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Abstract Intra-articular fractures of the distal radius require anatomical reduction and stable fixation. When the fracture encompasses the articular facet of the bone, maintaining the reduction is challenging due to the fragment’s size and high instability. While specific implants have been developed to fix this fragment, their effectives have been limited. This study evaluates the mechanical performance of a novel hook plate conceived to stabilize the small fragment of the semilunar facet of the radius in non-osteoporotic bones. A simulated lunate facet fracture was created in an adult radius in a virtual model, and a modification of a hook plate was developed using computer-aided design (CAD). Two groups were established for the finite element method (FEM) simulation: a control group (standard plate Medartis™ (Switzerland, A-5500.23) and an angled plate with hooks set at 60º, 90º and 120º. In the FEM simulation, an axial load of 100 N was applied in the Z-axis direction on the fragment. Fracture displacement along the Z axis was more pronounced in the control model (0.32 mm) and less in the angled models, ranging from 0.22 to 0.28 mm. Notably, the plate with a 90° angle showed a more effective reduction in fragment displacement. The distribution of stresses in the system showed the highest levels of stress in the control group (59.31 MPa), followed by the subgroup with a 60° angle (55.78 MPa). In the side view, the control model showed a higher concentration of stresses (59.74 MPa), while the model with a 90° angle showed a lower value of stresses (18.87 MPa). Critical stress regions were identified in the bolts of the control and 120° models (59.47 MPa and 57.64 MPa, respectively). However, in the 90° model, no critical regions were observed in the bolts, which showed lower stress values, reaching 26.33 MPa. In the bone, the greatest concentration of stress occurred in the region where the plate was anchored. Our results showed that the 90° hook plate had a superior mechanical performance in fixing simulate lunate facet fractures at the distal radius. This angle led to minor displacements and minimized stress concentrations in the hardware, thus contributing to enhance the stability of this specific fracture.

Abstract South America has experienced severe compound drought-heatwaves (CDHW), exacerbating fires. Recently, the unprecedented Pantanal 2020 fire season (P20F), burning a third of the biome, resulted in well-reported local impacts on the ecosystem, economy, and health. Nevertheless, the long-range ripple effects of this event remain unknown. We investigated the P20F-related cascading hazards, integrating models, observational and satellite-based data. P20F-related smoke elevated PM2.5 levels in the SA’s most populated area, exceeding WHO guidelines by up to 600%. Smoke-induced air pollution episodes coincided with widespread heatwaves, amplifying health risks. The mortality burden attributable to this multi-hazard short-term (14 days) exposure was estimated to be 2150 premature deaths (21% increase above expected levels). Our findings highlight that the impacts of CDHW-fires in SA are beyond the local level, implying growing challenges for risk management and public health and the need for governance based on telecoupled flows, linking different systems over multiple scales.

Abstract Alzheimer disease (AD) remains a significant global health concern. The progression from preclinical stages to overt dementia has become a crucial point of interest for researchers. This paper reviews the potential of neurophysiological biomarkers in predicting AD progression, based on a systematic literature search following PRISMA guidelines, including 55 studies. EEG-based techniques have been predominantly employed, whereas TMS studies are less common. Among the investigated neurophysiological measures, spectral power measurements and event-related potentials-based measures, including P300 and N200 latencies, have emerged as the most consistent and reliable biomarkers for predicting the likelihood of conversion to AD. In addition, TMS-based indices of cortical excitability and synaptic plasticity have also shown potential in assessing the risk of conversion to AD. However, concerns persist regarding the methodological discrepancies among studies, the accuracy of these neurophysiological measures in comparison to established AD biomarkers, and their immediate clinical applicability. Further research is needed to validate the predictive capabilities of EEG and TMS measures. Advancements in this area could lead to cost-effective, reliable biomarkers, enhancing diagnostic processes and deepening our understanding of AD pathophysiology.

Abstract When using the reverse-transcription quantitative polymerase chain reaction (RT-qPCR) technique for quantitative assessment of microRNA (miRNA) expression, normalizing data using a stable endogenous gene is essential; however, no universally adequate reference gene exists. Therefore, in this study, we aimed to determine, via the RNA-Seq technique, the most adequate endogenous normalizer for the expression assessment of plasma miRNAs in patients with coronavirus disease 2019 (COVID-19). Two massive sequencing procedures were performed (a) to identify differentially expressed miRNAs between patients with COVID-19 and healthy volunteers (n = 12), and (b) to identify differentially expressed miRNAs between patients with severe COVID-19 and those with mild COVID-19 (n = 8). The endogenous normalizer candidates were selected according to the following criteria: (1) the miRNA must have a fold regulation = 1; (2) the miRNA must have a p-value > 0.990; and (3) the miRNAs that were discovered the longest ago should be selected. Four miRNAs (hsa-miR-34a-3p, hsa-miR-194-3p, hsa-miR-17-3p, and hsa-miR-205-3p) met all criteria and were selected for validation by RT-qPCR in a cohort of 125 patients. Of these, only hsa-miR-205-3p was eligible endogenous normalizers in the context of COVID-19 because their expression was stable between the compared groups.

Abstract The Monticola series comprises two anthropophilic and widely distributed species in Brazil: Pintomyia (Pifanomyia) monticola (Costa Lima, 1932) and Pintomyia (Pifanomyia) misionensis (Castro, 1959). They mainly occur in the Atlantic Rainforest, and it is known that Pi. monticola comprises at least two well-structured genetic lineages regarding a fragment of the cytochrome c oxidase subunit I (COI) gene. Here, we aim to elucidate the taxonomic status of this group using integrative taxonomy tools. Collections were performed in nine localities of four Brazilian states, and COI fragments were sequenced and merged with publicly available data. Several single-locus species delimitation algorithms, genetic distance metrics, phylogenetic trees, and haplotype networks were used to uncover cryptic diversity and population structure within Pi. monticola and Pi. misionensis. The resulting genetic clusters were then tested for morphological differences through linear and geometric morphometry of several characters. We analyzed 152 COI sequences, comprising 48 haplotypes. The maximum intraspecific p distances were 8.21% (mean 4.17%) and 9.12% (mean 4.4%) for Pi. monticola and Pi. misionensis, respectively, while interspecific ones ranged from 10.94 to 14.09% (mean 12.33%). Phylogenetic gene trees showed well-supported clades for both species, with clear structuring patterns within them. Species-delimitation algorithms split our dataset into at least three putative species for each taxon. Moreover, population structure analysis showed a strong correlation between Atlantic Forest areas of endemism as sources of molecular variation in Pi. monticola. Morphometric analyses were significant for wing shape variation and some linear measurements (mainly of the head) when comparing specimens of different genetic clusters for both taxa. These results indicate strong genetic structuring of Monticola series species, confirmed by morphometry, indicating two possible cryptic species complexes.

Abstract In this pilot study, we assessed the role of autophagy in Crohn’s Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we identified a significant reduction in the autophagosomal marker Lc3b-II in patients with active inflammation and stenosis. This was paralleled by an increase in oxidative stress markers, including sNOX2-dp and H2O2, and a decrease in the antioxidant capacity measured by HBA, suggesting an imbalance in autophagy and oxidative stress mechanisms. Additionally, our findings show a correlation between autophagy markers and oxidative stress levels, indicating that autophagy dysfunction may play a pivotal role in CD and in the progression of a stenosing disease phenotype, by failing to eliminate detrimental molecules and pathogenic bacteria, thereby promoting fibrosis. This study is the first to demonstrate in vivo autophagy inhibition in stenosing CD patients and suggests that stimulating autophagic processes could offer a new avenue for the prevention and treatment of intestinal fibrosis in CD. Our results highlight the importance of exploring the interactions between autophagy, the fibrotic process, and the inflammatory cascade, opening avenues for potential therapeutic interventions in CD management.

Abstract A promising route towards the deterministic creation and annihilation of single-phonons is to couple a single-photon emitter to a mechanical resonator. The challenge lies in reaching the resolved-sideband regime with a large coupling rate and a high mechanical quality factor. We achieve this by coupling self-assembled InAs quantum dots to a small mode-volume phononic-crystal resonator with mechanical frequency Ωm/2π = 1.466 GHz and quality factor Q m = 2.1 × 103. Thanks to the high coupling rate of g ep/2π = 2.9 MHz, and by exploiting a matching condition between the effective Rabi and mechanical frequencies, we observe the interaction between the two systems via correlations in the emitted photons. Our results represent a major step towards quantum control of the mechanical resonator via a single-photon emitter.

Abstract Background Despite sea lavender being a medicinal species, research on its seeds’ biological properties and chemical composition is unexplored. Thus, this study evaluated the effect of different extraction solvents on the biological activities and chemical profile of greenhouse-cultivated sea lavender seeds, aiming at their potential use as a dermo-cosmetic ingredient. Therefore, ethyl acetate, acetone, ethanol, and water extracts were examined for their antioxidant activity, enzyme inhibition, photoprotection, and cytotoxicity, followed by phytochemical analysis through spectrophotometric methods, further detailed by Ultrahigh-Performance Liquid Chromatography Coupled with Electrospray Ionization Mass/Mass Spectrometry (UHPLC-Esi-MS/MS). Results The water extract demonstrated significant antioxidant activity, evidenced by low half maximal effective concentration (EC50) values in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, reducing iron and chelating copper (296, 478, 230 and 678 µg/mL, respectively). The ethanol extract was more effective in inhibiting cosmetic-related enzymes, particularly elastase and hyaluronidase (2.18 and 3.21 µg/mL, respectively). The water and acetone extracts had the highest sun protection factors (23.2 and 18.9, respectively). All the extracts had nil to weak cytotoxicity (70–120% cell viability) towards mammalian cell lines. The water extract had the highest phenolics and condensed tannins (115 and 78.30 mg/g extract, respectively), while the ethanol contained the most flavonoids (62.73 mg/g extract). UHPLC-ESI–MS/MS analysis identified ethyl gallate, myricetin, rutin, and quercetin as major components of the ethanol extract, whereas myricetin-O-rutinoside isomers are predominant in the water extract. Conclusions These findings highlight the potential of greenhouse-cultivated sea lavender seeds as potential dermo-cosmetic ingredients, with ethanol and water extracts demonstrating superior biological activities and chemical profiles, significantly contributing to general skin health and protection.

Abstract Background Diabetic macular edema (DME) is the main cause of visual loss in individuals with diabetic retinopathy (DR). This study aims to investigate the effects of central macular intraretinal cysts on the underlying outer retinal layer (ORL) in patients with diabetic macular edema (DME). Methods In this retrospective and cross-sectional study, diabetic patients with or without DR were categorized into three groups: without DME (group 1), with DME but without any cyst featuring a plateau in the lower region (group 2), and patients with cyst featuring an inferior cyst plateau (group 3), defined as a flat conformation at its posterior aspect. Variables such as central macular intraretinal cyst height, inferior cyst plateau, and ORL thickness were measured, and ellipsoid zone (EZ) disruption was assessed via Spectral-domain optical coherence tomography (SD-OCT) and compared between groups. Correlations between OCT-measured variables and best-corrected visual acuity (BCVA) were investigated. Results A total of 164 eyes were included: 48 in group 1, 47 in group 2 and 69 in group 3. Compared with Groups 1 and 2, Group 3 presented a greater intraretinal cyst height (p

Abstract Background Infection prevention and control (IPC) programs are essential to prevent and control the spread of multidrug-resistant organisms in healthcare facilities (HCFs). The current implementation of these programs in Latin America remains largely unknown. Methods We conducted a mixed-methods evaluation of IPC program implementation in HCFs from Guatemala, Panama, Ecuador, and Argentina, March-July 2022. We used the World Health Organization (WHO) IPC Assessment Framework (IPCAF) survey, a previously validated structured questionnaire with an associated scoring system that evaluates the eight core components of IPC (IPC program; IPC guidelines; IPC education and training; healthcare-associated infection [HAI] surveillance; multimodal strategies; monitoring and audit of IPC practices and feedback; workload, staffing, and bed occupancy; and the built environment and materials and equipment for IPC). Each section generates a score 0–100. According to the final score, the HCF IPC program implementation is categorized into four levels: inadequate (0–200), basic (201–400), intermediate (401–600), or advanced (601–800). Additionally, we conducted semi-structured interviews among IPC personnel and microbiologists using the Systems Engineering Initiative for Patient Safety model to evaluate barriers and facilitators for IPC program implementation. We performed directed content analysis of interview transcripts to identify themes that focused on barriers and facilitators of IPC program implementation which are summarized descriptively. Results Thirty-seven HCFs (15 for-profit and 22 non-profit) completed the IPCAF survey. The overall median score was 614 (IQR 569, 693) which corresponded to an “advanced” level of IPC implementation (32% [7/22] non-profit vs. 93% [14/15] for-profit HCFs in this category). The lowest scores were in workload, staffing and bed occupancy followed by IPC training and multimodal strategies. Forty individuals from 16 HCFs were interviewed. They perceived inadequate staffing and technical resources, limited leadership support, and cultural determinants as major barriers to effective IPC guideline implementation, while external accreditation and technical support from public health authorities were perceived as facilitators. Conclusions Efforts to strengthen IPC activities in Latin American HCFs should focus on improving support from hospital leadership and public health authorities to ensure better resource allocation, promoting safety culture, and improving training in quality improvement.

OBJETIVO: Identificar a prevalência do uso de benzodiazepínicos por idosos de Pelotas, RS, e fatores associados. MÉTODOS: Foi realizado um estudo transversal com uma população representativa de uma Unidade de Saúde da Família e de um ambulatório. RESULTADOS: A amostra constou de 389 idosos com idades entre 60 a 96 anos. A prevalência do uso de benzodiazepínicos encontrada foi de 10,3%. A análise multivariada identificou o sexo feminino (RR = 2,75; IC95% 1,33 - 5,68), a depressão referida (RR = 2,10; IC95% 1,07 - 4,14) e o uso de antidepressivos (RR = 1,91; IC95% 1,01 - 3,61) como fatores independentes associados ao uso de benzodiazepínicos nessa população. CONCLUSÃO: Esse estudo encontrou uma baixa prevalência do uso de benzodiazepínicos em idosos, estando no limite inferior dos valores evidenciados em estudos no Brasil e em outros países.

Abstract The complete mitochondrial genomes of the whip spiders Charinus carajas, C. ferreus, and Heterophrynus longicornis were sequenced, annotated, and compared with other mitogenomes of whip spiders and arachnids. The three new mitogenomes have the 37 genes usually observed in Metazoa: 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), and two ribosomal RNAs (rRNAs), plus a non-coding control region (CR). Most PCGs presented an ATN start codon, except cox1 in both Charinus species, initiating with TTA. Most PCGs terminated with stop codons TAA or TAG, except nad5 of C. carajas and cox3 of H. longicornis, which presented an incomplete stop codon (T). The Ka/Ks ratios were less than one for all the PCGs, indicating these genes are under purifying selection. All the tRNAs, except for serine 1 (trnS1), had the typical cloverleaf-shaped secondary structure. All the phylogenetic analyses resolved Charinus carajas and C. ferreus as monophyletic groups. Nonetheless, we did not recover the monophyly of Heterophrynus longicornis. The phylogenies under partitioned models did not recover suprageneric taxonomic groups as clades, but the Bayesian inference under the CAT infinite mixture model recovered the family Phrynidae and the superfamily Phrynoidea as monophyletic groups.

Social Impact Statement Cassava is a vital food source for millions worldwide, crucial for food security and economic stability. This study analyzed cell wall polysaccharides in cassava roots to understand their impact on cooking properties. We found these polysaccharides influence the textural attributes of cassava roots, essential for both cooking and consumption. The research highlights the need to further identify and analyze cassava cell wall components. By improving our understanding of these components, we can improve food security, affordability, and resilience in diverse regions, ultimately contributing to global food security and better aligning with consumer preferences. Summary The textural attributes of cassava roots significantly influence preferences in cooking and consumption as a food source, yet the specific components dictating these properties remain unclear. We aimed to identify the factors shaping the cooking properties of cassava roots. We conducted a compositional analysis of 22 traits in a diverse F1 biparental population derived from soft‐ and hard‐boiling progenitors. The traits encompassed cooking qualities, starch properties, and cell wall composition. Specific cell wall components including cellulose, xylan, un‐esterified, and methyl‐esterified homogalacturonan (HG) demonstrated a correlation with cooking quality attributes: sensory assessments related to texture (SAT) and water absorption during boiling (WAB). Correlation and regression analyses revealed that these wall components collectively contribute to 20% of SAT variability and 14% of WAB variability. SAT appeared to be influenced by methyl‐esterified and un‐esterified HGs, xylan, and cellulose, impacting the tensile strength of the cell wall. Conversely, WAB appeared to be associated with methyl‐esterified HG, potentially altering water absorption properties. Although genome‐wide association studies (GWAS) were unable to identify significant SNPs for SAT and WAB, notable associations emerged for cellulose, xylan, and un‐esterified‐ and methyl‐esterified HG. Candidate genes associated with these SNPs point towards diverse cell wall‐related proteins, transcription factors, sugar metabolism‐related genes, and glycosyl hydrolases. This study provides insights into the relationship between cassava root compositions and cooking characteristics and the role of wall components in determining the cooking quality of edible cassava. This information represents a substantial contribution towards the development of protocols for selecting varieties with texture preferences.

AIM: To evaluate the clinical outcomes after subsequent implantation of a new intrastromal corneal ring segment (ICRS) model followed by an additional short-arc ICRS implant in keratoconus patients. METHODS: This retrospective single-arm cohort study evaluated 25 eyes of 21 keratoconus patients implanted with the new ICRS followed by 140-arch length ICRS (140-ICRS) implantation. Uncorrected distance visual acuity (UDVA, logMAR), corrected distance visual acuity (CDVA, logMAR), sphere, astigmatism, keratometry, spherical equivalent (SE), and asphericity were compared preoperatively and postoperatively after both ICRS implantation. RESULTS: The average follow-up time after 140-ICRS implantation was 6.40±2.20mo. The mean preoperative UDVA improved from 1.27±0.14 preoperative to 0.52±0.26 after both ICRS implantation (P=0.03). The mean sphere value reduced from -5.34±2.74 preoperatively to -2.06±1.84 postoperatively (P

Calcific tendinopathy of the shoulder is a prevalent and painful condition marked by calcific deposits in the rotator cuff tendons or subacromial bursa, with an incidence of 2.7% to 20%, predominantly affecting individuals aged 30 to 50. Women are 1.5 times more likely to be affected than men. Deposits are frequently bilateral in 10%-20% of cases and most commonly found in the supraspinatus tendon. The pathogenesis remains unclear, with theories suggesting repetitive strain or ischemic degeneration leading to calcium deposition. The disease progresses through precalcific, calcific, and postcalcific phases, with symptoms ranging from mild pain to severe, disabling pain resistant to medication. Diagnosis primarily involves radiographs or CT scans, with ultrasound aiding in deposit staging. Conservative treatments include medication, physiotherapy, and subacromial corticosteroid injections. Novel nonsurgical treatments like ultrasound-guided needling (UGN) and extracorporeal shock wave therapy (ESWT) have shown promise. When conservative measures fail, surgical options achieve significant improvement. This case report details a 53-year-old woman with a 12 cm calcification treated successfully with UGN, demonstrating the efficacy of this minimally invasive technique for large deposits.

Abstract Building models that allow phenotypic evaluation of complex agronomic traits in crops of global economic interest, such as grain yield (GY) in soybean and maize, is essential for improving the efficiency of breeding programs. In this sense, understanding the relationships between agronomic variables and those obtained by high-throughput phenotyping (HTP) is crucial to this goal. Our hypothesis is that vegetation indices (VIs) obtained from HTP can be used to indirectly measure agronomic variables in annual crops. The objectives were to study the association between agronomic variables in maize and soybean genotypes with VIs obtained from remote sensing and to identify computational intelligence for predicting GY of these crops from VIs as input in the models. Comparative trials were carried out with 30 maize genotypes in the 2020/2021, 2021/2022 and 2022/2023 crop seasons, and with 32 soybean genotypes in the 2021/2022 and 2022/2023 seasons. In all trials, an overflight was performed at R1 stage using the UAV Sensefly eBee equipped with a multispectral sensor for acquiring canopy reflectance in the green (550 nm), red (660 nm), near-infrared (735 nm) and infrared (790 nm) wavelengths, which were used to calculate the VIs assessed. Agronomic traits evaluated in maize crop were: leaf nitrogen content, plant height, first ear insertion height, and GY, while agronomic traits evaluated in soybean were: days to maturity, plant height, first pod insertion height, and GY. The association between the variables were expressed by a correlation network, and to identify which indices are best associated with each of the traits evaluated, a path analysis was performed. Lastly, VIs with a cause-and-effect association on each variable in maize and soybean trials were adopted as independent explanatory variables in multiple regression model (MLR) and artificial neural network (ANN), in which the 10 best topologies able to simultaneously predict all the agronomic variables evaluated in each crop were selected. Our findings reveal that VIs can be used to predict agronomic variables in maize and soybean. Soil-adjusted Vegetation Index (SAVI) and Green Normalized Dif-ference Vegetation Index (GNDVI) have a positive and high direct effect on all agronomic variables evaluated in maize, while Normalized Difference Vegetation Index (NDVI) and Normalized Difference Red Edge Index (NDRE) have a positive cause-and-effect association with all soybean variables. ANN outperformed MLR, providing higher accuracy when predicting agronomic variables using the VIs select by path analysis as input. Future studies should evaluate other plant traits, such as physiological or nutritional ones, as well as different spectral variables from those evaluated here, with a view to contributing to an in-depth understanding about cause-and-effect relationships between plant traits and spectral variables. Such studies could contribute to more specific HTP at the level of traits of interest in each crop, helping to develop genetic materials that meet the future demands of population growth and climate change.

Este artigo tem como objetivo analisar e discutir, a partir da carga global de doenças, as vulnerabilidades e violações de direitos humanos sob a perspectiva da saúde como um direito. Para alcançar esse objetivo, foi realizada uma revisão integrativa, visando responder como a carga global de doenças influencia os fatores de vulnerabilidade individual, social e programática, bem como as violações de direitos humanos no acesso à saúde da população brasileira. Dos 428 artigos encontrados, 119 foram incluídos nesta revisão. O texto acrescenta análises e reflexões sobre as camadas interconectadas entre os indivíduos, suas redes de participação social e as instituições que deveriam protegê-los, mas que, por vezes, acentuam as desigualdades de acesso e desamparo. Sob essa perspectiva, a bioética se apresenta como uma ponte possível para compreender as estruturas que expõem os indivíduos, os profissionais de saúde, a coletividade e as instituições às vulnerabilidades no acesso à saúde.

Abstract Background A task force from the US National Institute of Health aimed to establish parameters for surveys with patients with chronic low back pain (LBP) by recommending the use of the Patient-Reported Outcome Measurement Information System 29-item (PROMIS-29) questionnaire and the stratification according to the Impact Score. We aimed to assess the internal consistency, reliability, measurement error, construct validity and responsiveness of the Brazilian-Portuguese version of the PROMIS-29 questionnaire (version 2.1) and the Impact Score in patients with chronic LBP. Methods A prospective cohort study was carried out with patients with chronic LBP who were receiving physiotherapy treatment in clinics in São Paulo and Vitória cities, Brazil. The sample included 102 patients with chronic LBP, aged between 18 and 80 years, and with the ability to read and write in the Brazilian-Portuguese language. Exclusion criteria were patients with serious spinal conditions, cognitive impairment, pregnant women, and patients who had undergone lumbar surgery within the past six months. The PROMIS-29 questionnaire, the 12-item Short-Form Health Survey and the Roland-Morris Disability Questionnaire were applied. The PROMIS-29 questionnaire was reapplied after 24 hours and 4 weeks. Results The PROMIS-29 questionnaire showed Cronbach’s Alpha values between 0.81 (anxiety) and 0.91 (depression). The ICC2.1 ranged from 0.85 (95% CI: 0.77 to 0.89) to 0,97 (CI 95%: 0.95 to 0.98). The SEM values ranged between 0.85 (physical function) and 2.62 (ability to participate in social roles and activities). The Impact Score showed Cronbach’s Alpha, ICC2.1 and SEM values of 0.91, 0.97 (95% CI: 0.95 to 0.98) and 0.56, respectively. The PROMIS-29 questionnaire and the Impact Score showed sufficient construct validity. The PROMIS-29 questionnaire showed moderate responsiveness, while the Impact Score showed sufficient responsiveness. Conclusions Both the Brazilian-Portuguese version of the PROMIS-29 questionnaire and the Impact Score showed sufficient internal consistency, reliability, construct validity and responsiveness in Brazilian patients with chronic LBP. The results support the US National Institutes of Health’s recommendation to use the PROMIS-29 questionnaire and the Impact Score in patients with chronic LBP. We suggest that future studies evaluate the structural validity of the Brazilian-Portuguese version of the PROMIS-29 questionnaire. Clinical trial number Not applicable.

Abstract Background Chronic obstructive pulmonary disease (COPD) represents an important health challenge, despite being preventable and manageable thanks to up-to-date recommendations. In Italy, the pharmaceutical care of COPD patients is still ill-timed and inaccurate. This study aimed to describe the treatment of COPD patients in Italy and possible switches following an exacerbation. Methods This observational retrospective analysis of Italian administrative healthcare data from the Fondazione Ricerca e Salute (ReS) database identified patients aged ≥ 45 years with COPD in 2019 and 2020. At least 6 years of look-back period and absence of concomitant asthma were required. COPD patients were categorized by treatment (SI–single/MI–multiple inhalers, TT–triple therapy, DT–dual therapy, other respiratory treatments, untreated) at index date (first dispensation during accrual period). Occurrence of moderate/severe exacerbation during one-year preceding index date and treatments during one-year preceding the exacerbation (possible switch) were evaluated. Results From ~ 4.7 million beneficiaries of the Italian National Health Service in 2019 and 2020, respectively, 105,828 and 103,729 (43 and 41 × 1,000 inhabitants aged ≥ 45 years) were identified as having COPD. Of 2019/2020 patients: 3.4%/5.2% received SI-TT, 20.7%/17.5% MI-TT, 35.9%/38.1% DT, 33.0%/33.1% other treatments, and 7.0%/6.0% were untreated. Males were prevalent and median age was > 73 years for all groups. Of 2019/2020 cohorts, heart failure and coronary artery disease affected 24/20%, 18/17%, and 11%/16% patients with SI-TT, MI-TT, DT, and other treatments, respectively. A previous moderate/severe exacerbation (2019/2020 patients) occurred to 60.5%/56.6%, 39.9%/37.4%, 30.8%/29.2% and 31.9%/29.7% patients treated with SI-TT, MI-TT, DT, and other treatments, respectively. Of 2019/2020 patients experiencing moderate/severe exacerbation: 6.0%/7.0% receiving DT, 5.1%/7.0% receiving other treatments and 4.5%/10.0% untreated, switched to SI-TT; 23.7%/16.9% receiving DT, 21.4%/17.7% receiving other treatments and 15.4%/12.0% untreated, switched to MI-TT. Conclusions COPD patients receiving TT were older and had more comorbidities, especially cardiovascular diseases, than patients receiving DT or other treatments. The limited number of patients switching after exacerbation suggests that many COPD patients may be inappropriately treated. Ensuring early and adequate treatment, combination of in-hospital and outpatient management, and integration of specialist and primary care is pivotal for the appropriate clinical management of COPD patients.

Abstract Background The COVID-19 pandemic has been the most significant health challenge of the last century. Multiple and successive waves of COVID-19 cases, driven particularly by the emergence of new SARS-CoV-2 variants, have kept the world in a constant state of alert. Methods We present an observational, descriptive, cross-sectional study aimed at identifying SARS-CoV-2 variants circulating during two local waves of COVID-19 cases in southern Bahia, Brazil (late 2021 and late 2022), and analyzing the association between the detected variants and the epidemiological and clinical characteristics of the disease. For this purpose, data and nasopharyngeal samples from individuals in southern Bahia, Brazil, with suspected COVID-19 were included. Viral detection was performed by RT-qPCR, and SARS-CoV-2 variants were identified by next-generation viral sequencing. Results A total of 368 nasopharyngeal samples were tested. Approximately 23% of the samples from late 2021 tested positive for SARS-CoV-2, while in 2022, the positivity rate was about 56%. All sequenced samples from 2021 were identified as the Delta variant, while in 2022, all samples were classified as the Omicron variant. Overall, individuals who tested positive for SARS-CoV-2 in 2022 were younger than those who tested positive in 2021. Moreover, we observed significant differences in the clinical spectrum of SARS-CoV-2 infection when comparing the two periods. Individuals who presented with anosmia/ageusia were more likely to test positive for SARS-CoV-2 infection in 2021 but not in 2022. Additionally, fever, dry cough, pharyngalgia, headache, and rhinorrhea were more frequent among individuals infected with the Omicron variant than among those infected with the Delta variant. Conclusions The profile of COVID-19 in southern Bahia differed when analyzing two distinct waves of the pandemic in the region. These differences are likely related to the variants, which may differ in transmissibility and virulence, thereby altering the dynamics of the pandemic. This underscores the importance of genomic surveillance in better understanding the behavior of viral infections.

Abstract Rapid restoration of access to essential goods and services has long been regarded as paramount for community recovery. Yet, there remains ambiguity in how access should be defined, measured, or operationalized. Defining accessibility as the ability to use available goods and services with a reasonable level of effort and cost requires evaluating it across six dimensions (proximity, availability, adequacy, acceptability, affordability, and awareness) while considering the perspective of both users and providers in the evaluation. But common distance-based metrics that focus solely on physical access and travel time often fall short of fully capturing these requirements, overlooking the user's perception. This paper introduces a new spatio-temporal accessibility metric that combines four out of these six dimensions, including proximity, acceptability, adequacy, and availability. The metric considers uncertainty in measuring each dimension and addresses both user and provider perspectives in measuring the acceptability and adequacy dimensions. The variation in the metric across the disaster timeline serves as a proxy for community recovery. The metric aligns with common engineering-oriented functionality-based resilience frameworks as the functionality level of the providers has been incorporated in its development. Operating at the household level, the metric determines the ratio of post-disruption access time to the intended good or service against its pre-disruption access time and yields a unitless ratio between zero and one, with zero expressing a total loss in accessibility and one signifying the same level of accessibility as pre-disruption. The proposed metric, while being scientifically principled, is a practical tool whose output is easily understood even by non-expert individuals. The metric is illustrated for schools and pharmacies using the Lumberton Testbed and data collected following the 2016 flood in Lumberton, North Carolina after Hurricane Matthew. Findings provide new insight into recovery plan prioritization and can be used to trigger protective actions. The paper concludes by discussing issues and barriers related to developing and validating accessibility metrics while highlighting areas for future research.

Abstract White matter lacks the kind of plasticity that is present in the cortex, and subcortical injuries often result in permanent neurological deficits. Because cortical regions share common subcortical nuclei, creating new intergyral connections may allow for the bypass of subcortical damage. In this manuscript, a surgical interhemispheric bridge is created in mice, providing a model for an intercortical transpial bypass. To model this bypass, a midline craniotomy followed by interhemispheric (IH) pial removal was performed in C57BL/6 mice, allowing for the juxtaposition of the right and left prefrontal cortices. Adeno-associated virus (AAV) expressing tdTomato under a neuronal-specific promoter were injected into the right hemisphere. Animals were sacrificed two and four weeks after surgery, and axonal sprouting and glial changes were assessed in the “bypass” (BP) operation and sham surgery. Surgery did not result in any clear functional impairments. Removing the pia resulted in the formation of a physical connection between the hemispheres and the loss of the normal pial IH barrier. Cortical layer I became thinner with neuronal bodies in closer proximity than in the sham group. New interhemispheric axonal crossings were visible at two and four weeks in the BP group but not in the sham mice. These findings constitute the first step in the development of a cortico–cortico transpial bypass, allowing us to test a new way to surgically restore neurological function.

Abstract During aging, changes in body composition can result in sarcopenic obesity, which is a condition in which obesity occurs accompanied by the loss of muscle mass and strength caused by sarcopenia. Although the effects of obesity and sarcopenia on body composition are known, the muscle-specific strength in older women with sarcopenic obesity remains under-researched. The objective of this study was to evaluate community-dwelling older women for the absence or presence of obesity, sarcopenia and sarcopenic obesity and compare them in terms of body composition, functional physical performance and muscle-specific strength. One hundred and fifty-six older women (± 74 years) were evaluated for body composition using Dual X-ray Absorptiometry, handgrip strength with a Jamar dynamometer and functional performance using gait speed and timed up and go tests. The presence of obesity, sarcopenia and sarcopenic obesity was found in 32.7%, 15.4% and 25% of the sample, respectively. Comparing groups, community-dwelling older women with sarcopenic obesity exhibited poorer functional physical performance (TUG ± 14 s), and lower muscle-specific strength (± 1.18). Sarcopenic obesity was associated with muscle-specific strength (95% IC 0.016–0.241), and TUG (95% CI 1.001–1.137). These findings indicate that the combination of obesity and sarcopenia has a negative impact on skeletal muscle, reducing muscle-specific strength and physical performance in older women with more declines than either disease alone. Therefore, this comprehensive assessment gives useful information for incorporating muscle-specific strength into the diagnosis of sarcopenic obesity in the older people.

Abstract Haemophilia is associated with reduced bone mass and mineral density. Due to the rarity of the disease and the heterogeneity among the studies, the pathogenesis of bone loss is still under investigation. We studied the effects of coagulation factors on bone cells and characterized in a pilot study the osteoclastogenic potential of patients’ osteoclast precursors. To evaluate the effect of coagulation factors on osteoclasts, we treated Healthy Donor-Peripheral Blood Mononuclear Cells (HD-PBMC) with Factor VIII (FVIII), von Willebrand Factor (VWF), FVIII/VWF complex, activated Factor IX (FIXa), activated Factor X (FXa) and Thrombin (THB). FVIII, VWF, FVIII/VWF, FXa and THB treatments reduced osteoclast differentiation of HD-PBMC and VWF affected also bone resorption. Interestingly, PBMC isolated from patients with moderate/severe haemophilia showed an increased osteoclastogenic potential due to the alteration of osteoclast precursors. Moreover, increased expression of genes involved in osteoclast differentiation/activity was revealed in osteoclasts of an adult patient with moderate haemophilia. Control osteoblasts treated with the coagulation factors showed that FVIII and VWF reduced ALP positivity; the opposite effect was observed following THB treatment. Moreover, FVIII, VWF and FVIII/VWF reduced mineralization ability. These results could be important to understand how coagulation factors deficiency influences bone remodeling activity in haemophilia.

Abstract Background Advancing age is associated with an increase in mortality among patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). This study aimed to determine risk factors for in-hospital mortality in patients over 60 years old with COVID-19-related ARDS (C-ARDS). Methods This was an observational, analytical, retrospective study conducted on a cohort that included all patients aged 60 years or older diagnosed with COVID-ARDSwho were admitted to a high-complexity hospital in Bogotá, Colombia, between March 2020 and July 2021. Results A total of 1563 patients were included in the analysis, with a median age of 73 years (interquartile range [IQR]: 67–80) and 811 deaths (51.8%). Independent risk factors for in-hospital mortality were identified as follows: patients aged 71–80 [OR 1.87 (95% CI 1.33–2.64)], age > 80 [OR 8.74 (95% CI 5.34–14.31)], lactate dehydrogenase (LDH) [OR 1.009 (95% CI 1.003–1.0015)], severe C-ARDS [OR 2.16 (95% CI 1.50–3.11)], use of invasive mechanical ventilation (IMV) [OR 12.94 (95% CI 9.52–17.60)], and use of steroids [OR 1.49 (95% CI 1.09–2.03)]. In patients over 80 years of age (n = 388), the primary risk factor associated with in-hospital mortality was the use of IMV (n = 76) [OR 6.26 (95% CI 2.67–14.69)], resulting in an in-hospital mortality rate of 89.4% (n = 68) when this therapy was implemented. Conclusions The primary risk factors for in-hospital mortality in patients older than 60 years were age, the use of IMV, the severity of C-ARDS, use of steroids and elevated LDH values. Among patients older than 80 years, the main risk factor for in-hospital mortality was the use of IMV. In cases of C-ARDS in older patients, the decision to initiate IMV should always be individualized; therefore, the use of alternative oxygen delivery systems as the first-line approach can be considered.

This study analyses five months of continuous monitoring of different lighting warning systems at a pedestrian crosswalk through video surveillance cameras during nighttime. Three different light signalling systems were installed near a pedestrian crossing to improve the visibility and safety of vulnerable road users: in-curb LED strips, orange flashing beacons, and asymmetric enhanced LED lighting. Seven different lighting configurations of the three systems were studied and compared with standard street lighting. The speed of vehicles for each pedestrian–driver interaction was also evaluated. This was then compared to the speed that vehicles should maintain in order to stop in time and allow pedestrians to cross the road safely. In all of the conditions studied, speeds were lower than those maintained in the five-month presence of standard street lighting (42.96 km/h). The results show that in conditions with dedicated flashing LED lighting, in-curb LED strips, and orange flashing beacons, most drivers (72%) drove at a speed that allowed the vehicle to stop safely compared to standard street lighting (10%). In addition, with this lighting configuration, the majority of vehicles (85%) stopped at pedestrian crossings, while in standard street lighting conditions only 26% of the users stopped to give way to pedestrians.

Esta pesquisa aproxima noções sobre a divulgação científica por meio da ficção literária, com foco no formato do mangá japonês. Busca-se aqui apontar o potencial narrativo da série Demon Slayer como instrumento de divulgação científica, bem como identificar as escolhas narrativas que têm como base o fazer científico na série. O aporte teórico recorre à contextualização do mangá e do anime enquanto produtos atravessados historicamente por noções sobre ciência, bem como as possibilidades de divulgação científica por meio da ficção. A pesquisa tem caráter Qualitativo, com uso da Análise Crítica da Narrativa, de Luiz Gonzaga Motta, como técnica de análise. Entre os principais resultados, identificou-se que a instrumentalização do fazer científico cria possibilidades resolutivas na série para os embates entre protagonistas e antagonistas; a narrativa traz foco no processo científico tanto quanto nos resultados alcançados por ele; e também realiza um movimento de trazer os experimentos científicos com base em problemas sociais, devolvendo seus resultados também para o uso social, se mostrando uma potente ferramenta para se abordar noções sobre ciência.

Abstract Background Archaea and Bacteria are distinct domains of life that are adapted to a variety of ecological niches. Several genome-based methods have been developed for their accurate classification, yet many aspects of the specific genomic features that determine these differences are not fully understood. In this study, we used publicly available whole-genome sequences from bacteria ( $$N=2546$$ N = 2546 ) and archaea ( $$N=109$$ N = 109 ). From these, a set of genomic features (nucleotide frequencies and proportions, coding sequences (CDS), non-coding, ribosomal and transfer RNA genes (ncRNA, rRNA, tRNA), Chargaff’s, topological entropy and Shannon’s entropy scores) was extracted and used as input data to develop machine learning models for the classification of archaea and bacteria. Results The classification accuracy ranged from 0.993 (Random Forest) to 0.998 (Neural Networks). Over the four models, only 11 examples were misclassified, especially those belonging to the minority class (Archaea). From variable importance, tRNA topological and Shannon’s entropy, nucleotide frequencies in tRNA, rRNA and ncRNA, CDS, tRNA and rRNA Chargaff’s scores have emerged as the top discriminating factors. In particular, tRNA entropy (both topological and Shannon’s) was the most important genomic feature for classification, pointing at the complex interactions between the genetic code, tRNAs and the translational machinery. Conclusions tRNA, rRNA and ncRNA genes emerged as the key genomic elements that underpin the classification of archaea and bacteria. In particular, higher nucleotide diversity was found in tRNA from bacteria compared to archaea. The analysis of the few classification errors reflects the complex phylogenetic relationships between bacteria, archaea and eukaryotes.

Abstract The microbial ecology of Mycobacterium avium subspecies paratuberculosis infections (MAP) within the context of Multiple Sclerosis (MS) is largely an unexplored topic in the literature. Thus, we have characterized the compositional and predicted functional differences of the gut microbiome between MS patients with MAP (MAP+) and without (MAP−) infection. This was done in the context of exposome differences (through self-reported filled questionnaires), principally in anthropometric and sociodemographic patterns to gain an understanding of the gut microbiome dynamics. 16S rRNA microbiome profiling of faecal samples (n = 69) was performed for four groups, which differed by disease and MAP infection: healthy cohort (HC) MAP−; HC MAP+ ; MS MAP−; and MS MAP+ . Using a dynamic strategy, with MAP infection and time of sampling as occupancy models, we have recovered the core microbiome for both HC and MS individuals. Additional application of neutral modeling suggests key genera that are under selection pressure by the hosts. These include members of the phyla Actinobacteriota, Bacteroidota, and Firmicutes. As several subjects provided multiple samples, a Quasi Conditional Association Test that incorporates paired-nature of samples found major differences in Archaea. To consolidate treatment groups, confounders, microbiome, and the disease outcome parameters, a mediation analysis is performed for MS cohort. This highlighted certain genera i.e., Sutterella, Akkermansia, Bacteriodes, Gastranaerophilales, Alistipes, Balutia, Faecalibacterium, Lachnospiraceae, Anaerostipes, Ruminococcaceae, Eggerthellaceae and Clostridia-UCG-014 having mediatory effect using disease duration as an outcome and MAP infection as a treatment group. Our analyses indicate that the gut microbiome may be an important target for dietary and lifestyle intervention in MS patients with and without MAP infection.

Abstract Background Community-acquired pneumonia (CAP) is associated with high morbidity and hospitalization rate. In infectious diseases, host genetics plays a critical role in susceptibility and immune response, and the immune pathways involved are highly dependent on the microorganism and its route of infection. Here we aimed to identify genetic risk loci for CAP using a case-control genome-wide association study (GWAS). Methods We performed a GWAS on 3,765 Spanish individuals, including 257 adult patients hospitalized with CAP and 3,508 population controls. Pneumococcal CAP was documented in 30% of patients; the remaining 70% were selected among patients with unidentified microbiological etiology. We tested 7,6 million imputed genotypes using logistic regressions. UK Biobank GWAS of bacterial pneumonia were used for results validation. Subsequently, we prioritized genes and likely causal variants based on Bayesian fine mapping and functional evidence. Imputation and association of classical HLA alleles and amino acids were also conducted. Results Six independent sentinel variants reached the genome-wide significance (p

Abstract Background Cancer-associated fibroblasts (CAFs), mainly responsible for the desmoplastic reaction hallmark of intrahepatic Cholangiocarcinoma (iCCA), likely have a role in tumor aggressiveness and resistance to therapy, although the molecular mechanisms involved are unknown. Aim of the study is to investigate how targeting hCAF/iCCA cross-talk with a Notch1 inhibitor, namely Crenigacestat, may affect cancer progression. Methods We used different in vitro models in 2D and established new 3D hetero-spheroids with iCCA cells and human (h)CAFs. The results were confirmed in a xenograft model, and explanted tumoral tissues underwent transcriptomic and bioinformatic analysis. Results hCAFs/iCCA cross-talk sustains increased migration of both KKU-M213 and KKU-M156 cells, while Crenigacestat significantly inhibits only the cross-talk stimulated migration. Hetero-spheroids grew larger than homo-spheroids, formed by only iCCA cells. Crenigacestat significantly reduced the invasion and growth of hetero- but not of homo-spheroids. In xenograft models, hCAFs/KKU-M213 tumors grew significantly larger than KKU-M213 tumors, but were significantly reduced in volume by Crenigacestat treatment, which also significantly decreased the fibrotic reaction. Ingenuity pathway analysis revealed that genes of hCAFs/KKU-M213 but not of KKU-M213 tumors increased tumor lesions, and that Crenigacestat treatment inhibited the modulated canonical pathways. Cell cycle checkpoints were the most notably modulated pathway and Crenigacestat reduced CCNE2 gene expression, consequently inducing cell cycle arrest. In hetero-spheroids, the number of cells increased in the G2/M cell cycle phase, while Crenigacestat significantly decreased cell numbers in the G2/M phase in hetero but not in homo-spheroids. Conclusions The hCAFs/iCCA cross-talk is a new target for reducing cancer progression with drugs such as Crenigacestat. Graphical abstract

The study aimed to select rice genotypes based on agronomic traits and commercial grain quality. The study was carried out in the 2014/15 and 2015/16 harvests in eight growing environments, located in the state of Rio Grande do Sul, Brazil. Fourteen rice genotypes were sown in each environment. The experiment was conducted in a randomized block design with four replications. The following agronomic traits were evaluated: number of days to flowering and grain yield as well as commercial grain quality traits: percentage of whole grains and percentage of chalky area in the grains. AMMI, GGE and MGIDI methodologies were used to select the best performing genotypes. Using the AMMI, GGE and MGDI methods, genotypes G9 and G1 performed close to the ideal ideotype for the number of days to grain flowering, yield and quality.

[Purpose] The research addresses the enforced self-regulation of interoperability between financial market infrastructures in Brazilian law, with the purpose of identifying and understanding the challenges associated with its implementation. [Methodology/approach/design] The research is exploratory in nature and analyses the recent regulations issued by the Central Bank of Brazil - Res. BCB Nos. 264/23, 304/23, 308/23 and 339/23. [Findings] The specificities linked to the concept of self-regulation are pointed out, such as the exercise of public interest competences by regulated agents and the requirement for accountability. [Practical implications] The practical challenges in implementing regulated self-regulation include technical regulation and economic regulation of the market. The study puts forward analyses and suggestions for improving implementation. [Originality/value] This self-regulation model is recent and has not been analysed in the literature. The study is relevant because it analyses regulations that have not yet been studied and which have a direct and current practical application.

Abstract Background Epigenetic clocks are mathematical models used to estimate epigenetic age based on DNA methylation at specific CpG sites. As new methylation microarrays are developed and older models discontinued, existing epigenetic clocks might become obsolete. Here, we explored the effects of the changes introduced in the new EPICv2 DNA methylation array on existing epigenetic clocks. Methods We tested the performance of four epigenetic clocks on the probeset of the EPICv2 array using a dataset of 10,835 samples. We developed a new epigenetic age prediction model compatible across the 450 k, EPICv1, and EPICv2 microarrays and validated it on 2095 samples. We estimated technical noise and intra-subject variation using two datasets with repeated sampling. We used data from (i) cancer survivors who had undergone different therapies, (ii) breast cancer patients and controls, and (iii) an exercise-based interventional study, to test the ability of our model to detect alterations in epigenetic age acceleration in response to theoretically antiaging interventions. Results The results of the four epiclocks tested are significantly distorted by the EPICv2 probeset, causing an average difference of up to 25 years. Our new model produced highly accurate chronological age predictions, comparable to a state-of-the-art epiclock. The model reported the lowest epigenetic age acceleration in normal populations, as well as the lowest variation across technical replicates and repeated samples from the same subjects. Finally, our model reproduced previous results of increased epigenetic age acceleration in cancer patients and in survivors treated with radiation therapy, and no changes from exercise-based interventions. Conclusion Existing epigenetic clocks require updates for full EPICv2 compatibility. Our new model translates the capabilities of state-of-the-art epigenetic clocks to the EPICv2 platform and is cross-compatible with older microarrays. The characterization of epigenetic age prediction variation provides useful metrics to contextualize the relevance of epigenetic age alterations. The analysis of data from subjects influenced by radiation, cancer, and exercise-based interventions shows that despite being good predictors of chronological age, neither a pathological state like breast cancer, a hazardous environmental factor (radiation), nor exercise (a beneficial intervention) caused significant changes in the values of the “epigenetic age” determined by these first-generation models.

Abstract Background The first 24 h of infection represent a critical time window in interactions between pathogens and host tissue. However, it is not possible to study such early events in human lung during natural infection due to lack of clinical access to tissue this early in infection. We, therefore, applied RNA sequencing to ex vivo cultured human lung tissue explants (HLTE) from patients with emphysema to study global changes in small noncoding RNA, mRNA, and long noncoding RNA (lncRNA, lincRNA) populations during the first 24 h of infection with influenza A virus (IAV), Mycobacterium bovis Bacille Calmette-Guerin (BCG), and Pseudomonas aeruginosa. Results Pseudomonas aeruginosa caused the strongest expression changes and was the only pathogen that notably affected expression of microRNA and PIWI-associated RNA. The major classes of long RNAs (> 100 nt) were represented similarly among the RNAs that were differentially expressed upon infection with the three pathogens (mRNA 77–82%; lncRNA 15–17%; pseudogenes 4–5%), but lnc-DDX60-1, RP11-202G18.1, and lnc-THOC3-2 were part of an RNA signature (additionally containing SNX10 and SLC8A1) specifically associated with IAV infection. IAV infection induced brisk interferon responses, CCL8 being the most strongly upregulated mRNA. Single-cell RNA sequencing identified airway epithelial cells and macrophages as the predominant IAV host cells, but inflammatory responses were also detected in cell types expressing few or no IAV transcripts. Combined analysis of bulk and single-cell RNAseq data identified a set of 6 mRNAs (IFI6, IFI44L, IRF7, ISG15, MX1, MX2) as the core transcriptomic response to IAV infection. The two bacterial pathogens induced qualitatively very similar changes in mRNA expression and predicted signaling pathways, but the magnitude of change was greater in P. aeruginosa infection. Upregulation of GJB2, VNN1, DUSP4, SerpinB7, and IL10, and downregulation of PKMYT1, S100A4, GGTA1P, and SLC22A31 were most strongly associated with bacterial infection. Conclusions Human lung tissue mounted substantially different transcriptomic responses to infection by IAV than by BCG and P. aeruginosa, whereas responses to these two divergent bacterial pathogens were surprisingly similar. This HLTE model should prove useful for RNA-directed pathogenesis research and tissue biomarker discovery during the early phase of infections, both at the tissue and single-cell level.

Abstract Background A large fraction of the disease burden in the Italian population is due to behavioral risk factors. The objective of this work is to provide a tool to estimate the impact of preventive interventions that reduce the exposure to smoking and sedentary lifestyle of the Italian population, with the goal of selecting optimal interventions. Methods We construct a Markovian model that simulates the state of each subject of the Italian population. The model predicts the distribution of subjects in each health status and risk factor status for every year of the simulation. Based on this distribution, the model provides a rich output summary, such as the number of incident and prevalent cases for each tracing disease and the Disability Adjusted Life Years (DALY), used to assess the impact of preventive interventions, and how this impact is shaped in time. Results This paper focuses on the methodological aspects of the model. The proposed model is flexible and can be applied to estimate the impact of complex interventions on the two risk factors and adapted to consider different cohorts. We validate the model by simulating the evolution of the Italian population from 2009 to 2017 and comparing the output with historical data. Furthermore, as a case-study, we simulate a counterfactual scenario where both tobacco and sedentary lifestyle are eradicated from the Italian population in 2019 and estimate the impact of such intervention over the following 20 years. Conclusions We propose a Markovian model to estimate how interventions on smoking and sedentary lifestyle can affect the reduction of the disease burden, and validate the model on historical data. The model is flexible and allows to extend the analysis to consider more risk factors in future research. However, we are aware that, given the ever-increasing availability of data, it is necessary in the future to increase the complexity of the model, to be closer to reality and to provide decision-making support to the policy-makers.

Abstract Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.

Bordetella's genome contains a large family of periplasmic binding proteins (PBPs) known as Bugs, whose functions are mainly unassigned. Two members, Bug27 and Bug69, have previously been considered potential candidates for the uptake of small pyridine precursors, possibly linked to NAD biosynthesis. Here, we show an in vitro affinity of Bug27 and Bug69 for quinolinate in the submicromolar range, with a marked preference over other NAD precursors. A combined sequence similarity network and genome context analysis identifies a cluster of Bug69/27 homologs that are genomically associated with the NAD transcriptional regulator NadQ and the enzyme quinolinate phosphoribosyltransferase (QaPRT, gene nadC), suggesting a functional linkage to NAD metabolism. Integrating molecular docking and structure‐based multiple alignments confirms that quinolinate is the preferred ligand for Bug27 and Bug69.

The "Serra da Concórdia" is part of the Atlantic Forest phytogeographical domain in the Brazilian state of Rio de Janeiro and it has a predominant phytophysiognomy of Semideciduous Seasonal Forest. This region underwent intense habitat loss and fragmentation during the 19th century, due to coffee plantations and later pastures. With the decline of these activities, the areas were abandoned, triggering secondary succession. In 2002, the "Parque Estadual da Serra da Concórdia" was established in this region to preserve the remaining forest fragments. The updated list of vascular plants recorded in this protected area, published in the "Catálogo de Plantas das Unidades de Conservação do Brasil", is presented here, along with information on richness, endemism, and conservation status.The "Parque Estadual da Serra da Concórdia" houses 231 vascular plant species, of which 90% are angiosperms, 10% ferns and lycophytes, and 27% endemic to the Atlantic Forest. Ten species are threatened with extinction, three are categorized as Endangered, and seven as Vulnerable. Although there have been expeditions in the "Parque Estadual da Serra da Concórdia", they have been limited, resulting in a low number of records and the species richness for a protected area. This is notable considering the 2,130 Brazilian native vascular plant species recorded in the semideciduous seasonal forest of Rio de Janeiro. Our data indicates that floristic inventories of Brazilian protected areas could help highlight gaps in flora knowledge and support the proposal of effective conservation actions.

Abstract Aim This study examined the association of low handgrip strength (HGS) for falls in middle-aged adults and older adults every half-decade of life. Methods This cross-sectional study was conducted using the public data from the first wave of the Brazilian Longitudinal Study of Aging (ELSI-Brazil). The participants were allocated into seven age groups 50–54, 55–59, 60–64, 65–69, 70–74, 75–79, and ≥ 80 years. Binary logistic regression analysis was performed to identify the odds ratio (OR) of low HGS to the falls regardless of confounding variables such as sex, balance, gait speed, and total number of health conditions. Results A total of 8,112 participants aged 50–105 years (median = 62.0 years): 3,490 males (median = 60.0 years) and 4,622 females (median = 63.0 years) attended the study. Altogether, 21.5% of participants experienced at least one fall. HGS gradually decreases over each half-decade of life. In addition, low HGS presented a significative OR (p

Abstract Background Childhood abuse and neglect pose important risk factors for the development of psychopathology during pregnancy. However, only a few studies have assessed the effects of a specific type of abuse during the perinatal period, namely, psychological maltreatment, which includes emotional abuse and neglect. These studies have found that women who have experienced psychological maltreatment exhibit higher levels of antenatal depressive symptoms and greater difficulties forming attachment with their babies than women who have not experienced this kind of adversity. The aim of this study was to examine how emotional abuse and neglect experiences may favor the occurrence of psychological distress in pregnant women, and whether prenatal attachment might explain this association. Methods Participants comprised 128 Italian pregnant women ranging in age from 21 to 46 years (Mage = 33.4; SD = 6.10). Women responded to the following self-report instruments: CECA.Q and CTQ-SF, for the assessment of psychological maltreatment experiences; MAAS, for the evaluation of prenatal attachment; and PAMA, for the assessment of perinatal psychological distress. Results Pearson correlations revealed a positive association between childhood neglect and perinatal psychological distress and a negative association between childhood neglect and prenatal attachment scores. No significant correlations were found for emotional abuse. Perinatal psychological distress was negatively associated with prenatal attachment. Mediation analyses showed significant associations between childhood neglect and the dimensions of perinatal affectivity and prenatal maternal attachment. Prenatal maternal attachment mediated the relationship between neglect and perinatal psychological distress. Conclusions The transition to motherhood is a sensitive period, particularly for women who have experienced abuse and neglect during childhood. These experiences may negatively impact a woman’s disposition to emotionally and behaviorally engage in the formation of a bond with their unborn baby. These results may have important prevention and clinical implications and thus warrant further exploration.

Background and objective: Patients diagnosed with grade group (GG) 1 prostate cancer (PCa) following treatment for benign disease (“incidental” PCa) are typically managed with active surveillance (AS). It is not known how their outcomes compare with those observed in patients diagnosed with GG1 on biopsy. We aimed at determining whether long-term oncologic outcomes of AS for patients with GG1 PCa differ according to the type of diagnosis: incidental versus biopsy detected. Methods: A retrospective, multi-institutional analysis of PCa patients with GG1 on AS at eight institutions was conducted. Competing risk analyses estimated the incidence of metastases, PCa mortality, and conversion to treatment. As a secondary analysis, we estimated the risk of GG ≥2 on the first follow-up biopsy according to the type of initial diagnosis. Key findings and limitations: A total of 213 versus 1900 patients with incidental versus biopsy-diagnosed GG1 were identified. Patients with incidental cancers were followed with repeated biopsies and multiparametric magnetic resonance imaging less frequently than those diagnosed on biopsy. The 10-yr incidence of treatment was 22% for incidental cancers versus 53% for biopsy (subdistribution hazard ratio [sHR] 0.34, 95% confidence interval [CI] 0.26–0.46, p

Objetivo: A área científica denominada Organização do Conhecimento engloba o estudo e desenvolvimento de Sistemas de Organização do Conhecimento, dentre os quais estão o glossário, a taxonomia, o sistema de classificação, o mapa conceitual ou rede semântica, o tesauro e a ontologia. O objetivo deste estudo é distinguir os principais tipos de Sistemas de Organização do Conhecimento por meio de uma contextualização teórica e relato de experiência. Método: Trata-se de um estudo descritivo, qualitativo, de natureza aplicada. Inicialmente, tendo como domínio um artigo científico, uma análise de conteúdo foi conduzida utilizando a técnica de análise categorial temática para identificação das categorias que representassem o conteúdo. Após codificação e categorização foram desenvolvidos seis instrumentos de representação do conhecimento com o auxílio de softwares (Atlas.ti, CMAP, THESA e Protégé). Resultado: O glossário e a taxonomia facetada desenvolvidos subsidiaram a elaboração do sistema de classificação, tesauro, mapa conceitual e ontologia. Para a ontologia, o instrumento mais complexo, além da taxonomia facetada, a prévia elaboração do mapa conceitual foi essencial. Conclusões: A associação da contextualização teórica com o desenvolvimento prático possibilitou maior clareza em relação aos aspectos distintivos de cada instrumento, bem como a observação da interdependência entre eles. A natureza iterativa, inerente ao processo de construção, foi destacada, bem como, a importância da utilização de softwares de apoio.

Objetivo: Analisar as desinformações em saúde checadas pela plataforma de fact-checking Agência Lupa a fim de entender como a desinformação em saúde foi compartilhada nas plataformas digitais nos primeiros meses após a pandemia da COVID-19, e quais foram as suas principais tendências no Brasil. Método: Adota-se a abordagem quali-quantitativa no processo de extração, interpretação e visualização dos conteúdos checados, por meio da técnica de raspagem de dados e análise de textos digitais. Resultado: Constata-se que os conteúdos desinformativos que imitam fontes confiáveis a partir de imagens e vídeos, circulados na plataforma WhatsApp, propagaram-se por múltiplos canais, dispersando a desinformação em saúde. Além disso, observa-se padrões de persistência e constância quanto ao termo Vacina, indicando-o como escopo de uma narrativa contínua de desinformação. Conclusões: Conclui-se que os aspectos das práticas de desinformação destacados pelo método adotado podem subsidiar estratégias de combate à desinformação em saúde no Brasil.

Abstract Introduction Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM). Methods The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project’s webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis. Results A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED. Conclusion This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance.

Background: Multiple Sclerosis (MS) is the most prevalent autoimmune neurological condition in the world, leading to a wide variety of symptoms, including balance disorders. Objective: To evaluate the angular vestibulo–ocular reflex (aVOR) of all six semicircular canals (SCCs) through Head Impulse (HIMP) and Suppression HIMP (SHIMP) paradigms and any correlations with clinical balance scales. Methods: All participants were assessed using the Expanded Disability Status Scale (EDSS), Berg Balance Scale (BBS), and Mini-BESTest (MBT). Vestibular function was measured by video Head Impulse Test (vHIT), obtaining aVOR gain for each SSC. Results: Twenty-seven PwMS (mean age 47.93 ± 8.51 years old, 18 females) were recruited. Most of the patients (81.48%) presented abnormal aVOR gains for at least one SSC. A moderate to strong correlation between aVOR gains of the left anterior SSC and, respectively, the MBT and the BBS was found. The subgroup analysis, based on the EDSS class, confirmed the correlation with the BBS in the patients with the most significant disability. Conclusions: People with MS may present impairments of the aVOR in one or more semicircular canals. The aVOR gain impairment of the vertical semicircular canals correlates with balance and gait disorders identified through clinical scales in PwMS.

Pesquisa bibliográfica e documental, de caráter exploratório, sobre o Documento Curricular do Território Maranhense: ensino médio (DCTM/EM), elaborado como decorrência da Lei 13.415/2017, a lei da reforma no ensino médio. Pretende-se analisar o referido documento problematizando a sua convergência com os fundamentos da reforma do ensino médio em geral. Esta análise se apoia no aporte teórico da Teoria Crítica da Sociedade e do Materialismo-histórico dialético. Destacam-se como aspectos nucleares da proposta curricular o caráter flexível da formação, a fragmentação do currículo, a formação de competências e habilidades e o “protagonismo” do estudante visando a formação de indivíduos empreendedores e socialmente responsáveis, com foco na gestão do seu próprio projeto de vida. Conclui-se que o escopo da formação empreendido pela reforma do ensino médio se coaduna ao processo de semiformação dos indivíduos de forma cada vez mais subordinada à materialidade alienada.

Abstract Psoriasis is a chronic, immune-mediated, inflammatory skin disease, associated with multiple comorbidities and psychological and psychiatric disorders. The quality of life of patients with this disease is severely compromised, especially in moderate-to-severe plaque psoriasis. Secukinumab, a fully humanized monoclonal antibody, was the first anti-interleukin (IL)-17 biologic approved for treating psoriasis. Secukinumab demonstrated long-lasting efficacy and a good safety profile in individuals with plaque psoriasis, and it is associated with an improvement in health-related quality of life. While there is evidence that early treatment with systemic therapy can affect disease progression and improve long-term outcomes in other autoimmune diseases, evidence is limited in psoriasis, especially in real-world settings. This review provides an overview of studies describing the effectiveness of secukinumab in the treatment of psoriasis summarizing the literature and focusing on real-world evidence and early intervention.