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Abstract Besides being responsible for olfaction and air intake, the nose contains abundant vasculature and autonomic nervous system innervations, and it is a cerebrospinal fluid clearance site. Therefore, the nose is an attractive target for functional MRI (fMRI). Yet, nose fMRI has not been possible so far due to signal losses originating from nasal air-tissue interfaces. Here, we demonstrated feasibility of nose fMRI by using novel ultrashort/zero echo time (TE) MRI. Results obtained in the resting-state from 13 healthy participants at 7T and in 5 awake mice at 9.4T revealed a highly reproducible resting-state nose functional network that likely reflects autonomic nervous system activity. Another network observed in humans involves the nose, major brain vessels and CSF spaces, presenting a temporal dynamic that correlates with heart rate and breathing rate. These resting-state nose functional signals should help elucidate peripheral and central nervous system integrations.

Introduction: Orthodontic treatment with fixed vestibular appliances is still widely used worldwide. When choosing the aesthetic alternative of ceramic brackets, the possibility of failure and cracking of braces should be considered. Therefore, the aim of the present study was to compare the failure rates of ceramic and metal brackets in a 12-month clinical study. Methods: Eighty patients undergoing fixed orthodontic treatment with vestibular appliances were enrolled and divided into 2 equal groups: MET for metal brackets and CER for ceramic brackets. After bonding, bracket failures were recorded for 12 months, along with the archwire placed at the time of failure. Angle's dental class, skeletal class, Wits appraisal, Little's irregularity index, overjet, overbite, age, and gender of the patients were recorded from pretreatment cephalometric tracings and study casts. The data were statistically analysed (P < .05). Results: Significantly higher failure rates were found for ceramic brackets in the overall analysis, in the mandibular arch, and in the posterior region. Regression analysis revealed a significant influence of round nickel-titanium archwires on higher failure rates, whilst a significant influence of rectangular archwires was found on lower failure rates. Conclusions: Ceramic brackets showed higher failure rates. Patients should be aware that orthodontic treatment with ceramic brackets may involve delays and inconvenience due to the higher failure rate compared to metal brackets.

Over the last two decades, proliferations of benthic cyanobacteria producing derivatives of anatoxin-a have been reported in rivers worldwide. Here, we follow up on such a toxigenic event happening in the Areuse river in Switzerland and investigate the diversity and genomics of major bloom-forming riverine benthic cyanobacteria. We show, using 16S rRNA-based community profiling, that benthic communities are dominated by Oscillatoriales. We correlate the detection of one Microcoleus sequence variant matching the Microcoleus anatoxicus species with the presence of anatoxin-a derivatives and use long-read metagenomics to assemble complete circular genomes of the strain. The main dihydro-anatoxin-a-producing strain in the Areuse is distinct from strains isolated in New Zealand, the USA, and Canada, but forms a monophyletic strain cluster with them with average nucleotide identity values close to the species threshold. Compared to the rest of the Microcoleus genus, the toxin-producing strains encode a 15 % smaller genome, lacking genes for the synthesis of some essential vitamins. Toxigenic mats harbor a distinct microbiome dominated by proteobacteria and bacteroidetes, which may support cyanobacterial growth by providing them with essential nutrients. We recommend that strains closely related to M. anatoxicus be monitored internationally in order to help predict and mitigate similar cyanotoxic events.

Resumo Objetivo Verificar o impacto da participação de programas de exercícios físicos em pessoas idosas com doença de Alzheimer (DA) e os fatores que comprometem a sua prática. Método Trata-se de uma revisão sistemática nas bases de dados United States National Library of Medicine (PubMed), Web of Science, Scopus, Biblioteca Scientific Electronic Library Online (SciELO); LILACS e Embase, a partir de 2014. Utilizaram-se as diretrizes do PRISMA – 2020 e a análise de risco de viés com o apoio da ferramenta Cochrane (RoB2). Resultados Foram incluídos onze estudos para análise qualitativa. O comprometimento da memória episódica ocasiona um declínio na DA e envolve uma complexidade de processos cognitivos contendo múltiplos aspectos do sistema neural Conclusão A depressão, a ansiedade e a dificuldade de compreensão são os principais fatores que comprometem a participação da pessoa idosa com Alzheimer aos exercícios com o propósito de estímulo físico, e são os principais preditores que dificultam o desenvolvimento perceptivo-motor. Os protocolos com exercícios combinados parecem favorecer melhor a função executiva no paciente com DA. A conscientização do exercício físico é fundamental desde o início dos tratamentos, com a sugestão de se priorizar melhorias na atenção das pessoas idosas com DA. As particularidades da relação entre as atividades da vida diária e a capacidade funcional do paciente com Alzheimer ainda correspondem a uma lacuna a ser explorada, assim como a prescrição de exercícios específicos que considerem tanto o grau de atenção quanto o nível da doença.

The population of the Venafro Valley (Southern Italy) faces various type of air pollution problems (industrial facilities, traffic, and biomass combustion). To estimate exposure to various pollution sources, a multi-stage random forest model was used, integrating particulate matter (PM) data with satellite observations, land-use patterns, and meteorological information generating maps of PM2.5 concentration. Four distinct PM2.5 exposure categories were established using the quartile method. To assess the association between PM2.5 and cause-specific mortality and morbidity, a time-dependent and sex-specific Cox multiple regression analysis was conducted, adjusting for age classes. In addition, the hazard ratios were accompanied by a probability measure of the strength of the evidence toward a hypothesis of health risk associated with the exposure under study (1−p value). The whole cohort was exposed to PM2.5 annual levels exceeding the 5 µg/m3 limit recommended by the World Health Organization. Mortality excesses were observed in class 3 for both sexes for cardiac heart diseases. Excesses of cardiovascular diseases were observed for both sexes in class 3 and 4. The study highlights significant signals warranting mitigation actions, which regional authorities are currently considering.

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT’s impact on patient management. Sixty castration-sensitive high-risk (ISUP 4–5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22–17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging.

Abstract Background Atmospheric pollution has been recognized as the greatest environmental threat to human health. The population of the Venafro Valley, southern Italy, is exposed to emissions from a Waste-To-Energy (WTE) and a cement plant and potentially also to another WTE located in the neighboring region of Lazio; also, the vehicular atmospheric pollution situation is critical. In order to assess the environmental health risk of residents in eight municipalities of the Venafro Valley, a retrospective residential cohort study during 2006–2019 was carried out. Methods Four exposure classes were defined by natural-break method, using a dispersion map of nitrogen dioxides (chosen as proxy of industrial pollution). The association between the industrial pollution and cause-specific mortality/morbidity of the cohort was calculated using the Hazard Ratio (HR) through a multiple time-dependent and sex-specific Cox regression adjusting for age, proximity to main roads and socio-economic deprivation index. Results Results showed, for both sexes, mortality and morbidity excesses in the most exposed class for diseases of the circulatory system and some signals for respiratory diseases. Particularly, mortality excesses in both sexes in class 3 for diseases of the circulatory system [men: HR = 1.37 (1.04–1.79); women: HR = 1.27 (1.01–1.60)] and for cerebrovascular diseases [men: HR = 2.50 (1.44–4.35); women: HR = 1.41 (0.92–2.17)] were observed and confirmed by morbidity analyses. Mortality excesses for heart diseases for both sexes [men-class 3: HR = 1.32 (0.93–1.87); men-class 4: HR = 1.95 (0.99–3.85); women-class 3: HR = 1.49 (1.10–2.04)] and for acute respiratory diseases among women [HR = 2.31 (0.67-8.00)] were observed. Morbidity excesses in both sexes for ischemic heart diseases [men-class 3: HR = 1.24 (0.96–1.61); women-class 4: HR = 2.04 (1.04–4.02)] and in class 4 only among men for respiratory diseases [HR = 1.43 (0.88–2.31)] were also found. Conclusions The present study provides several not-negligible signals indicating mitigation actions and deserve further investigations. For future studies, the authors recommend enriching the exposure and lifestyle profile using tools such as questionnaires and human biomonitoring.

The evaluation of the left atrial (LA) size using the LA volume index (LAVI) is clinically relevant due to its prognostic significance in various conditions. Nonetheless, adding a LA function assessment to the LAVI provides further clinical and prognostic information in different cardiovascular (CV) diseases. The assessment of LA function by echocardiography primarily includes volumetric measurements (LA ejection fraction [LAEF]), tissue Doppler imaging (TDI) (mitral annular late diastolic velocity [a’]), and speckle-tracking methods, such as LA longitudinal reservoir strain (LA strain). This review analyzes and discusses the current medical evidence and potential clinical usefulness of these different methods to analyze LA function.

Virgin olive oil (VOO) is a globally esteemed product renowned for its chemical composition, nutritional value, and health benefits. Consumers seeking natural, nutritious, and healthy foods increasingly favor VOO. The optimization of the extraction system ensures the production of high-quality VOO with abundant antioxidant compounds that naturally protect it from degradation. Proper storage is crucial in maintaining the quality of VOO, prompting the exploration of novel extraction and preservation techniques. Factors such as light, temperature, and oxygen greatly influence the degradation process, resulting in reduced levels of natural antioxidants like polyphenols. Undesirable by-products and non-aromatic compounds may be formed, making the oil unacceptable over time. On the basis of all this consideration, this study aimed to evaluate the synergic use of two different gases (CO2 and argon) during the malaxation phase to limit radical development and delay lipid autoxidation. Additionally, unconventional preservation systems, namely argon headspace, shellac, and bottle in bag, were assessed over a period of 150 days. The results evidenced that the use of CO2 and argon during the malaxation process resulted in an improvement in the oil quality compared to the one obtained with the traditional system. However, in traditional oils, the alternative packaging systems determined interesting outcomes as they were able to positively affect different parameters, while the packaging effect was more mitigated in the test oils.

Spinal cord epidural electrical stimulation (EES) has been successfully employed to treat chronic pain and to restore lost functions after spinal cord injury. Yet, the efficacy of this approach is largely challenged by the suboptimal spatial distribution of the electrode contacts across anatomical targets, limiting the spatial selectivity of stimulation. In this study, we exploited different ESS paradigms, designed as either Spatial-Selective Stimulation (SSES) or Orientation-Selective Epidural Stimulation (OSES), and compared them to Conventional Monopolar Epidural Stimulation (CMES). SSES, OSES, and CMES were delivered with a 3- or 4-contact electrode array. Amplitudes and latencies of the Spinally Evoked Motor Potentials (SEMPs) were evaluated with different EES modalities. The results demonstrate that the amplitudes of SEMPs in hindlimb muscles depend on the orientation of the electrical field and vary between stimulation modalities. These findings show that the electric field applied with SSES or OSES provides more selective control of amplitudes of the SEMPs as compared to CMES. We demonstrate that spinal cord epidural stimulation applied with SSES or OSES paradigms in the rodent model could be tailored to the functional spinal cord neuroanatomy and can be tuned to specific target fibers and their orientation, optimizing the effect of neuromodulation.

Felice Alfonso Nava,1 Alessandra Mangia,2 Marco Riglietta,3 Lorenzo Somaini,4 Francesco Giuseppe Foschi,5 Ernesto Claar,6 Ivana Maida,7 Claudio Ucciferri,8 Francesca Frigerio,9 Candido Hernandez,10 Melania Dovizio,11 Valentina Perrone,11 Luca Degli Esposti,11 Massimo Puoti12 1U.O. Sanità Penitenziaria e Area Dipendenze, Azienda ULSS 6 Euganea, Padova, Italy; 2UOS Epatologia, Istituto di Ricovero e Cura “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Italy; 3UOC Dipendenze, ASST Papa Giovanni XXIII, Bergamo, Italy; 4Servizio per le Dipendenze, SERT di Cossato, Biella, Italy; 5UOC Medicina Interna, Ospedale di Faenza, Faenza, Italy; 6UOC Medicina Interna, Ospedale Evangelico “Villa Betania”, Napoli, Italy; 7UOC Malattie Infettive e Parassitarie, Azienda Ospedaliero Universitaria di Sassari, Sassari, Italy; 8Clinica di Malattie Infettive Ospedale “SS Annunziata”, Chieti, Italy; 9Gilead Sciences, Milano, Italy; 10Gilead Sciences, Global Medical Affairs, Stockley Park, London, UB11 1BD, UK; 11CliCon S.R.L. Società Benefit, Health Economics and Outcomes Research, Bologna, Italy; 12SC Malattie Infettive, ASST Grande Ospedale Metropolitano Niguarda, Milano, ItalyCorrespondence: Luca Degli Esposti, CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, Via Murri, 9, Bologna, 40137, Italy, Tel +39 544 38393, Fax +39 544 212699, Email luca.degliesposti@clicon.itPurpose: Hepatitis C virus (HCV) spreads from contact with blood of an infected person. HCV infections are common among people who use drugs (PWUDs), when sharing needles, syringes, or other equipment for injected drugs. The advent of pangenotypic direct-antiviral agents (DAA) in 2017 transformed the treatment landscape for HCV, but PWUDs remain a complex and hard-to-treat population with high risk of HCV reinfection. The aim of this real-world analysis was to characterize the demographic and clinical features of PWUDs in Italy, also focusing on comorbidity profile, treatment with DAAs, resource consumptions for the National Health System (NHS).Patients and Methods: During 01/2011– 06/2020, administrative databases of Italian healthcare entities, covering 3,900,000 individuals, were browsed to identify PWUDs with or without HCV infection. Among HCV+ patients, a further stratification was made into treated and untreated with DAAs. The date of PWUD or HCV first diagnosis or DAA first prescription was considered as index-date. Patients were then followed-up for one year. Alcohol-dependency was also investigated.Results: Total 3690 PWUDs were included, of whom 1141 (30.9%) PWUD-HCV+ and 2549 (69.1%) PWUD-HCV-. HCV-positive were significantly older (43.6 vs 38.5 years, p < 0.001), had a worse comorbidity profile (Charlson-index: 0.8 vs 0.4, p < 0.001), and high rates of psychiatric, respiratory, dermatological, musculoskeletal diseases and genitourinary (sexually transmitted) infections. Moreover, they received more drug prescriptions (other than DAAs, like anti-acids, antiepileptics, psycholeptics) and had undergone more frequent hospitalization, predominantly for hepatobiliary, respiratory system and mental disorders. DDA-untreated had significantly higher Charlson-index than DAA-treated (0.9 vs 0.6, p = 0.003). Alcoholism was found in 436 (11.8%) cases.Conclusion: This Italian real-world analysis suggests that PWUDs with HCV infection, especially those untreated with DAAs, show an elevated drug consumption due to their complex clinical profile. These findings could help to ameliorate the healthcare interventions on PWUDs with HCV infection.Keywords: drug abuse, hepatitis C virus, alcohol dependency, real-world evidence

Aortic valve replacement (AVR) in a patient with a bio-Bentall conduit can be very challenging, especially if there was a previous endocarditis process for significant morbidity and mortality. We report a case of sutureless AVR in an old patient with a bio-Bentall conduit (Carpentier–Edwards Perimount Magna Ease 25 aortic valve and Hemashield 30 aortic conduit), who developed an endocarditis on aortic prosthesis valve. We believe that sutureless AVR is the best option for redo-operation in older patients with a high surgical risk because it allows for easy rapid deployment implantation, avoids anchoring sutures on a fragile aortic anulus, and reduces cardiopulmonary and aortic cross-clamp times. In this setting, it should be considered as a safe and valid alternative not only to traditional prosthesis but also in selected cases to transcatheter valve-in-valve solutions.

Given the substantial dependence of neurons on continuous supply of energy, the distribution of major cerebral arteries opens a question whether the distance from the main supply arteries constitutes a modulating factor for the microstructural and functional properties of brain tissue. To tackle this question, multimodal MRI acquisitions of 102 healthy volunteers over the full adult age span were utilised. Relaxation along a fictitious field in the rotating frame of rank n = 4 (RAFF4), adiabatic T1ρ, T2ρ, and intracellular volume fraction (fICVF) derived from diffusion-weighted imaging were implemented to quantify microstructural (cellularity, myelin density, iron concentration) tissue characteristics and degree centrality and fractional amplitude of low-frequency fluctuations to probe for functional metrics. Inverse correlation of arterial distance with robust homogeneity was detected for T1ρ, T2ρ and RAFF4 for cortical grey matter and white matter, showing substantial complex microstructural differences between brain tissue close and farther from main arterial trunks. Albeit with wider variability, functional metrics pointed to increased connectivity and neuronal activity in areas farther from main arteries. Surprisingly, multiple of these microstructural and functional distance-based gradients diminished with higher age, pointing to uniformization of brain tissue with ageing. All in all, this pilot study provides a novel insight on brain regionalisation based on artery distance, which merits further investigation to validate its biological underpinnings.

Objectives: This study aims to investigate the pattern of immunoexpression of proteins p16, p53 and Ki-67 in RRP, as well as to evaluate its influence on the number of surgeries that patients have undergone to date and to analyze the benefit of immunohistochemistry in this disease. Methods: Clinical-demographic data and tumor samples were obtained from 33 patients with RRP. The expression of proteins p16, p53 and Ki-67 was analyzed by immunohistochemical method. Results: Most patients had already undergone more than one surgery. The p16 marker was negative in 24.2% of the cases, with little positivity in 27.3% of the cases, moderate in 36.4% and intense in 12.1%. The p53 marker was positive in all cases, with little immunoexpression in 39.4% of cases, moderate in 36.4% and intense in 24.2%. The Ki-67 marker showed nuclear positivity in all lesions, although in varying degrees, with a mean proliferative index ± SD (standard deviation) of 51.7 ± 26. Conclusions: The papillomatous lesions had varying degrees of immunoexpression of proteins p16, p53 and Ki-67, but no specific immunohistochemical pattern was observed. It was found, with statistical difference, that the number of surgeries was higher in cases with greater intensity of p53 expression, without correlation with the other markers. The benefit of immunohistochemistry in recurrent respiratory papillomatosis may lie in the prognostic assessment. However, further studies are needed to evaluate the use of this technique for this purpose. Level of evidence: : 4.

The use of by-products as functional ingredients for bread recipes may open up new horizons in terms of product innovation to increase nutraceutical characteristics and/or shelf-life. In this research, the ability of residual products from important food chains (Citrus and wine) to influence the water binding capacity of dough and bread was investigated in order to create industrial breads of high quality with prolonged shelf-life in the absence of any chemical additives (e.g., ethanol, sorbic acid, and propionic acid). The product under study is the ‘Pan Bauletto bianco con olio EVO’ (white bakery bread with EVO oil), an ‘industrial bread’ type usually treated with ethanol before being marketed, aiming to prolong its short shelf-life. The effect of the addition of different amounts of pectin (Citrus supply chain) and grape pomace (wine supply chain), in combination or not, has shown promising results from both a technological point of view and the increasing shelf-life, allowing to obtain products with high nutraceutical value and interesting properties.

Stefano Fagiuoli,1 Pierluigi Toniutto,2 Nicola Coppola,3 Domenica Daniela Ancona,4 Margherita Andretta,5 Fausto Bartolini,6 Fulvio Ferrante,7 Alessandro Lupi,8 Stefano Palcic,9 Francesca Vittoria Rizzi,10 Davide Re,11 Gema Alvarez Nieto,12 Candido Hernandez,13 Francesca Frigerio,14 Valentina Perrone,14 Luca Degli Esposti,14 Alessandra Mangia15 1Department of Medicine and Surgery, University of Milan Bicocca & Gastroenterology Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy; 2Hepatology and Liver Transplantation Unit, Azienda Ospedaliero Universitaria, Udine, Italy; 3Infectious Diseases Unit, University of Campania L. Vanvitelli, Naples, Italy; 4Dipartimento Farmaceutico ASL BAT, Trani, Italy; 5UOC Assistenza Farmaceutica Territoriale, Azienda Ulss 8 Berica, Vicenza, Italy; 6Dipartimento Farmaceutico-Usl Umbria 2, Terni, Italy; 7Dipartimento Diagnostica Ed Assistenza Farmaceutica – ASL Frosinone, Frosinone, Italy; 8Struttura Complessa Di Cardiologia – ASL VCO, Omegna, Italy; 9Farmaceutica Territoriale- Azienda Sanitaria Universitaria Integrata Giuliano-Isontina (ASUGI), Trieste, Italy; 10UOS Farmacovigilanza e Monitoraggio Spesa Farmaceutica- ASL BAT, Trani, Italy; 11Servizio Farmaceutico Territoriale ASL Teramo, Teramo, Italy; 12Gilead Sciences, Medical Affairs Italy, Milan, Italy; 13Gilead Sciences, Global Medical Affairs, London, UK; 14Clicon S.r.l., Health Economics and Outcomes Research, Bologna, Italy; 15Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, 24127, ItalyCorrespondence: Luca Degli Esposti, CliCon S.r.l. Società Benefit, Health, Economics & Outcomes Research, Via Murri, 9, Bologna, 40137, Italy, Tel +390544 38393, Email luca.degliesposti@clicon.itPurpose: The study aims at investigating the impact of polymedication and aging in the prevalence of multiple drug-drug interactions (DDIs) on HCV patients treated with sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB).Patients and Methods: This is a retrospective analysis based on administrative data covering around 6.9 million individuals. Patients treated with SOF/VEL or GLE/PIB over November 2017–March 2020 were included. Index date corresponded to SOF/VEL or GLE/PIB first prescription during such period; patients were followed up for treatment duration. Analyses were then focused on patients with ≥ 2 comedications at risk of multiple DDIs. The severity and the effect of multiple DDI were identified using the Liverpool University tool.Results: A total of 2057 patients with SOF/VEL and 2128 with GLE/PIB were selected. Mean age of SOF/VEL patients was 58.5 years, higher than GLE/PIB ones (52.5 years) (p < 0.001), and patients > 50 years were more present in SOF/VEL vs GLE/PIB cohorts: 72% vs 58%, (p < 0.001). Most prescribed co-medications were cardiovascular, alimentary and nervous system drugs. Proportion of patients with ≥ 2 comedications was higher in SOF/VEL compared to GLE/PIB cohort (56.5% vs 32.3%, p < 0.001). Those at high-risk of multiple DDIs accounted for 11.6% (N = 135) of SOF/VEL and 19.6% (N = 135) of GLE/PIB (p < 0.001) patients with ≥ 2 comedications. Among them, the potential effect of DDI was a decrease of DAA serum levels (11% of SOF/VEL and GLE/PIB patients) and an increased concentration of comedication serum levels (14% of SOF/VEL and 42% of GLE/PIB patients).Conclusion: This real-world analysis provided a thorough characterization on the burden of polymedication regimens in HCV patients treated with SOF/VEL or GLE/PIB that expose such patients to an increased risk of DDIs. In our sample population, SOF/VEL regimen was more frequently detected on elderly patients and on those with ≥ 2 comedications at risk of multi-DDI, ie, among patients characterized by higher rates of comorbidities and polypharmacy.Keywords: administrative database, glecaprevir/pibrentasvir, hepatitis C, sofosbuvir/velpatasvir, polymedication

Ripened sheep sausages are widely consumed in Italy, particularly in Sardinia. Despite their driving role in flavor and color development, coagulase-negative staphylococci in these products have been rarely investigated. A total of 70 CoNS cultures isolated from Sardinian sheep sausages were characterized by rep-PCR and M13-RAPD typing and identified by 16S rDNA sequencing. S. xylosus and S. equorum accounted for more than 70% of the total isolates, whilst S. pasteuri (8.5%), S. succinus (2.8%), and S. haemolyticus (2.8%) were less represented. The genes encoding the synthesis of putrescine, tyramine, cadaverine, and histamine were evaluated by PCR. None of the strains hosted genes for decarboxylases, except one S. pasteuri strain that was potentially a tyramine-producer. Antibiotic resistance was evaluated, along with nitrate reductase, lipolytic, and proteolytic activity, in a pool of selected cultures. Resistance to the primary antibiotics was rather widespread. S. xylosus, S. equorum, and S. pasteuri strains were all resistant to amoxicillin and kanamycin. S. equorum strains were sensitive to all tested antibiotics. S. xylosus strains were all resistant to penicillin B. Conversely, all S. pasteuri strains were resistant to both ampicillin and penicillin B, and four out of five strains exhibited tetracycline resistance. The high variability in the production of sheep sausages makes the search for adjunct cultures of crucial relevance. According to this perspective, the characterization of the autochthonous CSN population represents the first step to approach a starter selection.

IntroductionDeep brain stimulation (DBS) is a rapidly developing therapeutic intervention with constantly expanding neurological and psychiatric indications. A major challenge for the approach is the precise targeting and limitation of the effect on the desired neural pathways. We have introduced a new approach, orientation selective stimulation (OSS) that allows free rotation of the induced electric field on a plane when using a probe with three parallel electrodes forming an equilateral triangle at the tip. Here, we expand the technique by introducing a tetrahedral stimulation probe that enables adjustment of the primary electric field direction freely at any angle in a 3D space around the stimulating probe. OSS in 3D will enable better targeting of the electric field according to the local brain anatomy. We tested its utility in a rat model of DBS for treatment-resistant depression. The stimulation directed to the subgenual anterior cingulate cortex (sgACC) has yielded dramatic improvement in individual patients suffering from therapy resistant depression, but no consistent benefit in larger series. This failure has been ascribed to the challenging anatomy of sgACC with several crossing neural tracts and individual differences in the local anatomy.MethodsWe stimulated infralimbic cortex (IL), the rat analog of sgACC, and recorded local electrical responses in amygdala (AMG) that is monosynaptically connected to IL and plays a central role in emotional states. We further traced AMG–IL connections using a viral vector and tractography using diffusion magnetic resonance imaging (MRI). Finally, we mimicked the clinical situation by delivering sustained 130 Hz stimulation at IL at the most effective field orientation and followed changes in resting-state functional connectivity with IL using functional MRI. To help interpretation of responses in functional connectivity, we stimulated only the left IL, which we did not expect to evoke measurable changes in the rat behavior.ResultsThe AMG evoked responses depended systematically on the IL stimulation field orientation and yielded the maximum response in near vertical field orientation in accordance with tractography. Sustained 130 Hz stimulation at a field orientation yielding the strongest AMG evoked responses increased functional connectivity between IL and AMG on the stimulation side.ConclusionThese findings suggest that OSS in 3D provides a new approach to optimize the DBS for every individual patient with a single stimulation probe implantation.

The advent of new, advanced quantitative MRI metrics allows for in vivo evaluation of multiple biological processes highly relevant for ageing. The presented study combines several MRI parameters hypothesised to detect distinct biological characteristics as myelin density, cellularity, cellular membrane integrity and iron concentration. 116 healthy volunteers, continuously distributed over the whole adult age span, underwent a multi-modal MRI protocol acquisition. Scatterplots of individual MRI metrics revealed that certain MRI protocols offer much higher sensitivity to early adulthood changes while plateauing in higher age (e.g., global functional connectivity in cerebral cortex or orientation dispersion index in white matter), while other MRI metrics provided reverse ability—stable levels in young adulthood with sharp changes with rising age (e.g., T1ρ and T2ρ). Nonetheless, despite the previously published validations of specificity towards microstructural biology based on cytoarchitectonic maps in healthy population or alterations in certain pathologies, several metrics previously hypothesised to be selective to common measures failed to show similar scatterplot distributions, pointing to further confounding factors directly related to age. Furthermore, other metrics, previously shown to detect different biological characteristics, exhibited substantial intercorrelations, be it due to the nature of the MRI protocol itself or co-dependence of relevant biological microstructural processes. All in all, the presented study provides a unique basis for the design and choice of relevant MRI parameters depending on the age group of interest. Furthermore, it calls for caution in simplistic biological inferences in ageing based on one simple MRI metric, even though previously validated under other conditions. Complex multi-modal approaches combining several metrics to extract the shared subcomponent will be necessary to achieve the desired goal of histological MRI.

This study explored the effectiveness of a short-term, low-cost experiential learning intervention on undergraduate students' development of innovation capacities. Data were collected from 90 students at a large Midwestern public institution across two randomly assigned conditions: those who received only a video-based innovation lecture and those who received the video-based lecture in addition to an in-class pedagogical intervention. Notably with respect to treatment validity, the instructor for the in-class pedagogical intervention was the same for all students. Results suggested that students who participated in the theoretically-derived pedagogical exercise developed their innovation capacities to a greater degree than their peers in the group that did not receive the in-class reinforcement. Study importance and implications are discussed.

Abstract The recently introduced orientation selective deep brain stimulation (OS-DBS) technique freely controls the direction of the electric field’s spatial gradient by using multiple contacts with independent current sources within a multielectrode array. The goal of OS-DBS is to align the electrical field along the axonal track of interest passing through the stimulation site. Here we utilized OS-DBS with a planar 3-channel electrode for stimulating the rat entorhinal cortex (EC) and medial septal nucleus (MSN), two promising areas for DBS treatment of Alzheimer’s disease. The brain responses to OS-DBS were monitored by whole brain functional magnetic resonance imaging (fMRI) at 9.4 T with Multi-Band Sweep Imaging with Fourier Transformation (MB-SWIFT). Varying the in-plane OS-DBS stimulation angle in the EC resulted in activity modulation of multiple downstream brain areas involved in memory and cognition. Contrary to that, no angle dependence of brain activations was observed when stimulating the MSN, consistent with predictions based on the electrode configuration and on the main axonal directions of the targets derived from diffusion MRI tractography and histology. We conclude that tuning the OS-DBS stimulation angle modulates the activation of brain areas relevant to Alzheimer’s disease, thus holding great promise in the DBS treatment of the disease.

Introduction: The role of objective parameters in terms of improvement of the accuracy of high-resolution computed tomography (HRCT) of the temporal bone in the diagnosis of otosclerosis remains unclear. Objectives: To investigate the relationship between the density of the fissula antefenestram (FAF) and of the width of the transversal section of the basal turn of the cochlea (BTC), and the diagnosis of otosclerosis. Methods: This is a retrospective study in which preoperative HRCT data from ears of patients submitted to stapedotomy due to otosclerosis (case group) were evaluated. For the control group, normal hearing ears having undergone HRCT for other purposes were included. Case and control HRCT images were objectively assessed by an experienced blinded radiologist. During this evaluation, measurements of the relative radiological density of the FAF and of the transversal section of the BTC were obtained. The results were compared between the groups. Also, a receiver operating characteristic curve was created and the area under the curve (AUC) was calculated for each variable. Significance level was set at .05. Results: 40 ears were included in each group. Case ears presented reduced values for the relative radiological density on the FAF (p-value

The population of the Venafro Valley (Southern Italy) faces various type of air pollution problems (industrial facilities, traffic, and biomass combustion). To estimate exposure to various pollution sources, a multi-stage random forest model was used, integrating particulate matter (PM) data with satellite observations, land-use patterns, and meteorological information generating maps of PM2.5 concentration. Four distinct PM2.5 exposure categories were established using the quartile method. To assess the association between PM2.5 and cause-specific mortality and morbidity, a time-dependent and sex-specific Cox multiple regression analysis was conducted, adjusting for age classes. In addition, the hazard ratios were accompanied by a probability measure of the strength of the evidence toward a hypothesis of health risk associated with the exposure under study (1−p value). The whole cohort was exposed to PM2.5 annual levels exceeding the 5 µg/m3 limit recommended by the World Health Organization. Mortality excesses were observed in class 3 for both sexes for cardiac heart diseases. Excesses of cardiovascular diseases were observed for both sexes in class 3 and 4. The study highlights significant signals warranting mitigation actions, which regional authorities are currently considering. [ABSTRACT FROM AUTHOR]

Gender medicine studies how health status and diseases differ between men and women in terms of prevention, therapeutic approach, prognosis, and psychological and social impact. Sex and gender analyses have been demonstrated to improve science, contributing to achieving real appropriateness and equity in the cure for each person. Therefore, it is fundamental to consider, both in preclinical and clinical research, the different clinical and biological features associated with sex and/or gender, where sex differences are mainly influenced by biological determinants and gender ones by socio-cultural and economic matters. This article was developed to provide knowledge and methodological tools for the development of studies/research protocols in which sex and gender should be taken into account. [ABSTRACT FROM AUTHOR]

This prospective study aimed to (1) compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with respect to conventional imaging (computed tomography (CT) and bone scintigraphy (BS)) in the primary staging of high-risk prostate cancer (PCa) patients and (2) validate PSMA-PET/CT accuracy in pelvic nodal staging in comparison with postoperative histopathology and assess PSMA-PET/CT's impact on patient management. Sixty castration-sensitive high-risk (ISUP 4–5 and/or PSA > 20 ng/mL and/or cT3) PCa patients eligible for radical prostatectomy were enrolled (median PSA 10.10 [IQR: 6.22–17.95] ng/mL). PSMA-PET/CT, compared with CT, identified nodal (N) and/or distant metastases (M1) in 56.7% (34/60) vs. 13.3% (8/60) (p < 0.001) of patients: N + 45% vs. 13.3% (p < 0.001), M1a 11.7% vs. 1.7% (p = 0.03), M1b 23.3% vs. 1.7% (p < 0.001). Compared with BS, PSMA-PET/CT localized unknown skeletal metastases in 15% (9/60) of cases, with no false negative findings. Overall, PSMA-PET/CT led to a TNM upstaging in 45.0% (27/60) of cases, with no evidence of downstaging, resulting in a change in management in up to 28.8% (17/59) of patients. Compared with histopathology data (n = 32 patients), the per-patient accuracy of PSMA-PET/TC for detecting pelvic nodal metastases was 90.6%. Overall, the above evidence supports the use of PSMA-PET/CT in the diagnostic workup of high-risk prostate cancer staging. [ABSTRACT FROM AUTHOR]