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Bioelectronic bone implants are being widely recognized as a promising technology for highly personalized bone/implant interface sensing and biophysical therapeutic stimulation. Such bioelectronic devices are based on an innovative concept with the ability to be applied to a wide range of implants, including in fixation and prosthetic systems. Recently, biointerface sensing using capacitive patterns was proposed to overcome the limitations of standard imaging technologies and other non-imaging technologies; moreover, electric stimulation using capacitive patterns was proposed to overcome the limitations of non-instrumented implants. We here provide an innovative low-power miniaturized electronic system with ability to provide both therapeutic stimulation and bone/implant interface monitoring using network-architectured capacitive interdigitated patterns. It comprises five modules: sensing, electric stimulation, processing, communication and power management. This technology was validated using in vitro tests: concerning the sensing system, its ability to detect biointerface changes ranging from tiny to severe bone-implant interface changes in target regions was validated; concerning the stimulation system, its ability to significantly enhance bone cells' full differentiation, including matrix maturation and mineralization, was also confirmed. This work provides an impactful contribution and paves the way for the development of the new generation of orthopaedic biodevices.

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OBJECTIVE: Youth who have been exposed to potentially traumatic events are at risk of developing chronic and severe adjustment problems. However, some youth exposed to potentially traumatic events exhibit better-than-expected adaptation. Person-centered analyses, based on multiple criteria for adaptive behavior and adversity, are well-suited to empirically identifying different patterns of adaptation among high-risk youth. METHOD: Data from 381 youth from three at-risk subgroups in Portugal were collected using self-reported measures of trauma history, trauma-related symptomatology, coping skills, and perceived social support. Distinct classes of adaptation after traumatic experiences were examined with latent class analysis. RESULTS: Four classes were identified: (a) trauma-related psychopathology class (13.6%), (b) adaptive resilience class (36.8%), (c) low resources class (11.4%), and (d) high resources class (38.2%). Trauma-related psychopathology class and low resources class were characterized by high levels of maladjustment. Similarly to the low resources class, the trauma-related psychopathology class reported a significantly higher likelihood of trauma-related psychopathology and higher levels of problem-solving skills. The adaptive resilience class and high resources class also reported lower levels of maladjustment, and the high resources class reported higher levels of coping skills and lower levels of externalizing problems than any other class. CONCLUSION: Clinicians treating children's internalizing mental health or externalizing behavior problems should assess trauma history and trauma-related psychopathology, as well as protective resources that may enhance resilience such as skills for problem solving and social support seeking. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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Introduction: Khat, a green leafy plant grown in East Africa and throughout the Arabian Peninsula, is chewed for its psychoactive and amphetamine-like effects, serving as a significant aspect of culture, economic livelihood, and global trade. Khat consumption during pregnancy has been associated with adverse effects, including anemia, premature rupture of membranes, and low birth weight, among others. Methods: This cross-sectional, explanatory sequential mixed methods study was conducted in the Haramaya District of eastern Ethiopia using a questionnaire and focus group discussions. Questionnaires assessed socio-demographic information, pregnancy history, and diet, including khat use. Data were analyzed using SPSS v28 to include descriptive statistics, proportions, odds ratios, binary logistic regression, and chi-square analysis. FGDs expanded on the knowledge, attitudes, and practices of khat in the region, including pregnant or lactating women from two different kebeles. Two independent reviewers conducted a qualitative content analysis to examine the qualitative findings from the FGDs. Transcripts from the focus groups were entered into NVivo 14 to aid in capturing salient themes. Results: A total of 444 pregnant women with a median age of 25 years completed the questionnaire. Two-thirds of the women, 66.9%, reported currently consuming khat while pregnant, and 72.7% of them reported daily consumption. The FGD analysis resulted in the discovery of five themes: Economic Livelihood, Maternal Significance, Medicinal Implications of Khat, Pesticide Use, and Social and Cultural Applications. Discussion: This study revealed an alarming high prevalence of khat consumption among pregnant women in the Haramaya District, highlighting the pressing need for long-term studies to assess the health consequences. The role of khat as both an economic staple and an energy source for daily activities underscores the challenges in curbing its use. The documented health risks associated with the chemicals used in khat cultivation, including cancer, call for interventions to enhance safe agricultural practices in households involved in khat farming.

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Sickle cell disease is characterised by episodes of vaso-occlusive crisis, a painful complication. Regional anaesthesia has shown promising results in reducing opioid consumption and pain scores. Patients with vaso-occlusive crises who underwent regional anaesthesia in the paediatric intensive care unit were studied. Data regarding pain location, regional analgesia technique, the local anaesthetic used and dose, daily opioid consumption, daily pain scores, use of adjuvants and complications were recorded. The primary outcome was to evaluate the effect of regional anaesthesia on opioid consumption. In this study, we describe 10 cases, referring to six paediatric patients with the vaso-occlusive crisis who underwent regional anaesthesia for severe pain and were unresponsive to increasing doses of opioids. Six cases received epidural analgesia, three continuous peripheral nerve blocks and one received both techniques. Opioid consumption was reduced (58%), and pain scores decreased (72%), both statistically significant reductions.

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In a great partnership, the Federation of European Neuroscience Societies (FENS) and the Hertie Foundation organized the FENS-Hertie 2022 Winter School on 'Neuro-immune interactions in health and disease'. The school selected 27 PhD students and 13 postdoctoral fellows from 20 countries and involved 14 faculty members experts in the field. The Winter School focused on a rising field of research, the interactions between the nervous and both innate and adaptive immune systems under pathological and physiological conditions. A fine-tuned neuro-immune crosstalk is fundamental for healthy development, while disrupted neuro-immune communication might play a role in neurodegeneration, neuroinflammation and aging. However, much is yet to be understood about the underlying mechanisms of these neuro-immune interactions in the healthy brain and under pathological scenarios. In addition to new findings in this emerging field, novel methodologies and animal models were presented to foment research on neuro-immunology. The FENS-Hertie 2022 Winter School provided an insightful knowledge exchange between students and faculty focusing on the latest discoveries in the biology of neuro-immune interactions while fostering great academic and professional opportunities for early-career neuroscientists from around the world.

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OBJECTIVES: To describe persistent symptoms and lung function in mild cases of COVID-19 six months after infection. METHODS: Data collection was performed through a semi-structured questionnaire containing information on the participants' demographic and anthropometric data, the disease in the acute phase, and persistent symptoms six months after COVID-19 using spirometry and manovacuometry. RESULTS: A total of 136 participants were evaluated, of whom 64% were male, with a mean age of 38.17 ± 14.08 years and a body mass index (BMI) of 29.71 ± 17.48 kg/m2. The main persistent symptoms reported were dyspnea on exertion (39.7%), memory loss (38.2%), and anxiety (48.5%). Considering lung function, the participants reached 88.87 ± 17.20% of the predicted forced vital capacity (FVC), 86.03 ± 22.01% of the forced expiratory volume in one second (FEV1), and 62.71 ± 25.04% of peak expiratory flow (PEF). Upon manovacuometry, 97.41 ± 34.67% of the predicted inspiratory force (Pimax) and 66.86 ± 22.97% of the predicted expiratory force (Pemax) were observed. CONCLUSIONS: Six months after COVID-19 infection, a reduction in PEF and MEP was observed. Among the most commonly reported persistent symptoms were fatigue, tiredness with the slightest exertion, anxiety and depression, memory loss, and deficits in concentration.

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PROTAC linker design remains mostly an empirical task. We employed the PRosettaC computational software in the design of sulfonyl-fluoride-based PROTACs targeting acyl protein thioesterase 1 (APT1). The software efficiently generated ternary complex models from empirically-designed PROTACs and suggested alkyl linkers to be the preferred type of linker to target APT1. Western blotting analysis revealed efficient degradation of APT1 and activity-based protein profiling showed remarkable selectivity of an alkyl linker-based PROTAC amongst serine hydrolases. Collectively, our data suggests that combining PRosettaC and chemoproteomics can effectively assist in triaging PROTACs for synthesis and providing early data on their potency and selectivity.

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ABSTRACT Objectives: To describe persistent symptoms and lung function in mild cases of COVID-19 six months after infection. Methods: Data collection was performed through a semi-structured questionnaire containing information on the participants' demographic and anthropometric data, the disease in the acute phase, and persistent symptoms six months after COVID-19 using spirometry and manovacuometry. Results: A total of 136 participants were evaluated, of whom 64% were male, with a mean age of 38.17 ± 14.08 years and a body mass index (BMI) of 29.71 ± 17.48 kg/m2. The main persistent symptoms reported were dyspnea on exertion (39.7%), memory loss (38.2%), and anxiety (48.5%). Considering lung function, the participants reached 88.87 ± 17.20% of the predicted forced vital capacity (FVC), 86.03 ± 22.01% of the forced expiratory volume in one second (FEV1), and 62.71 ± 25.04% of peak expiratory flow (PEF). Upon manovacuometry, 97.41 ± 34.67% of the predicted inspiratory force (Pimax) and 66.86 ± 22.97% of the predicted expiratory force (Pemax) were observed. Conclusions: Six months after COVID-19 infection, a reduction in PEF and MEP was observed. Among the most commonly reported persistent symptoms were fatigue, tiredness with the slightest exertion, anxiety and depression, memory loss, and deficits in concentration.

RESUMO Objetivos: Descrever os sintomas persistentes e a função pulmonar em casos leves de COVID-19 seis meses após a infecção. Métodos: A coleta de dados foi realizada por meio de um questionário semiestruturado contendo informações sobre dados demográficos e antropométricos dos participantes, a doença na fase aguda e os sintomas persistentes seis meses após a COVID-19, utilizando espirometria e manovacuometria. Resultados: Um total de 136 participantes foram avaliados, dos quais 64% eram do sexo masculino, com uma idade média de 38,17 ± 14,08 anos e índice de massa corporal (IMC) de 29,71 ± 17,48 kg/m2. Os principais sintomas persistentes relatados foram dispneia ao esforço (39,7%), perda de memória (38,2%) e ansiedade (48,5%). Considerando a função pulmonar, os participantes atingiram 88,87 ± 17,20% da capacidade vital forçada (CVF) prevista, 86,03 ± 22,01% do volume expiratório forçado no primeiro segundo (VEF1) e 62,71 ± 25,04% do pico de fluxo expiratório (PFE). Na manovacuometria, observou-se 97,41 ± 34,67% da força inspiratória prevista (Pimáx) e 66,86 ± 22,97% da força expiratória prevista (Pemáx). Conclusões: Seis meses após a infecção por COVID-19, observou-se uma redução no PFE e na PEM. Dentre os sintomas persistentes mais comumente relatados estavam fadiga, cansaço com o mínimo esforço, ansiedade e depressão, perda de memória e déficits de concentração.

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Childhood represents a period of significant growth and maturation for the brain, and is also associated with a heightened risk for mild traumatic brain injuries (mTBI). There is also concern that repeated-mTBI (r-mTBI) may have a long-term impact on developmental trajectories. Using an awake closed head injury (ACHI) model, that uses rapid head acceleration to induce a mTBI, we investigated the acute effects of repeated-mTBI (r-mTBI) on neurological function and cellular proliferation in juvenile male and female Long-Evans rats. We found that r-mTBI did not lead to cumulative neurological deficits with the model. R-mTBI animals exhibited an increase in BrdU + (bromodeoxyuridine positive) cells in the dentate gyrus (DG), and that this increase was more robust in male animals. This increase was not sustained, and cell proliferation returning to normal by PID3. A greater increase in BrdU + cells was observed in the dorsal DG in both male and female r-mTBI animals at PID1. Using Ki-67 expression as an endogenous marker of cellular proliferation, a robust proliferative response following r-mTBI was observed in male animals at PID1 that persisted until PID3, and was not constrained to the DG alone. Triple labeling experiments (Iba1+, GFAP+, Brdu+) revealed that a high proportion of these proliferating cells were microglia/macrophages, indicating there was a heightened inflammatory response. Overall, these findings suggest that rapid head acceleration with the ACHI model produces an mTBI, but that the acute neurological deficits do not increase in severity with repeated administration. R-mTBI transiently increases cellular proliferation in the hippocampus, particularly in male animals, and the pattern of cell proliferation suggests that this represents a neuroinflammatory response that is focused around the mid-brain rather than peripheral cortical regions. These results add to growing literature indicating sex differences in proliferative and inflammatory responses between females and males. Targeting proliferation as a therapeutic avenue may help reduce the short term impact of r-mTBI, but there may be sex-specific considerations.

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Malignant peritoneal mesothelioma (MPM) is a rare tumor of the serous membranes of the peritoneum and has been linked to exposure to asbestos and other risk factors. The clinical manifestations are vague, with a wide clinical spectrum, predominantly related to the abdominal involvement of the disease. Localized mesothelioma is an uncommon manifestation of the disease. Common symptoms include abdominal pain or abdominal distention, nausea, anorexia, and weight loss. Rarely, patients present with paraneoplastic syndrome. Due to the nonspecific symptoms, many patients already have advanced disease at the time of diagnosis. The authors report a case of a 75-year-old female patient who presented with symptoms of asthenia, anorexia, progressive paleness, and weight loss lasting five months. She reports later new-onset symptoms of diffuse abdominal pain and diarrhea associated with nausea. Laboratory tests showed anemia, mild leukocytosis, thrombocytosis, elevated C-reactive protein (CRP), and elevated liver enzymes. An abdominal and pelvic computed tomography (CT) scan revealed marked tissue thickening of an irregular and striated configuration of the leaflets and peritoneal reflections in an omental cake pattern, and a chest CT scan showed multiple bilateral pulmonary nodules, suggesting diffuse malignant disease. A CT-guided biopsy of a peritoneal implant was performed, establishing the diagnosis of malignant peritoneal mesothelioma. Due to rapid clinical deterioration, the patient did not receive any systemic treatment, surgery, or radiotherapy and was transitioned to comfort care. As in the presented case, most cases of MPM have diffuse peritoneal involvement at the time of diagnosis, although extra-abdominal involvement is very rare. This disease presentation is associated with high morbidity and mortality compared to cases of localized disease. There is no specific imaging diagnostic modality or valuable tumor markers for MPM. Although a CT scan remains important in the diagnostic approach, the changes found are not specific. Radiographically, MPM may present as mesenteric or parietal peritoneal nodules, visceral peritoneal thickening, ascites, or omental masses. Although these features may raise suspicion of MPM, a biopsy is necessary to confirm the diagnosis. Therefore, due to the rarity of this disease and its nonspecific signs or symptoms, MPM is difficult to diagnose, and the prognosis remains poor.

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Multicomponent reactions are of utmost importance at generating a unique, wide, and complex chemical space. Herein we describe a novel multicomponent approach based on the combination of the isonitrile-tetrazine (4+1) cycloaddition and the Ugi four-component reaction to generate pyrazole amide derivatives. The scope of the reaction as well as mechanistic insights governing the 4H-pyrazol-4-imine tautomerization are provided. This multicomponent process provides access to a new chemical space of pyrazole amide derivatives and offers a tool for peptide modification and stapling.

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Herpetic esophagitis (HE) is an esophageal infection caused by herpes simplex virus (HSV). Although less common, it can occasionally affect immunocompetent hosts. It can manifest as odynophagia and/or dysphagia and should lead to an investigation by upper digestive endoscopy with a biopsy. The authors report a case of a 65-year-old man with a past medical history relevant for schizophrenia, oligophrenia, and malnutrition, and no other history or evidence of immunosuppression, who presented with severe dysphagia over weeks and recent episodes of food aspiration with consequent pneumonia. An upper gastrointestinal endoscopy was performed, revealing severe stenosis at the level of the gastroesophageal junction with scar tissue, not transposable with the endoscope. The biopsy led to the diagnosis of hepatic esophagitis. Despite the immunocompetent status (excepting only the risk factor malnutrition) and treatment with acyclovir, with initial clinical improvement, the patient died a few weeks after diagnosis after multiple respiratory complications such as nosocomial infection. This case highlights that herpetic esophagitis is sometimes observed in immunocompetent hosts. HE has a self-limited course, with severe complications more frequent in immunosuppressed patients. However, it is also important to suspect this condition in immunocompetent patients and look for risk factors, given the potential morbidity this disease entails. In this group of patients, the presence of predisposing factors and associated comorbidities, such as malnutrition, alcohol consumption, or use of corticosteroids, have been associated with the development of viral esophagitis (including HE). HE remains a clinical challenge, especially in patients with risk factors for immunosuppression, such as malnutrition, as in the reported case.

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Neural tissue-related illnesses have a high incidence and prevalence in society. Despite intensive research efforts to enhance the regeneration of neural cells into functional tissue, effective treatments are still unavailable. Here, a novel therapeutic approach based on vertically aligned carbon nanotube forests (VA-CNT forests) and periodic VA-CNT micropillars produced by thermal chemical vapor deposition is explored. In addition, honeycomb-like and flower-like morphologies are created. Initial viability testing reveals that NE-4C neural stem cells seeded on all morphologies survive and proliferate. In addition, free-standing VA-CNT forests and capillary-driven VA-CNT forests are created, with the latter demonstrating enhanced capacity to stimulate neuritogenesis and network formation under minimal differentiation medium conditions. This is attributed to the interaction between surface roughness and 3D-like morphology that mimics the native extracellular matrix, thus enhancing cellular attachment and communication. These findings provide a new avenue for the construction of electroresponsive scaffolds based on CNTs for neural tissue engineering.

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The demand for new biomass-derived fine and commodity chemicals propels the discovery of new methodologies and synthons. Whereas furfural and 5-hydroxymethylfurfural are cornerstones of sustainable chemistry, 3-acetamido-5-acetyl furan (3A5AF), an N-rich furan obtained from chitin biomass, remains unexplored, due to the poor reactivity of the acetyl group relative to previous furanic aldehydes. Here we developed a reactive 3-acetamido-5-furfuryl aldehyde (3A5F) and demonstrated the utility of this synthon as a source of bio-derived nitrogen-rich heteroaromatics, carbocycles, and as a bioconjugation reagent.

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Spinal cord injury (SCI) is an as yet untreatable neuropathology that causes severe dysfunction and disability. Cell-based therapies hold neuroregenerative and neuroprotective potential, but, although being studied in SCI patients for more than two decades, long-term efficacy and safety remain unproven, and which cell types result in higher neurological and functional recovery remains under debate. In a comprehensive scoping review of 142 reports and registries of SCI cell-based clinical trials, we addressed the current therapeutical trends and critically analysed the strengths and limitations of the studies. Schwann cells, olfactory ensheathing cells (OECs), macrophages and various types of stem cells have been tested, as well as combinations of these and other cells. A comparative analysis between the reported outcomes of each cell type was performed, according to gold-standard efficacy outcome measures like the ASIA impairment scale, motor and sensory scores. Most of the trials were in the early phases of clinical development (phase I/II), involved patients with complete chronic injuries of traumatic aetiology and did not display a randomized comparative control arm. Bone marrow stem cells and OECs were the most commonly tested cells, while open surgery and injection were the main methods of delivering cells into the spinal cord or submeningeal spaces. Transplantation of support cells, such as OECs and Schwann cells, resulted in the highest ASIA Impairment Scale (AIS) grade conversion rates (improvements in ∼40% of transplanted patients), which surpassed the spontaneous improvement rate expected for complete chronic SCI patients within 1 year post-injury (5-20%). Some stem cells, such as peripheral blood-isolated and neural stem cells, offer potential for improving patient recovery. Complementary treatments, particularly post-transplantation rehabilitation regimes, may contribute highly to neurological and functional recovery. However, unbiased comparisons between the tested therapies are difficult to draw, given the great heterogeneity of the design and outcome measures used in the SCI cell-based clinical trials and how these are reported. It is therefore crucial to standardize these trials when aiming for higher value clinical evidence-based conclusions.

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The Lane-Hamilton syndrome (LHS) is an extremely rare association between celiac disease (CD) and idiopathic pulmonary hemosiderosis (IPH), with only a few cases reported in the literature. The authors report a case of a 32-year-old man with Down syndrome who presented to the emergency department with a history of hemoptysis and chronic diarrhea. The complementary investigation revealed iron deficiency anemia and features suggestive of diffuse alveolar hemorrhage on computed tomography (CT) scan of the chest. After excluding all competing diagnosis, the IPH diagnosis was made. The biopsy of the small intestine confirmed CD and the diagnosis of LHS was established. A gluten-free diet and steroids were given to the patient with a very good clinical response. Since there is an established association between IPH and CD, if the diagnosis of IPH is made, it's recommended to screen for CD even in patients without gastrointestinal symptoms.

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Fluorescence imaging is a powerful and widely used method to visualize and study living organisms. However, fungi are notoriously difficult to visualize using fluorescence microscopy, given that their cell wall represents a diffusion barrier, and the synthetic organic dyes available are very limited when compared to molecular probes available for other organisms. Moreover, these dyes are usually available in only one colour, preventing co-staining experiments. To fill this gap, curcumin-based molecular probes were designed based on the rationale that curcumin is fluorescent and has moderate toxicity toward fungi, implying its ability to cross the cell wall to reach targets in the intracellular compartments. A family of boron diketonate complexes was synthesized, based on a curcumin backbone, tuning their emission color from blue to red. These probes did not present noticeable toxicity to filamentous fungus and, when applied to their visualization, readily entered the cells and precisely localized in sub-cellular organelles, enabling their visualization.

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Unprovoked venous thromboembolism (VTE) may be the earliest manifestation of cancer. According to recent studies, approximately 5% of patients with unprovoked VTE will be diagnosed with cancer within the first year of follow-up. Although screening extensively at the time of VTE diagnosis is attractive for clinicians, current clinical guidance documents suggest only a limited cancer screening strategy. The authors describe a rare case of Krukenberg tumor of the ovary arising from a primary gastric adenocarcinoma whose first sign was an unprovoked venous thrombosis of the upper extremity.