Cognitive impact of anticholinergic and sedative burden in people living with HIV.

OBJECTIVE: This study aims to estimate the extent to which anticholinergic and sedative burden is associated with cognitive ability and self-reported cognitive difficulties (SCD) in middle-aged and older adults living with HIV. DESIGN: This cross-sectional analysis examined data from the inaugural visit of participants enrolled in the Positive Brain Health Now (BHN) study. METHODS: Cognitive ability was measured using the Brief Cognitive Ability Measure (B-CAM; higher is better) and SCD using the Perceived Deficits Questionnaire (PDQ; higher is worse). Medication burden was quantified using several scoring systems, including the Anticholinergic Cognitive Burden (ACB), Anticholinergic and Sedative Burden Catalog (ACSBC), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and the Sedative Load Model (SLM). Multivariable Ordinary Least Squares and quantile regression were utilized to estimate average effects and distribution-specific impacts, respectively. RESULTS: Of 824 participants (mean age 53 years, 84.7% men), 41.4% used anticholinergics (ACSBC) and 39% used sedatives (SLM). High anticholinergic burden was linked to worse cognitive ability (ß = -3.81; 95% CI: -7.16, -0.46) and SCD (ß = 3.89; 95% CI: 1.08, 6.71). Using three or more anticholinergics worsened cognitive ability (ß = -4.45; 95% CI: -8.54, -0.35), and using three or more sedatives increased SCD (ß = 4.35; 95% CI: 0.92 -7.78). Stronger negative associations were observed in participants with lower cognitive ability and more difficulties. CONCLUSIONS: These results suggest that anticholinergic and sedative burden may contribute to cognitive impairment in people with HIV. Personalized medication management and regular cognitive assessments could mitigate these adverse effects.

Medication utilization patterns in patients with post-COVID syndrome (PCS): Implications for polypharmacy and drug-drug interactions.

BACKGROUND: Post-COVID syndrome (PCS) causes lasting symptoms like fatigue and cognitive issues. PCS treatment is nonspecific, focusing on symptom management, potentially increasing the risk of polypharmacy. OBJECTIVES: To describe medication use patterns among patients with Post-COVID Syndrome (PCS) and estimate the prevalence of polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden. METHODS: A cross-sectional analysis of baseline data from the Quebec Action for Post-COVID cohort, consisting of individuals self-identifying with persistent COVID-19 symptoms beyond 12 weeks. Medications were categorized using Anatomical Therapeutic Classification (ATC) codes. Polypharmacy was defined as using 5 or more concurrent medications. The Anticholinergic and Sedative Burden Catalog assessed anticholinergic and sedative loads. The Lexi-Interact checker identified potential drug-drug interactions, which were categorized into 3 severity tiers. RESULTS: Out of 414 respondents, 154 (average age 47.7 years) were prescribed medications related to persistent COVID-19 symptoms. Drugs targeting the nervous system were predominant at 54.5%. The median number of medications was 2, while 11.7% reported polypharmacy. Over half of the participants prescribed medications used at least 1 anticholinergic or sedative medication, and 25% had the potential risk for clinically significant drug-drug interactions, primarily needing therapy monitoring. CONCLUSIONS: Our study reveals prescription patterns for PCS, underscoring the targeted management of nervous system symptoms. The risks associated with polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden stress the importance of judicious prescribing. While limitations like recall bias and a regional cohort are present, the findings underscore the imperative need for vigilant PCS symptom management.

The association between anticholinergic/sedative burden and physical frailty in people aging with HIV.

OBJECTIVE: This study aimed to estimate the strength of the association between anticholinergic/sedative burden and concurrent physical frailty in people aging with HIV. DESIGN: This cross-sectional analysis examined baseline data from 824 adults with a mean age of 53 enrolled in the Positive Brain Health Now study. METHODS: Anticholinergic medications were identified using four methods: Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Risk Scale (ARS), Anticholinergic Drug Scale (ADS), and the anticholinergic list of the Anticholinergic and Sedative Burden Catalog (ACSBC). Sedatives were identified using the Sedative Load Model (SLM) and the sedative list of the ACSBC. Physical frailty was assessed using a modified Fried Frailty Phenotype (FFP) based on self-report items. Multivariable logistic regression models, adjusted for sociodemographic factors, lifestyle considerations, HIV-related variables, comorbidities, and co-medication use, were used to estimate odds ratios (ORs). RESULTS: Anticholinergic burden demonstrated associations with frailty across various methods: total anticholinergic burden (OR range: 1.22-1.32; 95% confidence interval (CI) range: 1.03-1.66), sedative burden (OR range: 1.18-1.24; 95% CI range: 1.02-1.45), high anticholinergic burden (OR range: 2.12-2.74; 95% CI range: 1.03-6.19), and high sedative burden (OR range: 1.94-2.18; 95% CI: 1.01-4.34). CONCLUSION: The anticholinergic and sedative burdens may represent modifiable risk factors for frailty in people aging with HIV. Future studies should evaluate the effects of reducing anticholinergic and sedative burdens on frailty outcomes and explore the prognostic value of diverse scoring methods.

The Prognostic Utility of Anticholinergic Burden Scales: An Integrative Review and Gap Analysis.

BACKGROUND: Anticholinergic drugs are commonly prescribed, especially to older adults. Anticholinergic burden scales (ABS) have been used to evaluate the cumulative effects of multiple anticholinergics. However, studies have shown inconsistent results regarding the association between anticholinergic burden assessed with ABS and adverse clinical outcomes such as cognitive impairment, functional decline, and frailty. This review aims to identify gaps in research on the development, validation, and evaluation of ABS, and provide recommendations for future studies. METHOD: A comprehensive search of five databases (MEDLINE, Embase, PsychInfo, CINAHL, CENTRAL) was conducted for relevant studies published from inception until 25 May 2023. Two reviewers screened for eligibility and assessed the quality of studies using different tools based on the study design and stage of the review framework. Research evidence was evaluated, and gaps were identified and grouped into evidence, knowledge, and methodological gaps, using evidence tables to summarize data. RESULTS: Several evidence, knowledge, and methodological gaps in existing development, validation, and evaluation studies of ABS were identified. There is no universally accepted scale, and there is a need to define a clinically relevant threshold for measuring total anticholinergic burden. The current evidence has limitations, underrepresenting low- and middle-income countries, younger individuals, and populations with cognitive disabilities. The impact of anticholinergic burden on frailty is also understudied. Existing evaluation studies provide limited evidence on the benefit of reducing anticholinergic burden on clinical outcomes or the safety of anticholinergic deprescribing. There is also uncertainty regarding optimal reduction, clinically significant anticholinergic burden thresholds, and cost effectiveness. CONCLUSIONS: Future research recommendations to bridge knowledge gaps include developing a risk assessment framework, refining ABS scales, establishing a standardized consensus scale, and creating a longitudinal measure of cumulative anticholinergic risk. Strategies to minimize bias, consider frailty, and promote multidisciplinary and multinational collaborations are also necessary to improve patient outcomes.

An individual differences perspective on pragmatic abilities in the preschool years.

Pragmatic abilities are fundamental to successful language use and learning. Individual differences studies contribute to understanding the psychological processes involved in pragmatic reasoning. Small sample sizes, insufficient measurement tools, and a lack of theoretical precision have hindered progress, however. Three studies addressed these challenges in three- to 5-year-old German-speaking children (N = 228, 121 female). Studies 1 and 2 assessed the psychometric properties of six pragmatics tasks. Study 3 investigated relations among pragmatics tasks and between pragmatics and other cognitive abilities. The tasks were found to measure stable variation between individuals. Via a computational cognitive model, individual differences were traced back to a latent pragmatics construct. This presents the basis for understanding the relations between pragmatics and other cognitive abilities. RESEARCH HIGHLIGHTS: Individual differences in pragmatic abilities are important to understanding variation in language development. Research in this domain lacks a precise theoretical framework and psychometrically high-quality measures. We present six tasks capturing a wide range of pragmatic abilities with excellent re-test reliability. We use a computational cognitive model to provide a substantive theory of individual differences in pragmatic abilities.

Ganglion cell complex changes in wet AMD patients treated with anti-VEGF intravitreal injections according to a treat-and-extend protocol.

OBJECTIVE: To analyze changes in ganglion cell complex (GCC) thickness in wet age-related macular degeneration (AMD) patients receiving intravitreal injections. DESIGN: Retrospective cohort study involving 46 eyes at a single tertiary ophthalmology practice. PARTICIPANTS: The injection group consisted of wet AMD patients who received intravitreal injections for at least 3 years following a treat-and-extend protocol. Twenty-two patients received ranibizumab, and 1 patient received aflibercept. The control group consisted of dry AMD patients who were observed only and did not receive medical treatment over the same period. GCC thickness and visual acuity were recorded at baseline and at 1-, 2-, and 3-year follow-up visits. RESULTS: In the injection group, there was a nonsignificant trend toward reduction in GCC thickness over 3 years (-4.09 ± 8.47 µm; p = 0.09). Within the injection group, correlation analysis between the number of intravitreal injections and GCC thickness was nonsignificant but trended toward a direct relationship, with more injections correlated with a relatively thicker GCC at 3 years. There was no significant change in GCC thickness between baseline and year 3 for the control group. CONCLUSIONS: Study results suggest that that there is no significant GCC thinning in wet AMD patients following a treat-and-extend regimen over 3 years.

Great ape communication as contextual social inference: a computational modelling perspective.

Human communication has been described as a contextual social inference process. Research into great ape communication has been inspired by this view to look for the evolutionary roots of the social, cognitive and interactional processes involved in human communication. This approach has been highly productive, yet it is partly compromised by the widespread focus on how great apes use and understand individual signals. This paper introduces a computational model that formalizes great ape communication as a multi-faceted social inference process that integrates (a) information contained in the signals that make up an utterance, (b) the relationship between communicative partners and (c) the social context. This model makes accurate qualitative and quantitative predictions about real-world communicative interactions between semi-wild-living chimpanzees. When enriched with a pragmatic reasoning process, the model explains repeatedly reported differences between humans and great apes in the interpretation of ambiguous signals (e.g. pointing or iconic gestures). This approach has direct implications for observational and experimental studies of great ape communication and provides a new tool for theorizing about the evolution of uniquely human communication. This article is part of the theme issue 'Revisiting the human 'interaction engine': comparative approaches to social action coordination'.

Predicting pragmatic cue integration in adults' and children's inferences about novel word meanings.

Language is learned in complex social settings where listeners must reconstruct speakers' intended meanings from context. To navigate this challenge, children can use pragmatic reasoning to learn the meaning of unfamiliar words. A critical challenge for pragmatic reasoning is that it requires integrating multiple information sources, which have typically been studied separately. Here we study this integration process. First, we experimentally isolate two sources of pragmatic information: expectations about informative communication and common ground. Next, we use a probabilistic model of conversational reasoning to formalize how these information sources should be combined and how this process might develop. We use this model to generate quantitative predictions, which we test against new experimental data from 3- to 5-year-old children (N = 243) and adults (N = 694). Results show close alignment between model predictions and data. Furthermore, the model provided a better explanation of the data compared with simpler alternative models assuming that participants selectively ignore one information source. This work integrates distinct sets of findings regarding information sources for early language learning and suggests that pragmatic reasoning models can provide a quantitative framework for understanding developmental changes in language learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Warm (for Winter): Inferring Comparison Classes in Communication.

The meanings of natural language utterances depend heavily on context. Yet, what counts as context is often only implicit in conversation. The utterance it's warm outside signals that the temperature outside is relatively high, but the temperature could be high relative to a number of different comparison classes: other days of the year, other weeks, other seasons, etc. Theories of context sensitivity in language agree that the comparison class is a crucial variable for understanding meaning, but little is known about how a listener decides upon the comparison class. Using the case study of gradable adjectives (e.g., warm), we extend a Bayesian model of pragmatic inference to reason flexibly about the comparison class and test its qualitative predictions in a large-scale free-production experiment. We find that human listeners infer the comparison class by reasoning about the kinds of observations that would be remarkable enough for a speaker to mention, given the speaker and listener's shared knowledge of the world. Further, we quantitatively synthesize the model and data using Bayesian data analysis, which reveals that usage frequency and a preference for basic-level categories are two main factors in comparison class inference. This work presents new data and reveals the mechanisms by which human listeners recover the relevant aspects of context when understanding language.

Logic, Probability, and Pragmatics in Syllogistic Reasoning.

Syllogistic reasoning lies at the intriguing intersection of natural and formal reasoning of language and logic. Syllogisms comprise a formal system of reasoning yet make use of natural language quantifiers (e.g., all, some) and invite natural language conclusions. The conclusions people tend to draw from syllogisms, however, deviate substantially from the purely logical system. Are principles of natural language understanding to blame? We introduce a probabilistic pragmatic perspective on syllogistic reasoning: We decompose reasoning with natural language arguments into two subproblems: language comprehension and language production. We formalize models of these processes within the Rational Speech Act framework and explore the pressures that pragmatic reasoning places on the production of conclusions. We test our models on a recent, large data set of syllogistic reasoning and find that the selection process of conclusions from syllogisms are best modeled as a pragmatic speaker who has the goal of aligning the beliefs of a naive listener with those of their own. We compare our model to previously published models that implement two alternative theories-Mental Models and Probability Heuristics-finding that our model quantitatively predicts the full distributions of responses as well as or better than previous accounts, but with far fewer parameters. Our results suggest that human syllogistic reasoning may be best understood not as a poor approximation to ideal logical reasoning, but rather as rational probabilistic inference in support of natural communication.

Modeling Individual Differences in Children's Information Integration During Pragmatic Word Learning.

Pragmatics is foundational to language use and learning. Computational cognitive models have been successfully used to predict pragmatic phenomena in adults and children - on an aggregate level. It is unclear if they can be used to predict behavior on an individual level. We address this question in children (N = 60, 3- to 5-year-olds), taking advantage of recent work on pragmatic cue integration. In Part 1, we use data from four independent tasks to estimate child-specific sensitivity parameters to three information sources: semantic knowledge, expectations about speaker informativeness, and sensitivity to common ground. In Part 2, we use these parameters to generate participant-specific trial-by-trial predictions for a new task that jointly manipulated all three information sources. The model accurately predicted children's behavior in the majority of trials. This work advances a substantive theory of individual differences in which the primary locus of developmental variation is sensitivity to individual information sources.

A Meta-Analytic Review of the Effect of Antiretroviral Therapy on Neurocognitive Outcomes in Adults Living with HIV-1 in Low-and Middle-Income Countries.

HIV-associated neurocognitive impairment remains a challenge even in the era of antiretroviral therapy (ART). Over 90% of people living with HIV are in low- and middle-income countries. Hence, it is not surprising that such countries bear a considerable burden of comorbidities like HIV-associated neurocognitive impairment despite an overall increase in life expectancy. The literature suggests differences in patient characteristics, clinical profile, prevalent HIV subtypes, treatment choices, pharmacogenetics, and socioeconomic factors between low- and middle-income countries compared with high-income countries. Therefore, we aimed to evaluate the effect of ART on neurocognitive outcomes in low- and middle-income countries. A comprehensive search of five databases (PubMed, CINAHL, CENTRAL, PsychInfo, Google scholar) for studies published between 1996 to 2020 was performed to identify studies that reported neurocognitive outcomes in ART-treated and ART naïve HIV positive individuals. Two independent reviewers conducted study screening, data extraction, and evaluation of the risk of bias. Pooled effect size estimates (Hedges' g) and 95% CI were computed using random-effects models. Sensitivity analysis, subgroup analysis, meta-regression, and evaluation of publication bias were also conducted. Forty studies (24 cross-sectional, 13 longitudinal studies, and two randomized controlled trials) contributed to a series of meta-analyses. We found significant small to moderate effects of antiretroviral therapy for global cognition (Hedges' g observed = 0.30; 95% CI: 0.15, 0.44; k = 25; p = 0.0003; I2 = 92.1%; tau = 0.32; Q = 305.1), executive function (Hedges' g = 0.24, 95%CI: 0.02,0.46; p-0.04; k = 8; I2 = 37.5%; tau = 0.23; Q = 11.2), and speed of information processing (Hedges' g = 0.25, 95% CI: 0.05, 0.45; k = 9; p = 0.02; I2 = 86.4%; tau = 0.21; Q = 58.9). We found no significant ART effect on attention-working memory, learning and memory, motor function, and verbal fluency. No significant effect was seen with the duration of therapy, efavirenz use, and Central Penetrating Effectiveness (CPE) of antiretroviral therapy. Subgroup analyses identified study design (between-group and within-group; cross-sectional and longitudinal) and normative scores as significant sources of heterogeneity. Meta-regression analysis indicated that nadir CD4 modified the magnitude of ART's effect on cognitive outcomes. Age, gender, and country income-group were not significant moderators. Our findings provide systematic evidence that antiretroviral therapy improves neurocognitive outcomes in the domains of global cognition, executive function and speed of information processing, of people living with HIV in low- and middle-income countries, especially those with advanced immunosuppression. However, these findings are not definitive as they are limited by the probability of publication bias, high heterogeneity, and exclusion of significant confounders. Prospero registration number: CRD42020203791.

Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) mRNA vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of literature was performed and a total of 18 studies (N=15,980) were identified and reviewed. The percent difference of means of reported antibody titers were then calculated to determine the decline in humoral response after the peak levels post-vaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6 months post-vaccination. Additionally, results showed that regardless of age, sex, serostatus and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain (RBD) IgG and anti-spike IgG, ranging from 94-95% at 90-180 days and 55-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns (VoCs).

Protected Organic Acid and Essential Oils for Broilers Raised Under Field Conditions: Intestinal Health Biomarkers and Cecal Microbiota.

The objective of the present study was to evaluate the effect of protected organic acids (OA) and essential oils (EO) [P(OA + EO)] on the intestinal health of broiler chickens raised under field conditions. The study was conducted on four commercial farms. Each farm consisted of four barns, two barns under a control diet and two tested barns supplemented with P(OA + EO), totaling 16 barns [8 control and 8 under P(OA + EO)]. The control group was supplemented with antibiotic growth promoters [AGP; Bacitracin Methylene Disalicylate (50 g/ton) during starter, grower and finisher 1, and flavomycin (2 g/ton) during finisher 2]. The tested group was supplemented with 636, 636, 454, and 454 g/ton of P(OA + EO) during starter, grower, finisher 1 and 2, respectively. Eighty birds were necropsied (40/treatment; 20/farm; and 5/barn) to collect blood, jejunal tissue, and cecal contents. The data were submitted to analysis of variance (ANOVA) (P < 0.05) or Kruskal-Wallis' test and the frequency of antimicrobial resistant (AMR) genes was analyzed by Chi-Square test (P < 0.05). It was observed that the supplementation of P(OA + EO) reduced (P < 0.05) the histopathology scores, such as the infiltration of inflammatory cells in the epithelium and lamina propria and tended (P = 0.09) to reduce the serum concentration of calprotectin (CALP). The supplementation of P(OA + EO) reduced the serum concentration of IL-12 (P = 0.0001), IL-16 (P = 0.001), and Pentraxin-3 (P = 0.04). Additionally, P(OA + EO) maintained a cecal microbiota similar to birds receiving AGP. The substitution of AGP by P(OA + EO) reduced (P < 0.05) the frequency of four AMR genes, related to gentamicin (three genes), and aminoglycoside (one gene). Overall, the inclusion of P(OA + EO), and removal of AGP, in the diets of commercially raised broiler chickens beneficially changed the phenotype of the jejunum as shown by the lowered ISI scores which characterizes an improved intestinal health. Furthermore, P(OA + EO) significantly reduced the serum concentration of several inflammatory biomarkers, while maintaining the diversity and composition of the cecal microbiota similar to AGP fed chickens and reducing the prevalence of AMR genes.

Phenolics from Medicinal and Aromatic Plants: Characterisation and Potential as Biostimulants and Bioprotectants.

Biostimulants and bioprotectants are derived from natural sources and can enhance crop growth and protect crops from pests and pathogens, respectively. They have attracted much attention in the past few decades and contribute to a more sustainable and eco-friendly agricultural system. Despite not having been explored extensively, plant extracts and their component secondary metabolites, including phenolic compounds have been shown to have biostimulant effects on plants, including enhancement of growth attributes and yield, as well as bioprotectant effects, including antimicrobial, insecticidal, herbicidal and nematicidal effects. Medicinal and aromatic plants are widely distributed all over the world and are abundant sources of phenolic compounds. This paper reviews the characterisation of phenolic compounds and extracts from medicinal and aromatic plants, including a brief overview of their extraction, phytochemical screening and methods of analysis. The second part of the review highlights the potential for use of phenolic compounds and extracts as biostimulants and bioprotectants in agriculture as well as some of the challenges related to their use.

Effects of Age, Sex, Serostatus and Underlying Comorbidities on Humoral Response Post-SARS-CoV-2 Pfizer-BioNTech Vaccination: A Systematic Review

With the advent of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, several vaccines have been developed to mitigate its spread and prevent adverse consequences of the Coronavirus Disease 2019 (COVID-19). The mRNA technology is an unprecedented vaccine, usually given in two doses to prevent SARS-CoV-2 infections. Despite effectiveness and safety, inter-individual immune response heterogeneity has been observed in recipients of mRNA-based vaccines. As a novel disease, the specific immune response mechanism responsible for warding off COVID-19 remains unclear at this point. However, significant evidence suggests that humoral response plays a crucial role in affording immunoprotection and preventing debilitating sequelae from COVID-19. As such this paper focused on the possible effects of age, sex, serostatus, and comorbidities on humoral response (i.e., total antibodies, IgG and/or IgA) of different populations post-mRNA-based Pfizer-BioNTech vaccination. A systematic search of literature was performed through PubMed, Cochrane CENTRAL, and Google Scholar. Studies were included if they reported humoral response to COVID-19 mRNA vaccines. A total of 32 studies was identified and reviewed, and the percent difference of means of reported antibody levels were calculated for comparison. Findings revealed that older individuals, the male sex, seronegativity, and those with more comorbidities mounted less humoral immune response. Given these findings, several recommendations were proposed regarding the current vaccination practices. These include giving additional doses of vaccination for immunocompromised and elderly populations. Another recommendation is conducting clinical trials in giving a combined scheme of mRNA vaccines, protein vaccines, and vector-based vaccines.

Symptomatology associated with the diffusion of the SARS-CoV-2 Lambda variant in Peru: An infodemiologic analysis

The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) Lambda variant rapidly diffused across Peru following its identification in December 2020, and had now spread worldwide. In this study, we investigated infodemiologic trends in symptomatology associated with the Coronavirus Disease 2019 (COVID-19) following the spread of SARS-CoV-2 Lambda variant in Peru, enabling infodemiologic surveillance of SARS-CoV-2 in regions with high circulation of this new variant. Weekly Google Trends scores were obtained for key symptom keywords between March 1st, 2020 and July 4th, 2021, whilst case count data were obtained from Peruvian Ministry of Health. Multiple time series linear regression was used to assess trends in each score series, using the week of December 27th as cutoff for emergence of the Lambda variant. The significance of such trends was tested for each time period, before and after the cutoff date. A total 2,075,484 confirmed SARS-CoV-2 infections in Peru in relation to Google Trends data were analyzed. After Lambda variant emergence, searches for "diarrhea" demonstrated a change from a negative to positive correlation with weekly case counts and anticipated dynamic changes in case counts by 1-5 weeks. Searches for "shortness of breath" and "headache" remained consistently positively correlated to weekly case counts before and after Lambda emergence. No changes in searches for other common cold symptoms were observed, while no specific trends were observed for "taste loss" or "smell loss". Diarrhea, headache, and shortness of breath appear to be the most important symptoms for infodemiologic tracking the current outbreak in Peru and other regions with high circulation of SARS-CoV-2 Lambda variant.

How young children integrate information sources to infer the meaning of words.

Before formal education begins, children typically acquire a vocabulary of thousands of words. This learning process requires the use of many different information sources in their social environment, including their current state of knowledge and the context in which they hear words used. How is this information integrated? We specify a developmental model according to which children consider information sources in an age-specific way and integrate them via Bayesian inference. This model accurately predicted 2-5-year-old children's word learning across a range of experimental conditions in which they had to integrate three information sources. Model comparison suggests that the central locus of development is an increased sensitivity to individual information sources, rather than changes in integration ability. This work presents a developmental theory of information integration during language learning and illustrates how formal models can be used to make a quantitative test of the predictive and explanatory power of competing theories.

Comprehensive assessment of humoral response after Pfizer BNT162b2 mRNA Covid-19 vaccination: a three-case series

BackgroundSince universal vaccination is a pillar against coronavirus disease 2019 (COVID-19), monitoring anti-SARS-CoV-2 neutralizing antibodies is essential for deciphering post-vaccination immune response. MethodsThree healthcare workers received 30 g BNT162b2 mRNA Covid-19 Vaccine, followed by a second identical dose, 21 days afterwards. Venous blood was drawn at baseline and at serial intervals, up to 63 days afterwards, for assessing total immunoglobulins (Ig) anti-RBD (receptor binding domain), IgG anti-S1/S2, IgG anti-RBD, IgM anti-RBD, IgM anti-N/S1 and IgA anti-S1. ResultsAll subjects were SARS-CoV-2 seronegative at baseline. Total Ig anti-RBD, IgG anti-S1/S2 and IgG anti-RBD levels increased between 91-368 folds until 21 days after the first vaccine dose, then reached a plateau. The levels raised further after the second dose (by [~]30-, [~]8- and [~]8-fold, respectively), peaking at day 35, but then slightly declining and stabilizing [~]50 days after the first dose. IgA anti-S1 levels increased between 7-11 days after the first dose, slightly declined before the second dose, after which levels augmented by [~]24-fold from baseline. The anti-RBD and anti-N/S1 IgM kinetics were similar to that of anti-S1 IgA, though displaying substantially weaker increases and modest peaks, only 4 to 7-fold higher than baseline. Highly significant inter-correlation was noted between total Ig anti-RBD, anti-S1/S2 and anti-RBD IgG (all r=0.99), whilst other anti-SARS-CoV-2 antibodies displayed lower, though still significant, correlations. Serum spike protein concentration was undetectable at all time points. ConclusionsBNT162b2 mRNA vaccination generates a robust humoral immune response, especially involving IgG and IgA, magnified by the second vaccine dose.

Sudden rise in COVID-19 case fatality among young and middle-aged adults in the south of Brazil after identification of the novel B.1.1.28.1 (P.1) SARS-CoV-2 strain: analysis of data from the state of Parana

Brazil is currently suffering a deadly surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, which has been attributed to the spread of a new strain known as P.1 (B.1.1.28.1). In this investigation, we analyzed coronavirus disease 2019 (COVID-19) public health data from Parana, the largest state in southern half of Brazil, between September 1, 2020 and March 17, 2021, to evaluate recent trends in case fatality rates in different age groups. A total of 553,518 cases of SARS-CoV-2, 8,853 currently registered as fatal, were finally included in our analysis. All age groups showed either decline or stabilization of the case fatality rates (CFRs) between September 2020 and January 2021. In February 2021, an increase in CFR for almost all age groups could be instead observed. All groups above 20 years of age showed statistically significant increases in CFR when diagnosed in February 2021 as opposed to January 2021. Patients aged 20-29 years experienced a tripling of their CFR, from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling. Individuals between 20 and 29 years of age whose diagnosis was made in February 2021 had an over 3-fold higher risk of death compared to those diagnosed in January 2021 (Risk Ratio (RR): 3.15 [95%CI: 1.52-6.53], p<0.01), while those aged 30-39, 40-49, 50-59 years experienced 93% (1.93 [95%CI:1.31-2.85], p<0.01), 110% (RR: 2.10 [95%CI:1.62-2.72], p<0.01), and 80% (RR: 1.80 [95%CI:1.50-2.16], p<0.01) increases in risk of death, respectively. Notably, the observed CFR increase coincided with the second consecutive month of declining number of diagnosed SARS-CoV-2 cases. Taken together, these preliminary findings suggest significant increases in CFR in young and middle-aged adults after identification of a novel SARS-CoV-2 strain circulating in Brazil, and this should raise public health alarms, including the need for more aggressive local and regional public health interventions and faster vaccination.