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The COVID-19 lockdown affected children, especially those with autism spectrum disorder, due to the disruption in rehabilitation and educational activities. We conducted a cross-sectional study of 315 preschool-aged children, 35 of which had autism, to investigate this impact. A questionnaire was administered to explore socio-demographic status, familiar/home environment, and COVID-19 exposure. The clinical features of autistic subjects were also examined. Seven variables were considered to describe the effect of pandemic: "Remote learning, Behavior changes, Home activities, Sleep habits, Night awakenings, Physical activity, Information about the virus." The lockdown had a significant impact on Remote learning, Behavior changes, and Information about the virus in participants with autism. Moreover, we found a worsening in repetitive movements, echolalia, restricted interests, and aggressive behaviors.

Abstract S‐adenosylhomocysteine hydrolase deficiency is an autosomal recessive inborn error of metabolism affecting methylation by disrupting the methionine cycle. Its clinical spectrum spans from severe perinatal encephalomyopathy and liver failure to asymptomatic course in patients with isolated hypermethioninemia. We present two new cases of S‐adenosylhomocysteine hydrolase deficiency from Pakistani origin clinically asymptomatic at presentation. Both siblings showed mild chronic liver failure and elevation of creatine kinase. The older patient presented at 6 years of age with isolated verbal processing difficulty and mild diffuse leukodystrophy, reversible 12 months after introduction of methionine dietary restriction. The patient showed subtle atrophy in the muscle MRI at the age of 7 years. S‐adenosylhomocysteine hydrolase deficiency was confirmed with homozygous missense variant c.146G>A (p.Arg49His) in the AHCY gene, a genotype previously reported in Pakistani patients with mild presentation. Dietary methionine restriction decreased plasma methionine but not plasma S‐adenosylhomocysteine and S‐adenosylmethionine. This work expands the mild spectrum of S‐adenosylhomocysteine hydrolase deficiency with no noticeable clinical symptoms in children, highlighting a specific hotspot variant from South Asia. This mild form of the disease is likely underdiagnosed and raises the question of therapeutic management to prevent long‐term complications documented in the literature, such as hepatocellular carcinoma and myopathy in early adulthood.

IntroductionParkinson’s disease (PD) is commonly characterized by severe dopamine (DA) depletion within the substantia nigra (SN) leading to a myriad of motor and non-motor symptoms. One underappreciated and prevalent non-motor symptom, Parkinson’s disease-associated psychosis (PDAP), significantly erodes patient and caregiver quality of life yet remains vastly understudied. While the gold standard pharmacotherapy for motor symptoms Levodopa (LD) is initially highly effective, it can lead to motor fluctuations like LD-induced dyskinesia (LID) and non-motor fluctuations such as intermittent PDAP. One source of these fluctuations could be the serotonergic raphe nuclei and their projections. Serotonin (5-HT) neurons possess the machinery necessary to convert and release DA from exogenous LD. In DA-depleted brain regions these 5-HT projections can act as surrogates to the DA system initially compensating but chronically leading to aberrant neuroplasticity which has been linked to LID and may also contribute to non-motor fluctuations. In support, recent work from our lab established a positive relationship between LID and PDAP in parkinsonian rats. Therefore, it was hypothesized that normalizing 5-HT forebrain input would reduce the co-expression of LID and PDAP.MethodsTo do so, we expressed 5-HT projection specific inhibitory designer receptor exclusively activated by designer drugs (DREADDs) using Cre-dependent AAV9-hM4di in tryptophan hydroxylase 2 (TPH2)-Cre bilaterally 6-OHDA-lesioned rats. Thereafter we used the designer drug Compound 21 to selectively inhibit 5-HT raphe projections during LD treatment to modulate the expression of PDAP, assayed by prepulse inhibition (PPI) and LID, quantified by the abnormal involuntary movements (AIMs) test.ResultsOur results suggest that chemogenetic inhibition of 5-HT raphe-projecting cells significantly reduces LID without affecting stepping ability or established sensorimotor gating deficitsDiscussionOverall, this study provides further evidence for the complex influence of 5-HT raphe-projecting neurons on LD’s neurobehavioral effects.

Abstract Mitochondrial dysfunction represents one of the most common molecular hallmarks of both sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder caused by the selective degeneration and death of motor neurons. The accumulation of misfolded proteins on and within mitochondria, as observed for SOD1 G93A mutant, correlates with a drastic reduction of mitochondrial respiration and the inhibition of metabolites exchanges, including ADP/ATP and NAD+/NADH, across the Voltage-Dependent Anion-selective Channel 1 (VDAC1), the most abundant channel protein of the outer mitochondrial membrane. Here, we show that the AAV-mediated upregulation of VDAC1 in the spinal cord of transgenic mice expressing SOD1 G93A completely rescues the mitochondrial respiratory profile. This correlates with the increased activity and levels of key regulators of mitochondrial functions and maintenance, namely the respiratory chain Complex I and the sirtuins (Sirt), especially Sirt3. Furthermore, the selective increase of these mitochondrial proteins is associated with an increase in Tom20 levels, the receptor subunit of the TOM complex. Overall, our results indicate that the overexpression of VDAC1 has beneficial effects on ALS-affected tissue by stabilizing the Complex I-Sirt3 axis.

Abstract Background Non‐photosensitive trichothiodystrophies (TTDs) are a diverse group of genodermatoses within the subset of conditions known as “sulphur‐deficient brittle hair” syndromes. A part of them has only recently been identified, revealing novel causative genes and very rare phenotypes of these genetic skin disorders. At the same time, the molecular basis of previously published and unresolved cases has been revealed through the introduction of innovative genetic techniques. We have previously described the facial phenotype of patients with the Photosensitive form of TTD during childhood. This study marks the beginning of an effort to expand the analysis to include individuals of the same age who do not have photosensitivity. Methods A total of 26 facial portraits of TTD paediatric patients with Non‐photosensitivity from the literature were analysed using computer‐aided technologies, and their facial features were examined through a detailed clinical review. Results Distinct facial features were identified in both Photosensitive and Non‐photosensitive TTDs. Conclusion The present study has comprehensively elucidated the facial features in TTDs, encompassing the Non‐photosensitive clinical spectrum.

Abstract Instrumental activities of daily living (IADL) are significant health indicators closely related to executive functions and able to detect mild cognitive impairment. A decline in IADL usually precedes ADL limitation, including taking medications, and may therefore predict a cognitive decline. We aimed to investigate the association of patients’ IADL score with other clinical factors, with a particular focus on the presence of a caregiver, and the impact on adherence to androgen receptor pathway inhibitors (ARPIs) and survival outcomes within the Meet-URO 5—ADHERE study. It was a large prospective multicentre observational cohort study monitoring adherence to ARPIs in 234 metastatic castrate-resistant PC (mCRPC) patients aged ≥ 70. We observed an association between impaired IADL and lower geriatric G8 scores (p

Abstract How does threat from disease shape our cooperative actions and the social norms that guide such behaviour? To study these questions, we draw on a collective-risk social dilemma experiment that we ran before the emergence of the Covid-19 pandemic (Wave 1, 2018) and compare this to its exact replication, sampling from the same population, that we conducted during the first wave of the pandemic (Wave 2, 2020). Tightness-looseness theory predicts and evidence generally supports that both cooperation and accompanying social norms should increase, yet, we mostly did not find this. Contributions, the probability of reaching the threshold (cooperation), and the contents of the social norm (how much people should contribute) remained similar across the waves, although the strength of these social norms were slightly greater in Wave 2. We also study whether the results from Wave 1 that should not be affected by the pandemic—the relationship between social norms and cooperation and specific behavioural types—replicate in Wave 2 and find that these results generally hold. Overall, our work demonstrates that social norms are important drivers of cooperation, yet, communicable diseases, at least in the short term, have little or no effects on either.

Abstract Tropical Cyclones (TCs) cause significant socio-economic damages to the US and Caribbean coastal regions annually, making it important to understand TC risk at the local-to-regional scales. However, the short length of the observed record and the substantial computational expense associated with high-resolution climate models make it difficult to assess TC risk using either approach. To overcome these challenges, we developed a database of synthetic TCs using the Risk Analysis Framework for Tropical Cyclones (RAFT). The database includes 40,000 synthetic TC tracks, along-track intensities and storm-induced precipitation. TC tracks generated in RAFT are in reasonable agreement with the observed spatial distribution of TC tracks and basin-scale TC statistics. Specifically along the coast, spatial variations in TC crossing probability and extreme winds upon landfall are well-reproduced by RAFT with R-squared values of 0.81 and 0.73, respectively. In summary, the synthetic TC database constructed with RAFT provides a reasonable pathway for the robust assessment of North Atlantic TC wind and rainfall risks.

In this article, a sheet-beam type ring bar slow wave structure (RBSWS) capable of working at very low-voltage value is proposed. The structure is designed to work over the frequency range from 14 to 18 GHz with a cathodic voltage of 2.050 kV and a current of 100 mA. Simulation results for two 50-period sections, carried out by CST Studio Suite 2023, show a saturated output power of 30 W, a maximum gain of 0.795 dB/mm, and a radio frequency (RF) electronic efficiency higher than 15 %. The proposed structure is ideal for aerospace applications that usually require compact size, low weight and power consumption, while maintaining very high output power levels. Furthermore, this device is relatively easy to manufacture, making it a more accessible option than other structures that require complex and expensive manufacturing processes. Finally, the mechanical and thermal dissipation problems are kept under control thanks to the large surface contact between the slow wave structure and the dielectric rod realized in Boron Nitride.

Background/Objectives: Adolescence is an important period of psychophysical development. In this phase of life people acquire greater self-awareness and adopt behaviors that will later shape their lifestyle in adulthood. This study aimed to assess whether family structure can influence adolescents’ eating habits. Methods: Data were acquired from a survey titled ‘Italian Health Behaviour in School-aged Children’ (HBSC) given to a representative sample of Tuscan adolescents aged 11, 13, 15 and 17 years of age. Participants (3210) filled out a validated questionnaire answering questions about their eating habits and family structure. After adjusting for covariates, some interesting trends were highlighted in the survey results. Results: Adolescents living in single-mother families reported a lower intake of fruits (OR 0.68, 95% CI = 0.55–0.83) and vegetables (OR 0.66, 95% CI = 0.53–0.81) and a higher intake of sugar-added soft drinks (OR 1.33, 95% CI = 1.08–1.64). Living in a mother and stepfather family was associated with a higher intake of sugar-added soft drinks (OR 1.53, 95% CI = 1.02–2.28), whereas living in a father and stepmother family was associated only with a lower intake of fruits (OR 0.48, 95% CI = 0.26–0.87). Participants living with other family types reported a lower intake of vegetables (OR 0.68, 95% CI = 0.47–0.98). Conclusions: The results of this study show a correlation between family structure and adolescents’ eating habits.

Defects in the mitochondrial DNA (mtDNA) cause mtDNA depletion syndrome (MTDPS), a subclass of mitochondrial disorders that are genetically and phenotypically heterogeneous. MTDPS is a rare autosomal recessive disease caused by a mutation of a nuclear gene named FBXL4 (F-box and leucine-rich repeat protein 4), located on chromosome 6. This nuclear-encoded mitochondrial protein plays a vital role in mitochondrial bioenergetics, mtDNA maintenance, and mitochondrial dynamics. Pathogenic variants in the FBXL4 gene reduce mtDNA synthesis, resulting in a large decrease in the mtDNA content in cells, which is essential for normal energy production. These pathogenic variants in the FBXL4 gene are associated with an encephalomyopathy MTDPS type 13 (MTDPS13), a rare and severe mul­tisystemic disorder mainly characterized by infant-onset encephalomyopathy and lactic acidosis, developmental delay, hypotonia with feeding difficulties and failure to thrive. Other features may include the central nervous system and the ophthalmologic, cardiac, gastrointestinal, genito­urinary, and immunological systems. Herein, we report the case of an infant born to consanguineous Pakistani parents with an early onset of severe lactic acidosis, hypotonia, feeding difficulties, hypertro­phic cardiomyopathy, supraventricular tachycardia, and transient neutro­penia harboring a homozygous variant in the FBXL4 (c.370C>T [p.Q124*]) gene. This variant was identified in the patient’s parents in heterozygosity. He started medical treatment (with coenzyme Q10, propranolol, and sodium bicarbonate) and multidisciplinary support. As a result, a progressive improvement in postural tone and feeding autonomy was observed during the first months of life. Therefore, encephalomyopathy MTDPS13 should be suspected when dealing with patients with severe congenital lactic acidosis and developmental impairment.

Background and objectives: As microbes are developing resistance to antibiotics, natural, botanical drugs or traditional herbal medicine are presently being studied with an eye of great curiosity and hope. Hence, complementary and alternative treatments for uncomplicated pelvic inflammatory disease (uPID) are explored for their efficacy. Therefore, this study determined the therapeutic efficacy and safety of Sesamum indicum Linn seeds with Rosa damascena Mill Oil in uPID with standard control. Additionally, we analyzed the data with machine learning.Materials and methods: We included 60 participants in a double-blind, double-dummy, randomized standard-controlled study. Participants in the Sesame and Rose oil group (SR group) (n = 30) received 14 days course of black sesame powder (5 gm) mixed with rose oil (10 mL) per vaginum at bedtime once daily plus placebo capsules orally. The standard group (SC), received doxycycline 100 mg twice and metronidazole 400 mg thrice orally plus placebo per vaginum for the same duration. The primary outcome was a clinical cure at post-intervention for visual analogue scale (VAS) for lower abdominal pain (LAP), and McCormack pain scale (McPS) for abdominal-pelvic tenderness. The secondary outcome included white blood cells (WBC) cells in the vaginal wet mount test, safety profile, and health-related quality of life assessed by SF-12. In addition, we used AdaBoost (AB), Naïve Bayes (NB), and Decision Tree (DT) classifiers in this study to analyze the experimental data.Results: The clinical cure for LAP and McPS in the SR vs SC group was 82.85% vs 81.48% and 83.85% vs 81.60% on Day 15 respectively. On Day 15, pus cells less than 10 in the SR vs SC group were 86.6% vs 76.6% respectively. No adverse effects were reported in both groups. The improvement in total SF-12 score on Day 30 for the SR vs SC group was 82.79% vs 80.04% respectively. In addition, our Naive Bayes classifier based on the leave-one-out model achieved the maximum accuracy (68.30%) for the classification of both groups of uPID.Conclusion: We concluded that the SR group is cost-effective, safer, and efficacious for curing uPID. Proposed alternative treatment (test drug) could be a substitute of standard drug used for Female genital tract infections.

Copper is an essential element in the diet of mammals, including humans. It plays an important role in the physiological regulation of various enzymes and is consequently involved in several biological processes such as angiogenesis, oxidative stress regulation, neuromodulation, and erythropoiesis. Copper is essential for facilitating the transfer of iron from cells to the bloodstream, which is necessary for proper absorption of dietary iron and the distribution of iron throughout the body. In particular, patients with end-stage renal failure who require renal replacement therapy are at increased risk for disorders of copper metabolism. Many studies on hemodialysis, peritoneal dialysis, and kidney transplant patients have focused on serum copper levels. Some reported mild deficiency, while others reported elevated levels or even toxicity. In some cases, it has been reported that alterations in copper metabolism lead to an increased risk of cardiovascular disease, malnutrition, anemia, or mielopathy. The aim of this review is to evaluate the role of copper in patients undergoing hemodialysis and its potential clinical implications.

Background: Pulmonary hypertension (PH) often complicates mitral stenosis (MS). The prognostic impact of pulmonary vascular resistance (PVR) in MS patients remains unclear. Previous study has demonstrated the prognostic impact of right atrial pressure (RAP) in patients with primary PH. We aim to determine the prognostic impact of PVR and RAP in patients with rheumatic MS undergoing percutaneous mitral balloon valvuloplasty (PMBV). Methods: A total of 58 patients with symptomatic severe rheumatic MS who underwent PMBV between 2016 and 2020 were included. Patients were divided into two groups: PVR ≤ 2WU (N = 26) and PVR > 2WU (N = 32). The composite endpoint included death, reintervention or persistent NYHA functional class III-IV during follow-up. Results: The median age was 50 (42–60) years, with 82.8% being female. Median pulmonary artery systolic pressure (PASP) was 42 (35–50.5) mmHg. Patients with PVR ≤ 2WU had lower PASP on both echocardiogram and catheterization. The PMBV success rate was 75.9%. Multivariate analysis, adjusted for PVR, showed RAP as the only independent predictor of the composite endpoint (HR:1.507, 95% CI:1.015–2.237, p = 0.042). The optimal RAP cutoff was 9.5 mmHg (HR:3.481, 95% CI:1.041–11.641; p = 0.043). Conclusions: RAP was an independent predictor of adverse outcomes in patients with rheumatic MS undergoing PMBV, while PVR did not show prognostic significance. These findings suggest that the prognostic value of PVR may be lower than expected.

In invisible orthodontics, the role of composite attachments in facilitating complex tooth movements is crucial. This study, which evaluates the efficacy of a novel clinical attachment procedure, holds significant implications for the field. The technique used two templates (one pre-drilled and the other pre-loaded with high-viscosity composites) and was compared with the standard procedure. Fifty attachments were planned for four dental arch prototypes. Dental impressions were taken using digital scans for virtual planning and after tested techniques. The stereolithographic files (STL) obtained were aligned with those of the virtual planning, and a colorimetric map was used to evaluate the composite resin’s maximum excess and defect deviation. The enamel–resin interfaces were observed by scanning electron microscopy (SEM). The Fisher test for the distribution of detachments and morphological defects and the Mann–Whitney test for the maximum values of excess and defect were used. No significant results were found between groups for morphological defects and detachments, and the maximum values of defect and excess were reported. SEM images for the experimental technique showed integrated adhesion. This innovative procedure, which has proven reliable and operationally straightforward, holds promise, instilling confidence in its practicality and potential to advance the field of orthodontics.

Three-dimensional (3D) bioprinting technology enables the controlled deposition of cells and biomaterials (i.e., bioink) to easily create complex 3D biological microenvironments. Silk fibroin (SF) has recently emerged as a compelling bioink component due to its advantageous mechanical and biological properties. This study reports on the development and optimization of a novel bioink for extrusion-based 3D bioprinting and compares different bioink formulations based on mixtures of alginate methacrylate (ALMA), gelatin and SF. The rheological parameters of the bioink were investigated to predict printability and stability, and the optimal concentration of SF was selected. The bioink containing a low amount of SF (0.002% w/V) was found to be the best formulation. Light-assisted gelation of ALMA was exploited to obtain the final hydrogel matrix. Rheological analyses showed that SF-enriched hydrogels exhibited greater elasticity than SF-free hydrogels and were more tolerant to temperature fluctuations. Finally, MG-63 cells were successfully bioprinted and their viability and proliferation over time were analyzed. The SF-enriched bioink represents an excellent biomaterial in terms of printability and allows high cell proliferation over a period of up to 3 weeks. These data confirm the possibility of using the selected formulation for the successful bioprinting of cells into extracellular matrix-like microenvironments.

We conducted a cross-sectional study to compare the impact of social distancing and lifestyle changes that occurred during Corona Virus Disease 2019 (COVID-19) lockdown on children and adolescents with and without Neurodevelopmental Disorders (NDDs). An online questionnaire was administered in order to investigate the effects of NDD condition, socio-demographic status, familiar/home environment and COVID-19 exposure on their lives during a two months period of social isolation. We used logistic regression, focusing on five endpoints (remote learning, lifestyle, stress/anxiety, sociality, scolding) to define the extent of these effects. Most questions were paired up to parents and children, to verify the occurrence of agreement. 8305 questionnaires were analyzed, 1362 of which completed by NDDs and 6943 by controls. Results showed that the presence of a NDD, compared to controls, had a significant impact on: Remote Learning (i.e. subjects with NDDs experienced more difficulties in attending online classes and studying), Sociality (i.e. subjects with NDDs missed their schoolmates less), Scolding (i.e. subjects with NDDs were scolded more often) and Anxiety (i.e. subjects with NDDs were perceived by their parents as more anxious). Substantial agreement between parents and children arose from questions concerning Remote learning, Lifestyle and Scolding. The current study actually points out that having a NDD gives account for a stronger influence on school performance and on behavioral and psychological aspects, during a two months lockdown. Such results may provide useful information to governments and school authorities on how carrying through supportive strategies for youth affected by NDDs., Author(s): Cristiano Termine [sup.1] [sup.2] , Linda Greta Dui [sup.3] , Laura Borzaga [sup.1] , Vera Galli [sup.4] , Rossella Lipari [sup.1] , Marta Vergani [sup.5] , Valentina Berlusconi [sup.1] [...]