessment and treatment of depression and substance use.

Premenstrual Syndrome and Female Sexual Function.

PURPOSE: To examine the relationship between Premenstrual Syndrome (PMS) and female sexual function (FSF) with the luteal (LP) and follicular phases (FP). METHOD: We performed a cross-sectional survey using the Female Sexual Function Index (FSFI) questionnaire in the LP and FP. We used the Brazilian's version of the Premenstrual Symptoms Screen Tool (PSST) and the Daily Record of Severity of Problems (DRSP) for diagnosis of PMS. RESULTS: There was no difference in the FSF between groups in both cycle phases. We found an association between LP and worst scores on FSFI. CONCLUSION: PMS does not affect FSF.

Sleep quality and excessive daytime sleepiness in women with Premenstrual Syndrome.

OBJECTIVE: Examine the relationship between Premenstrual Syndrome (PMS) and sleep in different menstrual cycle phases. METHODS: Case-control survey conducted at the Primary Care Service and Clinical Research Center at Hospital de Clínicas de Porto Alegre with women aged between 18 and 45 years old. Women filled the Brazilian version of the Premenstrual Symptoms Screen Tool (PSST) for the screening of PMS; participants with positive screening completed the Daily Record of Severity of Problems (DRSP) to confirm PMS diagnosis. We applied the Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) Brazilian versions in the luteal phase (LP) and follicular phase (FP). RESULTS AND CONCLUSION: 69 women were characterized with PMS and 52 without PMS. The risk of poor sleep quality (SQ) was two times higher in women with PMS (p = .006; OR = 3.057; IC95% 1.44-6.45). An interaction between no PMS and LP was found in ESS (p = .014; generalized estimating equation - GEE - adjusted for multiple comparisons by the Bonferroni test and adjusted by age); besides that, women with PMS had greater scores in ESS (p = .022; GEE adjusted by age).

A survey of the training experiences and needs of paraprofessionals serving adults with brain injury.

Objective: To conduct a survey of the training experiences and needs of paraprofessionals (frontline staff) serving adults with moderate-severe TBI from the perspectives of four stakeholder groups: paraprofessionals, professionals, adults living with brain injury, and family members.Participants: Participants were (a) 28 paraprofessionals, (b) 45 professionals, (c) 41 adults living with brain injury, and (d) 22 family members, for a total of 136 participants.Design: We conducted an online, nationwide survey containing closed and open-ended questions. Four different versions of the survey were developed, one for each of the stakeholder groups, to capture their unique perspectives on the topic of paraprofessional training.Results: Descriptive statistics, non-parametric statistics, and qualitative, comment-based information across the four groups revealed that (a) paraprofessionals require comprehensive training to address the complex needs of persons with brain injury; (b) a range of training options and modalities is preferred; and (c) there are several challenges associated with providing paraprofessional training.Conclusions: This survey highlights the need for a comprehensive range of paraprofessional training options that address both knowledge and skill acquisition. These data have informed the development of an online, interactive training program for paraprofessionals serving this population.

A Unique Homeostatic Signaling Pathway Links Synaptic Inactivity to Postsynaptic mTORC1.

mTORC1-dependent translational control plays a key role in several enduring forms of synaptic plasticity such as long term potentiation (LTP) and mGluR-dependent long term depression. Recent evidence demonstrates an additional role in regulating synaptic homeostasis in response to inactivity, where dendritic mTORC1 serves to modulate presynaptic function via retrograde signaling. Presently, it is unclear whether LTP and homeostatic plasticity use a common route to mTORC1-dependent signaling or whether each engage mTORC1 through distinct pathways. Here, we report a unique signaling pathway that specifically couples homeostatic signaling to postsynaptic mTORC1 after loss of excitatory synaptic input. We find that AMPAR blockade, but not LTP-inducing stimulation, induces phospholipase D (PLD)-dependent synthesis of the lipid second messenger phosphatidic acid (PA) in rat cultured hippocampal neurons of either sex. Pharmacological blockade of PLD1/2 or pharmacogenetic disruption of PA interactions with mTOR eliminates mTORC1 signaling and presynaptic compensation driven by AMPAR blockade, but does not alter mTORC1 activation or functional changes during chemical LTP (cLTP). Overexpression of PLD1, but not PLD2, recapitulates both functional synaptic changes as well as signature cellular adaptations associated with homeostatic plasticity. Finally, transient application of exogenous PA is sufficient to drive rapid presynaptic compensation requiring mTORC1-dependent translation of BDNF in the postsynaptic compartment. These results thus define a unique homeostatic signaling pathway coupling mTORC1 activation to changes in excitatory synaptic drive. Our results further imply that more than one canonical mTORC1 activation pathway may be relevant for the design of novel therapeutic approaches against neurodevelopmental disorders associated with mTORC1 dysregulation.SIGNIFICANCE STATEMENT Homeostatic and Hebbian forms of synaptic plasticity are thought to play complementary roles in regulating neural circuit function, but we know little about how these forms of plasticity are distinguished at the single neuron level. Here, we define a signaling pathway that uniquely links mTORC1 with homeostatic signaling in neurons.

Group B Streptococcus detection in pregnant women: comparison of qPCR assay, culture, and the Xpert GBS rapid test.

BACKGROUND: Group B Streptococcus (GBS) is one of the most important causative agents of neonatal sepsis. As administration of prophylactic antibiotics during labor can prevent GBS infection, routine screening for this bacterium in prenatal care before the onset of labor is recommended. However, many women present in labor without having undergone such testing during antenatal care, and the turnaround time of detection methods is insufficient for results to be obtained before delivery. METHODS: Vaginal and anorectal specimens were collected from 270 pregnant women. Each sample was tested by Xpert GBS, qPCR, and culture for GBS detection. RESULTS: The overall prevalence of maternal GBS colonization was 30.7% according to Xpert GBS, 51.1% according to qPCR, and 14.3% according to cultures. Considering the qPCR method as the reference, the Xpert GBS had a sensitivity of 53% and specificity of 93%. Positive Xpert GBS results were correlated to marital status (married or cohabitating) and with prematurity as a cause of neonatal hospitalization. Positive cultures were related with ischemic-hypoxic encephalopathy requiring therapeutic hypothermia. CONCLUSIONS: Combined enrichment/qPCR and the Xpert GBS rapid test found a high prevalence of GBS colonization. The Xpert GBS technique gives faster results and could be useful for evaluating mothers who present without antenatal GBS screening results and are at risk of preterm labor, thus allowing institution of prophylactic antibiotic therapy.

Evidence for Central Sensitization in Patients with Temporomandibular Disorders: A Systematic Review and Meta-analysis of Observational Studies.

OBJECTIVES: Several authors have evaluated different pain measurements, including quantitative sensory testing (QST), temporal summation (TS), and conditioned pain modulation (CPM) in order to determine the presence of central sensitization (CS) and its influence on patients with temporomandibular disorders (TMD). Since there are no convincing studies about this topic, the purpose of this study was to conduct a review of the studies involving CS-related measures in TMD patients. METHODS: A meta-analysis of case-control and cohort/cross sectional studies was conducted. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated for relevant QST outcomes and pooled in a meta-analysis using the random effects model. Twenty-two studies (eleven case-control and eleven cross sectional studies) met the inclusion criteria; eight were included in the meta-analysis (five cross-sectional and three case-control). Patients with TMD had decreased pressure pain thresholds in both trigeminal (five studies; n = 1,985; SMD = -1.55, 95% CI -2.23 to -0.77; P < 0.01) and remote areas (five studies; n = 1,985; SMD = -1.92, 95% CI -2.95 to -0.89; P < 0.01). When analyzing for thermal hyperalgesia (hot and cold pain thresholds), differences were not found in trigeminal areas or remote areas in patients with TMD. The TS qualitative analysis showed strong evidence of spinal hyperexcitability for mechanically evoked pain. CONCLUSION: These meta-analyses support the existence of differences in widespread pressure pain sensitivity in patients with TMD when compared with asymptomatic subjects. Spinal and central hyperexcitability can be found in TMD patients as shown by an increase in mechanical TS.

Performance of PRP associated with porous chitosan as a composite scaffold for regenerative medicine.

This study aimed to evaluate the in vitro performance of activated platelet-rich plasma associated with porous sponges of chitosan as a composite scaffold for proliferation and osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells. The sponges were prepared by controlled freezing (-20, -80, or -196°C) and lyophilization of chitosan solutions (1, 2, or 3% w/v). The platelet-rich plasma was obtained from controlled centrifugation of whole blood and activated with calcium and autologous serum. The composite scaffolds were prepared by embedding the sponges with the activated platelet-rich plasma. The results showed the performance of the scaffolds was superior to that of activated platelet-rich plasma alone, in terms of delaying the release of growth factors and increased proliferation of the stem cells. The best preparation conditions of chitosan composite scaffolds that coordinated the physicochemical and mechanical properties and cell proliferation were 3% (w/v) chitosan and a -20°C freezing temperature, while -196°C favored osteogenic differentiation. Although the composite scaffolds are promising for regenerative medicine, the structures require stabilization to prevent the collapse observed after five days.

Fibrin network architectures in pure platelet-rich plasma as characterized by fiber radius and correlated with clotting time.

Fibrin networks are obtained through activation of platelet-rich plasma (PRP) for use in tissue regeneration. The importance of fibrin networks relies on mediation of release of growth factors, proliferation of tissue cells and rheological properties of the fibrin gels. Activation of PRP usually involves the decomposition of fibrinogen by agonists, in a wide range of concentrations. Therefore fibrin networks with a large structural diversity are formed, making comparative evaluations difficult. In order to standardize the fibrin networks, we used the statistical techniques central composite rotatable design and response-surface analysis, to correlate the radius of the fibers with the ratios between the agonists (autologous serum/calcium chloride) and agonist/PRP. From an individual and interactive analysis of the variables, architectures characterized by thick, medium and thin fibers were delineated on the response-surface. Furthermore, the architectures were correlated with coagulation time. This approach is valuable for standardizing the PRP preparation for clinical applications.

An organizational capacity-building program to enhance adolescent sexual and reproductive health.

OBJECTIVES: To present a new practice for promoting sexual health among youth, and a pilot evaluation. The Afterschool Health and Sexuality Education Project is a capacity-building program that provides staff training, technical assistance, resource materials, and policy recommendations to create organizational change that facilitates staff members' abilities to promote sexual and reproductive health for adolescents. METHOD: The evaluation included assessment of (a) sexual health educational materials, resources, and referral lists; (b) organizational policies that guide provision of sexual information and referrals; and (c) communication about sexual health. Data were collected prior to intervention, 7 months later, and 1 year later using anonymous surveys of staff and adolescents, and researcher observations. RESULTS: Results indicate that organizational support for addressing youth sexual health increased as did communication between staff and youth, with decreased barriers. Most, but not all, improvements were maintained at the 1-year follow-up. Organizational policies that support youth sexual health and the availability of educational materials, resources such as condoms, and referral lists also increased and were maintained at follow-up. CONCLUSIONS: Organizational systems change may create a broader, more sustainable environment for increasing communication between youth and adults and increasing resources to promote sexual health.

Body mass index and mortality in critically ill patients with COVID-19: another brick in the wall of the obesity paradox.

OBJECTIVE: The objective of this study was to assess the existence of the obesity paradox in patients with COVID-19 admitted to the intensive care unit. METHODS: This was a multicentric retrospective cohort study including individuals aged 18 years or older admitted to the intensive care unit with SARS-CoV-2. Data were obtained from electronic medical records. The primary outcome was in-hospital mortality. Multiple logistic regression and restricted cubic splines analyses were conducted to assess the association between BMI and mortality. RESULTS: From March 2020 to December 2021, 977 patients met the inclusion criteria, and 868 were included in the analysis. Obesity was identified in 382 patients (44%). Patients with obesity more often underwent prone positioning (42% vs. 28%; p < 0.001), although they used less vasoactive medications (57% vs. 68%; p < 0.001). The overall in-hospital mortality was 48%, with 44% observed in the subgroup of individuals with obesity and 50% in those without obesity (p = 0.06). Patients with BMI < 25 kg/m2 had the highest mortality. CONCLUSIONS: Obesity was not associated with higher mortality rates in critically ill patients with COVID-19. Moreover, patients with BMI < 25 kg/m2 had a higher mortality rate compared with those in higher BMI categories.