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Background: Treatment-resistant obsessive–compulsive disorder (OCD) is a heterogeneous and clinically challenging condition. Growing evidence suggests alterations in glutamatergic signaling within cortico–striatal–thalamo–cortical circuits, including those involving medium spiny neurons (MSNs), as well as genetic factors affecting synaptic organization, although the biological mechanisms underlying differential treatment response remain incompletely understood. Methods: This multicenter study presents a translational research framework aimed at investigating potential molecular and cellular correlates of treatment response in a cohort of patients with OCD, stratified according to their response to pharmacological treatments and transcranial magnetic stimulation (TMS). Peripheral blood mononuclear cells from clinically defined subgroups are reprogrammed into human induced pluripotent stem cells and differentiated into MSN-enriched neuronal cultures, enabling in vitro investigation of morphological, biochemical, and transcriptomic features associated with different clinical profiles. Optogenetic and pharmacological stimulation paradigms are applied to probe selected aspects of neuronal activation in vitro, providing a controlled and simplified experimental framework to explore cellular responses under different treatment conditions. By integrating clinical phenotyping with patient-derived cellular models, this study establishes a translational platform for hypothesis generation in the investigation of treatment response in OCD. Results and Conclusions: Preliminary clinical observations from an initial cohort undergoing neuromodulation are also reported to document feasibility and early clinical implementation of the study, providing an initial characterization of the cohort.

Background: Animal-assisted activities (AAA) are participative interventions, designed to lower hospitalization-related stress and anxiety, enhance communicative readiness, improve quality of life and encourage human–animal interaction. The aim of the present study was to evaluate AAA effects in the context of intensive rehabilitation of patients with spinal cord injury (SCI), traumatic brain injury (TBI), stroke. Methods: AAA in this study were structured by a local specialized association, for small groups of patients (5/7 a time), biweekly; each session lasted 60 min. Each patient participated in 10 sessions of AAA. Evaluation rating scales were administered at T0 (before the first session) and T1 (after the last session, five weeks later) as follows: Neurobehavioral Rating Scale (NRS) in case of patient with stroke/TBI without disorder of consciousness; Hospital Anxiety and Depression Scale (HADS) for SCI patients. Results: A total of 50 patients concluded the study. NRS score for joined TBI and stroke populations varied from a T0 mean value of 32.34 [C.I. 26.83–37.35] to 17.21 [C.I. 12.66–21.76] (46.7%); this difference proved to be statistically significant (p = 0.000). Stroke patients had a 57.6% NRS lowering by mean 28.10 [C.I. 20.55–35.65] points to 12 [C.I. 6.6–17.36], which was significant (p = 0.000); similarly, TBI patients showed a mean decrease of 35.8% points from the initial 41.6 points [C.I. 37.29–45.93] to 26.76 [C.I. 21.94–31.59] (p = 0.002). As for HADS scores a smaller improvement was found in the cohort of SCI patients: anxiety registered a 1 mean point decrease at T1 (21.5%), from the initial 6.5 points [C.I. 3.80–9.34] to 5.1 ones [C.I. 3.17–7.11]. This variation was near the threshold of significance (p = 0.05). Depression domain, instead, improved by 2.35 mean points (37%), from the 6.35 initial points [C.I. 3.45–9.26] to the final 4 [C.I. 2.15–5.98] with reaching of a significant p value (p = 0.03). ANCOVA did not confirm this last value and showed no influence of age and gender on outcome variations. Discussion: AAA showed preliminary evidence to decrease neurobehavioral disorders in patients with high-complexity neurological diseases, particularly stroke and TBI. The role of AAA in SCI patients remains unclear. Future studies should address confounders’ role for these populations, particularly severity of disease. Furthermore, AAA interventions will have to be studied on larger samples, deepening the exact phase to introduce AAA for neurological patients. Lastly, qualitative studies are needed to explore patients’ lived experiences.

Cytomegalovirus (CMV) infection during pregnancy is the leading cause of congenital infection subsequent to viral transplacental transmission. CMV placental infection can contribute to the development of adverse outcomes likely through placental dysfunction. This case report shows the potential utility of angiogenic markers, such as placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), in assessing CMV-related placental involvement and monitoring the effect of antiviral therapy on placental function, and highlights the possibility of integrating these markers into the clinical management of CMV infection.

Downy mildew, caused by the oomycete Plasmopara viticola , is one of the diseases causing the most severe economic losses to grapevine ( Vitis vinifera ) production. To date, the application of fungicides is the most efficient method to control the pathogen and the implementation of novel and sustainable disease control methods is a major challenge. RNA interference (RNAi) represents a novel biotechnological tool with a great potential for controlling fungal pathogens. Recently, a candidate susceptibility gene ( VviLBDIf7 ) to downy mildew has been identified in V. vinifera . In this work, the efficacy of RNAi triggered by exogenous double-stranded RNA (dsRNA) in controlling P. viticola infections has been assessed in a highly susceptible grapevine cultivar (Pinot noir) by knocking down VviLBDIf7 gene. The effects of dsRNA treatment on this target gene were assessed by evaluating gene expression, disease severity, and development of vegetative and reproductive structures of P. viticola in the leaf tissues. Furthermore, the effects of dsRNA treatment on off-target ( EF1α , GAPDH , PEPC , and PEPCK ) and jasmonic acid metabolism ( COI1 ) genes have been evaluated. Exogenous application of dsRNA led to significant reductions both in VviLBDIf7 gene expression, 5 days after the treatment, and in the disease severity when artificial inoculation was carried out 7 days after dsRNA treatments. The pathogen showed clear alterations to both vegetative (hyphae and haustoria) and reproductive structures (sporangiophores) that resulted in stunted growth and reduced sporulation. Treatment with dsRNA showed signatures of systemic activity and no deleterious off-target effects. These results demonstrated the potential of RNAi for silencing susceptibility factors in grapevine as a sustainable strategy for pathogen control, underlying the possibility to adopt this promising biotechnological tool in disease management strategies.

COVID-19 and preeclampsia (preE) share the ANG-II mediated endothelial dysfunction, resulting from a significant dysregulation of RAS and an imbalanced proportion of anti-angiogenic and pro-angiogenic soluble plasmatic factors. Of note, an increased incidence of preE has been reported among COVID-19-infected mothers compared to the general pregnant population. The two most promising angiogenic markers are the soluble fms-like tyrosine kinase receptor-1 (sFlt-1), the major antiangiogenic factor, and the placental growth factor (PlGF), a powerful angiogenic factor. Since these markers have proven useful in the prediction, diagnosis, and severity of preE, this study aimed to evaluate their maternal serum levels in pregnancies complicated by SARS-CoV-2 infection and to assess their potential use to guide the management of these women. A retrospective analysis of SARS-CoV-2-positive pregnant women was performed. The serum levels of sFlt-1 and PlGF were collected at the diagnosis of SARS-CoV-2 infection at the hospital, before the beginning of steroid/hydroxychloroquine and/or antithrombotic therapy. The sFlt-1/PlGF ratio was stratified using cut-off values clinically utilized in the diagnosis and prediction of preE (low < 38, intermediate 38–85/110* and high >85/110*, * if before or after the 34th week of gestation). A total of 57 women were included, of whom 20 (35%) had signs and symptoms of COVID-19 at hospital presentation and 37 (65%) were asymptomatic. None were vaccinated. The mean gestational age at diagnosis of SARS-CoV-2 infection was 32 weeks in symptomatic patients and 37 weeks and 5 days in asymptomatic ones (p = 0.089). sFlt-1 serum levels were higher in SARS-CoV-2 positive asymptomatic patients compared to women with COVID-19 related symptoms (4899 ± 4357 pg/mL vs. 3187 ± 2426 pg/mL, p = 0.005). sFlt-1/PlGF at admission was <38 in 18 of the 20 symptomatic women (90%) compared to 22 (59%) of the asymptomatic patients (p = 0.018). Of note, two of the three women admitted to the intensive care unit had a very low ratio (<2). In turn, rates of patients with sFlt-1/PlGF at admission > 85/110 were not significantly different between the two groups: 11% in asymptomatic patients (4/37) vs. none of the symptomatic patients (p = 0.286), and all of them presented a placental dysfunction, like preE (n = 1) and FGR (n = 3). Of note, there were no stillbirths or maternal or neonatal deaths among symptomatic patients; also, no cases of preE, FGR, or small for gestational age neonates were diagnosed. In conclusion, our data suggest that SARS-CoV-2 infection during pregnancy could influence the angiogenic balance. A significant pathological alteration of the sFlt-1/PlGF ratio cannot be identified during the symptomatic phase; however, if left untreated, SARS-CoV-2 infection could potentially trigger placental dysfunction.

Endothelial dysfunction is a crucial event in the early pathogenesis of cardiovascular diseases and is linked to magnesium (Mg) deficiency. Indeed, in endothelial cells, low Mg levels promote the acquisition of a pro-inflammatory and pro-atherogenic phenotype. This paper investigates the mechanisms by which Mg deficiency promotes oxidative stress and affects endothelial behavior in human umbilical vascular endothelial cells (HUVECs). Our data show that low Mg levels trigger oxidative stress initially by increasing NAPDH oxidase activity and then by upregulating the pro-oxidant thioredoxin-interacting protein TXNIP. The overproduction of reactive oxygen species (ROS) activates NF-κB, leading to its increased binding to the inducible nitric oxide synthase (iNOS) promoter, with the consequent increase in iNOS expression. The increased levels of nitric oxide (NO) generated by upregulated iNOS contribute to disrupting endothelial cell function by inhibiting growth and increasing permeability. In conclusion, we provide evidence that multiple mechanisms contribute to generate a pro-oxidant state under low-Mg conditions, ultimately affecting endothelial physiology. These data add support to the notion that adequate Mg levels play a significant role in preserving cardiovascular health and may suggest new approaches to prevent or manage cardiovascular diseases.

Despite therapeutic advances, multiple myeloma (MM) remains characterized by progression and relapse, underscoring the need for reliable biomarkers for early detection and monitoring. Extracellular vesicles (EV) are cell‐derived, lipid bilayer–enclosed particles that mediate intercellular communication and circulate in body fluids, making them promising biomarkers. This study compares the proteome of MM‐derived EV with parental cells and evaluates whether EV represent a superior source of MM‐specific biomarkers. We used high‐resolution mass spectrometry to analyze MM cell lines and their EV. Cell line–derived EV offer a cleaner, tumor‐specific protein profile, minimizing background from nonmalignant cells and improving biomarker accuracy. MS datasets were subjected to bioinformatic analysis, followed by functional enrichment using gene set libraries such as Gene Ontology, Jensen Compartments, TRRUST and DisGeNET, to extend interpretation beyond limited protein databases. Compared to cellular proteins, the EV proteome was enriched in functions related to oncogenic signaling, transcriptional regulation and MM pathophysiology, strengthening its potential as a cancer‐related biomarker source. DisGeNET identified cancer‐related proteins that were further evaluated to identify MM‐specific candidates analyzing MM patients' gene expression databases containing clinical data. This led to the identification of macrophage migration inhibitory factor (MIF) and prohibitin. ELISA on plasma from MM patients detected significantly increased MIF levels in smoldering and active MM compared with healthy donors. Approximately half of circulating MIF was EV‐associated in MM patients, indicating that MIF is distributed between vesicular and soluble plasma fractions and underscoring its potential as a noninvasive biomarker for MM early detection and patient monitoring.

Xylella fastidiosa is a fastidious Gram-negative bacterium that is associated with several important plant diseases, and is regulated as a quarantine pest in many countries where strategies are implemented to prevent its introduction and spread. To enact efficient quarantine measures, effective and early detection of the pathogen are essential, especially because global trade of goods increases the risks of introduction of alien pathogens. this study aimed to adapt two qPCR-based diagnostic methods (SYBR Green and Probe based qPCR), already in use to detect X. fastidiosa, for use with a nanoplate based digital PCR assay. Detection of the pathogen using the two digital PCR assays (EvaGreen- and Probe-based) was similar to standard qPCR, giving 100% sensitivity, specificity, and accuracy, while providing accurate absolute quantification of the pathogen when using experimental samples that had low concentrations of host DNA. Using undiluted plant DNA added with low concentrations of X. fastidiosa, only the TaqMan method maintained satisfactory performance and quantification, and is therefore preferred. These results are a first step demonstrating the usefulness of nanoplate-based digital PCR for detection of plant pathogens, which allows greater throughput than qPCR, reducing the time and cost of diagnostic assays.

Nirsevimab is a long-acting monoclonal antibody designed to prevent infections due to respiratory syncytial virus (RSV). Here we report on a retrospective, multicenter study encompassing a total of 19 Italian neonatal and pediatric centers evaluating the epidemiology of lower respiratory tract infection (LRTI)-related hospitalizations in infants younger than 2 years during the first RSV season following the introduction of nirsevimab prophylaxis. A total of 401 hospitalizations were reported, with 40.4% being in children with previous prophylaxis with nirsevimab. Respiratory syncytial virus was the most frequently identified pathogen (47.5%), followed by rhinovirus/enterovirus (20.2%) and human metapneumovirus (hMPV; 6.9%). In multivariable analyses adjusted for age, sex, and month of diagnosis, prior nirsevimab immunization was associated with a significantly reduced likelihood of RSV-related hospitalization (adjusted odds ratio [aOR], 0.259; 95% CI, 0.157–0.427), corresponding to an estimated effectiveness of 74.1% (95% CI, 57.3–84.3). Conversely, nirsevimab-immunized infants showed increased odds of hospitalization due to hMPV (aOR, 2.490; 95% CI, 1.019–6.085) and rhinovirus/enterovirus (aOR, 2.573; 95% CI, 1.424–4.650). Lower respiratory tract infections associated with hMPV predominantly occurred outside the typical RSV season, being associated with moderate-to-severe clinical presentations. These findings confirm the real-world effectiveness of nirsevimab against RSV hospitalizations, also highlighting the need for the continued surveillance of non-RSV respiratory pathogens in the context of universal RSV immunoprophylaxis.

COVID-19 has been primarily identified as a respiratory infection characterized by signs and symptoms associated with the dysfunction of the renin-angiotensin system (RAS). This is attributed to the SARS-CoV-2 virus invading the respiratory mucosa via angiotensin-converting enzyme 2 (ACE2), which is an important element of the RAS. Meanwhile, preeclampsia is an obstetric pathology that, surprisingly, resembles the pathology of COVID-19. It is a systemic syndrome that occurs during the second half of pregnancy and is determined to be a major cause of maternal and perinatal morbidity and mortality. This disease typically presents with new-onset hypertension and proteinuria or other specific end-organ dysfunctions. RAS-mediated mechanisms may explain its primary clinical-pathological features, which are suggestive of an underlying microvascular dysfunction in both diseases, with induction of vasculopathy, coagulopathy, and inflammation. In this report, we review the medical literature on this subject. Further, the underlying similarities between the two conditions are discussed to assess preeclampsia as a model for COVID-19. These considerations are valid in the case of original SARS-CoV-2 primary infection. Emerging SARS-CoV-2 variants as well as the vaccination could alter various aspects of the virus biology, including human ACE-2 receptor binding affinity and therefore the RAS mediated consequences.