Search

Bedwetting, or enuresis, represents a socially stigmatizing and distressing condition that significantly impacts the quality of life for both children and their parents. This article seeks to assess and consolidate the current understanding of traditional and innovative treatments, both pharmacological and non-pharmacological, for children with enuresis. The article discusses the various treatment modalities which have been developed and validated to alleviate symptoms of enuresis, enhance quality of life, and address the social and emotional challenges faced by affected children. Finally the article emphasizes the important primary role of general pediatricians that is to tailor therapy protocols to each individual child, considering their unique needs and circumstances, and working closely with their families to identify the most effective approach.

Abstract Background Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients. Methods The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes. Results 177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02). Conclusions Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients. Trial Registration Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018

Introdução: A Leucemia de Células Pilosas (Tricoleucemia) é uma rara neoplasia linfoproliferativa crônica de células B, corresponde a 2% de todas as leucemias. Em geral apresenta curso indolente e é caracterizada pela presença de linfócitos com projeções citoplasmáticas finas, conhecidas como células pilosas. Os sintomas mais comuns incluem fadiga, fraqueza, esplenomegalia, pancitopenia e infecções oportunistas recorrentes. O diagnóstico é baseado na morfologia das células em sangue periférico ou da medula óssea, que caracteristicamente apresentam projeções citoplasmáticas, e na positividade de marcadores CD11c, CD103, CD123 e CD25 pela imunofenotipagem. Objetivo: Relatar um caso de um paciente idoso com pancitopenia, sendo diagnosticado como portador de Leucemia de Células Pilosas. Relato de caso: Paciente de 80 anos, masculino, previamente hígido, sem comorbidades, internado por adinamia e constipação, exame físico sem esplenomegalia e o hemograma admissional evidenciou pancitopenia, com Hb de 10,2 g/dL; Leucócitos de 2330 /mm3 (Sg 1470/mm3 e Li 820/ mm3) e Plaquetas 27.000/mm3. O paciente realizou mielograma e imunofenotipagem para investigação diagnóstica. O mielograma revelou medula óssea hipocelular apresentando disteritropoiese discreta e predominância de linfócitos maduros, além de formas anômalas, sugerindo tricoleucócitos. A imunofenotipagem por citometria de fluxo revelou um perfil imunofenotípico positivo para marcadores de Leucemia de Células Pilosas: Kappa, CD19, IgM forte, CD20 forte, CD25, CD11c, CD103, CD123, CD79b forte, CD200, CD81 e CD45. O perfil imunofenotípico foi negativo para CD3, CD4, CD8, CD56, CD10, ROR1, CD5, CD11b, CD13, CD33, CD34, CD43, CD23 e Lambda. A conclusão foi compatível com o diagnóstico de Leucemia de Células Pilosas. Com estabilidade clínica e hemodinâmica, o paciente recebeu alta com encaminhamento ambulatorial para um serviço de referência em Hematologia. Discussão: A Tricoleucemia frequentemente se apresenta com pancitopenia devido à infiltração da medula óssea por células pilosas. Mais frequente em homens, e a partir da 5°década de vida, pode mimetizar ou coexistir com outras doenças hematológicas clonais e associar-se a desordens auto-imunes. O tratamento padrão para a doença inclui análogos de purina, como cladribina e pentostatina, que demonstram altas taxas de resposta e prolongam a sobrevida livre de doença. A combinação com rituximabe é uma abordagem terapêutica que vem ganhando destaque e sendo cada vez mais aplicada na prática clínica. Para pacientes que apresentam doença refratária ou recidivante, novas opções estão disponíveis, incluindo inibidores de BRAF, inibidores de MEK e terapias direcionadas. Resposta completa pode ser alcançada em 80 a 85% dos pacientes e mais de 90% tem sobrevida global estimada em 10 anos. Conclusão: A Leucemia de Células Pilosas de forma clássica é um distúrbio linfoproliferativo crônico e indolente. Diante de um paciente com pancitopenia, podemos estar diante de patologias variadas, clonais e não clonais, bem como reacionais, de base imunológicas ou como efeito de tratamentos variados. É imprescindível anamnese detalhada, laboratório e avaliação de medula óssea para excluir doenças neoplásicas.

Introdução: A Púrpura Trombocitopênica Idiopática (PTI) é uma doença autoimune caracterizada por trombocitopenia isolada, sem outras anormalidades hematológicas. A patogênese envolve a produção de autoanticorpos contra glicoproteínas na superfície das plaquetas, como GpIIb/IIIa e GpIb/IX, levando à destruição acelerada das plaquetas pelo sistema reticuloendotelial, sobretudo no território esplênico. Objetivo: Relatar o caso de um portador de PTI que evoluiu com hemorragia digestiva alta grave e refratariedade ao emprego de corticosteroides e imunoglobulina humana. Relato de caso: Paciente masculino, 24 anos, previamente hígido foi admitido no setor de emergência com quadro de hematêmese importante e foi submetido a intubação orotraqueal para proteção de via aérea. Em exames admissionais, foi constatado plaquetopenia (34 mil). Foi realizada transfusão de plaquetas, com piora da plaquetopenia (9 mil). Aventada a hipótese diagnóstica de PTI, iniciada pulsoterapia com Metilprednisolona 1g EV por 72 horas, sem resposta. Foi realizada nova pulsoterapia com Dexametasona 1g EV por 72 horas e novamente sem resposta, inclusive houve deterioração clínica importante com choque hemorrágico. Por fim, optado administrar Imunoglobulina Humana 1g/Kg EV por 48 horas. O paciente não apresentou melhora e houve queda da plaquetometria. Foi iniciado Eltrombopague 50 mg, com incremento plaquetário, entretanto o paciente cursou com hepatite medicamentosa secundária ao Eltrombopague. Suspensa terapia e, após normalização de enzimas hepáticas, reintroduzida a medicação (25 mg/dia). Posteriormente, paciente apresentou melhora clínica e laboratorial e recebeu alta hospitalar com 50 mil plaquetas, prescrição de Eltrombopague 25 mg/dia e Prednisona 30 mg/dia e retorno breve ao Hematologista. Discussão: A apresentação clínica da PTI pode incluir desde o surgimento de púrpura, equimose e, em casos mais graves, hemorragias mucocutâneas, trato gastrointestinal ou do sistema nervoso central. O diagnóstico desta condição é de exclusão, sendo assim necessário afastar condições que geram trombocitopenia, como infecções, neoplasias hematológicas e uso de medicamentos. O tratamento de primeira linha é a corticoterapia, podendo ser necessário o uso de imunoglobulina, agonistas da trombopoetina, anticorpo monoclonal como Rituximabe, outros imunossupressores e até mesmo esplenectomia. O Eltrombopague, utilizado no paciente acima, é um agonista do receptor de trombopoetina e interage com o domínio transmembrana do TPO-R e inicia cascatas de sinalização similares às da trombopoietina endógena, induzindo a proliferação e a diferenciação de megacariócitos provenientes das células progenitoras da medula óssea. Conclusão: A PTI pode ser considerada como leve à grave a depender das manifestações clínicas do paciente. O tratamento de primeira linha envolve o uso de corticosteroides, entretanto, em caso de resistência à esses, lança-se a mão de outras linhas de tratamento.

Abstract Objective In elderly people loneliness represents a risk factor for dementia and may negatively impact on mental and physical health. The specific contribute of loneliness to cognitive and behavioral functioning have not yet been determined in amyotrophic lateral sclerosis (ALS). Our hypothesis was that loneliness may be related to motor dysfunction with a negative impact on cognitive and behavioral decline, possibly related to specific cortical involvement. Methods In 200 ALS patients (ALSpts) and 50 healthy controls (HCs) we measured loneliness, mood, and quality of life (QoL). ALSpts underwent comprehensive clinical, genetic, and neuropsychological assessment to define phenotypes. Seventy‐seven ALSpts performed 3T MRI scans to measure cortical thickness. Between‐group, partial correlation and regression analyses were used to examined clinical, neuropsychological, and cortical signatures of loneliness. Results Feelings of loneliness were documented in 38% of ALSpts (ALS/L+pts) and in 47% of HCs. In both groups loneliness was associated with anxiety (P

Abstract Objective The resting‐state functional connectome has not been extensively investigated in amyotrophic lateral sclerosis (ALS) spectrum disease, in particular in relationship with patients' genetic status. Methods Here we studied the network‐to‐network connectivity of 19 ALS patients carrying the C9orf72 hexanucleotide repeat expansion (C9orf72+), 19 ALS patients not affected by C9orf72 mutation (C9orf72−), and 19 ALS‐mimic patients (ALSm) well‐matched for demographic and clinical variables. Results When compared with ALSm, we observed greater connectivity of the default mode and frontoparietal networks with the visual network for C9orf72+ patients (P = 0.001). Moreover, the whole‐connectome showed greater node degree (P

BackgroundAdipose tissue (AT) wasting in cancer is an early catabolic event with negative impact on outcomes. Circulating miRNAs may promote body weight loss and cachexia. We measured circulating miRNAs linked to AT alterations and compared their levels between i) gastrointestinal (GI) cancer patients and controls, ii) cachectic and non-cachectic cancer patients, and iii) according to adiposity level and its distribution.MethodsPatients with GI cancer and subjects with benign diseases as controls were considered. Cachexia was assessed and adiposity evaluated by CT-scan for subcutaneous AT area (SAT), visceral AT area and the total AT area (TAT). MiRNAs involved were measured in plasma by RT-qPCR.Results37 naïve GI cancer patients and 14 controls were enrolled. Patients with cachexia presented with lower SAT compared to non-cachectic (p < 0.05). In cancer patients, we found higher levels of miR-26a, miR-128, miR-155 and miR-181a vs. controls (p < 0.05). Cancer patients with BMI < 25 kg/m2 showed higher levels of miR-26a vs. those with BMI ≥ 25 (p = 0.035). MiR-26a and miR-181a were higher in cachectic and non-cachectic vs. controls (p < 0.05). Differences between cachectic and controls were confirmed for miR-155 (p < 0.001) but not between non-cachectic vs. control (p = 0.072). MiR-155 was higher in cachectic patients with low TAT vs. those without cachexia and high TAT (p = 0.036).ConclusionOur data confirm a modulation of specific and different miRNAs involved in AT metabolism in cancer and cachexia. MiR-155 levels were higher in patients presenting with cachexia and low adiposity with implications in the pathogenic mechanisms and clinical consequences of GI cancer patients.

Abstract Background Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different types of GI cancers, and in cachexia. Methods We considered patients with GI cancer (gastric, pancreatic, and colorectal) at their first diagnosis, with/without cachexia, and controls with benign diseases. We collected SAT and total RNA was extracted and ATGL, HSL, PPARα, and MCP1 were analyzed by qRT-PCR. Western blot was performed to evaluate CGI-58, PLIN1 and PLIN5. Results We found higher expression of ATGL and HSL in GI cancer patients with respect to controls (p ≤ 0.008) and a trend of increase for PPARα (p = 0.055). We found an upregulation of ATGL in GI cancer patients with cachexia (p = 0.033) and without cachexia (p = 0.017) vs controls. HSL was higher in patients with cachexia (p = 0.020) and without cachexia (p = 0.021), compared to controls. ATGL was upregulated in gastric cancer vs controls (p = 0.014) and higher HSL was found in gastric (p = 0.008) and in pancreatic cancer (p = 0.033) vs controls. At the protein level, we found higher CGI-58 in cancer vs controls (p = 0.019) and in cachectic vs controls (p = 0.029), as well as in gastric cancer vs controls (p = 0.027). Conclusion In our cohort of GI cancer patients, we found a modulation in the expression of genes and proteins involved in lipolysis, and differences were interestingly detected according to cancer type.

Abstract Background Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition. Methods We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients. Results Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior–superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found. Conclusions We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.

Abstract Background Small non‐coding (snc)RNAs, including microRNAs and P‐element induced wimpy testis (PIWI)‐interacting‐RNAs (piRNAs), crucially regulate gene expression in both physiological and pathological conditions. In particular, some muscle‐specific microRNAs (myomiRs) have been involved in the pathogenesis of cancer‐induced muscle wasting. The aims of the present study were (i) to profile sncRNAs in both skeletal muscle and plasma of gastrointestinal cancer patients and (ii) to investigate the association among differentially expressed sncRNAs and the level of muscularity at body composition analysis. Methods Surgical patients with gastrointestinal cancer or benign disease were recruited. Blood samples and muscle biopsies (rectus abdominis) were collected during surgery. Low muscularity patients were those at the lowest tertile of skeletal muscle index (SMI; CT‐scan), whereas moderate/high muscularity patients were in the middle and highest SMI tertiles. SncRNAs in the muscle were assessed by RNAseq, circulating microRNAs were evaluated by qPCR. Results Cancer patients (n = 25; 13 females, 52%) showed a mean age of 71.6 ± 11.2 years, a median body weight loss of 4.2% and a mean BMI of 27.0 ± 3.2 kg/m2. Control group (n = 15; 9 females, 60%) showed a mean age 58.1 ± 13.9 years and a mean BMI of 28.0 ± 4.3 kg/m2. In cancer patients, the median L3‐SMI (cm2/m2) was 42.52 (34.42; 49.07). Males showed a median L3‐SMI of 46.08 (41.17–51.79) and females a median L3‐SMI of 40.77 (33.73–42.87). Moderate‐high and low muscularity groups included 17 and 8 patients, respectively. As for circulating microRNAs, miR‐21‐5p and miR‐133a‐3p were up‐regulated in patients compared with controls, whereas miR‐15b‐5p resulted down‐regulated in the same comparison (about 30% of control values). Sample clustering by muscularity and sex revealed increased miR‐133a‐3p and miR‐206 only in moderate‐high muscularity males. SncRNA profiling in the muscle identified 373 microRNAs and 190 piRNAs (72.5% and 18.7% of raw reads, respectively). As for microRNAs, 10 were up‐regulated, and 56 were down‐regulated in cancer patients versus controls. Among the 24 dysregulated piRNAs, the majority were down‐regulated, including the top two most expressed piRNAs in the muscle (piR‐12790 and piR‐2106). Network analysis on validated mRNA targets of down‐regulated microRNAs revealed miR‐15b‐5p, miR‐106a‐5p and miR‐106b‐5p as main interactors of genes related to ubiquitin ligase/transferase activities. Conclusions These results show dysregulation of both muscle microRNAs and piRNAs in cancer patients compared with controls, the former following a sex‐specific pattern. Changes in circulating microRNAs are associated with the degree of muscularity rather than body weight loss.

Pancreatic ductal adenocarcinoma (PDA) tumor cells are deprived of oxygen and nutrients and therefore must adapt their metabolism to ensure proliferation. In some physiological states, cells rely on ketone bodies to satisfy their metabolic needs, especially during nutrient stress. Here, we show that PDA cells can activate ketone body metabolism and that β-hydroxybutyrate (βOHB) is an alternative cell-intrinsic or systemic fuel that can promote PDA growth and progression. PDA cells activate enzymes required for ketogenesis, utilizing various nutrients as carbon sources for ketone body formation. By assessing metabolic gene expression from spontaneously arising PDA tumors in mice, we find HMG-CoA lyase (HMGCL), involved in ketogenesis, to be among the most deregulated metabolic enzymes in PDA compared to normal pancreas. In vitro depletion of HMGCL impedes migration, tumor cell invasiveness, and anchorage-independent tumor sphere compaction. Moreover, disrupting HMGCL drastically decreases PDA tumor growth in vivo, while βOHB stimulates metastatic dissemination to the liver. These findings suggest that βOHB increases PDA aggressiveness and identify HMGCL and ketogenesis as metabolic targets for limiting PDA progression.

Abstract Biomarker-based differential diagnosis of the most common forms of dementia is becoming increasingly important. Machine learning (ML) may be able to address this challenge. The aim of this study was to develop and interpret a ML algorithm capable of differentiating Alzheimer’s dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal control subjects based on sociodemographic, clinical, and magnetic resonance imaging (MRI) variables. 506 subjects from 5 databases were included. MRI images were processed with FreeSurfer, LPA, and TRACULA to obtain brain volumes and thicknesses, white matter lesions and diffusion metrics. MRI metrics were used in conjunction with clinical and demographic data to perform differential diagnosis based on a Support Vector Machine model called MUQUBIA (Multimodal Quantification of Brain whIte matter biomArkers). Age, gender, Clinical Dementia Rating (CDR) Dementia Staging Instrument, and 19 imaging features formed the best set of discriminative features. The predictive model performed with an overall Area Under the Curve of 98%, high overall precision (88%), recall (88%), and F1 scores (88%) in the test group, and good Label Ranking Average Precision score (0.95) in a subset of neuropathologically assessed patients. The results of MUQUBIA were explained by the SHapley Additive exPlanations (SHAP) method. The MUQUBIA algorithm successfully classified various dementias with good performance using cost-effective clinical and MRI information, and with independent validation, has the potential to assist physicians in their clinical diagnosis.

Abstract Background Mindfulness gained considerable attention for migraine management, but RCTs are lacking. We aimed to assess the efficacy of a six-sessions mindfulness-based treatment added to treatment as usual (TaU) in patients with Chronic Migraine (CM) and Medication Overuse Headache (MOH) on headache frequency, medication intake, quality of life, disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. Methods In this Phase-III single-blind RCT carried out in a specialty Italian headache center, 177 patients with CM and MOH were randomized 1:1 to either TaU (withdrawal from overused drugs, education on proper medication use and lifestyle issues, and tailored prophylaxis) or mindfulness-based intervention added to TaU (TaU + MIND). The mindfulness-based intervention consisted of six group session of mindfulness practice and 7–10 min daily self-practice. The primary endpoint was the achievement of ≥ 50% headache frequency reduction at 12 months compared to baseline, and was analyzed on an intention-to-treat principle using Pearson’s Chi-Squared test. Secondary endpoints included medication intake, quality of life (QoL), disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. The secondary endpoints were analyzed using per-protocol linear mixed models. Results Out of the 177 participants 89 were randomized to TaU and 88 to TaU + MIND. Patients in the TaU + MIND group outperformed those in TaU for the primary endpoint (78.4% vs. 48.3%; p

The IntelliCage (IC) permits the assessment of the behavior and learning abilities of mice in a social home cage context. To overcome water deprivation as an aversive driver of learning, we developed protocols in which spatial learning is motivated appetitively by the preference of mice for sweetened over plain water. While plain water is available at all times, only correct task responses give access to sweetened water rewards. Under these conditions, C57BL/6J mice successfully mastered a corner preference task with the reversal and also learned a more difficult time-place task with reversal. However, the rate of responding to sweetened water decreased strongly with increasing task difficulty, indicating that learning challenges and reduced success in obtaining rewards decreased the motivation of the animals to seek sweetened water. While C57BL/6J mice of both sexes showed similar initial taste preferences and learned similarly well in simple learning tasks, the rate of responding to sweetened water and performance dropped more rapidly in male than in female mice in response to increasing learning challenges. Taken together, our data indicate that male mice can have a disadvantage relative to females in mastering difficult, appetitively motivated learning tasks, likely due to sex differences in value-based decision-making.

BackgroundUnderstanding causes and contributors to maternal mortality is critical from a quality improvement perspective to inform decision making and monitor progress toward ending preventable maternal mortality. The indicator "maternal death review coverage" is defined as the percentage of maternal deaths occurring in a facility that are audited. Both the numerator and denominator of this indicator are subject to misclassification errors, underreporting, and bias. This study assessed the validity of the indicator by examining both its numerator-the number and quality of death reviews-and denominator-the number of facility-based maternal deaths and comparing estimates of the indicator obtained from facility- versus district-level data.Methods and findingsWe collected data on the number of maternal deaths and content of death reviews from all health facilities serving as birthing sites in 12 districts in three countries: Argentina, Ghana, and India. Additional data were extracted from health management information systems on the number and dates of maternal deaths and maternal death reviews reported from health facilities to the district-level. We tabulated the percentage of facility deaths with evidence of a review, the percentage of reviews that met the World Health Organization defined standard for maternal and perinatal death surveillance and response. Results were stratified by sociodemographic characteristics of women and facility location and type. We compared these estimates to that obtained using district-level data. and looked at evidence of the review at the district/provincial level. Study teams reviewed facility records at 34 facilities in Argentina, 51 facilities in Ghana, and 282 facilities in India. In total, we found 17 deaths in Argentina, 14 deaths in Ghana, and 58 deaths in India evidenced at facilities. Overall, >80% of deaths had evidence of a review at facilities. In India, a much lower percentage of deaths occurring at secondary-level facilities (61.1%) had evidence of a review compared to deaths in tertiary-level facilities (92.1%). In all three countries, only about half of deaths in each country had complete reviews: 58.8% (n = 10) in Argentina, 57.2% (n = 8) in Ghana, and 41.1% (n = 24) in India. Dramatic reductions in indicator value were seen in several subnational geographic areas, including Gonda and Meerut in India and Sunyani in Ghana. For example, in Gonda only three of the 18 reviews conducted at facilities met the definitional standard (16.7%), which caused the value of the indicator to decrease from 81.8% to 13.6%. Stratification by women's sociodemographic factors suggested systematic differences in completeness of reviews by women's age, place of residence, and timing of death.ConclusionsOur study assessed the validity of an important indicator for ending preventable deaths: the coverage of reviews of maternal deaths occurring in facilities in three study settings. We found discrepancies in deaths recorded at facilities and those reported to districts from facilities. Further, few maternal death reviews met global quality standards for completeness. The value of the calculated indicator masked inaccuracies in counts of both deaths and reviews and gave no indication of completeness, thus undermining the ultimate utility of the measure in achieving an accurate measure of coverage.

The use of waste in the field of civil engineering is one of the solutions to reduce the harmful impact of waste on the environment on the one hand and preserve natural resources on the other. This study aims to investigate the effect of using waste materials such as plastic and tire chips that can be used as backfill in retaining walls. A numerical study has been carried out by using PLAXIS 2D software version 8.6 to model three types of rigid retaining walls, namely: scale wall test, cantilever wall, and gravity wall. In addition, the backfills of those retaining walls are composed of two mixtures. The first is a mixture of sand and tire chips (TC) with different percentages (10%, 30%, 50%, and 70%). The second is a mixture of sand and PET plastic flakes at different percentages (12.5%, 22.5%, and 32.5%). The results obtained from this study confirmed that the use of PET plastic waste and tire chips waste mixed with sand in the backfills of rigid retaining walls contributes effectively to the reduction of horizontal and vertical displacements as well as the earth pressures behind the retaining walls, therefore improving the stability of the retaining walls.

Abstract Aim When studying brain networks in patients with Disorders of Consciousness (DoC), it is important to evaluate the structural integrity of networks in addition to their functional activity. Here, we investigated whether structural MRI, together with clinical variables, can be useful for diagnostic purposes and whether a quantitative analysis is feasible in a group of chronic DoC patients. Methods We studied 109 chronic patients with DoC and emerged from DoC with structural MRI: 65 in vegetative state/unresponsive wakefulness state (VS/UWS), 34 in minimally conscious state (MCS), and 10 with severe disability. MRI data were analyzed through qualitative and quantitative approaches. Results The qualitative MRI analysis outperformed the quantitative one, which resulted to be hardly feasible in chronic DoC patients. The results of the qualitative approach showed that the structural integrity of HighOrder networks, altogether, had better diagnostic accuracy than LowOrder networks, particularly when the model included clinical variables (AUC = 0.83). Diagnostic differences between VS/UWS and MCS were stronger in anoxic etiology than vascular and traumatic etiology. MRI data of all LowOrder and HighOrder networks correlated with the clinical score. The integrity of the left hemisphere was associated with a better clinical status. Conclusions Structural integrity of brain networks is sensitive to clinical severity. When patients are chronic, the qualitative analysis of MRI data is indicated.

The IntelliCage allows automated testing of cognitive abilities of mice in a social home cage environment without handling by human experimenters. Restricted water access in combination with protocols in which only correct responses give access to water is a reliable learning motivator for hippocampus-dependent tasks assessing spatial memory and executive function. However, water restriction may negatively impact on animal welfare, especially in poor learners. To better comply with the 3R principles, we previously tested protocols in which water was freely available but additional access to sweetened water could be obtained by learning a task rule. While this purely appetitive motivation worked for simple tasks, too many mice lost interest in the sweet reward during more difficult hippocampus-dependent tasks. In the present study, we tested a battery of increasingly difficult spatial tasks in which water was still available without learning the task rule, but rendered less attractive either by adding bitter tasting quinine or by increasing the amount of work to obtain it. As in previous protocols, learning of the task rule provided access to water sweetened with saccharin. The two approaches of dual motivation were tested in two cohorts of female C57BL/6 N mice. Compared to purely appetitive motivation, both novel protocols strongly improved task engagement and increased task performance. Importantly, neither of the added disincentives had an adverse impact on liquid consumption, health status or body weight of the animals. Our results show that it is possible to refine test protocols in the IntelliCage so that they challenge cognitive functions without restricting access to water.

Resenha do livro Recortes do Mundo: espaço e paisagem no cinema (2023), escrito por Angela Prysthon. Nesta obra, a autora reúne uma série de ensaios que interligam questões relativas ao cinema e à paisagem. As ideias de uma geografia afetiva, da heterotopia foucaultiana e das deambulações surrealistas, provenientes de estudos em fotografia, arquitetura e cinema, se mostram essenciais para pensar a paisagem e as possibilidades críticas do espaço.

IntroductionWithin Pediatric Cerebellar Ataxias (PCAs), patients with non-progressive ataxia (NonP) surprisingly show postural motor behavior comparable to that of healthy controls, differently to slow-progressive ataxia patients (SlowP). This difference may depend on the building of compensatory strategies of the intact areas in NonP brain network.MethodsEleven PCAs patients were recruited: five with NonP and six with SlowP. We assessed volumetric and axonal bundles alterations with a multimodal approach to investigate whether eventual spared connectivity between basal ganglia and cerebellum explains the different postural motor behavior of NonP and SlowP patients.ResultsCerebellar lobules were smaller in SlowP patients. NonP patients showed a lower number of streamlines in the cerebello-thalamo-cortical tracts but a generalized higher integrity of white matter tracts connecting the cortex and the basal ganglia with the cerebellum.DiscussionThis work reveals that the axonal bundles connecting the cerebellum with basal ganglia and cortex demonstrate a higher integrity in NonP patients. This evidence highlights the importance of the cerebellum-basal ganglia connectivity to explain the different postural motor behavior of NonP and SlowP patients and support the possible compensatory role of basal ganglia in patients with stable cerebellar malformation.

The IntelliCage is an automated home-cage system that allows researchers to investigate the spontaneous behavior and learning abilities of group-housed mice. The IntelliCage enables us to increase the standardization and reproducibility of behavioral outcomes by the omission of experimenter–mouse interactions. Although the IntelliCage provides a less stressful environment for animals, standard IntelliCage protocols use controlled water access as the motivational driver for learning. To overcome possible water restrictions in slow learners, we developed a series of novel protocols based on appetitive learning, in which mice had permanent access to plain water but were additionally rewarded with sweetened water upon solving the task. C57BL/6NCrl female mice were used to assess the efficacy of these sweet reward-based protocols in a series of learning tasks. Compared to control mice tested with standard protocols, mice motivated with a sweet reward did equal to or better in operant performance and place learning tasks. Learning of temporal rules was slower than that in controls. When faced with a combined temporal x spatial working memory task, sweet-rewarded mice learned little and chose plain water. In a second set of experiments, the impact of environmental enrichment on appetitive learning was tested. Mice kept under enriched environment (EE) or standard housing (SH) conditions prior to the IntelliCage experiments performed similarly in the sweet-rewarded place learning task. EE mice performed better in the hippocampus-dependent spatial working memory task. The improved performance of EE mice in the hippocampus-dependent spatial working memory task might be explained by the observed larger volume of their mossy fibers. Our results confirm that environmental enrichment increases complex spatial learning abilities and leads to long-lasting morphological changes in the hippocampus. Furthermore, simple standard IntelliCage protocols could easily be adapted to sweet rewards, which improve animal welfare by removing the possibility of water restriction. However, complex behavioral tasks motivated by sweet reward-based learning need further adjustments to reach the same efficacy as standard protocols.

Refinery industrial processes are very complex with nonlinear dynamics resulting from varying feedstock characteristics and also from changes in product prioritization. Along these processes, there are key properties of intermediate compounds that must be monitored and controlled since they directly affect the quality of the end products commercialized by these manufacturers. However, most of these properties can only be measured through time-consuming and expensive laboratory analysis, which is impossible to obtain in high frequencies, as required to properly monitor them. In this sense, developing soft sensors is the most common way to obtain high-frequency estimations for these measurements, helping advanced control systems to establish the correct setpoints for temperatures, pressures, and other sensors along the refining process, controlling the quality of end products. Since the amount of labeled data is scarce, most academic research has focused on employing semi- supervised learning strategies to develop machine learning (ML) models as soft sensors. Our research, on the other hand, goes in another direction. We aim to elaborate a framework that leverages the knowledge of domain experts and employs data augmentation techniques to build an enhanced fully labeled dataset that could be fed to any supervised ML algorithm to generate a quality soft sensor. We applied our framework together with Automated ML to train a model capable of predicting a specific key property associated with the production of Naphtha compounds in a refinery: the ASTM 95% distillation temperature of the Heavy Naphtha. Although our framework is model agnostic, we opted by using Automated ML for the optimization strategy, since it applies a diverse set of models to the dataset, reducing the bias of utilizing a single optimization algorithm. We evaluated the proposed framework on a case study carried out in an industrial refinery in Brazil, where the previous model in production for estimating the ASTM 95% distillation temperature of the Heavy Naphtha was based entirely on the physicochemical knowledge of the process. By adopting our framework with Automated ML, we were capable of improving the R2 score by 120%. The resulting ML model is currently operating in real-time inside the refinery, leading to significant economic gains.

Abstract Objective Spinal cord degeneration is a hallmark of amyotrophic lateral sclerosis. The assessment of gray matter and white matter cervical spinal cord atrophy across clinical stages defined using the King's staging system could advance the understanding of amyotrophic lateral sclerosis progression. Methods We assessed the in vivo spatial pattern of gray and white matter atrophy along cervical spinal cord (C2 to C6 segments) using 2D phase‐sensitive inversion recovery imaging in a cohort of 44 amyotrophic lateral sclerosis patients, evaluating its change across the King's stages and the correlation with disability scored by the amyotrophic lateral sclerosis functional rating scale revised (ALSFRS‐R) and disease duration. A mathematical model inferring the potential onset of cervical gray matter atrophy was developed. Results In amyotrophic lateral sclerosis patients at King's stage 1, significant cervical spinal cord alterations were mainly identified in gray matter, whereas they involved both gray and white matter in patients at King's stage ≥ 2. Gray and white matter areas correlated with clinical disability at all cervical segments. C3–C4 level was the segment showing early gray matter atrophy starting about 7 to 20 months before symptom onset according to our model. Interpretation Our findings suggest that cervical spinal cord atrophy spreads from gray to white matter across King's stages in amyotrophic lateral sclerosis, making spinal cord magnetic resonance imaging an in vivo assessment tool to measure the progression of the disease.

In this article we start from the analysis of the film Minority Report (Steven Spielberg, 2002) in order to study the consequences of the use of Artificial Intelligence as a crime prevention tool. We explore the ethical issues of these technologies as accessories - and protagonists - of contemporary law and raise the challenges for criminal law theory in the face of a possible total prevention of crime. Finally, we conclude with the prospects that these changes may have for governments, their justice administration policies and power relations in the near future of “algorithmic republics”.

Abstract In many low-mortality countries, life expectancy at birth increased steadily over the last century. In particular, both Italian females and males benefited from faster improvements in mortality compared to other high-income countries, especially from the 1960s, leading to an exceptional increase in life expectancy. However, Italy has not become the leader in longevity. Here, we investigate life expectancy trends in Italy during the period 1960–2015 for both sexes. Additionally, we contribute to the existing literature by complementing life expectancy with an indicator of dispersion in ages at death, also known as lifespan inequality. Lifespan inequality underlies heterogeneity over age in populating health improvements and is a marker of uncertainty in the timing of death. We further quantify the contributions of different age groups and causes of death to recent trends in life expectancy and lifespan inequality. Our findings highlight the contributions of cardiovascular diseases and neoplasms to the recent increase in life expectancy but not necessarily to the decrease in lifespan inequality. Our results also uncover a more recent challenge across Italy: worsening mortality from infectious diseases and mortality at older age.