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Coxiella burnetii is the causative agent of Q fever. The main reservoirs for this bacterium, which can lead to human infection, in our region are typically cattle, goats, and sheep. In animals, C. burnetii infection is often detected due to reproductive problems. European Member States are required to report confirmed cases annually, but the lack of uniform reporting methods makes the data rather inconsistent. The Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise is involved in official controls to identify the causes of abortions, monitor suspected or positive herds, evaluate suspected infections in pets and humans, monitor the spread in wildlife, etc. In this paper, we summarize the presence of C. burnetii over the last five years (2019-2023). Additionally, a detailed overview of C. burnetii infection in wild and domestic animals is provided. Five hundred sixty animals-including cattle; goats; sheep; wild animals, such as deer, boars, wolves, roe deer, owls, and otters; buffalo; dogs; horses; cats; and a donkey-and six human samples were tested by real-time PCR on the transposase gene IS1111 to detect C. burnetii . The MST profile was identified in some of the samples. Outbreaks of C. burnetii occurred in four herds. In one of them, it was possible to follow the outbreak from inception to eradication by evaluating the effect of vaccination on real-time PCR Ct values. A total of 116 animals tested positive for C. burnetii , including 73 goats, 42 sheep, and one bovine. None of the other samples tested positive. The strains for which the ST was performed were identified as ST79, a strain that has been present in the area for more than ten years. The effect of vaccination on the reduction of positive samples and the variation of real-time PCR Ct values was evaluated in strict correlation.

Background: The balance between comprehensive intraoperative neurophysiological monitoring (IONM) for both upper and lower limbs while ensuring the reliability of motor evoked potentials (MEPs) is paramount in motor area surgery. It is commonly difficult to obtain good simultaneous stimulation of both upper and lower limbs. A series of factors can bias MEP accuracy, and inappropriate stimulation intensity can result in unreliable monitoring. The presented IONM technique is based on the concurrent use of both transcranial and cortical strip electrodes to facilitate simultaneous monitoring of both upper and lower limbs at optimized stimulation intensities to increase IONM accuracy during motor area surgery., Methods: Ten nonconsecutive motor area tumors were studied. Good visualization of both limbs was observed in the series at a low amperage (1.2 mA from the strip electrode and 165.3 mA from the transcranial electrode)., Results: Our analysis confirms concordance between the IONM data and postoperative outcomes. An MEP reduction >20% and >50% correlated with postoperative modified Rankin scale score changes without false-negative IONM findings., Conclusions: The technique was demonstrated to be accurate in providing a good simultaneous neurophysiological evaluation of both upper and lower limbs with an optimized and stimulation amplitude. The technique results in a low encumbrance of electrodes in the surgical field. Our results have confirmed the "proof of concept," its reliability and feasibility., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Usutu virus (USUV), an arbovirus from the Flaviviridae family, genus Flavivirus, has recently gained increasing attention because of its potential for emergence. After his discovery in South Africa, USUV spread to other African countries, then emerged in Europe where it was responsible for epizootics. The virus has recently been found in Asia. USUV infection in humans is considered to be most often asymptomatic or to cause mild clinical signs. However, a few cases of neurological complications such as encephalitis or meningo-encephalitis have been reported in both immunocompromised and immunocompetent patients. USUV natural life cycle involves Culex mosquitoes as its main vector, and multiple bird species as natural viral reservoirs or amplifying hosts, humans and horses can be incidental hosts. Phylogenetic studies carried out showed eight lineages, showing an increasing genetic diversity for USUV. This work describes the development and validation of a novel whole-genome amplicon-based sequencing approach to Usutu virus. This study was carried out on different strains from Senegal and Italy. The new approach showed good coverage using samples derived from several vertebrate hosts and may be valuable for Usutu virus genomic surveillance to better understand the dynamics of evolution and transmission of the virus., (© 2024. The Author(s).)

The cross-talk between the innate and adaptive immune response represents the first defense weapon against the threat of pathogens. Substantial evidence has shown a relationship between immune phenotype lymphocytes and COVID-19 disease severity and/or implication in susceptibility to SARS-CoV-2 infection. Recently, belonging to ABO blood groups has been investigated as a correlation factor to COVID-19 disease. This pilot study investigated lymphocyte typing in a cohort of blood donors to understand the underlying mechanism in SARS-CoV-2 infection linked to the blood group. The study cohort consisted of 20-64-year-old subjects, without comorbidities, from both sexes, who were COVID-19 vaccinated with previous or no infection history. Whole blood samples, collected at A.O.R.N. Sant'Anna and San Sebastiano Hospital (Campania Region), were processed by multiparametric cytofluorimetric assay, to characterize CD4+ helper and CD8+ cytotoxic T cell CD3+ subpopulations. The CD45RA, CCR7, CD27, CD28, CD57 and PD-1 markers were investigated to delineate the peripheral T-cell maturation stages. Differences were detected in ABO blood types in CD3+, CD4+ gated on CD3+, CD8+ and CD8+ gated on CD3+ percentage. These results contribute to identifying a memory cell "identikit" profile in COVID-19 disease, thus leading to a useful tool in precision medicine.

Background : In cancer care, the MLH1 gene is crucial for DNA mismatch repair (MMR), serving as a vital tumor suppressor. Evaluating MLH1 protein expression status, followed by analysis of MLH1 promoter methylation, has become a key diagnostic and prognostic approach. Our study investigates the complex link between MLH1 methylation and prognosis in endometrial adenocarcinoma (EA) patients. Methodology : MLH1 methylation status was accessed by a Pyrosequencing (PSQ) assay. Qualitative positivity for methylation was established if it exceeded the 11% cut-off; as well, a quantitative methylation analysis was conducted to establish correlations with clinicopathological data, relapse-free survival, and disease-free survival. Results: Our study revealed that 33.3% of patients without MLH1 methylation experienced relapses, surpassing the 23.3% in patients with methylation. Furthermore, 16.7% of patients without methylation succumbed to death, with a slightly higher rate of 17.6% in methylated patients. Qualitative comparisons highlighted that the mean methylation rate in patients experiencing relapse was 35.8%, whereas in those without relapse, it was 42.2%. This pattern persisted in disease-specific survival (DSS), where deceased patients exhibited a higher mean methylation level of 49.1% compared to living patients with 38.8%. Conclusions : Our findings emphasize the efficacy of PSQ for evaluating MLH1 methylation. While unmethylation appears to be associated with a higher relapse rate, the survival rate does not seem to be influenced by methylation. Quantitative percentages suggest that elevated MLH1 methylation is linked to relapse and mortality, though a study with a larger sample size would be essential for statistically significant results.

The COVID-19 pandemic impacted all areas of daily life, including medical care. Unfortunately, to date, no specific treatments have been found for the cure of this disease, and therefore, it is advisable to implement all possible strategies to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. There is sufficient evidence to demonstrate that immune response can be weakened by inadequate nutrition. Nutrition management and treatment are very important to enhance the immune response of an infected person against RNA viral infection. A complete nutritional assessment should include anthropometric, dietary, and laboratorial assessment, as well as a multidisciplinary discussion about the patient's clinical condition. In this way, it is possible to establish an individualized nutritional approach to contribute to improving clinical and nutritional prognoses. From this point of view, diet, through intake of vitamins and trace elements and maintaining adequate functioning of the intestinal barrier, can reduce the severity of the COVID-19 infection. In this study, we provide an overview of the effects of diet on COVID-19 infection in non-cancer patients. This notion needs to be further evaluated, and thus, identification, characterization, and targeting of the right nutrition principles related to the management of patients with COVID-19 are likely to improve outcomes and may prevent the infection or lead to a cure., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Intramedullary melanocytomas are exceedingly rare, with only twenty-four cases reported up to now. They present as local invasive tumors despite their benign biological behavior. Attempting a complete safe resection often results in severe post-operative neurological deficits, as in our case presented here., Methods: A systematic review was conducted across the PubMed and Scopus databases including studies published till February 2024., Results: A total of 19 studies were included, encompassing 24 cases. A similar distribution between sexes was noted (M:F 13:11), with ages ranging from 19 to 79 years. The thoracic segment was most affected, and intermediate-grade melanocytoma (19 cases) was the most common histotype. Radiographically, intramedullary melanocytomas usually appear as hyperintense hemorrhagic lesions peripheral to the central canal with focal nodular enhancement. Intraoperatively, they are black-reddish to tan and are tenaciously adherent lesions. In the sampled studies, IONM employment was uncommon, and post-operative new-onset neurological deficits were described in 16 cases. Adjuvant RT was used in four cases and its value is debatable. Recurrence is common (10 cases), and adjuvant therapies (RT or repeated surgery) seem to play a palliative role., Case Presentation: A 68-year-old woman presented with a three-year history of worsening spastic paraparesis and loss of independence in daily activities (McCormick grade 4). An MRI revealed an intramedullary tumor from Th5 to Th7, characterized by T1-weighted hyperintensity and signs of recent intralesional hemorrhage. Multimodal neuromonitoring, comprising the D-Wave, guided the resection of a black-tan-colored tumor with hyper-vascularization and strong adherence to the white matter. During final dissection of the lesion to obtain gross total resection (GTR), a steep decline in MEPs and D-Wave signals was recorded. Post-operatively, the patient had severe hypoesthesia with Th9 level and segmental motor deficits, with some improvement during neurorehabilitation. Histopathology revealed an intermediate-grade melanocytoma (CNS WHO 2021 classification). A four-month follow-up documented the absence of relapse., Conclusions: This literature review highlights that intramedullary T1 hyperintense hemorrhagic thoracic lesions in an adult patient should raise the suspicion of intramedullary melanocytoma. They present as locally aggressive tumors, due to local invasiveness, which often lead to post-operative neurological deficits, and frequent relapses, which overwhelm therapeutic strategies leading to palliative care after several years.

Background & Aims: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects., Methods: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3., Results: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3)., Conclusions: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Galiero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There is a growing body of literature investigating the relationship between the frequency domain analysis of heart rate variability (HRV) and cognitive Stroop task performance. We proposed a combined assessment integrating trunk mobility in 72 healthy women to investigate the relationship between cognitive, cardiac, and motor variables using principal component analysis (PCA). Additionally, we assessed changes in the relationships among these variables after a two-month intervention aimed at improving the perception-action link. At baseline, PCA correctly identified three components: one related to cardiac variables, one to trunk motion, and one to Stroop task performance. After the intervention, only two components were found, with trunk symmetry and range of motion, accuracy, time to complete the Stroop task, and low-frequency heart rate variability aggregated into a single component using PCA. Artificial neural network analysis confirmed the effects of both HRV and motor behavior on cognitive Stroop task performance. This analysis suggested that this protocol was effective in investigating embodied cognition, and we defined this approach as "embodimetrics".

Background: Paravertebral block (PVB) is effective in controlling postoperative pain after video-assisted thoracoscopic surgery (VATS) lobectomy but is subject to a high rate of failure because of incorrect site of injection. We compared methylene blue PVB with thoracic epidural anesthesia (TEA) for postoperative pain after VATS lobectomy., Methods: We conducted a prospective randomized trial of patients undergoing VATS lobectomy; 120 patients were randomly assigned to the PVB or TEA group. The end points were postoperative pain at 1 hour, 12 hours, 24 hours, and 48 hours; time to perform TEA and PVB; opioid consumption; and postoperative outcomes., Results: PVB was associated with reduction of local anesthesia time ( P < .0001). In 2 cases, methylene blue showed that the block was not well performed; thus, it was repeated. No significant differences were found in postoperative pain, opioid consumption, and postoperative outcomes., Conclusions: PVB with methylene blue is as effective as TEA for controlling postoperative pain. Methylene blue use could help reduce PVB failure., (© 2024 The Authors.)

Background and Aims: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19., Methods: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study., Results: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Šidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001)., Conclusions: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

The O-6-methylguanine-DNA methyltransferase (MGMT) gene is a critical guardian of genomic integrity. MGMT methylation in diffuse gliomas serves as an important determinant of patients' prognostic outcomes, more specifically in glioblastomas (GBMs). In GBMs, the absence of MGMT methylation, known as MGMT promoter unmethylation, often translates into a more challenging clinical scenario, tending to present resistance to chemotherapy and a worse prognosis. A pyrosequencing (PSQ) technique was used to analyze MGMT methylation status at different cut-offs (5%, 9%, and 11%) in a sample of 78 patients diagnosed with IDH-wildtype grade 4 GBM. A retrospective analysis was provided to collect clinicopathological and prognostic data. A statistical analysis was used to establish an association between methylation status and treatment response (TR) and disease-specific survival (DSS). The patients with methylated MGMT status experienced progressive disease rates of 84.6%, 80%, and 78.4% at the respective cut-offs of 5%, 9%, and 11%. The number was considerably higher when considering unmethylated patients, as all patients (100%), regardless of the cut-off, presented progressive disease. Regarding disease-specific survival (DSS), the Hazard Ratio (HR) was HR = 0.74 (0.45-1.24; p = 0.251); HR = 0.82 (0.51-1.33; p = 0.425); and HR = 0.79 (0.49-1.29; p = 0.350), respectively. Our study concludes that there is an association between MGMT unmethylation and worse TR and DSS. The 9% cut-off demonstrated a greater potential for patient survival as a function of time, which may shed light on the future need for standardization of MGMT methylation positivity parameters in PSQ.

Microplastic contamination is a growing marine environmental issue with possible consequences for seafood safety. Filter feeders are the target species for microplastic (MPs) pollution because they filter large quantities of seawater to feed. In the present study, an experimental contamination of Mytilus galloprovincialis was conducted using a mixture of the main types of MPs usually present in the seawater column (53% filaments, 30% fragments, 3% granules) in order to test the purification process as a potential method for removing these contaminants from bivalves intended for human consumption. A set of molecular biomarkers was also evaluated in order to detect any variations in the expression levels of some genes associated with biotransformation and detoxification, DNA repair, cellular response, and the immune system. Our results demonstrate that: (a) the purification process can significantly reduce MP contamination in M. galloprovincialis ; (b) a differential expression level has been observed between mussels tested and in particular most of the differences were found in the gills, thus defining it as the target organ for the use of these biomarkers. Therefore, this study further suggests the potential use of molecular biomarkers as an innovative method, encouraging their use in next-generation marine monitoring programs.

In the present study, we analyzed the genome of two S. enterica strains TS1 and TS2 from stool and blood cultures, respectively, and one strain of C. freundii TS3, isolated from a single hospitalized patient with acute myeloid leukemia. The S. enterica Goldcoast ST358 (O:8 (C2-C3) serogroup), sequenced by the MiSeq Illumina system, showed the presence of β-lactamase genes ( bla VIM-1 , bla SHV-12 and bla OXA-10 ), aadA1 , ant(2″)-Ia , aac(6')-Iaa , aac(6')-Ib3 , aac(6')-Ib-cr , qnrVC6 , parC(T57S), and several incompatibility plasmids. A wide variety of insertion sequences (ISs) and transposon elements were identified. In C. freundii TS3, these were the bla VIM-1 , bla CMY-150 , and bla SHV-12 , aadA1 , aac(6')-Ib3 , aac(6')-Ib-cr , mph(A) , sul1 , dfrA14 , ARR-2 , qnrVC6 , and qnrB38 . IncA plasmid isolated from E.coli /K12 transconjugant and C. freundii exhibited a sequence identity >99.9%. The transfer of IncA plasmid was evaluated by conjugation experiments.

Objective: To refine a reliable and reproducible intraoperative visual evoked potentials (iVEPs) monitoring protocol during endoscopic transsphenoidal surgery. To assess the reliability of baseline iVEPs in predicting preoperative visual status and perioperative iVEP variation in predicting postoperative visual outcome., Methods: Sixty-four patients harboring tumors of the pituitary region were included. All patients underwent endoscopic endonasal approach (EEA) with iVEPs monitoring, using a totally intravenous anesthetic protocol. Ophthalmological evaluation included visual acuity and visual field studies., Results: Preoperatively, visual acuity was reduced in 86% and visual field in 76.5% of cases. Baseline iVEPs amplitude was significantly correlated with preoperative visual acuity and visual field (p = 0.001 and p = 0.0004, respectively), confirming the reliability of the neurophysiological/anesthetic protocol implemented. Importantly, perioperatively the variation in iVEPs amplitude was significantly correlated with the changes in visual acuity (p < 0.0001) and visual field (p = 0.0013). ROC analysis confirmed that iVEPs are an accurate predictor of perioperiative visual acuity improvement, with a 100% positive predictive value in patients with preoperative vision loss., Conclusions: iVEPs during EEA is highly reliable in describing preoperative visual function and can accurately predict postoperative vision improvement., Significance: iVEPs represent a promising resource for carrying out a more effective and safe endoscopic transsphenoidal surgery., (© 2023. The Author(s).)

Epizootic hemorrhagic disease virus (EHDV) is a Culicoides-transmitted virus circulating in multiple serotypes. It has become a concern in the European Union as a novel strain of the serotype 8 (EHDV-8) of clear Northern African origin, has been recently discovered in symptomatic cattle in Italy (islands of Sardinia and Sicily), Spain, and Portugal. Current molecular typing methods targeting the S2 nucleotide sequences -coding for the outermost protein of the virion VP2- are not able to detect the novel emerging EHDV-8 strain as they enrolled the S2 sequence of the unique EHDV-8 reference strain isolated in Australia in 1982. Thus, in this study, we developed and validated a novel typing assay for the detection and quantitation of the novel EHDV-8 RNA from field samples, including blood of ruminants and insects. This molecular tool will certainly support EHDV-8 surveillance and control., Competing Interests: Declaration of Competing Interest Authors declare that no competing interests exist. Mention of trade names or commercial products in this article is solely for providing specific information and does not imply recommendation or endorsement by the IZSAM., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Within public health control strategies for SARS-CoV-2, whole genome sequencing (WGS) is essential for tracking viral spread and monitoring the emergence of variants which may impair the effectiveness of vaccines, diagnostic methods, and therapeutics. In this manuscript different strategies for SARS-CoV-2 WGS including metagenomic shotgun (SG), library enrichment by myBaits® Expert Virus-SARS-CoV-2 (Arbor Biosciences), nCoV-2019 sequencing protocol, ampliseq approach by Swift Amplicon® SARS-CoV-2 Panel kit (Swift Biosciences), and Illumina COVIDSeq Test (Illumina Inc.), were evaluated in order to identify the best approach in terms of results, labour, and costs. The analysis revealed that Illumina COVIDSeq Test (Illumina Inc.) is the best choice for a cost-effective, time-consuming production of consensus sequences., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

It is unclear whether West Nile virus (WNV) circulates between Africa and Europe, despite numerous studies supporting an African origin and high transmission in Europe. We integrated genomic data with geographic observations and phylogenetic and phylogeographic inferences to uncover the spatial and temporal viral dynamics of WNV between these two continents. We focused our analysis towards WNV lineages 1 (L1) and 2 (L2), the most spatially widespread and pathogenic WNV lineages. Our study shows a Northern-Western African origin of L1, with back-and-forth exchanges between West Africa and Southern-Western Europe; and a Southern African origin of L2, with one main introduction from South Africa to Europe, and no back introductions observed. We also noticed a potential overlap between L1 and L2 Eastern and Western phylogeography and two Afro-Palearctic bird migratory flyways. Future studies linking avian and mosquito species susceptibility, migratory connectivity patterns, and phylogeographic inference are suggested to elucidate the dynamics of emerging viruses., (© 2023. Springer Nature Limited.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic in the years 2020-2022. With a high prevalence, an easy route of transmission, and a long incubation time, SARS-CoV-2 spread quickly and affected public health and socioeconomic conditions. Several points need to be elucidated about its mechanisms of infection, in particular, its capability to evade the immune system and escape from neutralizing antibodies. Extracellular vesicles (EVs) are phospholipid bilayer-delimited particles that are involved in cell-to-cell communication; they contain biological information such as miRNAs, proteins, nucleic acids, and viral components. Abundantly released from biological fluids, their dimensions are highly variable, which are used to divide them into exosomes (40 to 150 nm), microvesicles (40 to 10,000 nm), and apoptotic bodies (100-5000 nm). EVs are involved in many physiological and pathological processes. In this article, we report the latest evidence about EVs' roles in viral infections, focusing on the dual role of exosomes in promoting and inhibiting SARS-CoV-2 infection. The involvement of mesenchymal stromal/stem cells (MSCs) and MSC-derived EVs in COVID-19 treatment, such as the use of translational exosomes as a diagnostical/therapeutic approach, is also investigated. These elucidations could be useful to better direct the discovery of future diagnostical tools and new exosome-derived COVID-19 biomarkers, which can help achieve optimal therapeutic interventions and implement future vaccine strategies.

Background: Early intervention in psychosis (EIP) is a well-established approach aimed at detecting and treating early signs and symptoms of psychosis to prevent its long-term consequences. The present study aimed at detailing the current status of EIP services in Italy, covering all the Departments of Mental Health (DMHs) operating in 2018., Methods: All directors of public DMHs operating in Italy in 2018 (n = 127) were invited to fill in a Census form about EIP structure and activities. The first episode psychosis services fidelity scale (FEPS-FS) was used to investigate fidelity to the EIP model of the centre., Results: An active EIP service was reported by 41 DMHs (32% of the total DMHs; 56% of those who took part in the survey). Most EIP services had an autonomous team. The large majority of the Italian EIP centres provided psychosocial interventions to their patients, principally psychotherapy, family support, and psychoeducation. Among those with an active EIP, 29 DMHs filled in the FEPS-FS. Internal consistency was good when based on the replies of the respondents, but reliability was weak when measured on the basis of an independent evaluation (Cohen's kappa = 0.571). The fidelity to the guidelines for early intervention was uneven, with some criteria met by most centres, especially those peculiar to the Italian community psychiatry., Conclusion: A further spreading of the early intervention model across the Italian DMHs was found. A lack of resources might limit the use of specific psychosocial treatments, such as cognitive-behavioural therapy or manualized family support., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Objective: COVID-19 is an extremely contagious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that will keep broadly circulating and evolving. Collected evidence revealed the clinical profile of COVID-19 patients as a potential predictor of their outcome. The aim of this study was to investigate the causal relationship between poor outcomes and laboratory parameters in hospitalized COVID-19 patients, in this sense observing how SARS-CoV-2 infection affects other organs., Patients and Methods: We retrospectively evaluated a cohort of 133 patients, positive for SARS-CoV-2, aged between 30 to 94 years, between January 12th and April 25th, 2021. Discharge from the hospital, transferral to the ordinary ward or nursing home, intensive care unit (ICU) admission, and in-hospital mortality were recorded, along with demographic, laboratory and clinical parameters. The whole sample was summarized by median (interquartile range) for quantitative data, and absolute and relative percentage frequencies for qualitative variables. Univariable logistic regression models were performed to assess the association between all the parameters of interest and COVID-19 adverse outcomes, single (in-hospital mortality) and composite (in-hospital mortality and ICU admission). Hence, a multivariable model was fitted to identify potential independent predictors of the composite outcome. The accuracy of the model was assessed through appropriate fitting indices, such as the C-statistic and Hosmer-Lemeshow test. Moreover, to detect multicollinearity, the variance inflation factor (VIF) was used., Results: Our study sample had a median age of 72 years old (59.0-83.0). The most common comorbidities were hypertension (63.7%), cardiovascular disease (41.9%), diabetes (33.6%), and cerebrovascular disease (21.5%); while as the most common symptoms, we observed dry cough (32.5%), dyspnoea (50.8%), and fatigue (29.8%). Totally, 18 patients died during hospitalization (13.5%), 10 required ICU admission (7.5%), 78 (58.6%) were discharged from the hospital, and 27 (20.3%) were transferred to either ordinary wards or nursing homes. We disclosed an association of older age with both composite [OR 1.06, 95% CI 1.02-1.09; p=0.003] and single outcome [OR 1.10, 95% CI 1.04-1.16; p=0.001]. A higher oxygen saturation (SpO2) was associated with a better outcome [OR 0.75, 95% CI 0.60-0.93; p=0.009 and OR 0.76, 95% CI 0.61-0.95, p=0.009]. Among laboratory parameters, higher levels of neutrophils increased the risk of a poor outcome [OR 1.05, 95% CI 1.00-1.10; p=0.043]; while higher levels of lymphocytes seem associated with a better outcome [OR 0.94, 95% CI 0.88-0.99; p=0.043]. Higher levels of creatinine were associated with a higher risk of both adverse outcomes [OR 6.20, 95% CI 2.16-17.81; p<0.001 and OR 19.90, 95% CI 5.07-78.06; p<0.001, respectively]. Higher levels of sodium (Na) were associated with a higher risk of adverse events [OR 1.15, 95% CI 1.03-1.28; p=0.014 and OR 1.14, 95% CI 1.01-1.27]. Similar findings were also observed for C-reactive protein (CRP) levels [OR 1.01, 95% CI 1.00-1.02; p=0.010 and OR 1.01, 95% CI 1.00-1.02; p=0.024]. Conversely, being positive to IgM and IgG decreases the risk of adverse outcomes [IgM: OR 0.33, 95% CI 0.14-0.77; p=0.011 and OR 0.23, 95% CI 0.08-0.66; p=0.006. IgG: OR 0.30 95% CI 0.13-0.72; p=0.007 and OR 0.22 95% CI 0.07-0.66; p=0.007]. Hence, a multivariable model was fitted to identify potential independent laboratory predictors of the composite outcome, with laboratory parameters that showed an association with composite outcome. The model can be considered accurate according to LH-Test and C-statistic [p>0.83, C-stat=0.90]., Conclusions: Our findings confirm that COVID-19 is a multiorgan disease. In fact, the analysis of laboratory parameters has revealed a strong relationship between poorer outcomes and multiple organ dysfunction, particularly established by higher levels of neutrophils, creatinine, sodium, and CRP. Alongside, cerebrovascular diseases, chronic kidney disease and older age supported this finding. Of note, higher levels of SpO2, and lymphocytes, as well as positivity to IgM and IgG were associated with a lower risk of a poor outcome.

The role of migratory birds in the spread of ticks and tick-borne pathogens along their routes from Africa to Europe is increasingly emerging. Wild birds can host several tick species, often infected by bacteria responsible for zoonoses. The aim of the study is to assess the possible introduction of exotic ticks carried by migratory birds into Italy from Africa and to detect the presence of Rickettsia species and Coxiella burnetii they may harbor. During a two-year survey, we collected ticks from migratory birds captured during their short stop-over on Ventotene Island. Specimens were first identified by morphology or sequencing molecular targets when needed, and then tested by real-time PCR for the presence of selected pathogens. A total of 91% of the collection consisted of sub-Saharan ticks, more than 50% of which were infected by Rickettsia species belonging to the spotted fever group, mainly represented by R. aeschlimannii . In contrast, the suspected C. burnetii detected in two soft ticks were confirmed as Coxiella -like endosymbionts and not the pathogen. Although there are still gaps in the knowledge of this dispersal process, our findings confirm the role of migratory birds in the spread of ticks and tick-borne pathogens, suggesting the need for a continuous surveillance to monitor the potential emergence of new diseases in Europe.

Intraoperative neurophysiological monitoring (IONM) represents one of the available technologies able to assess ischemia and aimed to improve surgical outcome reducing the treatment related morbidity in surgery for intracranial aneurysms. Many studies analyzing the impact of IONM are poised by the heterogeneity bias affecting the cohorts. We report our experience with IONM for surgery of unruptured middle cerebral artery (MCA) aneurysm in order to highlight its influence on functional and radiological outcome and surgical strategy. We retrospectively reviewed all MCA unruptured aneurysms treated between January 2013 and June 2021 by our institutional neurovascular team. Patients were divided into 2 groups according to the use of IONM. A total of 153 patients were included in the study, 52 operated on without IONM and 101 with IONM. The groups did not differ preoperatively regarding clinical status and aneurysm characteristics. Patients operated with IONM had better functional outcomes at discharge as well as at follow-up (p= 0.048, p=0.041) due to lower symptomatic ischemia and better radiological outcome due to lower rate of unexpected aneurysmal remnants (p= 0.0173). The introduction of IONM changed the use of temporary clipping (TeC), increasing its average duration (p= 0.01) improving the safety of dissecting and clipping the aneurysm. IONM in surgery for unruptured MCA aneurysm could improve the efficacy and safety of clipping strategy in the way it showed a role in changing the use of TeC and was associated to the reduction of unexpected aneurysmal remnants' rate and improvement in both short- and long-term patient's outcome., (© 2023. The Author(s).)

Campylobacter is one of the most common foodborne diseases worldwide with increasing rates of antibiotic resistance. Most cases of campylobacteriosis can be traced back to the consumption of poultry meat. Despite many efforts to reduce contamination in farms and in slaughterhouses, the persistence of this pathogen in poultry products remains a problem. This study aimed to evaluate the genetic diversity and antibiotic resistance of 542 C. jejuni and C. coli in Italian poultry, in the framework of two National Monitoring Programs. Genomes were screened for antibiotic resistance, virulence determinants and contextualized within a global collection of C. jejuni . ST2116, ST2863 and ST 832 were the most prevalent and significantly associated with Italian poultry. A worrying increase in resistance to quinolones, fluoroquinolones and tetracycline was observed in C. jejuni , while an increased occurrence of multidrug resistant (MDR) strains and strains resistant to macrolides was detected in C. coli . Low resistance rates were found for aminoglycosides. Molecular resistance determinants were consistent with the phenotypic resistance for tetracycline and quinolones. In silico analysis revealed 119 genes associated with virulence factors, with a notably higher prevalence of some genes in ST2863 genomes. This study highlights the increased resistance to macrolides and the emergence of MDR strains for C. coli , the genetic basis of AMR and the predominance of two genotypes among Campylobacter strains isolated from the Italian poultry farms.

While intraoperative neurophysiological monitoring (IONM) is considered a standard for intramedullary spinal cord tumor surgery, the effective role of IONM in intradural extramedullary (IDEM) tumors is still debated. We present the results of 60 patients affected by IDEM tumors undergoing surgery with the aid of IONM. Each patient was evaluated according to the modified McCormick scale (MMS) at admission, discharge and at follow-up. During surgery, motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs) were studied using the Medtronic NIM-eclipse ® 32-channel system (Medtronic Xomed, Inc. 6743 Southpoint Drive North Jacksonville FL USA). Patients' age, gender and tumor location did not affect MMS modifications. Tumors involving more than three levels had an increased likelihood of MMS worsening, while meningioma pathology was associated with worse preoperative and 1-year follow-up MMS. No MEP amplitude ratio was able to predict clinical variations, while intraoperative SEP worsening was associated with 100% risk of poor MMS at discharge and with 50% risk of poor MMS at long-term follow-up. In our opinion, SEP monitoring is a valid tool that may contribute to the preservation of the patient's neurological status. MEP monitoring is not mandatory in IDEM surgery while more studies are required to explore the feasibility and the role of D-wave in this kind of surgery.

Objectives: Sars-CoV-2 acute infection is clinically heterogeneous, ranging from asymptomatic cases to patients with a severe, systemic clinical course. Among the involved factors age and preexisting morbidities play a major role; genetic host susceptibility contributes to modulating the clinical expression and outcome of the disease. Mannose-binding lectin is an acute-phase protein that activates the lectin-complement pathway, promotes opsonophagocytosis and modulates inflammation, and is involved in several bacterial and viral infections in humans. Understanding its role in Sars-CoV-2 infection could help select a better therapy., Methods: We studied MBL2 haplotypes in 419 patients with acute COVID-19 in comparison to the general population and related the haplotypes to clinical and laboratory markers of severity., Results: We recorded an enhanced frequency of MBL2 null alleles in patients with severe acute COVID-19. The homozygous null genotypes were significantly more frequent in patients with advanced WHO score 4-7 (OR of about 4) and related to more severe inflammation, neutrophilia, and lymphopenia., Conclusions: Subjects with a defective MBL2 genotype (i.e., 0/0) are predisposed to a more severe acute Sars-CoV-2 infection; they may benefit from early replacement therapy with recombinant MBL. Furthermore, a subset of subjects with the A/A MBL genotype develop a relevant increase of serum MBL during the early phases of the disease and develop a more severe pulmonary disease; in these patients, the targeting of the complement may help. Therefore, COVID-19 patients should be tested at hospitalization with serum MBL analysis and MBL2 genotype, to define the optimal therapy., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Oral disorders including non-homogeneous leukoplakia, erythroplakia, erosive lichen planus, and many others can potentially progress to oral squamous cell carcinoma (OSCC). Currently, the late diagnosis of OSCC contributes to high mortality rates, emphasizing the need for specific markers and early intervention. In this study, we present a novel, quick, sensitive, and non-invasive method for the early detection and screening of oral cancer, enabling the qualitative assessment of neoplastic forms even before the onset of symptoms. Our method directly examines the expression of oral cancer biomarkers, such as the epithelial growth factor receptor (EGFR), and steroid receptors, including the androgen receptor (AR) and the estrogen receptor (ER). The crosstalk between sexual hormones and the EGF receptor plays a crucial role in the progression of different types of cancers, including head and neck squamous cell carcinoma. To implement our method, we developed a kit box comprising nine wells or stations, each containing buffers, lysis systems, and dried/lyophilized antibodies stored at room temperature. The kit includes instruments for sample collection and a PVDF strip (Immobilon) with specific primary antibodies immobilized on it. These antibodies capture the target proteins from cytological samples. Additionally, complementary tools are provided to ensure efficient utilization and optimal test performance. The technique can be performed outside the laboratory, either "patient side" with an instant chemocolorimetric response or with a digital reader utilizing the enzyme-linked immunosorbent assay (ELISA) method.

West Nile virus is a re-emerging arbovirus whose impact on public health is increasingly important as more and more epidemics and epizootics occur, particularly in America and Europe, with evidence of active circulation in Africa. Because birds constitute the main reservoirs, migratory movements allow the diffusion of various lineages in the world. It is therefore crucial to properly control the dispersion of these lineages, especially because some have a greater health impact on public health than others. This work describes the development and validation of a novel whole-genome amplicon-based sequencing approach to West Nile virus. This study was carried out on different strains from lineage 1 and 2 from Senegal and Italy. The presented protocol/approach showed good coverage using samples derived from several vertebrate hosts and may be valuable for West Nile genomic surveillance.

In Italy, from January 2021, the Ministry of Health indicated a vaccination plan against COVID for frail patients and physicians based on a three-dose scheme. However, conflicting results have been reported on which biomarkers permit immunization assessment. We used several laboratory approaches (i.e., antibodies serum levels, flow cytometry analysis, and cytokines release by stimulated cells) to investigate the immune response in a cohort of 53 family pediatricians (FPs) at different times after the vaccine. We observed that the BNT162b2-mRNA vaccine induced a significant increase of specific antibodies after the third (booster) dose; however, the antibody titer was not predictive of the risk of developing the infection in the six months following the booster dose. The antigen stimulation of PBMC cells from subjects vaccinated with the third booster jab induced the increase of the activated T cells (i.e., CD4 + CD154 + ); the frequency of CD4 + CD154 + TNF-α + cells, as well as the TNF-α secretion, was not modified, while we observed a trend of increase of IFN-γ secretion. Interestingly, the level of CD8 + IFN-γ + (independently from antibody titer) was significantly increased after the third dose and predicts the risk of developing the infection in the six months following the booster jab. Such results may impact also other virus vaccinations.

The Selenga River basin, located in southern Siberia, is an important component of the Lake Baikal ecosystem, and comprises approximately 80 % of the Baikal watershed. Within the Selenga River basin, two localized study regions were chosen. The first, the Selenga Delta, is one of the largest inland freshwater floodplains in the world and plays an important role in the ecosystem functioning of Baikal. It purifies the river waters before they enter the lake and acts as a refuge for many of Baikal's endemic species. The second location, the Gusinoozersk region, is southwest of Lake Baikal and the Selenga Delta, and was chosen as a more heavily industrialized region within the Selenga River basin. Anthropogenic activities, including industry, urban settlements, aquaculture and agriculture, have historically increased ecological damage within this area. We assessed possible drivers of changes in sedimentary organic matter (OM) composition within two shallow lakes (SLNG04 and Black Lake), located in the Selenga Delta and the Selenga watershed, respectively. We focused on individual n-alkanes, one of the most abundant and common lipids used to provide information on past vegetation and used multivariate statistics to disentangle changes in the sources of sedimentary OM over time. The depositional OM history of SLNG04B core can be divided in four zones: (i) major influence of non-emergent vascular plants, typically found in transitional environments (ca. 1835 to ca. 1875); (ii) increased influence of grasses/herbs (ca. 1880 to ca. 1910); (iii) transition from non-emergent vascular plants and grasses/herbs to submerged and floating macrophytes and phytoplankton (ca. 1915 to ca. 1945); (iv) maintenance of autochthonous OM from submerged and floating macrophytes and phytoplankton (ca. 1945 to ca. 2014). The depositional OM history of the Black Lake core can be divided in two main zones: (i) major influence of non-emergent vascular plants and submerged and floating macrophytes (ca. 1915 to ca. 1980); (ii) increased influence of grasses/herbs and phytoplankton (ca. 1980 to ca. 2010). Natural events (e.g., an earthquake in 1862 caused flooding and subsidence of much of the land surrounding SLNG04 lake and a further catastrophic flood event in 1897) and anthropogenic activities (e.g., nutrient pollution from expansion of agricultural and livestock population) changed the composition of sedimentary OM resulting in ecological shifts across trophic levels in the Selenga River basin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

During November 2021-May 2022, we identified 37 clinical cases of Streptococcus equi subspecies zooepidemicus infections in central Italy. Epidemiologic investigations and whole-genome sequencing showed unpasteurized fresh dairy products were the outbreak source. Early diagnosis by using sequencing technology prevented the spread of life-threatening S. equi subsp. zooepidemicus infections.

Fever represents an elevation of body temperature, that exerts a protective effect against pathogens. Innate immune cells and neurons are implicated in the regulation of body temperature. Pathogen-associated molecular patterns, i.e., lipopolysaccharides from Gram-negative bacteria and peptidoglycan and lipoteichoic acid from Gram-positive bacteria are exogenous pyrogens, that bind to Toll-like receptors on immune and non-immune cells. The subsequent release of pro-inflammatory cytokines [interleukin-1 (IL-1), IL-6 and Tumor necrosis factor-alpha] and their passage through the brain trigger the febrile response. In fact, neurons of the pre-optic area produce prostaglandin E2 (PGE2), that, in turn, bind to the PGE2 receptors; thus, generating fever. Apart from classical non-steroidal anti-inflammatory drugs, i.e., aspirin and acetaminophen, various botanicals are currently used as antipyretic agents and, therefore, their mechanisms of action will be elucidated.

Preservation of facial nerve function (FNF) during neurosurgery for cerebellopontine angle (CPA) tumors is paramount in elderly patients. Corticobulbar facial motor evoked potentials (FMEPs) allow assessment intraoperatively of the functional integrity of facial motor pathways, thus improving safety. We aimed to evaluate the significance of intraoperative FMEPs in patients 65 years and older. A retrospective cohort of 35 patients undergoing CPA tumors resection was reported; outcomes of patients aged 65-69 years vs. ≥70 years were compared. FMEPs were registered both from upper and lower face muscles, and amplitude ratios (minimum-to-baseline, MBR; final-to-baseline, FBR; and recovery value, FBR minus MBR) were calculated. Overall, 78.8% of patients had a good late (at 1 year) FNF, with no differences between age groups. In patients aged ≥70 years, MBR significantly correlated with late FNF. At receiver operating characteristics (ROC) analysis, in patients aged 65-69 years, FBR (with 50% cut-off value) could reliably predict late FNF. By contrast, in patients aged ≥70 years, the most accurate predictor of late FNF was MBR, with 12.5% cut-off. Thus, FMEPs are a valuable tool for improving safety in CPA surgery in elderly patients as well. Considering literature data, we noticed higher cut-off values for FBR and a role for MBR, which suggests an increased vulnerability of facial nerves in elderly patients compared to younger ones., Competing Interests: The authors declare no conflicts of interest.

Background: Currently, one of the most discouraging aspects for many patients undergoing dental procedures is the administration of local anaesthesia. Therefore, there is a constant search for new techniques to avoid the invasive and painful nature of the injection. This study aimed to compare the clinical efficacy of local anaesthetics with articaine 4% or mepivacaine 2% (both with epinephrine 1:100.000), using different anaesthetic techniques to perform germectomy of lower third molars and to assess patients' feelings and pain during surgery., Methods: Totally 50 patients (ranged 11-16 years) who required germectomy of mandibular third molars were recruited. Each patient received local anaesthesia on one side with articaine inoculated with plexus technique while on the other side with mepivacaine using inferior alveolar nerve block technique. The patients' evaluation was performed on pre and intraoperative tactile-pressure feelings and intraoperative pain with four levels on the Visual Analogue Scale (VAS)., Results: Surgical operations lasted less with more efficient analgesia when articaine was used. The additional intraosseous injection was required mainly in the mepivacaine group intraoperatively. A few patients had tactile-pressure feelings while intraoperative pain sensation was absent in 90% of cases with articaine. Significant differences were found in the cases who reported "absent" and "moderate" VAS values, favoring the use of articaine., Conclusions: Articaine injected with a plexus anaesthetic technique seems to be more clinically manageable than mepivacaine for the mandibular third molar germectomy. The discomfort of tactile-pressure feelings and pain experienced was lower using articaine anaesthetic technique used.

Intraoperative neurophysiologic monitoring (IONM) is an innovation introduced in neurosurgery in the past decades. It aims to support and guide the neurosurgeon to obtain the best surgical result possible, preventing the occurrence of neurological deficits. The somatosensory evoked potentials (SSEP) assess the integrity of the sensory pathways monitoring the dorsal column-medial lemniscus pathway during spine and cerebral surgery. Motor evoked potentials (MEPs) provide information on the integrity of the motor pathway monitoring the efferent motor pathways from the motor cortex to the muscle through corticospinal (or corticobulbar) tracts. Free-running EMG is the standard technique to monitor peripheral nerves, roots, or cranial motor nerves during surgery. Intraoperative EMG signals are activated during cranial motor nerves damaging or after an irritative stimulus. The duration, morphology, and persistence of EMG reflects the severity of neural injury. Nerve mapping consists of recording muscle activations given by direct nerve stimulation. This technique makes use of a stimulation probe available to the neurosurgeon which allows administering current directly to the nervous tissue (nerves, roots, etc.). Intraoperative neurophysiological monitoring (IONM) represents the standard of care during many procedures, including spinal, intracranial, and vascular surgeries, where there is a risk of neurological damage. Close communication and collaboration between the surgical team, neurophysiologist, and anesthesiologist is mandatory to obtain high-quality neuromonitoring, thus preventing neurologic injuries and gaining the best surgical "safe" results., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Use of antibiotics has dramatically eradicated bacterial infections in humans and animals. However, antibiotic overdose and abuse are responsible for the emergence of so-called multi-drug resistant bacteria. Gut microbiota deserves many functions in the host, and among them, integrity of epithelial barrier and enhancement of protective immune responses are included. There is evidence that antibiotic treatment decreases the diversity of gut microbiota species, also provoking metabolic changes, increased susceptibility to colonization and decrease of antimicrobial peptide secretion, leading to antibiotic resistance. In this review, the major mechanisms involved in antibiotic resistance will be illustrated. However, novel findings on the potential use of alternative treatments to overcome antibiotic resistance will be elucidated. In this regard, special emphasis will be placed on microcins, prebiotics, probiotics and postbiotics, as well as phage therapy and fecal microbial transplantation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Microglia, the innate immune cells of the central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply of genes, receptors and released cytokines, chemokines and neurotrophic factors. Moreover, microglia functions are closely linked to the constant communication with other cell types, among them neurons. Depending on the signaling pathway and type of stimuli involved, the outcome of microglia operation can be neuroprotective or neurodegenerative. Accordingly, microglia are increasingly becoming considered cellular targets for therapeutic intervention. Among signals controlling microglia activity, the endocannabinoid (EC) system has been shown to exert a neuroprotective role in many neurological diseases. Like neurons, microglia express functional EC receptors and can produce and degrade ECs. Interestingly, boosting EC signaling leads to an anti-inflammatory and neuroprotective microglia phenotype. Nonetheless, little evidence is available on the microglia-mediated therapeutic effects of EC compounds. This review focuses on the EC signals acting on the CNS microglia in physiological and pathological conditions, namely on the CB1R, CB2R and TRPV1-mediated regulation of microglia properties. It also provides new evidence, which strengthens the understanding of mechanisms underlying the control of microglia functions by ECs. Given the broad expression of the EC system in glial and neuronal cells, the resulting picture is the need for in vivo studies in transgenic mouse models to dissect the contribution of EC microglia signaling in the neuroprotective effects of EC-derived compounds., (© 2022 Wiley Periodicals LLC.)

Background: Increased levels of oxidative stress/cell inflammation contribute to colorectal cancer (CRC) onset. Nuclear factor-erythroid 2-related factor 2 (Nrf2) and its controlled growth factor erv1-like (Gfer) gene regulate redox-sensitive and anti-inflammatory mechanisms, respectively, which can contribute to promoting cancer development., Aim: We evaluated Nrf2 and Gfer RNA expression and Nrf2 protein expression in colon mucosa in order to establish their possible involvement in the early stage of CRC., Methods: Forty subjects were enrolled after a histological evaluation of their colon biopsies. They included 20 subjects with a sporadic colorectal adenoma (SpCA group) and 20 without precancerous lesions (controls). Biopsy samples were processed for gene expression analysis and protein expression, using Real-time PCR and immunofluorescence confocal microscopy, respectively., Results: Nrf2 and Gfer mRNA expression were significantly reduced (p=0.007 and p<0.003, respectively) in SpCA tissues compared to normal mucosa from controls. Furthermore, immunofluorescence analysis confirmed a relevant reduction of Nrf2 in SpCA tissue compared to normal tissue from controls., Conclusions: Our data confirm the hypothesis that Nrf2 and Gfer expression may be involved in the initial hits contributing to the multistep process of colon carcinogenesis. Further larger studies are needed to confirm if Nrf2 and Gfer are potential risk/prognostic factors for cancer development., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to characterize the fecal microbiota of broiler chickens reared in the presence of different shades of light-emitting diode (LED) lights, correlating this information with biochemical and molecular evidence that allowed drawing conclusions on the state of health of the animals., Methods: Overall, the metagenomic approach on fecal samples was associated with evaluations on enzymes involved in the cellular response to oxidative stress: glutathione peroxidase (GPX), superoxide dismutase and catalase; while the inflammatory aspect was studied through the dosage of a proinflammatory cytokine, the interleukin 6 (IL-6), and the evaluation of the matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9). Specifically, analysis was performed on distinct groups of chickens respectively raised in the presence of neutral (K = 3,300 to 3,700), cool (K = 5,500 to 6,000), and warm (K = 3,000 to 2,500) LED lightings, and a direct comparison was performed with animals reared with traditional neon lights., Results: The metagenomic analysis highlighted the presence of two most abundant bacterial phyla, the Firmicutes and the Bacteroidetes, with the latter characterized by a greater relative abundance (p<0.05) in the group of animals reared with Neutral LED light. The analysis on the enzymes involved in the antioxidant response showed an effect of the LED light, regardless of the applied shade, of reducing the expression of GPX (p<0.01), although this parameter is not correlated to an effective reduction in the tissue amount of the enzyme. Regarding the inflammatory state, no differences associated with IL-6 and MMP-9 were found; however, is noteworthy the significant reduction of MMP-2 activity in tissue samples obtained from animals subjected to illumination with neutral LED light., Conclusion: This evidence, combined with the metagenomic findings, supports a potential positive effect of neutral LED lighting on animal welfare, although these considerations must be reflected in more targeted biochemical evaluations.

Vitamin D promotes kidney calcium reabsorption and regulates calcium and phosphate metabolism, as well as the intestinal absorption of calcium and phosphorus and bone mineralization events. Vitamin D is also known for its immunomodulatory properties. It has been shown in the literature that the active form of vitamin D, 1,25-dihydroxyvitamin D, performs multiple functions in the adaptive and innate immune system, as well as acting on the endothelial membrane. Recent evidence shows that vitamin D is a negative endocrine modulator of the renin-angiotensin system (RAS), with protection from diseases leading to lung damage, such as pneumonia caused by various pathogens. Vitamin D support associated with the use of antibiotics could be crucial to counteract these infectious diseases.

Introduction: Autism spectrum disorders (ASD) are the most prevalent neurobiological disorders in children. The etiology comprises genetic, epigenetic, and environmental factors such as dysfunction of the immune system. Epigenetic mechanisms are mainly represented by DNA methylation, histone modifications, and microRNAs (miRNA). The major explored epigenetic mechanism is mediated by miRNAs which target genes known to be involved in ASD pathogenesis. Salivary poly-omic RNA measurements have been associated with ASD and are helpful to differentiate ASD endophenotypes. This study aims to comprehensively examine miRNA expression in children with ASD and to reveal potential biomarkers and possible disease mechanisms so that they can be used to improve faction between individuals by promoting more personalized therapeutic approaches., Materials and Methods: Saliva samples were collected from 10 subjects: 5 samples of children with ASD and 5 from healthy controls. miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system., Results: Preliminary data highlighted the presence of 365 differentially expressed miRNAs. Pathway analysis, molecular function, biological processes, and target genes of 41 dysregulated miRNAs were assessed, of which 20 were upregulated, and 21 were downregulated in children with ASD compared to healthy controls., Conclusion: The results of this study represent preliminary but promising data, as the identified miRNA pathways could represent useful biomarkers for the early non-invasive diagnosis of ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kalemaj, Marino, Santini, Tomaselli, Auti, Cagetti, Borsello, Costantino, Inchingolo, Boccellino, Di Domenico and Tartaglia.)

The global COVID-19 pandemic is underway. In recent weeks, several countries throughout the globe, and particularly in Europe, have experienced an exponential increase in the number of individuals infected with COVID-19, probably induced by a new variant of SARS-CoV-2, called the "Omicron variant." Mass vaccination against COVID-19 continues worldwide. Are authorized mRNA vaccines effective against the new Omicron variant? Recently, several pharmaceutical companies have developed oral antiviral pills against SARS-CoV-2, i.e., molnupiravir and paxlovid, that inhibit SARS-CoV-2 viral replication by acting on the RNA polymerase of SARS-CoV. In pre-registration clinical trials, molnupiravir and paxlovid have shown excellent clinical efficacy results, but what impact will these new oral antiviral agents have against pandemic COVID-19? In what specific clinical situations are they preferred over other antivirals such as remdesivir? In this brief review, we explore these important aspects., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Fundão dam failure, the worst environmental disaster in Brazilian history, launched 50 million m 3 of iron ore tailings mud through the Doce River, reaching the Atlantic Ocean. Generally, mine tailings increase the sediment inflow, leading to mud burial of epibenthic macrofauna, and the raise of metal(oid)s concentration causing macrofauna long-term changes. After almost four years, tailings mud was still spreading on the Doce River Shelf, while impacts on marine macrofauna were still unknown. Herein, the IMS index (a tracer of Fundão dam tailings mud), sediment variables, organic pollutants, and metal(oid)s were integrated to uncover the drives of macrofauna structure from Costas da Algas to Abrolhos bank MPAs. Tailings mud was present only in Doce River Mouth and Degredo, organic pollutants and metal(oid)s above safety levels were concentrated in those same areas. Tailings mud (IMS index) drastically reduced species richness and diversity, favoring the abundance of opportunistic species. Mud, IMS index and Al, Ba, and V, metal(oid)s linked to dam failure, structured macrofauna composition in this impacted area, dominated by resistant groups as Nuculidae, Spionidae, and Magelonidae. Conversely, an opposite pattern was found for further and deeper sites with high CaCO3 content and total nitrogen that also showed large grain size, in areas known to harbour biogenic structures, sustaining a macrofauna composition distinct from the impacted areas, dominated by Syllidae and Crassatellidae, sensitives to impacts. Macrofauna composition was most structured by sediment variables, followed by the intersection between metal(oid)s-IMS and Mud, both gradients acting almost entirely on a broad spatial scale. Benthic macrofauna at the Doce River Shelf is still impacted by Fundão dam tailings mud, even after almost four years of the disaster, and may continue to, since the influx of tailings does not stop, and sediment resuspension is a recurrent source for those impacts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Intraoperative neuromonitoring is crucial for facial nerve preservation in cerebellopontine angle (CPA) surgery. Among the available techniques, the role of intraoperative corticobulbar facial motor evoked potentials (FMEPs) is unclear., Objective: To evaluate the significance of intraoperative FMEPs as indicators for early and late postoperative facial nerve function (FNF) in CPA tumor resection and the feasibility of their integration with standard monitoring techniques., Methods: An institutional series of 83 patients who underwent surgery under intraoperative monitoring for CPA extra-axial tumor resection was reported. A pair of needle electrodes was used to record FMEP from orbicularis oculi (OOc) and orbicularis oris (OOr) muscles at baseline, at the end of surgery and minimum values recorded. From FMEP amplitudes, minimum-to-baseline amplitude ratio (MBR), final-to-baseline amplitude ratio (FBR), and recovery value, intended as FBR minus MBR, were calculated. These indices were correlated with early and late postoperative FNF., Results: Our analysis demonstrated that higher FBR (both from OOc and OOr) and MBR (from OOr only) were associated with a good early and late FNF; a higher MBR from OOc was significantly associated with a good late FNF. The most accurate index in predicting early FNF was FBR measured from OOr with a cutoff of 35.56%, whereas the most accurate index in predicting late FNF was FBR as measured from OOc with a cutoff of 14.29%., Conclusion: Our study confirmed that FMEPs are reliable predictors of early and late postoperative FNF in CPA surgery and could be easily integrated with standard intraoperative neuromonitoring techniques., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

The use of innovative approaches to elucidate the pathophysiological mechanisms of autoimmune diseases, as well as to further study of the factors which can have either a positive or negative effect on the course of the disease, is essential. In this line, the development of new molecular techniques and the creation of the Human Genome Program have allowed access to many more solutions to the difficulties that exist in the identification and characterization of the microbiome, as well as changes due to various factors. Such innovative technologies can rekindle older hypotheses, such as molecular mimicry, allowing us to move from hypothesis to theory and from correlation to causality, particularly regarding autoimmune diseases and dysbiosis of the microbiota. For example, Prevotella copri appears to have a strong association with rheumatoid arthritis; it is expected that this will be confirmed by several scientists, which, in turn, will make it possible to identify other mechanisms that may contribute to the pathophysiology of the disease. This article seeks to identify new clues regarding similar correlations between autoimmune activity and the human microbiota, particularly in relation to qualitative and quantitative microbial variations therein.

The cerebellopontine angle (CPA) is a highly complex anatomical compartment consisting of numerous nervous and vascular structures that present mutual and intricate spatial relationships. CPA surgery represents, therefore, a constant challenge for neurosurgeons. Over the years, neurosurgeons have developed and refined several solutions with the aim of maximizing the surgical treatment effects while minimizing the invasiveness and risks for the patient. In this paper, we present our integrated approach to CPA surgery, describing its advantages in treating pathologies in this anatomical district. Our approach incorporates the use of technology, such as neuronavigation, along with advanced and multimodal intraoperative neuromonitoring (IONM) techniques, with the final goal of making this surgery safe and effective.

The accumulation and disposal of by-products deriving from the agro-food industry represents a problem both from an economic and environmental point of view. The use of these matrices in zootechnical nutrition could represent a feasible solution. The aim of the study was to examine the effect of a diet containing olive leaves (OL), a by-product of the olive industry, on the ruminal microbial community of Saanen goat kids and on volatile organic compounds (VOCs) produced during the digestion. Twenty goat kids were randomly divided into two groups of ten goat kids each. The control group (CTR) was fed with a standard diet, while the experimental group (OL+) received a custom-formulated diet containing 10 % OL on a dry matter (DM) basis. After 30 days of trial, genomic DNA was extracted from the rumen liquor and prepared for 16S rRNA-gene sequencing to characterize the rumen microbiota; furthermore, rumen VOCs were also characterized by solid-phase microextraction coupled with gas chromatography-mass spectrometry. The Shannon’s alpha index was not significantly different between the two groups, on the contrary, Bray-Curtis (p < 0.01) and Jaccard (p < 0.01) distances evidenced that feed affected microbial community. Eleven genera were influenced by OL supplementation, with a significant increase (p < 0.05) in Paludibacter, Fibrobacter, Sphaerochaeta Christensenella, Rikenella, Oligosphaera, Candidatus Endomicrobium, Anaerovorax, and Atopobium was observed, while the percentages of Bacteroides and Selenomonas were reduced (p < 0.05). Differences were also observed between the two groups at the family level (p < 0.004). Fibrobacteriaceae, Christensenellaceae, Coriobacteriaceae, Oligosphaeraceae, Candidatus Endomicrobium, and Planctomycetaceae were significantly higher (p < 0.05) in goat kids fed OL diet compared to CTR, while the levels of other identified families, Succinivibrionaceae and Bifidobacteriaceae, were opposite (p < 0.05). Finally, results showed that the main phyla in both groups were Bacteroidetes and Firmicutes; however, no significant differences in the relative abundance of any phyla were observed between the two groups. In addition to what has been reported, the analysis of VOCs at the rumen level showed the ability of the OL integration to induce an increase in hexanoic acid and a parallel decrease in decanal. Furthermore, only in OL+ samples there was the accumulation of α-terpineol to which a wide range of interesting biological properties is attributed. The presence of VOCs associated with health status suggests a favorable role of OL in preserving and improving animal welfare.

Oxidative stress plays an important role in brain aging and in neurodegenerative diseases. New therapeutic agents are necessary to cross the blood-brain barrier and target disease pathogenesis without causing disagreeable side effects. Resveratrol (RSV) may act as a neuroprotective compound, but little is known about its potential in improving the cognitive and metabolic aspects that are associated with neurodegenerative diseases. The objective of this study was to investigate the protective effects and the underlying mechanisms of RSV against hypoxia-induced oxidative stress in neuronal PC12 cells. For the induction of the hypoxia model, the cells were exposed to oxygen-deprived gas in a hypoxic chamber. Cell cycle and apoptosis were analyzed by a fluorescence activated cell sorting (FACS) analysis. The intracellular reactive oxygen species (ROS) level was analyzed by using dichlorodihydrofluorescein diacetate (DCFDA) and 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) tests. The expression of activated caspase-3, -9, Bcl-2, Bax, p53, and SOD was investigated by a Western blot analysis. We found that hypoxia reduced PC12 viability by inducing apoptosis, while RSV treatment attenuated the ROS-induced damage by reducing caspase-3, -9, and the Bax/Bcl-2 ratio. The RSV treated groups were found to improve cellular health, with a 7.41% increase in the S phase population in the 10 µM group, compared to the control. Hence, RSV has a protective effect in neuronal cells and may halt the cell cycle in the G1/S phase to repair the intracellular damage. Therefore, RSV could be a good candidate to act as an antioxidant and promising preventive therapeutic agent in neurodegenerative diseases for personalized medicine.

A major challenge in the clinical management of prostate cancer (PC) is to inhibit tumor growth and prevent metastatic spreading. In recent years, considerable efforts have been made to discover new compounds useful for PC therapy, and promising advances in this field were reached. Drugs currently used in PC therapy frequently induce resistance and PC progresses toward metastatic castration-resistant forms (mCRPC), making it virtually incurable. Curcumin, a commercially available nutritional supplement, represents an attractive therapeutic agent for mCRPC patients. In the present study, we compared the effects of chemotherapeutic drugs such as docetaxel, paclitaxel, and cisplatin, to curcumin, on two PC cell lines displaying a different metastatic potential: DU145 (moderate metastatic potential) and PC-3 (high metastatic potential). Our results revealed a dose-dependent reduction of DU145 and PC-3 cell viability upon treatment with curcumin similar to chemotherapeutic agents (paclitaxel, cisplatin, and docetaxel). Furthermore, we explored the EGFR-mediated signaling effects on ERK activation in DU145 and PC-3 cells. Our results showed that DU145 and PC-3 cells overexpress EGFR, and the treatment with chemotherapeutic agents or curcumin reduced EGFR expression levels and ERK activation. Finally, chemotherapeutic agents and curcumin reduced the size of DU145 and PC-3 spheroids and have the potential to induce apoptosis and also in Matrigel. In conclusion, despite different studies being carried out to identify the potential synergistic curcumin combinations with chemopreventive/therapeutic efficacy for inhibiting PC growth, the results show the ability of curcumin used alone, or in combinatorial approaches, to impair the size and the viability of PC-derived spheroids.