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This narrative essay describes a basic writing instructor's engagement with student confusion in a hybrid Accelerated Learning Program (ALP) course. The story examines the ways confusion can mark sites of engagement for students and teachers and how ALP courses, in particular, might mediate effective (and ineffective) forms of confusion.

Abstract The Epigravettian human remains from Riparo Tagliente in northern Italy represent some of the earliest evidence of human occupation in the southern Alpine slopes after the Last Glacial Maximum. Genomic analyses of the 17,000-year-old Tagliente 2 mandible revealed the oldest presence of a genetic profile with affinities to the Near East in the Italian peninsula, which later became the most widespread hunter-gatherer ancestry across Europe. However, a comparable biomolecular characterization of the Tagliente 1 burial remains unavailable, preventing us from defining its biological relationships with Tagliente 2. Here, we apply paleogenomic, isotopic, and radiocarbon dating analyses on a femur fragment of Tagliente 1 and compare the reconstructed data with previously reported results from Tagliente 2. Despite their different isotopic signatures and non-overlapping radiocarbon dates, we reveal that the two human remains belong to the same male individual. We determine that the distinct isotopic values can be explained by different dietary practices during lifetime, whereas the non-overlapping radiocarbon dates can be caused by minimal radiocarbon contamination, possibly deriving from chemical treatments for conservation purposes. These findings highlight the importance of interdisciplinary biomolecular studies in offering new perspectives on the Palaeolithic fossil record and addressing long-standing bioarchaeological questions.

Este estudo analisa os usos da literatura infantil (LI) durante os processos de alfabetização de crianças camponesas, destacando as contribuições da educação literária para a formação de leitores. Desenvolveu-se uma pesquisa qualitativa de campo, em que se utilizou as entrevistas semiestruturadas como dispositivos de produção de dados. As interlocutoras foram cinco professoras alfabetizadoras, que atuam em duas escolas rurais da rede municipal de educação de Novo Santo Antônio (PI), cidade localizada a 116 km de Teresina, capital do estado do Piauí. Os resultados apontam que as professoras utilizam a LI, a priori, como estratégia metodológica para o ensino da leitura e da escrita, privilegiando a função pedagógica em detrimento do que é proposto pela educação literária, a saber: as propriedades singulares da criação artística. Conclui-se que é necessário desenvolver ações de formação continuada para que as professoras concebam a alfabetização como processo de compreensão do sistema alfabético de escrita, e o letramento como uso desse sistema em práticas sociais que envolvem a leitura e a escrita, garantindo que a LI seja trabalhada a partir da perspectiva da educação literária.

Influenza A/H9 viruses circulate worldwide in wild and domestic avian species, continuing to evolve and posing a zoonotic risk. A substantial increase in human infections with A/H9N2 subtype avian influenza viruses (AIVs) and the emergence of novel reassortants carrying A/H9N2-origin internal genes has occurred in recent years. Different names have been used to describe the circulating and emerging A/H9 lineages. To address this issue, an international group of experts from animal and public health laboratories, endorsed by the WOAH/FAO Network of Expertise on Animal Influenza, has created a practical lineage classification and nomenclature system based on the analysis of 10,638 hemagglutinin sequences from A/H9 AIVs sampled worldwide. This system incorporates phylogenetic relationships and epidemiologic characteristics designed to trace emerging and circulating lineages and clades. To aid in lineage and clade assignment, an online tool has been created. This proposed classification enables rapid comprehension of the global spread and evolution of A/H9 AIVs.

Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

Identifying landscapes that are suitable for both biodiversity conservation and agricultural production is a major challenge. Traditionally, much research has focused on biodiversity conservation outside of agricultural production areas, e.g., in semi-natural habitats. In contrast, recent research has mainly focused on the potential of crop heterogeneity. This includes both compositional (crop diversity) and configurational heterogeneity (field border density). However, if and how crop heterogeneity, and semi-natural habitats interact to shape insect diversity in agricultural landscapes remains poorly understood. Here we investigated the combined effects of crop diversity, field border density, and semi-natural habitats (i.e., grassland proportion, hedge density) on insect diversity. We sampled insect communities from 14 – 17 June 2021 with pan traps in 27 study landscapes (500 m x 500 m) covering independent gradients of these landscape variables and identified a total of 587 insect species with DNA metabarcoding. We found that field border density mediated the effects of crop diversity, grassland proportion, and hedge density on insect richness. At low levels of field border density (i.e., landscapes with mostly large fields), effects were either neutral (crop diversity), negative (grassland proportion) or weakly positive (hedge density). By contrast, at high levels of field border density, crop diversity, grassland proportion, and hedge density all exerted positive effects on insect richness. Responses to crop heterogeneity and semi-natural habitat differed among trophic groups of insects (decomposers, herbivores, parasitoids, predators). While variation in richness of herbivorous insects followed the patterns of the overall richness, decomposer richness was not related to any of the investigated variables. Predator richness increased with hedge density in landscapes, whereas parasitoid richness increased when high levels of field border density and grassland proportion coincided. Our study shows that increasing crop heterogeneity is a viable strategy for promoting insect diversity in agricultural landscapes. However, the effects of the amount of remaining semi-natural habitats, such as grassland or hedges, are mediated by configurational heterogeneity, and vary between trophic groups. Efforts to conserve insects in agricultural landscapes must therefore focus on both increasing the heterogeneity of the crop matrix by promoting crop diversity and increasing the density of field borders, while also maintaining or restoring semi-natural habitats as important source habitats for insect species.

Silkworms have been farmed for their silk since ancient times. After silk reeling, their chrysalides are consumed as food in several Asian countries. Despite the long rearing tradition of this insect, few studies have investigated the silkworm’s microbiological safety all along the life cycle, focusing on detecting silkworm pathogens or on the safety of the dried chrysalis for food consumption. However, the in-farm rearing process, which takes around forty days, may affect the microbial load of the silkworm and of the rearing environment, as well as the quality of fresh cocoon and other performance parameters. No data is available on how microbial contamination changes during the rearing period and between different farmers. Furthermore, in light of the possible use of the chrysalis as food, it is crucial to understand how its microbial load varies according to the water content. To address these specific questions, we conducted an investigation involving the analysis of specific microbial indicators commonly used in the food chain. We collected environmental and silkworm samples from several farms. The examination covered the entire life cycle of silkworms, beginning with the first instar larvae and concluding with the scrutiny of both freshly harvested and dried pupae. Silkworm farms in Northeast Italy proved to be an appropriate model system for carrying out the experimentation. Additionally, an evaluation of rearing performance was conducted, with a focus on the quality of fresh cocoons and the survival rate of the insects.

According to the Domestic Animal Diversity Information System (DAD-IS) of the FAO, Italy has one of the largest numbers of local small ruminant breeds among European countries. In Southern Italy, namely the Campania Region, Bagnolese and Laticauda sheep breeds and Cilentana goat breeds are considered endangered according to the DAD-IS. Conservation of endangered animal breeds is a goal of the European Union (EU). However, the role of infectious diseases as risk factors for endangered breeds has rarely been considered. Small ruminant lentiviruses (SRLV) infect sheep and goats, causing slow-progressive, persistent, and debilitating diseases that can lead to animal death and productivity loss. In this study, we investigated the presence of SRLV in Bagnolese, Laticauda, and Cilentana breeds using a commercial ELISA in parallel with an in-house ELISA. The results of the two tests were in good agreement (Cohen Kappa 0.84, 95 % CI = 0.76–0.93). Discrepancies between the two tests were resolved using western blotting. In total, 430 samples were tested (248 Bagnolese, 125 Laticauda, and 57 Cilentana). The apparent prevalence rates were 12.5 %, 6.4 %, and 1.7 % in Bagnolese, Laticauda, and Cilentana, respectively. In the molecular analysis of 11 proviral partial sequences, subtypes B2 and A24 were identified in two Bagnolese herds. Owing to the beneficial role of sheep and goat breeding in marginal areas, it is important to screen the entire population and implement control/eradication of SRLV infections in conjunction with each conservation program.

The Brazilian higher education scenario has completely shifted with the entry, since 1997, of private companies that started acting in the segment with a focus on profit achievement. The goal of this article is understanding and analyzing the increased number of higher education institutions with a profit profile, being led by their chief executive officers (CEOs) and guiding their management by a financial logic (and not academic), as well as the impacts to the higher education segment. It is a bibliographic and documentary study to support the premises and conclusions proposed. It sought to demonstrate that education companies dominate Brazilian higher education, amassing enrollment and establishing, with no public debate, education policies.

Although the link between gut microbiota and obesity is increasingly reported, the pathophysiological mechanisms and clinical outcomes are still under debate. This overview of human and animal data addresses several pathophysiologic mechanisms, dietary habits, exercise and probiotic and symbiotic supplementation in the fields of gut microbiota and obesity. Overall, obesity impairs gut microbiota composition due to factors that may be linked to the onset of the disease, such as excessive consumption of high-energy foods, sugars and fats, as well as a low fiber intake and physical inactivity. Conversely, low-energy diets, physical exercise, and probiotic and prebiotic supplementations can enhance gut microbiota in patients with obesity, in addition to improving cardiometabolic markers. As for perspectives, further research is warranted to ascertain proper dietary manipulation, physical exercise protocols and dosing regimens of probiotics. Regarding the latter, the effects on indicators of obesity are clinically modest, and hence skepticism must be exercised.

Abstract Background We have previously shown that the slow Wallerian degeneration mutation, whilst delaying axonal degeneration after optic nerve crush, does not protect retinal ganglion cell (RGC) bodies in adult rats. To test the effects of a combination approach protecting both axons and cell bodies we performed combined optic nerve crush and lens injury, which results in both enhanced RGC survival as well as axon regeneration past the lesion site in wildtype animals. Results As previously reported we found that the WldS mutation does not protect RGC bodies after optic nerve crush alone. Surprisingly, we found that WldS transgenic rats did not exhibit the enhanced RGC survival response after combined optic nerve crush and lens injury that was observed in wildtype rats. RGC axon regeneration past the optic nerve lesion site was, however, similar in WldS and wildtypes. Furthermore, activation of retinal glia, previously shown to be associated with enhanced RGC survival and axon regeneration after optic nerve crush and lens injury, was unaffected in WldS transgenic rats. Conclusions RGC axon regeneration is similar between WldS transgenic and wildtype rats, but WldS transgenic rats do not exhibit enhanced RGC survival after combined optic nerve crush and lens injury suggesting that the neuroprotective effects of lens injury on RGC survival may be limited by the WldS protein.

Abstract Radiocarbon dating provides a key chronological framework for studying past environmental changes. Raw radiocarbon ages measured in samples must be converted to calendar ages using an appropriate calibration curve. Tree-ring datasets provide the gold-standard for developing a precise curve of atmospheric radiocarbon levels over long-time scales. Here, we reconstruct atmospheric radiocarbon levels using a millennium-long section of tree-ring chronology segments that extend into the last glacial period. The samples were obtained from subfossil larch trees recovered from clay quarries at Revine, Italy. Our reconstruction shows higher variations in the amplitude of atmospheric radiocarbon between 18,475 and 17,350 calendar years before the present than that detected in the IntCal20 calibration curve. Comparing the new tree-ring based reconstruction with Beryllium-10 fluxes derived from ice cores, we hypothesise that these variations are driven by solar variability. Our results demonstrate the unique value of sub-decadal radiocarbon sequences derived from glacial tree-ring chronologies.

Nel suo articolato studio sulle Riscritture cavalleresche nel romanzo contemporaneo, Monica Fekete apre in maniera originale e puntualmente documentata una serie di tracciati lungo una serie di elementi portanti per la narrativa a noi contemporanea, considerando quegli aspetti di contaminazione e rielaborazione inventiva provenienti dalla letteratura medievale e umanistica europea. E per converso, e con un necessario ribaltamento delle cronologie, propone in contesto medievistico e umanistico una sorta di arricchimento da prospettiva diversa, ovvero quella a noi contemporanea, operazione che troppo spesso viene disertata dagli specialisti di quest’ultima storiografia critica, con grave danno per la complessità delle ricezioni possibili. Complessità che non sfugge ai nostri scrittori, da Calvino a Camilleri, così come non sfuggiva nella pratica intertestuale disinvolta tra Boccaccio e Ariosto. Tale ampia e coinvolgente chiave di lettura, emersa chiaramente dalle analisi testuali e dagli accurati commenti di Fekete, sottintende e ripropone la considerazione di quel fondo di veri e propri ipotesti, riferiti secondo un’ampia e fruttuosa funzionalità, che nella nostra epoca riguarda, fra fedeltà e improprietas, anche altri linguaggi narrativi, e in specie il film nei suoi vari generi e modalità, come ha ben dimostrato in un suo recente volume Gian Mario Anselmi, a cui dobbiamo peraltro autentiche illuminazioni nello studio della letteratura umanistica e rinascimentale. Qui è, appunto, di letteratura che stiamo parlando, e considerando che i tempi in questioni sono quelli interni alla storia, riguardanti l’ambientazione, così come sono esterni a essa, per ciò che appartiene al “falso” storico messo in atto dagli scrittori di ogni epoca che si calano in un tempo diverso dal proprio, e travestono i propri personaggi di un’impossibile attendibilità, in quanto a sicura riconoscibilità del Medioevo di cui si parla, fornendoci un filtro narrativo che ha un valore ben maggiore e soprattutto ha un legame profondo con la nostra mente moderna, eccezionalmente guardata da altra prospettiva (ma non era lo stesso per l’Ariosto e per Manzoni?). Author Biography Luigi TASSONI Università di Pécs, Ungheria. luigitassoni57@gmail.com. Università di Pécs, Ungheria. Email: luigitassoni57@gmail.com.

Abstract Preliminary validity of a computer‐based test of everyday function (Virtual Kitchen Challenge [VKC]) was examined against brain‐imaging markers of cerebrovascular disease and in contrast to conventional neuropsychological and self‐report measures. Twenty community‐dwelling older adults (n = 6 mild cognitive impairment) performed simulated breakfast and lunch tasks using a computer touchscreen (VKC). Automated measures (completion time, proportion time off screen, etc.) were computed during training and test conditions. White matter hyperintensity (WMH) volumes from brain magnetic resonance imaging and conventional measures of cognition and function also were obtained. VKC completion time and proportion time off screen improved significantly from training to test and were significantly associated with WMH volume (r > 0.573). VKC measures and WMH were not significantly correlated with conventional cognitive or self‐report measures. The VKC holds promise as a valid measure of subtle functional difficulties in older adults that is sensitive to change and cerebrovascular pathology, highlighting its potential for clinical trials. Highlights Virtual Kitchen Challenge (VKC) scores showed significant improvement from training to test conditions. VKC scores (completion time and proportion of time off screen) were associated with a neuroimaging biomarker of brain health (white matter hyperintensities).

Multiple sclerosis (MS) is a neuroinflammatory multifocal disorder. Optic neuritis is common in MS and leads to visual disability. No current treatments repair this damage. Discerning gene expression changes within specific cell types in optic nerve (ON) may suggest new treatment targets for visual disability in MS. Astrocytes are pivotal regulators of neuroinflammation, playing either detrimental or beneficial roles. Here, we used RiboTag technology to characterize the astrocyte-specific transcriptome in ON in the experimental autoimmune encephalomyelitis (EAE) model of MS. RNA sequencing analysis showed the Complement Cascade and Cholesterol Biosynthesis Pathways as the most enriched and de-enriched pathways, respectively, in ON astrocytes in EAE. Expression of complement component 3 (C3) was confirmed to be increased in ON astrocytes at the protein level during EAE. A bigger increase in C3 expressing ON astrocytes was found in EAE females versus healthy females, as compared to that in EAE males versus healthy males. Also, there was worse retinal ganglion cell (RGC) and axonal loss in EAE females. Regression analyses showed a negative correlation between C3 expressing astrocytes and RGC density. This cell-specific and sex-specific investigation of the optic nerve provides targets for the development of therapeutic strategies tailored for optic neuritis in MS.

Abstract Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.

Abstract Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.

This study presents an exceptional collection of 54 Late Pleistocene human remains that correspond to at least three Neanderthal individuals from Simanya Gran, the main gallery of Cova Simanya, located in the northeastern Iberian Peninsula. The collection comprised 53 unpublished remains that were unearthed during the 1970s and an additional tooth discovered during 2021 excavations. The specimens represent an adult with a small stature, a periadolescent aged approximately 11.5 years, and an immature individual aged approximately 7.7 years, thus offering a more complete demographic perspective. The collection encompasses diverse anatomical parts including upper and lower dentition, mandible, vertebrae, and limb bones from both the upper and lower extremities. Attempts to extract aDNA were unsuccessful. Renewed archaeological investigations at Cova Simanya have facilitated the reevaluation of the original stratigraphic context of these remains, leading to the discovery of the additional tooth, aligning with the periadolescent individual. This assemblage is currently the most extensive Neanderthal collection from the northeastern Mediterranean Iberia, offering invaluable insights into the morphology and evolutionary trajectory of Late Pleistocene hominins. Hence, Simanya Neanderthals will enhance our understanding of Neanderthal demographics and evolution, paving the way for an in-depth examination of the morphological diversity and evolutionary context of Iberian Neanderthals.

Resumo Ao mesmo tempo que viabilizou o ingresso e a permanência de estudantes na educação superior privada, o Fundo de Financiamento Estudantil (Fies) também foi uma ferramenta de financeirização do setor, especialmente na primeira metade da década de 2010. Este artigo focaliza as consequências para o segmento educacional, do progressivo encolhimento do Fies a partir de 2015, bem como a Educação a Distância (EaD) como estratégia comercial para minimizar os impactos deste encolhimento no processo de captação de alunos. Trata-se de uma pesquisa documental que pretende demonstrar que, na míngua de fontes públicas estatais de financiamento estudantil, a continuidade do processo de expansão e a manutenção dos resultados das empresas educacionais foram viabilizadas pela expansão da EaD.

Introdução: Frente às recomendações de distanciamento social adotadas durante a pandemia de Covid-19, a assistência nutricional passou a incluir a modalidade de telenutrição na rotina da Atenção Primária à Saúde. Objetivo: Avaliar o teleatendimento de nutrição realizado na Atenção Primária à Saúde durante a pandemia de Covid-19, nas dimensões das orientações de cuidado e manejo de tecnologias. Métodos: Estudo descritivo com usuários adultos e idosos em teleatendimento nutricional de uma Unidade Básica de Saúde no Sul do Brasil, no período entre março de 2020 e março de 2021. Os dados foram coletados dos registros de prontuários eletrônicos e de entrevistas por chamada telefônica. Foram analisadas as características socioeconômicas dos participantes, bem como a avaliação da teleconsulta de nutrição e mudanças alimentares e de estilo de vida resultantes do acompanhamento nutricional, sendo os dados antropométricos obtidos por autorrelato. Utilizou-se estatística descritiva com cálculo de frequência absoluta e relativa, média e desvio padrão. Resultados: Total de 100 usuários entrevistados, sendo 53,0% adultos, a maioria mulheres (72,0%), de cor da pele branca (85,9%) e ensino médio completo (44,0%). O excesso de peso atingiu 78,6% das pessoas. A maioria negou dificuldades para compreender as orientações nutricionais (91,0%) ou necessitar de ajuda para utilizar as tecnologias (81,0%). A avaliação do usuário acerca do atendimento por meio remoto foi positiva, apontando melhora da qualidade da alimentação (79,7%),nos aspectos comportamentais (46,8%) e na prática de atividade física (53,2%). Conclusão: Usuários apresentaram avaliação positiva e boa adaptação ao método de atendimento remoto.

The utilization of the homogeneous (S)-2-pyrrolidine-tetrazole organocatalyst (Ley catalyst) in the self-condensation of ethyl pyruvate and cross-aldol reactions of ethyl pyruvate donor with non-enolizable pyruvate acceptors, namely the sterically hindered ethyl 3-methyl-2-oxobutyrate or the highly electrophilic methyl 3,3,3-trifluoropyruvate, is described as the key enantioselective step toward the synthesis of the corresponding biologically relevant isotetronic acids featuring a quaternary carbon functionalized with ester and alkyl groups. The transition from homogeneous to heterogeneous flow conditions is also investigated, detailing the fabrication and operation of packed-bed reactors filled with a silica-supported version of the pyrrolidine-tetrazole catalyst (SBA-15 as the matrix). [ABSTRACT FROM AUTHOR]

Abstract Sjogren's Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients.

Davide Benedetti,1 Umberto Olcese,2 Simone Bruno,1 Marta Barsotti,3 Michelangelo Maestri Tassoni,3,4 Enrica Bonanni,3,4 Gabriele Siciliano,3,4 Ugo Faraguna1,5 1Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, Italy; 2Cognitive and Systems Neuroscience Group, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands; 3Neurological Clinics, University Hospital of Pisa, Pisa, Italy; 4Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 5Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, Pisa, ItalyCorrespondence: Ugo Faraguna, Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via San Zeno, 31, Pisa, 56123, Italy, Tel +39 050 2213470, Email ugo.faraguna@unipi.itPurpose: A large portion of the adult population is thought to suffer from obstructive sleep apnoea syndrome (OSAS), a sleep-related breathing disorder associated with increased morbidity and mortality. International guidelines include the polysomnography and the cardiorespiratory monitoring (CRM) as diagnostic tools for OSAS, but they are unfit for a large-scale screening, given their invasiveness, high cost and lengthy process of scoring. Current screening methods are based on self-reported questionnaires that suffer from lack of objectivity. On the contrary, commercial smartbands are wearable devices capable of collecting accelerometric and photoplethysmographic data in a user-friendly and objective way. We questioned whether machine-learning (ML) classifiers trained on data collected through these wearable devices would help predict OSAS severity.Patients and Methods: Each of the patients (n = 78, mean age ± SD: 57.2 ± 12.9 years; 30 females) underwent CRM and concurrently wore a commercial wrist smartband. CRM’s traces were scored, and OSAS severity was reported as apnoea hypopnoea index (AHI). We trained three pairs of classifiers to make the following prediction: AHI < 5 vs AHI ≥ 5, AHI < 15 vs AHI ≥ 15, and AHI < 30 vs AHI ≥ 30.Results: According to the Matthews correlation coefficient (MCC), the proposed algorithms reached an overall good correlation with the ground truth (CRM) for AHI < 5 vs AHI ≥ 5 (MCC: 0.4) and AHI < 30 vs AHI ≥ 30 (MCC: 0.3) classifications. AHI < 5 vs AHI ≥ 5 and AHI < 30 vs AHI ≥ 30 classifiers’ sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and diagnostic odds ratio (DOR) are comparable with the STOP-Bang questionnaire, an established OSAS screening tool.Conclusion: Machine learning algorithms showed an overall good performance. Unlike questionnaires, these are based on objectively collected data. Furthermore, these commercial devices are widely distributed in the general population. The aforementioned advantages of machine-learning algorithms applied to smartbands’ data over questionnaires lead to the conclusion that they could serve a population-scale screening for OSAS.Keywords: obstructive sleep apnoea syndrome, screening, wearable devices, wrist-worn smartbands, artificial intelligence

ABSTRACT BACKGROUND: Osteoporosis compromises bone strength and increases the risk of fractures. Zoledronate prevents loss of bone mass and reduces the risk of fractures. OBJECTIVES: To determine the efficacy and safety of zoledronate in postmenopausal women with osteopenia and osteoporosis. DESIGN AND SETTINGS A systematic review and meta-analysis was conducted within the evidence-based health program at the Universidade Federal de São Paulo. METHODS: An electronic search of the CENTRAL, MEDLINE, Embase, and LILACS databases was performed until February 2022. Randomized controlled trials comparing zoledronate with placebo or other bisphosphonates were included. Standard methodological procedures were performed according to the Cochrane Handbook and the certainty of evidence for the Grading of Recommendations Assessment, Development, and Evaluation Working Group. Two authors assessed the risk of bias and extracted data on fractures, adverse events, bone turnover markers (BTM), and bone mineral density (BMD). RESULTS: Twelve trials from 6,652 records were included: nine compared zoledronate with placebo, two trials compared zoledronate with alendronate, and one trial compared zoledronate with ibandronate. Zoledronate reduced the incidence of fractures in osteoporotic [three years: morphometric vertebral fractures (relative risk, RR = 0.30 (95% confidence interval, CI: 0.24–0.38))] and osteopenic women [six years: morphometric vertebral fractures (RR = 0.39 (95%CI: 0.25–0.61))], increased incidence of post-dose symptoms [RR = 2.56 (95%CI: 1.80–3.65)], but not serious adverse events [RR = 0.97 (95%CI: 0.91–1.04)]. Zoledronate reduced BTM and increased BMD in osteoporotic and osteopenic women. CONCLUSION: This review supports the efficacy and safety of zoledronate in postmenopausal women with osteopenia for six years and osteoporosis for three years. PROSPERO REGISTRATION NUMBER: CRD42022309708, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=309708.