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Objectives: To describe the symptoms, duration, severity, and microbiology of lower respiratory tract infection (LRTI) in outpatients., Methods: Prospective cohort study of adults in US primary or urgent care with a chief complaint of cough and symptoms consistent with LRTI. Baseline data included demographics, signs, symptoms, and PCR for 46 viruses and bacteria. The severity of symptoms reported for ≤28 days follow-up via diary and text message. The Bronchitis severity score assessed severity at baseline; overall severity was defined as the area under the symptom severity curve., Results: Of 718 patients with complete baseline data, 618 had valid PCR results, and 443 were followed until symptoms resolved. Of those with valid PCR, 100 (16.2%) had 1+ viruses detected, 211 (34.1%) had 1+ bacteria, and 168 (27.2%) had both. Symptoms more likely with viral or mixed infection included feverishness (36.7-38.4% vs. 18.5%), chills or sweats (36.0-38.1% vs. 17.9%), being generally unwell (78.2-81.3% vs. 64.9%), and myalgias (42.7-48.2% vs. 28.6%). Coloured sputum (42.9% vs. 23.2-29.5%) was more common with a bacterial infection. The mean duration of cough was 14.7 days with viruses (95% CI: 13.2-16.2), 17.3 with bacteria (95% CI: 15.9-18.6), 16.9 with mixed infection (95% CI: 15.2-18.6), and 18.4 with no detection (95% CI: 16.1-20.8). Overall severity of cough was lower for viral infections (20.9 points, 95% CI: 18.6-23.3) than for other groups (range 24.2-26.3). The most common potential bacterial pathogens were Haemophilus influenza (28.0%), Moraxella catarrhalis (16.2%), and Streptococcus pneumoniae (10.2%), whereas the most common viral pathogens were rhinovirus (17.3%), influenza (12.8%), SARS-CoV-2 (11.5%), and seasonal coronaviruses (8.1%)., Discussion: The mean duration of cough was 16.4 days. Consistent with European studies, the type of infection or potential pathogen was not an important predictor of the duration or severity of LRTI., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The objective of this network meta-analysis was to compare rates of clinical response and mortality for empiric oral antibiotic regimens in adults with mild-moderate community-acquired pneumonia (CAP)., Methods: We searched PubMed, Cochrane, and the reference lists of systematic reviews and clinical guidelines. We included randomized trials of adults with radiologically confirmed mild to moderate CAP initially treated orally and reporting clinical cure or mortality. Abstracts and studies were reviewed in parallel for inclusion in the analysis and for data abstraction. We performed separate analyses by antibiotic medications and antibiotic classes and present the results through network diagrams and forest plots sorted by p-scores. We assessed the quality of each study using the Cochrane Risk of Bias framework, as well as global and local inconsistency., Results: We identified 24 studies with 9361 patients: six at low risk of bias, six at unclear risk, and 12 at high risk. Nemonoxacin, levofloxacin, and telithromycin were most likely to achieve clinical response (p-score 0.79, 0.71, and 0.69 respectively), while penicillin and amoxicillin were least likely to achieve clinical response. Levofloxacin, nemonoxacin, azithromycin, and amoxicillin-clavulanate were most likely to be associated with lower mortality (p-score 0.85, 0.75, 0.74, and 0.68 respectively). By antibiotic class, quinolones and macrolides were most effective for clinical response (0.71 and 0.70 respectively), with amoxicillin-clavulanate plus macrolides and beta-lactams being less effective (p-score 0.11 and 0.22). Quinolones were most likely to be associated with lower mortality (0.63). All confidence intervals were broad and partially overlapping., Conclusion: We observed trends toward a better clinical response and lower mortality for quinolones as empiric antibiotics for CAP, but found no conclusive evidence of any antibiotic being clearly more effective than another. More trials are needed to inform guideline recommendations on the most effective antibiotic regimens for outpatients with mild to moderate CAP., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objectives: We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients., Methods: RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events., Results: 126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported., Conclusions: Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.

Background: Testing for influenza in patients with acute lower respiratory tract infection (LRTI) is common and in some cases is performed for all patients with LRTI. A more selective approach to testing could be more efficient., Methods: We used data from two prospective studies in the US primary and urgent care settings that enrolled patients with acute LRTI or influenza-like illness. Data were collected in the 2016, 2019, 2021, and 2022 flu seasons. All patients underwent polymerase chain reaction (PCR) testing for influenza and the FluScore was calculated based on patient-reported symptoms at their initial visit. The probability of influenza in each risk group was reported, as well as stratum-specific likelihood ratios (SSLRs) for each risk level., Results: The prevalence of influenza within risk groups varied based on overall differences in flu seasons and populations. However, the FluScore exhibited consistent performance across various seasons and populations based on the SSLRs. The FluScore had a consistent SSLR range of 0.20 to 0.23 for the low-risk group, 0.63 to 0.99 for the moderate-risk group, and 1.46 to 1.67 for the high-risk group. The diagnostic odds ratio based on the midpoints of these ranges was 7.25., Conclusions: The FluScore could streamline patient categorization, identifying patients who could be exempted from testing, while identifying candidates for rapid influenza tests. This has the potential to be more efficient than a "one size fits all" test strategy, as it strategically targets the use of tests on patients most likely to benefit. It is potentially usable in a telehealth setting., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome of unknown aetiopathogenesis. Its development and maintenance are related to the interplay of biological, psychological, and contextual factors. Among the contextual factors, sociodemographic aspects are poorly elucidated. This study aimed to evaluate the relationships between sociodemographic/clinical factors and symptom severity measures using a web-based registry of patients with FM., Methods: Adult patients with an ACR 2010/2011 diagnosis of FM underwent a clinical evaluation and were asked to complete questionnaires covering their sociodemographic data (gender, age, marital status, educational level), and disease-specific measures (the revised Fibromyalgia Impact Questionnaire (FIQR), and the Polysymptomatic Distress Scale (PDS))., Results: Data relating to 3,221 patients (3001 women and 220 men) was collected. The ANOVA showed significant difference in mean FIQR scores when the five marital conditions (cohabiter, married, separated/divorced, single, widowed) were compared (F 3.321, p<0.01). While males and females were found to have comparable FIQR scores, the interaction between gender and marital status indicated that separated/divorced males have higher FIQR scores (F 5.684, p=0.001). The multiple regression analysis demonstrated that patients who reported lower educational level experienced more severe FM symptoms, as scored with FIQR (p<0.0001)., Conclusions: Our results indicated that being male and separated/divorced is associated to higher severity of FM symptoms, as rated with FIQR. Furthermore, a relationship between educational level and FIQR scores has been detected. This study supports the importance of collecting simple SES measures to identify environmental risk factors for FM severity.

Objectives: The role of age in influencing the severity of fibromyalgia (FM) is still controversial. The aim of this study is to define the contribution of age in the severity of FM from data from a large national database., Methods: This cross-sectional study included adult patients with FM diagnosed according to the 2010/2011 American College of Rheumatology criteria. Disease severity was assessed with the revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FAS 2019mod). Patients were grouped into five age categories (between 18-40 years, between 41-50 years, between 51-60 years, between 61-70 years, and ≥71 years). Differences in disease severity between groups were assessed by one-way analysis of variance (ANOVA)., Results: The study included 2889 patients (199 males and 2690 females), mean age of 52.58 (±11.82) years, with a mean FIQR score of 59.22 (±22.98) and a mean FAS 2019mod of 25.50 (±8.66). Comparing the mean values of the various indices between age categories, there were no statistically significant differences between the groups for FIQR total score and FAS 2019mod. However, the 60-70 years category showed the lowest scores for both scales. The main difference emerged for the FIQR physical function subscale, where the ≥71 years category showed significantly higher scores (p<0.05) compared the 18-40 years category., Conclusions: The severity of FM has a significant level of stationarity according to age categories. Patients between 60-70 years have a lower disease burden. Physical function is the health domain with the most significant difference between the groups.

Introduction: Universities are unique settings with large populations, congregate housing, and frequent attendance of events in large groups. However, the current prevalence of previous COVID-19 infection in university students, including symptomatic and asymptomatic disease, is unknown. Our goal therefore was to determine the prevalence of previous infection, risk factors for infection, and the prevalence of persistent symptoms following infection among university students., Methods: This was a cross-sectional study set in a large public university between January 22 and March 22, 2021. We surveyed students about demographics, risk factors, and symptoms, and simultaneously tested their saliva for IgA antibodies to SARS-CoV-2. To estimate the prevalence of previous infection we adjusted our intentional sample of a diverse student population for year in school and age to resemble the composition of the entire student body and adjusted for the imperfect sensitivity and specificity of the antibody test. Univariate and multiple regression analysis was used to identify independent risk factors for infection, and the proportion of students with persistent symptoms following acute infection was determined., Results: A total of 488 students completed the survey, 432 had a valid antibody result, and 428 had both. The estimated prevalence of previous infection for 432 participants with valid antibody results was 41%. Of 145 students in our sample with a positive antibody test, 41.4% denied having a previous positive polymerase chain reaction (PCR) test for SARS-CoV-2 and presumably had an asymptomatic infection; in our adjusted analysis we estimate that approximately 2-thirds of students had asymptomatic infections. Independent risk factors for infection included male sex, having a roommate with a known symptomatic infection, and having two or fewer roommates. More frequent attendance of parties and bars was a univariate risk factor, but not in the multiple regression analysis. Of 122 students reporting a previous symptomatic infection, 14 (11.4%) reported persistent symptoms consistent with postacute COVID-19 a median of 132 days later., Conclusions and Relevance: Previous COVID-19 infection, both symptomatic and asymptomatic, was common at a large university. Measures that could prevent resurgence of the infection when students return to campus include mandatory vaccination policies, mass surveillance testing, and testing of sewage for antigen to SARS-CoV-2., Competing Interests: Conflict of interest: None., (© Copyright 2022 by the American Board of Family Medicine.)

Background: Clinical prediction rules (CPRs) can assist clinicians by focusing their clinical evaluation on the most important signs and symptoms, and if used properly can reduce the need for diagnostic testing. This study aims to perform an updated systematic review of clinical prediction rules and classification and regression tree (CART) models for the diagnosis of influenza., Methods: We searched PubMed, CINAHL, and EMBASE databases. We identified prospective studies of patients presenting with suspected influenza or respiratory infection and that reported a CPR in the form of a risk score or CART-based algorithm. Studies had to report at a minimum the percentage of patients in each risk group with influenza. Studies were evaluated for inclusion and data were extracted by reviewers working in parallel. Accuracy was summarized descriptively; where not reported by the authors the area under the receiver operating characteristic curve (AUROCC), predictive values, and likelihood ratios were calculated., Results: We identified 10 studies that presented 14 CPRs. The most commonly included predictor variables were cough, fever, chills and/or sweats, myalgias, and acute onset, all which can be ascertained by phone or telehealth visit. Most CPRs had an AUROCC between 0.7 and 0.8, indicating good discrimination. However, only 1 rule has undergone prospective external validation, with limited success. Data reporting by the original studies was in some cases inadequate to determine measures of accuracy., Conclusions: Well-designed validation studies, studies of interrater reliability between telehealth an in-person assessment, and studies using novel data mining and artificial intelligence strategies are needed to improve diagnosis of this common and important infection., Competing Interests: Conflict of interests: None., (© Copyright 2021 by the American Board of Family Medicine.)

Overnutrition and modern diets containing high proportions of saturated fat are among the major factors contributing to a low-grade state of inflammation, hyperglycemia and dyslipidemia. In the last decades, the global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to an increased risk for premature brain aging and the development of neurodegenerative disorders such as Alzheimer's disease (AD). Cognitive impairment and decreased neurogenic capacity could be a consequence of metabolic disturbances. In these scenarios, the interplay between inflammation and insulin resistance could represent a potential therapeutic target to prevent or ameliorate neurodegeneration and cognitive impairment. The present review aims to provide an update on the impact of metabolic stress pathways on AD with a focus on inflammation and insulin resistance as risk factors and therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vinuesa, Pomilio, Gregosa, Bentivegna, Presa, Bellotto, Saravia and Beauquis.)

Objective: Various studies have shown that overweight and obesity are central features of FM, but the real impact of a high BMI on clinical severity in patients with FM is still controversial. The aim of this study was to analyse the relationships between BMI categories and measures of symptom severity and functional impairment using data from a Web-based registry of patients with FM., Methods: Adult patients with an ACR 2010/2011 diagnosis of FM underwent a complete physical examination and laboratory tests and were asked to complete a package of questionnaires covering their sociodemographic and treatment details, in addition to the following disease-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status questionnaire (ModFAS) and the Polysymptomatic Distress Scale (PDS)., Results: A total of 2339 patients were recruited and divided into two weight categories, underweight/normal (U/N, n  = 1127, 48.2%) and overweight/obese (O/O, n  = 1212, 51.8%). The total and subscales of FIQR, ModFAS and PSD scores were significantly higher in the O/O patients, as were all the mean scores of the individual FIQR items ( P  < 0.001 for all)., Conclusion: Our findings demonstrate that O/O patients with FM are significantly more impaired than U/N patients in all the symptomatological and functional domains as measured using the FIQR, ModFAS and PDS, thus suggesting that being O/O has an additional effect on symptoms and function., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The aim of this systematic review is to summarize the best available evidence regarding individual risk factors, simple risk scores, and multivariate models that use patient characteristics, vital signs, comorbidities, and laboratory tests relevant to outpatient and primary care settings., Methods: Medline, WHO COVID-19, and MedRxIV databases were searched; studies meeting inclusion criteria were reviewed in parallel, and variables describing study characteristics, study quality, and risk factor data were abstracted. Study quality was assessed using the Quality in Prognostic Studies tool. Random effects meta-analysis of relative risks (categorical variables) and unstandardized mean differences (continuous variables) was performed; multivariate models and clinical prediction rules were summarized qualitatively., Results: A total of 551 studies were identified and 22 studies were included. The median or mean age ranged from 38 to 68 years. All studies included only inpatients, and mortality rates ranged from 3.2% to 50.5%. Individual risk factors most strongly associated with mortality included increased age, c-reactive protein (CRP), d-dimer, heart rate, respiratory rate, lactate dehydrogenase, and procalcitonin as well as decreased oxygen saturation, the presence of dyspnea, and comorbid coronary heart and chronic kidney disease. Independent predictors of adverse outcomes reported most frequently by multivariate models include increasing age, increased CRP, decreased lymphocyte count, increased lactate dehydrogenase, elevated temperature, and the presence of any comorbidity. Simple risk scores and multivariate models have been proposed but are often complex, and most have not been validated., Conclusions: Our systematic review identifies several risk factors for adverse outcomes in COVID-19-infected inpatients that are often available in the outpatient and primary care settings: increasing age, increased CRP or procalcitonin, decreased lymphocyte count, decreased oxygen saturation, dyspnea on presentation, and the presence of comorbidities. Future research to develop clinical prediction models and rules should include these predictors as part of their core data set to develop and validate pragmatic outpatient risk scores., Competing Interests: Conflict of interest: None., (© Copyright 2021 by the American Board of Family Medicine.)

Objective: To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity., Methods: Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: 'In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?'-which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach., Results: The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th-75th percentiles) were respectively 61.16 (41.16-77.00), 27.00 (19.00-32.00) and 19.0 (13.00-24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0-23 for remission, 24-40 for mild disease, 41-63 for moderate disease, 64-82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0-12 for remission, 13-20 for mild disease, 21-28 for moderate disease, 29-33 for severe disease and >33 for very severe disease; PDS: 0-5 for remission, 6-15 for mild disease, 16-20 for moderate disease, 21-25 for severe disease and >25 for very severe disease., Conclusions: Disease severity cut-offs can represent an important improvement in interpreting FM., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Benefit of lung cancer screening using low-dose computed tomography (LDCT) in reducing lung cancer-specific and all-cause mortality is unclear. We undertook a meta-analysis to assess its associations with outcomes., Methods: We searched the literature and previous systematic reviews to identify randomized controlled trials comparing LDCT screening with usual care or chest radiography. We performed meta-analysis using a random effects model. The primary outcomes were lung cancer-specific mortality, all-cause mortality, and the cumulative incidence ratio of lung cancer between screened and unscreened groups as a measure of overdiagnosis., Results: Meta-analysis was based on 8 trials with 90,475 patients that had a low risk of bias. There was a significant reduction in lung cancer-specific mortality with LDCT screening (relative risk = 0.81; 95% CI, 0.74-0.89); the estimated absolute risk reduction was 0.4% (number needed to screen = 250). The reduction in all-cause mortality was not statistically significant (relative risk = 0.96; 95% CI, 0.92-1.01), but the absolute reduction was consistent with that for lung cancer-specific mortality (0.34%; number needed to screen = 294). In the studies with the longest duration of follow-up, the incidence of lung cancer was 25% higher in the screened group, corresponding to a 20% rate of overdiagnosis., Conclusions: This meta-analysis showing a significant reduction in lung cancer-specific mortality, albeit with a tradeoff of likely overdiagnosis, supports recommendations to screen individuals at elevated risk for lung cancer with LDCT., (© 2020 Annals of Family Medicine, Inc.)

Background: Community-acquired pneumonia (CAP) is an important source of morbidity and mortality. However, overtreatment of acute cough illness with antibiotics is an important problem, so improved diagnosis of CAP could help reduce inappropriate antibiotic use., Methods: This was a meta-analysis of prospective cohort studies of patients with clinically suspected pneumonia or acute cough that used imaging as the reference standard. All studies were reviewed in parallel by two researchers and quality was assessed using the QUADAS-2 criteria. Summary measures of accuracy included sensitivity, specificity, likelihood ratios, the diagnostic odds ratio, and the area under the receiver operating characteristic curve (AUROCC) and were calculated using bivariate meta-analysis., Results: We identified 17 studies, of which 12 were judged to be at low risk of bias and the remainder at moderate risk of bias. The prevalence of CAP was 10% in nine primary care studies and was 20% in seven emergency department studies. The probability of CAP is increased most by an abnormal overall clinical impression suggesting CAP (positive likelihood ratio [LR+] = 6.32, 95% CI = 3.58 to 10.5), egophony (LR+ = 6.17, 95% CI = 1.34 to 18.0), dullness to percussion (LR+ = 2.62, 95% CI = 1.14 to 5.30), and measured temperature (LR+ = 2.52, 95% CI = 2.02 to 3.20), while it is decreased most by the absence of abnormal vital signs (LR- = 0.25, 95% CI = 0.11 to 0.48). The overall clinical impression also had the highest AUROCC at 0.741., Conclusions: While most individual signs and symptoms were unhelpful, selected signs and symptoms are of value for diagnosing CAP. Teaching and performing these high value elements of the physical examination should be prioritized, with the goal of better targeting chest radiographs and ultimately antibiotics., (© 2020 by the Society for Academic Emergency Medicine.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of misfolded proteins, amyloid-β (Aβ) aggregates, and neuroinflammation in the brain. Microglial cells are key players in the context of AD, being capable of releasing cytokines in response to Aβ and degrading aggregated proteins by mechanisms involving the ubiquitin-proteasome system and autophagy. Here, we present in vivo and in vitro evidence showing that microglial autophagy is affected during AD progression. PDAPPJ20 mice-murine model of AD-exhibited an accumulation of the autophagy receptor p62 and ubiquitin+ aggregates in Iba1+ microglial cells close to amyloid deposits in the hippocampus. Moreover, cultured microglial BV-2 cells showed an enhanced autophagic flux during a 2-h exposure to fibrillar Aβ, which was decreased if the exposure was prolonged to 24 h, a condition analogous to the chronic exposure to Aβ in the human pathology. The autophagic impairment was also associated with lysosomal damage, depicted by membrane permeabilization as shown by the presence of the acid hydrolase cathepsin-D in cytoplasm and altered LysoTracker staining. These results are compatible with microglial exhaustion caused by pro-inflammatory conditions and persistent exposure to aggregated Aβ peptides. In addition, we found LC3-positive autophagic vesicles accumulated in phagocytic CD68+ microglia in human AD brain samples, suggesting defective autophagy in microglia of AD brain. Our results indicate that the capacity of microglia to degrade Aβ and potentially other proteins through autophagy may be negatively affected as the disease progresses. Preserving autophagy in microglia thus emerges as a promising approach for treating AD. Graphical abstract.

Background: Biomarkers such as C-reactive protein (CRP) and procalcitonin may help distinguish community-acquired pneumonia (CAP) from other causes of lower respiratory tract infection., Methods: We performed a systematic review of the literature to identify prospective studies evaluating the accuracy of a biomarker in patients with acute cough or suspected CAP. We performed parallel abstraction of data regarding study inclusion, characteristics, quality, and test accuracy. Study quality was evaluated using QUADAS-2. Bivariate meta-analysis was performed using the mada package in R, and summary receiver operating characteristic (ROC) curves were created., Results: Fourteen studies met our inclusion and exclusion criteria; three were at low risk of bias and four at moderate risk of bias, largely due to failure to prespecify diagnostic thresholds. Considering all studies regardless of the cutoff used, CRP was most accurate (area under the ROC curve = 0.802), followed by leukocytosis (0.777) and procalcitonin (0.771). Lipopolysaccharide-binding protein and fibrinogen are promising, but were only studied in a single report. For CRP and procalcitonin, the positive and negative likelihood ratios (LR+ and LR-, respectively) varied inversely based on the cutoff. For CRP, LR+ and LR- were 2.08 and 0.32 for a cutoff of 20 mg/L, 3.64 and 0.36 for a cutoff of 50 mg/L, and 5.89 and 0.47 for a cutoff of 100 mg/L. For procalcitonin, LR+ and LR- were 2.50 and 0.39 for a cutoff of 0.10 µg/L, 5.43 and 0.62 for a cutoff of 0.25 µg/L, and 8.25 and 0.76 for a cutoff of 0.50 µg/L. The combination of CRP >49.5 mg/L and procalcitonin >0.1 µg/L had LR+ of 2.24 and LR- of 0.44., Conclusions: The best evidence supports CRP as the preferred biomarker for diagnosis of outpatient CAP given its accuracy, low cost, and point-of-care availability., (© 2020 by the Society for Academic Emergency Medicine.)

Dietary restriction promotes cell regeneration and stress resistance in multiple models of human diseases. One of the conditions that could potentially benefit from this strategy is Alzheimer's disease, a chronic, progressive and prevalent neurodegenerative disease. Although there are no effective pharmacological treatments for this pathology, lifestyle interventions could play therapeutic roles. Our objectives were 1) to evaluate the effects of dietary restriction on cognition, hippocampal amyloid deposition, adult neurogenesis and glial reactivity and autophagy in a mouse model of familial Alzheimer's disease, and 2) to analyze the role of glial cells mediating the effects of nutrient restriction in an in vitro model. Therefore, we established a periodic dietary restriction protocol in adult female PDAPP-J20 transgenic mice for 6 weeks. We found that dietary restriction, not involving overall caloric restriction, attenuated cognitive deficits, amyloid pathology and microglial reactivity in transgenic mice when compared with ad libitum-fed transgenic animals. Also, transgenic mice showed an increase in the astroglial positive signal for LC3, an autophagy-associated protein. In parallel, hippocampal adult neurogenesis was decreased in transgenic mice whereas dietary-restricted transgenic mice showed a neurogenic status similar to controls. In vitro experiments showed that nutrient restriction decreased astroglial and, indirectly, microglial NFκB activation in response to amyloid β peptides. Furthermore, nutrient restriction was able to preserve astroglial autophagic flux and to decrease intracellular amyloid after exposure to amyloid β peptides. Our results suggest neuroprotective effects of nutrient restriction in Alzheimer's disease, with modulation of glial activation and autophagy being potentially involved pathways., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Adolescence is a transitional period from childhood to adulthood characterized by puberty and brain maturation involving behavioral changes and environmental vulnerability. Diet is one of the factors affecting brain health, potentially leading to long-lasting effects. Hence, we studied the impact of early exposure (P21-60) to a high-fat diet (HFD) on mouse hippocampus, analyzing inflammation, adult neurogenesis, dendritic spine plasticity, and spatial memory. Glycemia and seric pro-inflammatory IL1β were higher in HFD mice without differences on body weight. In the HFD hippocampus, neuroinflammation was evidenced by Iba1+ cells reactivity together with a higher expression of TNFα and IL1β while the neurogenic capability in the dentate gyrus was strongly reduced. We found a predominance of immature Dil-labeled dendritic spines from CA1 neurons along with diminished levels of the scaffold protein Shank2, suggesting a defective connectivity. Moreover, the HFD group exhibited spatial memory alterations. To elucidate whether microglia could be mediating HFD-associated neuronal changes, the lipotoxic context was emulated by incubating primary microglia with palmitate, a saturated fatty acid present in HFD. Palmitate induced a pro-inflammatory profile as shown by secreted cytokine levels. The isolated exosome fraction from palmitate-stimulated microglia induced an immature dendritic spine phenotype in primary GFP+ hippocampal neurons, in line with the in vivo findings. These results provide novel data concerning microglia to neuron communication and highlight that fat excess during a short and early period of life could negatively impact on cognition and synaptic plasticity in a neuroinflammatory context, where microglia-derived exosomes could be implicated. Graphical Abstract ᅟ.

The number of parameters describing a quantum state is well known to grow exponentially with the number of particles. This scaling limits our ability to characterize and simulate the evolution of arbitrary states to systems, with no more than a few qubits. However, from a computational learning theory perspective, it can be shown that quantum states can be approximately learned using a number of measurements growing linearly with the number of qubits. Here, we experimentally demonstrate this linear scaling in optical systems with up to 6 qubits. Our results highlight the power of the computational learning theory to investigate quantum information, provide the first experimental demonstration that quantum states can be "probably approximately learned" with access to a number of copies of the state that scales linearly with the number of qubits, and pave the way to probing quantum states at new, larger scales.

Particle indistinguishability is at the heart of quantum statistics that regulates fundamental phenomena such as the electronic band structure of solids, Bose-Einstein condensation and superconductivity. Moreover, it is necessary in practical applications such as linear optical quantum computation and simulation, in particular for Boson Sampling devices. It is thus crucial to develop tools to certify genuine multiphoton interference between multiple sources. Our approach employs the total variation distance to find those transformations that minimize the error probability in discriminating the behaviors of distinguishable and indistinguishable photons. In particular, we show that so-called Sylvester interferometers are near-optimal for this task. By using Bayesian tests and inference, we numerically show that Sylvester transformations largely outperform most Haar-random unitaries in terms of sample size required. Furthermore, we experimentally demonstrate the efficacy of the transformation using an efficient 3D integrated circuits in the single- and multiple-source cases. We then discuss the extension of this approach to a larger number of photons and modes. These results open the way to the application of Sylvester interferometers for optimal assessment of multiphoton interference experiments., (Copyright © 2018 Science China Press. Published by Elsevier B.V. All rights reserved.)

Quantum teleportation establishes a correspondence between an entangled state shared by two separate parties that can communicate classically and the presence of a quantum channel connecting the two parties. The standard benchmark for quantum teleportation, based on the average fidelity between the input and output states, indicates that some entangled states do not lead to channels which can be certified to be quantum. It was recently shown that if one considers a finer-grained witness, then all entangled states can be certified to produce a nonclassical teleportation channel. Here we experimentally demonstrate a complete characterization of a new family of such witnesses, of the type proposed in Phys. Rev. Lett. 119, 110501 (2017)PRLTAO0031-900710.1103/PhysRevLett.119.110501 under different conditions of noise. We report nonclassical teleportation using quantum states that cannot achieve average fidelity of teleportation above the classical limit. We further use the violation of these witnesses to estimate the negativity of the shared state. Our results have fundamental implications in quantum information protocols and may also lead to new applications and quality certification of quantum technologies.

The time evolution of quantum many-body systems is one of the most important processes for benchmarking quantum simulators. The most curious feature of such dynamics is the growth of quantum entanglement to an amount proportional to the system size (volume law) even when interactions are local. This phenomenon has great ramifications for fundamental aspects, while its optimisation clearly has an impact on technology (e.g., for on-chip quantum networking). Here we use an integrated photonic chip with a circuit-based approach to simulate the dynamics of a spin chain and maximise the entanglement generation. The resulting entanglement is certified by constructing a second chip, which measures the entanglement between multiple distant pairs of simulated spins, as well as the block entanglement entropy. This is the first photonic simulation and optimisation of the extensive growth of entanglement in a spin chain, and opens up the use of photonic circuits for optimising quantum devices.