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Excessive levels of dopamine in the synaptic cleft, induced by cocaine for example, activates dopaminergic receptors, mainly D

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis presents commonly with psychiatric symptoms. One cohort of these patients reported that antipsychotic administration led to neuroleptic intolerance (NI) in 19% of them, which was preventable by a prompt encephalitis diagnosis. To date, there is no clear description of the "neuroleptic intolerance" spectrum in general or during anti-NMDAR encephalitis. We aimed to synthesize epidemiological and clinical characteristics of patients with NI and confirmed anti-NMDAR encephalitis, the time to the encephalitis diagnosis, the disease course, outcomes at discharge, and associated factors. We systematically searched three databases, to include clinical cases, case series, and observational studies. Additionally, we reported one clinical case. Results were summarized using narrative synthesis and the quality of the included studies was assessed. We included 22 records representing 40 patients (28 females; mean age, 24.6). Overall, the evidence quality was low. Initially, most cases were admitted in psychiatric wards (70%) with purely psychiatric symptoms (37.5%). However, most of them developed subtle concomitant neurological symptoms. The mean time to anti-NMDAR encephalitis diagnosis was 26.7 days, which was triggered by the NI in six patients. We found no association between clinical variables as delayed diagnosis, admission to psychiatric wards or the presence of malignancy with outcome variables as unfavorable outcomes at discharge, ICU, or mechanical ventilation requirement. A thorough neurological examination in young patients with new-onset psychiatric symptoms could help emergency physicians, neurologists, and psychiatrists suspect anti-NMDAR encephalitis earlier. Awareness of NI as a potential side effect during suspected or confirmed anti-NMDAR encephalitis is encouraged.

The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables. ispartof: SCIENTIFIC DATA vol:10 issue:1 ispartof: location:England status: published

In the light of cancellation of the 50th Annual Meeting of the European Histamine Research Society (EHRS) due to continuing challenges and restrictions imposed by the coronavirus disease 2019 (COVID-19) outbreak, the EHRS Council decided to organize a series of online events spread in 2021 to allow dissemination of histamine research progress and advancement among the Society members and beyond. This report summarizes the outcomes of the EHRS Council initiative that comprised the organization of four webinars, each focusing on a highly relevant histamine research scientific area. These included insights into novel therapeutic targets related to the histaminergic system in the eye, histamine intolerance, and the role of histamine and the histaminergic system in the regulation of the nervous system, as well as an update on studies leading to the development of novel methods for histamine detection. The outcome of this series of virtual events conformed that histamine research continued to develop despite the pandemic, and we witnessed stimulating advancements in 2021. Importantly, the EHRS Council brought histaminologists together in this unprecedented time.

This study aims to investigate the associative and multivariate relationship between different sociodemographic and clinical variables with cortical excitability as indexed by transcranial magnetic stimulation (TMS) markers in subjects with chronic pain caused by knee osteoarthritis (OA). This was a cross-sectional study. Sociodemographic and clinical data were extracted from 107 knee OA subjects. To identify associated factors, we performed independent univariate and multivariate regression models per TMS markers: motor threshold (MT), motor evoked potential (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). In our multivariate models, the two markers of intracortical inhibition, SICI and CSP, had a similar signature. SICI was associated with age (β: 0.01), WOMAC pain (β: 0.023), OA severity (as indexed by Kellgren–Lawrence Classification) (β: − 0.07), and anxiety (β: − 0.015). Similarly, CSP was associated with age (β: − 0.929), OA severity (β: 6.755), and cognition (as indexed by the Montreal Cognitive Assessment) (β: − 2.106). ICF and MT showed distinct signatures from SICI and CSP. ICF was associated with pain measured through the Visual Analogue Scale (β: − 0.094) and WOMAC (β: 0.062), and anxiety (β: − 0.039). Likewise, MT was associated with WOMAC (β: 1.029) and VAS (β: − 2.003) pain scales, anxiety (β: − 0.813), and age (β: − 0.306). These associations showed the fundamental role of intracortical inhibition as a marker of adaptation to chronic pain. Subjects with higher intracortical inhibition (likely subjects with more compensation) are younger, have greater cartilage degeneration (as seen by radiographic severity), and have less pain in WOMAC scale. While it does seem that ICF and MT may indicate a more acute marker of adaptation, such as that higher ICF and MT in the motor cortex is associated with lesser pain and anxiety.

The goal of this study was to investigate whether the semantic processing of the audiovisual combination of communicative gestures with speech differs between men and women. We recorded event-related brain potentials in women and men during the presentation of communicative gestures that were either congruent or incongruent with the speech.Our results showed that incongruent gestures elicited an N400 effect over frontal sites compared to congruent ones in both groups. Moreover, the females showed an earlier N2 response to incongruent stimuli than congruent ones, while larger sustained negativity and late positivity in response to incongruent stimuli was observed only in males. These results suggest that women rapidly recognize and process audiovisual combinations of communicative gestures and speech (as early as 300 ms) whereas men analyze them at the later stages of the process.

BACKGROUND: AKI is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here, we hypothesize that quantification of the viral load of SARS-CoV-2 in urine sediment from patients with COVID-19 correlates with occurrence of AKI and mortality. METHODS: The viral load of SARS-CoV-2 in urine sediments (U-viral load) was quantified by qRT-PCR in 52 patients with PCR-confirmed COVID-19 diagnosis, who were hospitalized between March 15 and June 8, 2020. Immunolabeling of SARS-CoV-2 proteins Spike and Nucleocapsid was performed in two COVID-19 kidney biopsy specimens and urine sediments. Viral infectivity assays were performed from 32 urine sediments. RESULTS: A total of 20 patients with COVID-19 (39%) had detectable SARS-CoV-2 U-viral load, of which 17 (85%) developed AKI with an average U-viral load four-times higher than patients with COVID-19 who did not have AKI. U-viral load was highest (7.7-fold) within 2 weeks after AKI diagnosis. A higher U-viral load correlated with mortality but not with albuminuria or AKI stage. SARS-CoV-2 proteins partially colocalized with the viral receptor ACE2 in kidney biopsy specimens in tubules and parietal cells, and in urine sediment cells. Infective SARS-CoV-2 was not detected in urine sediments. CONCLUSION: Our results further support SARS-CoV-2 kidney tropism. A higher SARS-CoV-2 viral load in urine sediments from patients with COVID-19 correlated with increased incidence of AKI and mortality. Urinary viral detection could inform the medical care of patients with COVID-19 and kidney injury to improve prognosis.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.

Background Stroke burden characterization studies in low‐ and middle‐income countries are scarce. We estimated the burden of stroke and its risk factors in Latin America and the Caribbean (LAC). Methods and Results We extracted GBD (Global Burden of Disease) study 2019 data on overall stroke and 3 subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) for 20 LAC countries. We estimated absolute and age‐standardized rates of disability‐adjusted life years, years of life lost, years lived with disability, and deaths. The population‐attributable fractions of 17 risk factors were estimated. All analyses were performed at regional and national levels by stroke subtype, sex, and age subgroups. In 2019, the LAC region had the fourth largest stroke burden worldwide (6.8 million disability‐adjusted life years), predominantly attributable to premature deaths (89.5% of disability‐adjusted life years). Intracerebral hemorrhage was the primary cause of the overall stroke burden (42% of disability‐adjusted life years), but ischemic stroke was the leading cause of disability (69% of total years lived with disability). Haiti and Honduras had the highest age‐standardized rates. Older adults and men had the largest burdens, although women had the highest rate of disability. Socioeconomic development level did not influence the burden. The major risk factor clusters were metabolic (high systolic blood pressure [population‐attributable fraction=53%] and high body mass index [population‐attributable fraction=37%]), which were more influential in hemorrhagic events, women, and older adults. Household air pollution was an important risk factor in low‐income countries in LAC. Conclusions The stroke burden and stroke‐related mortality in LAC are higher than the worldwide averages. However, stroke is a highly preventable disease in this region. Up to 90% of the burden could be reduced by targeting 2 modifiable factors: blood pressure and body mass index. Further research and implementation of primary and secondary prevention interventions are needed, as well as integrated national stroke care programs for acute, subacute, and rehabilitation management in LAC.

Funder: Research Council of Norway through its Centres of Excellence Scheme, FAIR project No 262675, Funder: J. William Fulbright Program, Funder: Institute for Lifecourse Development, University of Greenwich, Funder: Economic Social Research Council Impact Acceleration Award, University of Oxford, Funder: Institute of Social Sciences Ivo Pilar, Funder: Academy of Finland (Suomen Akatemia); doi: https://doi.org/10.13039/501100002341, Funder: Universität Wien (University of Vienna); doi: https://doi.org/10.13039/501100003065, Funder: Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan); doi: https://doi.org/10.13039/501100004663, Funder: NOMIS Stiftung (NOMIS Foundation); doi: https://doi.org/10.13039/501100008483, Funder: Princeton Graduate Student Research Funding (Program in Cognitive Science), Funder: Corruption Laboratory on Ethics, Accountability, and the Rule of Law (CLEAR), University of Virginia, Funder: Project Pro.Co.P.E., IMT School (PAI2019), Funder: Italian Ministry of University and Research - PRIN 2017 (20178293XT), Funder: Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada); doi: https://doi.org/10.13039/501100000038, Funder: Australian Research Council (DP180102384), Funder: Ernst and Young (EY); doi: https://doi.org/10.13039/501100003064, Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.

Epidemiological patterns for lung cancer among never smokers (LCNS) are largely unknown, even though LCNS cases comprise 15% of lung cancers. Past studies were based on epidemiologic or health system cohorts, and not fully representative of the underlying population. The objective was to analyze rates (and trends) of LCNS by sex, age group, and race and ethnicity based on all-inclusive truly population-based sources.Individual-level data from 2014 to 2018 on smoking status among microscopically-confirmed lung cancer cases from Florida's cancer registry were combined with population denominators adjusted with NHIS data on smoking prevalence to compute population-based LCNS incidence rates and rate ratios. Incidence rates and proportional mortality were ranked against other cancers. Joinpoint regression analyses examined trends.Proportions of LCNS ranged from 9% among White men to 83% among Chinese women. Overall, LCNS was 13% (IRR 1.13, 95%CI 1.08-1.17) more common among men than women, but variation occurred by age group, with female rates exceeding male in younger ages. Age-adjusted rates per 100,000 were highest among Asian/Pacific Islander (API) men and women (15.3 and 13.5, respectively) and Black populations (14.6, 12.9), intermediate for White (13.2, 11.8) and lowest among the Hispanic population (12.1, 10.6). Among API women, LCNS was the second leading cause of cancer death, surpassed only by breast cancer. LCNS trends were stable over time.LCNS is the 11th most frequently occurring cancer in men and 8th in women. LCNS differences by race/ethnicity are small, within a 15% range of the White population's rates. Surprisingly, API men and women have the highest LCNS rates and proportional mortality. As smoking prevalence decreases in the US, LCNS cases will inevitably increase, warranting inquiry into risk factors across the lifespan.

Background: Asian American and Native Hawaiian/Pacific Islanders (AANHPI) are the fastest growing minority in the United States. Cancer is the leading cause of death for AANHPIs, despite relatively lower cancer morbidity and mortality. Their recent demographic growth facilitates a detailed identification of AANHPI populations with higher cancer risk. Methods: Age-adjusted, sex-stratified, site-specific cancer mortality rates from California for 2012 to 2017 were computed for AANHPI groups: Chinese, Filipino, South Asian, Vietnamese, Korean, Japanese, Southeast Asian (i.e., Cambodian, Hmong, Laotian, Thai), and Native Hawaiian and Other Pacific Islander (NHOPI). Regression-derived mortality rate ratios (MRR) were used to compare each AANHPI group to non-Hispanic whites (NHW). Results: AANHPI men and women (total 40,740 deaths) had lower all-sites-combined cancer mortality rates (128.3 and 92.4 per 100,000, respectively) than NHWs (185.3 and 140.6) but higher mortality for nasopharynx, stomach, and liver cancers. Among AANHPIs, both NHOPIs and Southeast Asians had the highest overall rates including for colorectal, lung (men only), and cervical cancers; South Asians had the lowest. NHOPI women had 41% higher overall mortality than NHWs (MRR = 1.41; 95% CI, 1.25–1.58), including for breast (MRR = 1.33; 95% CI, 1.08–1.65) and markedly higher for endometrial cancer (MRR = 3.34; 95% CI, 2.53–4.42). Conclusions: AANHPI populations present with considerable heterogeneous cancer mortality patterns. Heightened mortality for infection, obesity, and tobacco-related cancers in Southeast Asians and NHOPI populations highlight the need for differentiated priorities and public health interventions among specific AANHPI populations. Impact: Not all AANHPIs have favorable cancer profiles. It is imperative to expand the focus on the currently understudied populations that bear a disproportionate cancer burden.

Duchene muscular dystrophy (DMD) is caused by the absence of the protein dystrophin, which leads to muscle weakness, progressive degeneration, and eventually death due to respiratory failure. Low-intensity eccentric training (LIET) has been used as a rehabilitation method in skeletal muscles after disuse. Recently, LIET has also been used for rehabilitating dystrophic muscles, but its effects are still unclear. The purpose of this study was to investigate the effects of 21 days of LIET in dystrophic soleus muscle. Thirty-six male mdx mice were randomized into six groups (n = 6/each): mdx sedentary group; mdx training group-3 days; mdx training group-21 days; wild-type sedentary group; wild-type training group-3 days and wild-type training group-21 days. After the training sessions, animals were euthanized, and fragments of soleus muscles were removed for immunofluorescence and histological analyses, and measurements of active force and Ca2+ sensitivity of the contractile apparatus. Muscles of the mdx training group-21 days showed an improvement in morphological characteristics and an increase of active force when compared to the sedentary mdx group. The results show that LIET can improve the functionality of dystrophic soleus muscle in mice.

Fluorescent silica nanoparticles with a polymer shell of poly (D, L-lactide-co-glycolide) (PLGA) can provide traceable cell-triggered delivery of the anticancer drug doxorubicin (DOX), protecting the cargo while in transit and releasing it only intracellularly. PLGA with 50:50 lactide:glycolide ratio was grown by surface-initiated ring-opening polymerization (ROP) from silica nanoparticles of ca. 50 nm diameter, doped with a perylenediimide (PDI) fluorescent dye anchored to the silica structure. After loading DOX, release from the core-shell particles was evaluated in solution at physiological pH (7.4), and in human breast cancer cells (MCF-7) after internalization. The hybrid silica-PLGA nanoparticles can accommodate a large cargo of DOX, and the release in solution (PBS) due to PLGA hydrolysis is negligible for at least 72 h. However, once internalized in MCF-7 cells, the nanoparticles release the DOX cargo by degradation of the PLGA. Accumulation of DOX in the nucleus causes cell apoptosis, with the drug-loaded nanoparticles found to be as potent as free DOX. Our fluorescently traceable hybrid silica-PLGA nanoparticles with cell-triggered cargo release offer excellent prospects for the controlled delivery of anticancer drugs, protecting the cargo while in transit and efficiently releasing the drug once inside the cell.

Previous studies demonstrated that exposure to humor has beneficial effects on psychological well-being. In the present work, we investigated the behavioral and psychophysiological effects of different types of humor on psychological well-being and on the performance during the execution of a stressful cognitive task. To this aim, we examined the behavioral and psychophysiological effects of ToM humorous and Slapstick humorous comic strips before and after executing a stressful cognitive task. We hypothesized that only slapstick humor could reduce the level of anxiety, increase positive affect and improve performance on the cognitive task. Our findings revealed that, at a specific point in time, exposure to ToM Humor and No Humor strips were associated with lower IBI (higher HR, increase in cardiac recruitment) than slapstick humor. This result suggests that humor involving ToM abilities and No Humor strips elicited a greater cognitive engagement level than slapstick humor. Moreover, in an exploratory analysis we found a positive correlation between cardiac deactivation during the exposure to slapstick Humor and individual empathy scores, suggesting that the empathy skills might influence cardiac recruitment and the level of cognitive engagement during the exposure to humorous material.

The Internet of Things (IoT) fosters the development of smart city systems for sustainable living and increases comfort for people. One of the current challenges for sustainable buildings is the optimization of energy management. Temperature monitoring in buildings is of prime importance, as heating account for a great part of the total energy consumption. Here, a solar optical temperature sensor is presented with a thermal sensitivity of up to 1.23% °C-1 based on sustainable aqueous solutions of enhanced green fluorescent protein and C-phycocyanin from biological feedstocks. These photonic sensors are presented under the configuration of luminescent solar concentrators widely proposed as a solution to integrate energy-generating devices in buildings, as windows or façades. The developed mobile sensor is inserted in IoT context through the development of a self-powered system able to measure, record, and send data to a user-friendly website. published

Instream wood plays important chemical, physical and ecological functions in aquatic systems, benefiting biota directly and indirectly. However, human activities along river corridors have disrupted wood recruitment and retention, usually leading to reductions in the amount of instream wood. In the tropics, where wood is believed to be more transient, the expansion of agriculture and infrastructure might be reducing instream wood stock even more than in the better studied temperate streams. However, research is needed to augment the small amount of information about wood in different biomes and ecosystems of neotropical streams. Here we present the first extensive assessment of instream wood loads and size distributions in streams of the wet-tropical Amazon and semi-humid-tropical Cerrado (the Brazilian savanna). We also compare neotropical wood stocks with those in temperate streams, first comparing against data from the literature, and then from a comparable dataset from temperate biomes in the USA. Contrary to our expectations, Amazon and Cerrado streams carried similar wood loads, which were lower than the world literature average, but similar to those found in comparable temperate forest and savanna streams in the USA. Our results indicate that the field survey methods and the wood metric adopted are highly important when comparing different datasets. But when properly compared, we found that most of the wood in temperate streams is made-up of a small number of large pieces, whereas wood in neotropical streams is made up of a larger number of small pieces that produce similar total volumes. The character of wood volumes among biomes is linked more to the delivery, transport and decomposition mechanisms than to the total number of pieces. Future studies should further investigate the potential instream wood drivers in neotropical catchments in order to better understand the differences and similarities here detected between biomes and climatic regions.

Latinos are the largest minority group in the United States. We assessed cancer mortality by birthplace and generation status of Mexican Latinos in the Multiethnic Cohort.We included 26 751 Latinos of Mexican origin and 6093 non-Latino Whites aged 45-74 years at cohort entry (1993-1996) from the California Multiethnic Cohort component. The Mexican Latinos comprised 42% first-generation Mexico-born immigrants, 42% second-generation (28% US-born with both parents Mexico-born and 14% US-born with 1 parent US-born and 1 parent Mexico-born), and 16% third-generation or more who were US-born with both parents US-born. Multivariable Cox models were used to calculate covariate adjusted hazard ratios and 95% confidence intervals for overall and site-specific cancer mortality by birthplace and generation status. All statistical tests were 2-sided.Cancer death rate was highest among the US-born with 1 parent US-born and 1 parent Mexico-born (age-adjusted rate = 471.0 per 100 000 person-years) and US-born with both parents US-born (age-adjusted rate = 469.0 per 100 000 person-years) groups. The US-born with both parents Mexico-born group had a 30% (hazard ratio = 1.30, 95% confidence interval = 1.18 to 1.44) higher risk of cancer death than the first-generation Mexico-born immigrants group, showing US birthplace was associated with an elevated cancer mortality. For cancer-specific mortality, US birthplace was positively associated with colorectal, liver and lung, and ovarian cancer (P values ranged from .04 to .005). Among US-born Mexican Latinos, generation status was not statistically significantly associated with overall cancer or site-specific cancer mortality.Our findings suggest that US birthplace is a risk factor for cancer death in Mexican Americans. Identification of the contributing factors is important to curtail patterns of increasing cancer mortality in US-born Mexican Latinos.

Oral dysfunctions are common in the elderly but the literature lacks a multidisciplinary approach on the relationship between polypharmacy, saliva flow, xerostomia, taste and swallowing complaints. This cross-sectional study included 204 non-institutionalized elderly (>60y; 123 women/81 men), free of severe disabilities and non-alcohol/tobacco consumers, from whom specific pharmacological therapies were evaluated, as well xerostomia (Xerostomia Inventory-XI) and swallowing complaints (EAT-10 questionnaire), salivary flow rate and gustatory sensitivity. Statistical analysis included Chi-square, Mann-Whitney, Two-way ANCOVA and linear multiple regression. Polypharmacy (≥5 drugs daily), hyposalivation and severe taste dysfunction were found in 18%, 46% and 10% of the participants, respectively. Polypharmacy was related with xerostomia (p=0.041) and swallowing complaints (p

Study design A retrospective subgroup analysis of a prospective observational study was carried out. Summary of background data Patients' baseline characteristics may influence the clinical outcomes after minimally invasive lumbar interbody fusion (MILIF). Objective This study aimed to investigate the influence of patient's age and body mass index (BMI) on the clinical outcomes of MILIF for degenerative lumbar disorder. Materials and methods A total of 252 patients underwent MILIF. The clinical outcomes, including time to first ambulation, time to postsurgical recovery, back/leg pain in visual analog scale, Oswestry Disability Index, and EuroQol-5 Dimension, were collected at baseline, 4 weeks, 6, and 12 months. Patients were subgrouped by age (50 y and below: N=102; 51-64 y: N=102; 65 y and above: N=48) and BMI (≤25.0: N=79; 25.1-29.9: N=104; ≥30.0: N=69). Data from baseline to 12 months were compared for all clinical outcomes within age/BMI subgroups. Adverse events (AEs) and serious adverse events (SAEs) were summarized by age and BMI subgroups. Results All age and BMI subgroups showed significant improvements in clinical outcomes at 12 months compared with the baseline. The median time to first ambulation was similar for all subgroups (age groups: P=0.8707; BMI: P=0.1013); older people show a trend of having longer time to postsurgical recovery (age groups: P=0.0662; BMI: P=0.1591). Oswestry Disability Index, back, and leg pain visual analog scale, and EuroQol-5 Dimension were similar in all subgroups at every timepoint. A total of 50 AEs (N=39) were reported, 9 of which were SAEs; 3 AEs and 1 SAE were considered to be related to surgical procedure. No differences were observed in safety by age groups and BMI groups. Conclusion MILIF appears to be safe and effective, independent of age or weight in the treatment of degenerative lumbar disorder. Level of evidence Level II.

Background: The present study evaluated factors associated with losses in the latent tuberculosis infection (LTBI) cascade of care in contacts of tuberculosis (TB) patients, in a referral center from a highly endemic region in Brazil. Methods: Contacts of 1672 TB patients were retrospectively studied between 2009 and 2014. Data on TB screening by clinical investigation, radiographic examination and tuberculin skin test (TST) were extracted from medical records. Losses in the cascade of care and TB incidence within 2-year follow-up were calculated. Results: From a total of 1180 TB contacts initially identified, only 495 were examined (58% loss), and 20 were diagnosed with active TB at this stage. Furthermore, 435 persons returned for TST result interpretation and 351 (∼81%) were TST positive. Among those with positive TST, 249 (73%) were treated with isoniazid for 6 months whereas 51 abandoned therapy early. Three individuals who did not receive LTBI treatment, one with incomplete treatment and another who completed treatment developed active TB. A logistic regression analysis revealed that increases in age were associated with losses in the LTBI cascade independent of other clinical and epidemiological characteristics. Conclusions: Major losses occur at initial stages and older patients are at higher risk of not completing the LTBI cascade of care. Keywords: Tuberculosis, Latent TB infection, LTBI cascade, Treatment for latent TB

The present study aimed to evaluate the influence of holding the chair handles during the assessment of older women’s knee flexion and extension isokinetic and isometric strength. Of 57 older women (≥60 years) selected from a convenience sample for this research, 23 were randomly chosen to perform the tests twice for reliability analyses. Each participant performed maximal isokinetic knee extension and flexion at 60°/s and 180°/s angular velocities and isometric tests under two conditions: (a) holding the lateral handle of the chair (HOLD) and (b) supporting the hands on the shoulders with the arms crossed (i.e., not holding the handle [NHOLD]). Participants performed significantly better in the HOLD compared with the NHOLD condition. Slightly lower intraclass correlation coefficients (ICC = 0.870–0.956) were noted for the HOLD than for the NHOLD condition (ICC = 0.900–0.981) so that the HOLD performance on Days 1 and 2 was different on some measures. Owing to the higher reliability coefficients in the NHOLD condition, results suggest that, when assessing knee strength in older women, the evaluee should place their hands over their shoulders with arms crossed in front of the chest (NHOLD) to maximize assessment reliability (reproducibility of performance).

The polarized phenotype of the retinal pigment epithelium is critical for the outer retina-blood barrier and support of photoreceptors and underlying choroid, and its disruption plays a central role in degenerative retinopathies. Although the mechanisms of polarization remain mostly unknown, they are fundamental for homeostasis of the outer retina. Recent research is revealing a growing picture of interconnected tissues in the outer retina, with the retinal pigment epithelium at the center. This review discusses how elements of epithelial polarity relate to emerging apical interactions with the neural retina, basolateral cross-talk with the underlying Bruch’s membrane and choriocapillaris, and tight junction biology. An integrated view of outer retina physiology is likely to provide insights into the pathogenesis of blinding diseases.

Background Postmenopausal breast cancer (PMBC) is the most commonly diagnosed and the second leading cause of cancer death among women in the US. Research examining the association between PMBC and education level has been inconsistent; no study in the US has examined how educational level impacts PMBC mortality in Asian American women, a largely immigrant population with above-average educational attainment. Methods California Vital Statistics data from 2012–2017 were analyzed to derive age-adjusted mortality rate ratios (MRRs) by education level (associates degree or above referred to as “higher education”, high school, less than high school) and race [Non-Hispanic White (NHW), Asian/Pacific Islander (Asian), and its two largest subpopulations: Chinese and Filipino] from negative binomial regression models. Results PMBC mortality for both NHWs and Asians was greater among women with higher education compared to those who did not complete high school: NHWs had 22% higher PMBC mortality (MRR 1.22; 95% CI: 1.14–1.31) and Asians had 2.6 times greater PMBC mortality (MRR 2.64; 95% CI: 2.32–3.00) than their counterparts who did not complete high school. Asians in the lowest education level had 70% lower mortality than NHWs (MRR 0.30; 95% CI: 0.27–0.34). This mortality advantage among Asians was greatly reduced to only 27% lower among the highest educated (MRR 0.73; 95% CI: 0.68–0.78). For higher educated Filipina women, no mortality advantage was evident compared to NHWs (MRR 0.96; 95% CI: 0.88–1.05). Conclusion PMBC mortality for higher educated Asian women is elevated in comparison to their counterparts with less education. Given that PMBC survival is greater among those with higher education, our findings strongly suggest an excess in the incidence of PMBC (more than double) among higher educated Asian women; this warrants more research into potentially modifiable causes of PMBC in this burgeoning population.

CoronaVac is an inactivated SARS-CoV-2 vaccine that has been rolled out in several low and middle-income countries including Brazil, where it was the mainstay of the first wave of immunization of healthcare workers and the elderly population. We aimed to assess the T cell and antibody responses of vaccinated individuals as compared to convalescent patients. We detected IgG against SARS-CoV-2 antigens, neutralizing antibodies against the reference Wuhan SARS-CoV-2 strain and used SARS-CoV-2 peptides to detect IFN-g and IL-2 specific T cell responses in a group of CoronaVac vaccinated individuals (N = 101) and convalescent (N = 72) individuals. The frequency among vaccinated individuals, of whom 96% displayed T cell and/or antibody responses to SARS-CoV-2, is comparable to 98.5% responses of convalescent individuals. We observed that among vaccinated individuals, men and individuals 55 years or older developed significantly lower anti-RBD, anti-NP and neutralization titers against the Wuhan strain and antigen-induced IL-2 production by T cells. Neutralizing antibody responses for Gamma variant were even lower than for the Wuhan strain. Even though some studies indicated CoronaVac helped reduce mortality among elderly people, considering the appearance of novel variants of concern, CoronaVac vaccinated individuals above 55 years old are likely to benefit from a heterologous third dose/booster vaccine to increase immune response and likely protection.

Made available in DSpace on 2022-04-29T08:46:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Recurrence of COVID-19 in recovered patients has been increasingly reported. However, the immune mechanisms behind the recurrence have not been thoroughly investigated. The presence of neutralizing antibodies (nAbs) in recurrence/reinfection cases suggests that other types of immune response are involved in protection against recurrence. Here, we investigated the innate type I/III interferon (IFN) response, binding and nAb assays and T-cell responses to severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) with IFN gamma (IFNγ) enzyme-linked spot assay (ELISPOT) in three pairs of young adult monozygotic (MZ) twins with previous confirmed COVID-19, one of them presenting a severe recurrence four months after the initial infection. Twin studies have been of paramount importance to comprehend the immunogenetics of infectious diseases. Each MZ twin pair was previously exposed to SARS-CoV-2, as seen by clinical reports. The six individuals presented similar overall recovered immune responses except for the recurrence case, who presented a drastically reduced number of recognized SARS-CoV-2 T-cell epitopes on ELISPOT as compared to her twin sister and the other twin pairs. Our results suggest that the lack of a broad T-cell response to initial infection may have led to recurrence, emphasizing that an effective SARS-CoV-2-specific T-cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19. Human Genome and Stem Cell Research Center (HUG-CELL) Biosciences Institute Universidade de São Paulo, SP Laboratory of Immunology Heart Institute (InCor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), SP Institute for Investigation in Immunology Instituto Nacional de Ciência e Tecnologia - Iii-INCT, SP Division of Clinical Immunology and Allergy Department of Medicine Faculdade de Medicina da Universidade de São Paulo (FMUSP), SP Department of Microbiology Immunology and Parasitology Universidade Federal de São Paulo (UNIFESP/EPM), SP Department of Parasitology Biosciences Institute Universidade de São Paulo, SP School of Medicine Universidade Estadual Paulista (UNESP), SP Fleury Laboratory, SP School of Medicine Universidade Estadual Paulista (UNESP), SP

Chronic pain is a major health issue, and the search for new analgesics has become increasingly important because of the addictive properties and unwanted side effects of opioids. To explore potentially new drug targets, we investigated mutations in the NTRK1 gene found in individuals with congenital insensitivity to pain with anhidrosis (CIPA). NTRK1 encodes tropomyosin receptor kinase A (TrkA), the receptor for nerve growth factor (NGF) and that contributes to nociception. Molecular modeling and biochemical analysis identified mutations that decreased the interaction between TrkA and one of its substrates and signaling effectors, phospholipase Cγ (PLCγ). We developed a cell-permeable phosphopeptide derived from TrkA (TAT-pQYP) that bound the Src homology domain 2 (SH2) of PLCγ. In HEK-293T cells, TAT-pQYP inhibited the binding of heterologously expressed TrkA to PLCγ and decreased NGF-induced, TrkA-mediated PLCγ activation and signaling. In mice, intraplantar administration of TAT-pQYP decreased mechanical sensitivity in an inflammatory pain model, suggesting that targeting this interaction may be analgesic. The findings demonstrate a strategy to identify new targets for pain relief by analyzing the signaling pathways that are perturbed in CIPA.

This study aims to investigate the multivariate relationship between different sociodemographic, clinical, and neurophysiological variables with resting-state, high-definition, EEG spectral power in subjects with chronic knee osteoarthritis (OA) pain. This was a cross-sectional study. Sociodemographic and clinical data were collected from 66 knee OA subjects. To identify associated factors, we performed independent univariate and multivariate regression models by frequency bands (delta, theta, alpha, beta, low-beta, and high-beta) and by pre-defined regions (frontal, central, and parietal). From adjusted multivariate models, we found that: (1) increased frontocentral high-beta power and reduced central theta activity are positively correlated with pain intensity (β = 0.012, 95% CI 0.004–0.020; and β = − 0.008; 95% CI 0.014 to − 0.003; respectively); (2) delta and alpha oscillations have a direct relationship with higher cortical inhibition; (3) diffuse increased power at low frequencies (delta and theta) are associated with poor cognition, aging, and depressive symptoms; and (4) higher alpha and beta power over sensorimotor areas seem to be a maladaptive compensatory mechanism to poor motor function and severe joint degeneration. Subjects with higher pain intensity and higher OA severity (likely subjects with maladaptive compensatory mechanisms to severe OA) have higher frontocentral beta power and lower theta activity. On the other hand, subjects with less OA severity and less pain have higher theta oscillations power. These associations showed the potential role of brain oscillations as a marker of pain intensity and clinical phenotypes in chronic knee OA patients. Besides, they suggest a potential compensatory mechanism of these two brain oscillators according to OA severity.

The ongoing COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Treatment of COVID-19 patients is challenging, and specific treatments to reduce COVID-19 aggravation and mortality are still necessary. Here, we describe the discovery of a novel class of epiandrosterone steroidal compounds with cationic amphiphilic properties that present antiviral activity against SARS-CoV-2 in the low micromolar range. Compounds were identified in screening campaigns using a cytopathic effect-based assay in Vero CCL81 cells, followed by hit compound validation and characterization. Compounds LNB167 and LNB169 were selected due to their ability to reduce the levels of infectious viral progeny and viral RNA levels in Vero CCL81, HEK293, and HuH7.5 cell lines. Mechanistic studies in Vero CCL81 cells indicated that LNB167 and LNB169 inhibited the initial phase of viral replication through mechanisms involving modulation of membrane lipids and cholesterol in host cells. Selection of viral variants resistant to steroidal compound treatment revealed single mutations on transmembrane, lipid membrane-interacting Spike and Envelope proteins. Finally, in vivo testing using the hACE2 transgenic mouse model indicated that SARS-CoV-2 infection could not be ameliorated by LNB167 treatment. We conclude that anti-SARS-CoV-2 activities of steroidal compounds LNB167 and LNB169 are likely host-targeted, consistent with the properties of cationic amphiphilic compounds that modulate host cell lipid biology. Although effective in vitro, protective effects were cell-type specific and did not translate to protection in vivo, indicating that subversion of lipid membrane physiology is an important, yet complex mechanism involved in SARS-CoV-2 replication and pathogenesis. ispartof: VIRULENCE vol:13 issue:1 pages:1031-1048 ispartof: location:United States status: published

Occupational stress is a complex process affecting health and performance. Air Traffic Control is a complex and demanding profession. The current study demonstrates the concept of using a biomonitoring wearable platform (BWP), that combines self-report measures with biomarkers, to track stress among Air Traffic Controllers. A wearable ECG device was used to gather continuously medical-grade ECG data along with a mobile app for daily stress perception, symptoms and events annotation. A total of 256 hours of data from 32 routine work shifts and 5 days-off, from 5 ATCs was recorded with 35 tagged events using Heart Rate Variability metrics- AVNN, RMSSD, pNN50 and LF/HF were computed from ECG data and analyzed during a) shifts vs days off; b) events vs non-events and c) before and after working pauses. ATCs showed low levels of chronic stress using self-reports. Results showed that stress symptomatology slightly increase from the beginning to the end of the shift (Md=1 to Md=2; p0.05). Statistical significant physiological changes were found between shifts and days off for AVNN and LF/HF (p0.05), showing higher physiological activation during shifts. A significant reduction of physiological arousal was verified after working pauses, particularly for AVNN and LF/HF (p0.001). Self-reported data also suggests the same trend (p0.005). Findings reinforced the discriminatory power of AVNN and LF/HF for short-term stress classification using HRV measurements. Results suggest that the rotating working system, with pause/resting periods included, effective acted as a recovery period.Clinical Relevance-Results provide important clues to the impact of stress on health, particularly cardiac reactivity and the identification of stress quantitative biomarkers as diagnostic indicators, providing a more reliable source for stress monitoring than currently behavioral or subjective measures. Findings will help on the design of stress management programs and prevention actions in order to avoid the negative effects of stress.

Endometrial cancer (EC) often occurs subsequently to a primary cancer arising from a different site. However, little is known regarding the survival experience of EC as a second primary (ECSP) malignancy, specifically in relation to the original primary site and prior treatment.Using Florida's cancer registry, all EC cases (first, second, or higher-order) diagnosed from 2005-2016 were analyzed. Kaplan-Meier methods and Cox Regression were used in a cause-specific survival analysis.A total of 2879 clinically independent ECSPs and 42,714 first primary ECs were analyzed. The most common first primary sites for ECSPs were breast cancer (BC) (n = 1422) and colorectal cancer (CRC) (n = 359). Five-year cause-specific survival was 84.0% (95% CI: 83.6-84.3) for first primary ECs and 81.8% (95% CI: 80.0-83.4) for ECSPs. After adjusting for age, race/ethnicity, histology, and stage at diagnosis, ECSPs had a lower risk of EC mortality than first primary ECs (hazard ratios [HR] 0.88, 95% CI: 0.79-0.97). ECSPs with a first primary CRC had a higher risk of EC-specific death (HR 1.47, 95% CI: 1.04-2.06) compared to ECSPs that followed BC in multivariable analysis. Finally, women who had chemotherapy for ECSP and preceding BC did not have a higher risk of death (HR 0.80, 95% CI: 0.49-1.31) compared to those who only received chemotherapy for first primary EC.ECSPs present a complex clinical profile. ECSP survival is superior to that of first primary EC. However, ECSPs following CRC may constitute a population of interest for their worse prognosis. Chemotherapy for a previous BC does not seem to impact the effectiveness of chemotherapy for ECs.

International audience; Background: Africa and the Caribbean are projected to have greater increases in Head and neck cancer (HNC) burden in comparison to North America and Europe. The knowledge needed to reinforce prevention in these populations is limited. We compared for the first time, incidence rates of HNC in black populations from African, the Caribbean and USA. Methods: Annual age-standardized incidence rates (IR) and 95% confidence intervals (95%CI) per 100,000 were calculated for 2013-2015 using population-based cancer registry data for 14,911 HNC cases from the Caribbean (Barbados, Guadeloupe, Trinidad and Tobago, N = 443), Africa (Kenya, Nigeria, N = 772) and the United States (SEER, Florida, N = 13,696). We compared rates by sub-sites and sex among countries using data from registries with high quality and completeness. Results: In 2013-2015, compared to other countries, HNC incidence was highest among SEER states (IR: 18.2, 95%CI = 17.6-18.8) among men, and highest in Kenya (IR: 7.5, 95%CI = 6.3-8.7) among women. Nasopharyngeal cancer IR was higher in Kenya for men (IR: 3.1, 95%CI = 2.5-3.7) and women (IR: 1.5, 95% CI = 1.0-1.9). Female oral cavity cancer was also notably higher in Kenya (IR = 3.9, 95%CI = 3.0-4.9). Blacks from SEER states had higher incidence of laryngeal cancer (IR: 5.5, 95%CI = 5.2-5.8) compared to other countries and even Florida blacks (IR: 4.4, 95%CI = 3.9-5.0). Conclusion: We found heterogeneity in IRs for HNC among these diverse black populations; notably, Kenya which had distinctively higher incidence of nasopharyngeal and female oral cavity cancer. Targeted etiological investigations are warranted considering the low consumption of tobacco and alcohol among Kenyan women. Overall, our findings suggest that behavioral and environmental factors are more important determinants of HNC than race.

BACKGROUNDCountries have focused research on developing strategies to fight COVID-19, prevent hospitalizations, and maintain economic activities.OBJECTIVEThis study aimed to establish a survival analysis and identify risk factors for patients with COVID-19 in a upper middle-income city in Brazil.METHODSWe performed a retrospective cohort study with 280 hospitalized patients with COVID-19. The eCOVID platform provided data used to monitor COVID-19 cases and help communication between professionals.RESULTSSurvival analysis showed that age ≥ 65 years was associated with decreased survival (54.8%). Females had lower survival rate than males (p=0.01). Regarding risk factors, urea concentration (pCONCLUSIONAge, hospital LOS, high blood urea concentration, and low oxygen concentration were associated with death by COVID-19 in the studied population. These findings corroborate with studies conducted in research centers worldwide.Key FindingsSome parameters assessed during hospital admission may identify patients with COVID-19 with high risk of progressing to severe conditions and early identification of risk factors and continuous monitoring of laboratory tests may prevent progression to severe disease.Key ImplicationsKnowledge regarding main signs and symptoms of COVID-19 and associated risk factors helps the population manage and monitor the disease at home and identify early signs of severity. Also, more information about COVID-19, such as prevalence, specific characteristics in certain regions, and treatments, must become public to encourage the population to participate in the control and contingency of the pandemic.

The Hispanic/Latino population is the second largest racial/ethnic group in the continental United States and Hawaii, accounting for 18% (60.6 million) of the total population. An additional 3 million Hispanic Americans live in Puerto Rico. Every 3 years, the American Cancer Society reports on cancer occurrence, risk factors, and screening for Hispanic individuals in the United States using the most recent population-based data. An estimated 176,600 new cancer cases and 46,500 cancer deaths will occur among Hispanic individuals in the continental United States and Hawaii in 2021. Compared to non-Hispanic Whites (NHWs), Hispanic men and women had 25%-30% lower incidence (2014-2018) and mortality (2015-2019) rates for all cancers combined and lower rates for the most common cancers, although this gap is diminishing. For example, the colorectal cancer (CRC) incidence rate ratio for Hispanic compared with NHW individuals narrowed from 0.75 (95% CI, 0.73-0.78) in 1995 to 0.91 (95% CI, 0.89-0.93) in 2018, reflecting delayed declines in CRC rates among Hispanic individuals in part because of slower uptake of screening. In contrast, Hispanic individuals have higher rates of infection-related cancers, including approximately two-fold higher incidence of liver and stomach cancer. Cervical cancer incidence is 32% higher among Hispanic women in the continental US and Hawaii and 78% higher among women in Puerto Rico compared to NHW women, yet is largely preventable through screening. Less access to care may be similarly reflected in the low prevalence of localized-stage breast cancer among Hispanic women, 59% versus 67% among NHW women. Evidence-based strategies for decreasing the cancer burden among the Hispanic population include the use of culturally appropriate lay health advisors and patient navigators and targeted, community-based intervention programs to facilitate access to screening and promote healthy behaviors. In addition, the impact of the COVID-19 pandemic on cancer trends and disparities in the Hispanic population should be closely monitored.

Metformin is an oral hypoglycemic drug widely used in the management of type 2 diabetes mellitus. We have recently demonstrated that metformin exhibits activity in models of nociceptive and neuropathic pain. However, little is known about its effects in experimental models of inflammation and inflammatory pain. Thus, the present study aimed to evaluate the activity of metformin in experimental models of inflammation and inflammatory pain in mice, as well as the underlying mechanisms. Previous (1 h) per os (p.o.) administration of metformin (250, 500 or 1000 mg/kg) inhibited the mechanical allodynia and paw edema induced by intraplantar (i.pl.) injection of carrageenan (600 μg) and also the pleurisy induced by this stimulus (200 μg, intrapleural). In the model of mechanical allodynia and paw edema induced by carrageenan, metformin also exhibited activity when administered after (1 h) the inflammatory stimulus. Metformin (1000 mg/kg) reduced the production of tumor necrosis factor-α induced by i.pl. injection of carrageenan. Metformin antiallodynic effect was not affected by previous administration of naltrexone (5 or 10 mg/kg, intraperitoneal) or cyproheptadine (5 or 10 mg/kg, p.o). However, this effect was abolished by previous administration of glibenclamide (20 or 40 mg/kg, p.o). In conclusion, the results demonstrate the activity of metformin in models of inflammation and inflammatory pain. In addition, the results indicate that the activity of metformin may be mediated by activation of ATP-sensitive potassium channels and reduction of production of inflammatory mediators. Altogether, these results stimulate the conduction of studies aiming to evaluate whether metformin may be repositioned in the treatment of patients with painful and inflammatory disorders.

The synaptic expression of glutamate receptors of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) type is dynamically controlled by interaction with binding partners and auxiliary proteins. These proteins can be regulated by posttranslational modifications, including ubiquitination. In this work, we investigated the regulation of glutamate receptor interacting protein-associated protein 1 (GRASP1) by ubiquitin-dependent mechanisms and its impact on surface expression and activity of synaptic AMPA receptors. Cotransfection of GFP-ubiquitin decreased myc-GRASP1 protein levels in HEK293T cells, and this effect was inhibited upon transfection of an ubiquitin mutant that cannot be ubiquitinated on Lys48. In addition, transfection of cultured hippocampal neurons with GFP-ubiquitin reduced the dendritic levels of endogenous GRASP1 and decreased the surface expression of GluA1 AMPA receptor subunits, an effect that was partly reversed by cotransfection with GRASP1. Similarly, transfection of hippocampal neurons with GFP-ubiquitin decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) mediated by Ca2+ -impermeable AMPA receptors, and this effect was abrogated by cotransfection of GRASP1. Together, the results show a role for ubiquitination in the regulation of the postsynaptic protein GRASP1, which has an impact on the surface distribution of AMPA receptors and on their activity at the synapse.

OBJECTIVES Because the population in Florida is 25.6% Hispanic, it is possible to evaluate the influence of race and ethnicity within clinically relevant subgroups of women with epithelial ovarian cancer (EOC), including histology and tumor grade. This study explores racial/ethnic disparities in the incidence of EOC in Florida by histology and tumor grade. METHODS This study is an analysis of the Florida Cancer Database System. All incidence EOC cases from 2001 through 2015 were identified. Age-adjusted incidences were calculated and trends modeled by race/ethnicity and histology using Joinpoint and Poisson regression. RESULTS In total, 80% of the 21,731 women with EOC were White, followed by Hispanic (13.1%) and non-Hispanic Black (7.9%). All races/ethnicities had statistically significant declines in incidence, with non-Hispanic White and non-Hispanic Black women having the steepest declines (annual percentage change -2.5, 95% confidence interval [CI] -5.9 to -2.1 and annual percentage change -2.8, 95% CI -4.8 to -1.5, respectively). A decreased incidence trend across the time period was seen for all subgroups (relative risk 0.97 [95% CI 0.96-0.98], 0.96 [95% CI 0.96-0.99], and 0.98 [95% CI 0.96-0.99] for non-Hispanic White, non-Hispanic Black, and Hispanic). High-grade EOC incidence for all groups did not change with time. CONCLUSIONS We found significant declines in the incidence of EOC for all races/ethnicities, but not for high-grade EOC. The observed incidence decline in Hispanic women differs from previous research. More research is needed to understand women the causes of overall racial/ethnic differences and the decline in EOC.

We investigated the semantic processing of the multimodal audiovisual combination of visual narratives with auditory descriptive words and auditory sounds in individuals with ASD. To this aim, we recorded ERPs to critical auditory words and sounds associated with events in visual narrative that were either semantically congruent or incongruent with the climactic visual event. A similar N400 effect was found both in adolescents with ASD and neurotypical adolescents (ages 9-16) when accessing different types of auditory information (i.e. words and sounds) into a visual narrative. This result might suggest that verbal information processing in ASD adolescents could be facilitated by direct association with meaningful visual information.In addition, we observed differences in scalp distribution of later brain responses between ASD and neurotypical adolescents. This finding might suggest ASD adolescents differ from neurotypical adolescents during the processing of the multimodal combination of visual narratives with auditory information at later stages of the process. In conclusion, the semantic processing of verbal information, typically impaired in individuals with ASD, can be facilitated when embedded into a meaningful visual information.

The purpose of this study was to investigate whether the comprehension of a specific type of humorous situation requires the involvement of brain regions associated to mentalization or Theory of Mind processing and if the electrical stimulation of these areas would facilitate the comprehension of humor. To this aim, we analyzed the effects of tDCS stimulation on the MPFC and rTPJ during the presentation of humorous and non-humorous comic strips. In particular, the stimulus set included strips containing humorous scenes that required ToM abilities in order to be comprehended (Humorous ToM), non-ToM humorous strips (Humorous non-ToM), non-humorous strips which were semantically coherent but not funny (Congruent), and non-humorous strips which were semantically incoherent (Incongruent). Results suggest that the MPFC appears to be involved in both humor processing and in the incongruity resolution process: MPFC stimulation improved the ability to identify a non-humorous incongruent element and to recognize the humorous element of the scene. On the other hand, RTPJ activity doesn’t seem to be specifically involved in humorous processing network and appears to be more related to the ability to understand the cognitive element of a social context.

Background Cachexia is a paraneoplastic syndrome related with poor prognosis. The tumour micro‐environment contributes to systemic inflammation and increased oxidative stress as well as to fibrosis. The aim of the present study was to characterise the inflammatory circulating factors and tumour micro‐environment profile, as potentially contributing to tumour fibrosis in cachectic cancer patients. Methods 74 patients (weight stable cancer n = 31; cachectic cancer n = 43) diagnosed with colorectal cancer were recruited, and tumour biopsies were collected during surgery. Multiplex assay was performed to study inflammatory cytokines and growth factors. Immunohistochemistry analysis was carried out to study extracellular matrix components. Results Higher protein expression of inflammatory cytokines and growth factors such as epidermal growth factor, granulocyte–macrophage colony‐stimulating factor, interferon‐α, and interleukin (IL)‐8 was observed in the tumour and serum of cachectic cancer patients in comparison with weight‐stable counterparts. Also, IL‐8 was positively correlated with weight loss in cachectic patients (P = 0.04; r = 0.627). Immunohistochemistry staining showed intense collagen deposition (P = 0.0006) and increased presence of α‐smooth muscle actin (P

Here, a prototypical metallic nanoglass is proposed as a new alloy for balloon expandable stents. Traditionally, the stainless steel SS 316L alloy has been used as a preferred material for this application due to its proper combination of mechanical properties, corrosion resistance, and biocompatibility. Recently, metallic glasses (MGs) have been considered as promising materials for biodevice applications. MGs often display outstanding mechanical properties superior to those of conventional metallic alloys and overcome some of the weaknesses of SS 316L, such as radiopacity, stainless steel allergy, and thrombosis-induced restenosis. However, commonly used monolithic MGs, which have an amorphous homogeneous microstructure, suffer from lack of ductility that is necessary for deployment of balloon expandable stents. In contrast, nanoglasses, that is, amorphous alloys with heterogeneous microstructure, exhibit enhanced ductility which makes them promising materials for balloon expandable stents. We evaluate the feasibility of a prototypical Zr64 Cu36 nanoglass with a grain size of 5 nm for balloon expandable stents by performing finite element method modeling of the stent deployment process in a coronary artery. We consider the BX-Velocity stent design and the nanoglass mechanical properties calculated from atomistic simulations. The results suggest that nanoglasses are suitable materials for balloon expandable stent applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:73-79, 2020.

Purpose The Global Burden of Diseases (GBD) Studies have estimated that low back pain is one of the costliest ailments worldwide. Subsequent to GBD publications, leadership of the four largest global spine societies agreed to form SPINE20. This article introduces the concept of SPINE20, the recommendations, and the future of this global advocacy group linked to G20 annual summits. Methods The founders of SPINE20 advocacy group coordinated with G20 Saudi Arabia to conduct the SPINE20 summit in 2020. The summit was intended to promote evidence-based recommendations to use the most reliable information from high-level research. Eight areas of importance to mitigate spine disorders were identified through a voting process of the participating societies. Twelve recommendations were discussed and vetted. Results The areas of immediate concern were “Aging spine,” “Future of spine care,” “Spinal cord injuries,” “Children and adolescent spine,” “Spine-related disability,” “Spine Educational Standards,” “Patient safety,” and “Burden on economy.” Twelve recommendations were created and endorsed by 31/33 spine societies and 2 journals globally during a vetted process through the SPINE20.org website and during the virtual inaugural meeting November 10–11, 2020 held from the G20 platform. Conclusions This is the first time that international spine societies have joined to support actions to mitigate the burden of spine disorders across the globe. SPINE20 seeks to change awareness and treatment of spine pain by supporting local projects that implement value-based practices with healthcare policies that are culturally sensitive based on scientific evidence.

The Zika virus infects progenitor neuron cells, disrupts cerebral development, and, in mice, drives hypothalamic defects. Patients with microcephaly caused by congenital Zika infection present with midline cerebral defects, which may result in hypopituitarism. OBJECTIVE To analyze postnatal growth and the presence of clinical and biochemical features associated with hypopituitarism in children with congenital Zika infections. DESIGN, SETTING, AND PARTICIPANTS In this prospective cohort study at 2 public referral hospitals in Bahia, Brazil, specializing in the treatment of congenital Zika infection, clinical data and growth parameters of 65 patients with the infection were evaluated. Data were analyzed from April 2017 through July 2018. EXPOSURE Congenital Zika infection. MAIN OUTCOMES AND MEASURES Length, weight, and head circumference were measured at birth and during follow up (ie, at 27 months of life) for each patient. Basal levels of free thyroxine, thyrotropin, cortisol, corticotropin, prolactin, insulin-like growth factor 1, insulin-like growth factor binding protein 3, urine and plasma osmolality, electrolytes, glucose, and insulin were evaluated at the age of 26 months to 28 months. All patients underwent central nervous system computed tomography scans and ophthalmic and otoacoustic evaluations at the time of this investigation or had done so previously. RESULTS Among 65 patients (38 [58.4%] male; median [interquartile range] age at enrollment, 27 [26-28] months), 61 patients presented with severe brain defects (93.8%), including corpus callosum agenesis or hypoplasia (ie, midline brain defects; 25 patients [38.5%]) and optic nerve atrophy (38 patients [58.5%]). Most patients presented with severe neurodevelopmental delay (62 of 64 patients [96.9%]). Past or present clinical signs of hypopituitarism were rare, occurring in 3 patients (4.6%). Severe microcephaly, compared with mild or moderate microcephaly, was associated with a shorter length by median (interquartile range) z score at birth (−1.9 [−2.5 to −1.0] vs −0.3 [−1.0 to 0]; P < .001), but this difference did not persist at 27 months (−1.6 [−2.3 to −0.3] vs −2.9 [−4.0 to −1.2]; P = .06). Growth hormone deficiency or hypothyroidism were not observed in any patients, and glucose and insulin levels were within reference ranges for all patients. Low cortisol levels (ie, below 3.9 μg/dL) were observed in 4 patients (6.2%). These 4 patients presented with low (ie, below 7.2 pg/mL) or inappropriately low (ie, below 30 pg/mL) corticotropin levels. Low corticotropin levels (ie, below 7.2 pg/mL) were observed in 6 patients (9.2%). Diabetes insipidus was evaluated in 21 patients; it was confirmed in 1 patient (4.8%) and suggested in 3 patients (14.3%). CONCLUSIONS AND RELEVANCE This study found that congenital Zika infection with microcephaly was associated with midline brain defects and optic nerve atrophy. Children with congenital Zika infections presented with prenatal growth impairments with a lack of postnatal catch-up, as shown by persistent short length from birth until 27 months; these impairments were not associated with growth hormone deficiency. Patients also presented with severe developmental delay thatwas not associated with hypothyroidism, while central adrenal insufficiency and diabetes insipidus occurred in some patients.

The role of histamine and acetylcholine in cognitive functions suggests that compounds able to increase both histaminergic and cholinergic neurotransmissions in the brain should be considered as promising therapeutic options. For this purpose, dual inhibitors of histamine H

Leveraging 3D bioprinting for processing stem cell-laden biomaterials has unlocked a tremendous potential for fabricating living 3D constructs for bone tissue engineering. Even though several bioinks developed to date display suitable physicochemical properties for stem cell seeding and proliferation, they generally lack the nanosized minerals present in native bone bioarchitecture. To enable the bottom-up fabrication of biomimetic 3D constructs for bioinstructing stem cells pro-osteogenic differentiation, herein we developed multi-bioactive nanocomposite bioinks that combine the organic and inorganic building blocks of bone. For the organic component gelatin methacrylate (GelMA), a photocrosslinkable denaturated collagen derivative used for 3D bioprinting was selected due to its rheological properties display of cell adhesion moieties to which bone tissue precursors such as human bone marrow derived mesenchymal stem cells (hBM-MSCs) can attach to. The inorganic building block was formulated by incorporating mesoporous silica nanoparticles functionalized with calcium, phosphate and dexamethasone (MSNCaPDex), which previously proven to induce osteogenic differentiation. The newly formulated photocrosslinkable nanocomposite GelMA bioink incorporating MSNCaPDex nanoparticles and laden with hBM-MSCs was successfully processed into a 3D bioprintable construct with structural fidelity, and well dispersed nanoparticles throughout the hydrogel matrix. These nanocomposite constructs could induce the deposition of apatite in vitro, thus showing attractive bioactivity properties. Viability and differentiation studies showed that hBM-MSCs remained viable and exhibited osteogenic differentiation biomarkers when incorporated in GelMA/MSNCaPDex constructs and without requiring further biochemical, nor mechanical stimuli. Overall, our nanocomposite bioink has demonstrated excellent processability via extrusion bioprinting into osteogenic constructs with potential application in bone tissue repair and regeneration.

Background: Population age structure may confound the comparison of age at cancer diagnosis across racial/ethnic groups. We compared age at cancer diagnosis for U.S. Hispanics, a population that is younger on average, and non-Hispanic whites (NHW), before and after adjustment for the age structure of the source population. Methods: We used Surveillance, Epidemiology, and End Results data from 18 U.S. regions in 2015 for 34 cancer sites to calculate crude and adjusted (using age- and sex-specific weights) mean ages at diagnosis. Differences in age at diagnosis comparing Hispanics to NHWs (δ) were assessed using independent sample t tests. Results: Crude mean ages at diagnosis were lower among Hispanic males and females for all sites combined and for most cancer sites. After age-adjustment, Hispanic (vs. NHW) males remained younger on average at diagnosis of chronic myeloid leukemia [δ = −6.1; 95% confidence interval (CI), −8.1 to −4.1 years], testicular cancer (δ =−4.7; 95% CI, −5.4 to −4.0), Kaposi sarcoma (δ =−3.6; 95% CI,−6.3 to −0.8), mesothelioma (δ =−3.0; 95% CI,−4.3 to −1.7), and anal cancer (δ =−2.4; 95% CI, −3.9 to −0.8), and older at diagnosis of gallbladder cancer (δ = +3.8; 95% CI, 1.8 to 5.7) and Hodgkin's lymphoma (δ = +7.5; 95% CI, 5.7 to 9.4), and Hispanic (vs. NHW) females remained younger at diagnosis of mesothelioma (δ = −3.7; 95% CI, −6.7 to −0.7) and gallbladder cancer (δ = −3.0; 95% CI, −4.3 to −1.7) and older at diagnosis of skin cancer (δ = +3.8; 95% CI, 3.1 to 4.5), cervical cancer (δ = +4.1; 95% CI, 3.3 to 4.8), and Hodgkin's lymphoma (δ = +7.0; 95% CI, 5.0 to 9.1). Conclusions: On average, Hispanics are diagnosed with cancer at younger ages than NHWs; however, for many cancers these differences reflect the younger age structure in Hispanics. Impact: Population age structure should be considered when comparing age at cancer diagnosis across racial/ethnic groups.

Protecting children from prenatal cocaine exposure is a significant challenge for physicians and childbearing women with cocaine use disorder. Cocaine use is highly prevalent among reproductive-aged women and prenatal cocaine exposure produces obstetric, foetal neurodevelopmental and long-term behavioural impairments. Cocaine crosses the maternal and foetal blood-brain barrier and the placenta by diffusion. The best approach to prevent prenatal cocaine exposure is to stop cocaine use. However, only 25% of cocaine users can discontinue their use during pregnancy. Anti-cocaine vaccination decreases cocaine passage through the blood-brain barrier. This study describes an innovative approach for preventing prenatal cocaine exposure using the GNE-KLH anti-cocaine vaccine, a novel use for the named anti-drug vaccines. Here, we show that anti-cocaine vaccination with GNE-KLH produced and maintained anti-cocaine IgG antibody titres and avidity during pregnancy. These antibodies protected the pregnant rats and their pups against prenatal cocaine damage during pregnancy until weaning. The present work is the first preclinical evidence of the efficacy of an innovative mechanism to prevent prenatal cocaine exposure damage, a worldwide public health care issue. In the future, this mechanism may be useful in pregnant women with cocaine use disorder. Further studies to understand the mechanisms of how anti-cocaine antibodies exert their protective effects in pregnancy are warranted.