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Recycling waste in cementitious materials promotes sustainable construction. It helps to prevent the depletion of natural resources while also reusing abundant recyclable wastes. Eggshells are one of these wastes that is being generated in large quantities because eggs are not expensive and have high nutritional value. On the other side, eggshell has a high content of calcium carbonate. It has a similar composition to the limestone powder used to produce Portland cement. This work investigates the effect of replacing a part of the cement with eggshell powder on mortar properties. The substitution rates were 5 %, 10 %, and 15 % of the cement’s mass. The results were compared with those of an ordinary mortar for the following properties: workability, compressive strength, flexural tensile strength, density in the hardened state, water absorption by total immersion, porosity accessible to water, depth of water penetration under pressure and chemical attack by sulfuric acid. The experimental results show that adding eggshell powder as a partial cement substitute up to 10% improved workability, increased compressive strength by about 10 % and flexural tensile strength by about 20 %, reduced density, and produced a more durable mortar by reducing porosity, water absorption, and water penetration depth under pressure. On the other hand, it decreased resistance to chemical attack by sulfuric acid. Thus, eggshell powder could be used in future construction materials to reduce carbon dioxide emissions.

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

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

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 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.

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 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.

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.

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.