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Abstract Late onset multiple sclerosis (LOMS) represents between 0.6 and 12% of all MS patients. However, little is known on the incidence of LOMS in the general population. Therefore, we aimed to study the annual incidence of LOMS in a population-based cohort. The study was conducted in the province of Catania, Italy. Case ascertainment was conducted retrospectively including all patients aged ≥ 50 years at onset and with the onset between 2005 and 2020. Incidence rates (IR) have been calculated for all the study period, according to sex, age classes and for subperiods. Incidence rate ratios (IRR) have been computed to compare incidence rates. During the study period, 183 patients with LOMS were identified (113 women; 61.8%). The mean age at onset was 55.8 ± 5.4 years and the main phenotype was Relapsing Remitting MS (n = 123; 67.2%). The average annual crude IR was 2.87/100,000 person-years (95% Confidence Intervals, CI 2.31–3.13). IR increased from 2.54/100,000 in 2005–2010 to 3.32/100,000 in 2016–2020, especially in in the age group 60–69 (IRR 3.48; 95%CI 1.41–9.76; p-value 0.002). In conclusion, an increased IR over the time was observed in the age-group 60–69, possibly reflecting an increased age at onset of MS.

The present study is aimed at the characterization of artifacts excavated in the necropolis surrounding the mausoleum of the Aga Khan in Aswan (Egypt), as part of the Mummies Investigations Anthropological & Scientific West Aswan Necropolis (MIASWAN) project. Four cartonnages and some pottery shards were investigated on-site by means of non-destructive and micro-destructive techniques, such as attenuated total reflection/Fourier transform infrared spectroscopy (ATR/FTIR) and visible reflectance spectroscopy Vis-RS). Thanks to the use of these techniques, several pigments employed in the creation of the artifacts were identified. Due to the impossibility of transporting the investigated objects out of Egypt, a first-ever on-site characterization of the artifacts from this important excavation was carried out through scientific methodologies. These extreme conditions made the use of analytical instrumentation very challenging. Nevertheless, several characteristic pigments and hues were successfully identified.

Wernicke encephalopathy (WE) is a rare but severe neurological syndrome characterized, in its classic form, by the acute onset of ocular disturbances, ataxia, and cognitive impairment. It is caused by a deficiency of thiamine (vitamin B1) and mainly affects chronic alcoholics, although it can also affect patients with pathologies that lead to malnutrition. We present a case of a 58-year-old woman, who presented with significant weight loss over the past 6 months and who came to the emergency department for episodes of repetitive vomiting and a sleepy state. The patient underwent blood chemistry tests and a brain CT scan, which revealed symmetrical and bilateral hypodensity of the medial portion of the thalamus, tectal plate, and periaqueductal gray matte, suggestive of WE. She was subsequently referred to the Department of Neurology and underwent a brain MRI, which confirmed the clinical suspicion. She also had an abdominal CT scan and ileo-colonoscopy and was diagnosed with Crohn's disease. Immediately after the clinical diagnosis of WE, a replacement therapy based on intravenous thiamine at high doses was promptly set up, and the patient improved from a clinical point of view.Wernicke encephalopathy can be difficult to diagnose when it occurs in non-alcoholic patients; WE associated with IBD is a rare condition, and it can present with atypical and more subtle symptoms. Radiologists and physicians must be aware of this condition and imaging findings for rapid diagnosis and treatment.

We present a review of the latest framework achievements in geoarchaeological sciences applied to microstratigraphic and biomolecular studies of prehistoric archaeological contexts, highlighting the importance of musealized archaeological stratigraphies. We assess how today's scientific and technological accomplishments can be tailored for archaeological human ecology studies with analytical ensembles that provide unprecedented results. Sampling and processing workflows originating from resin consolidation and thin section micromorphology of undisturbed blocks of archaeological soils and sediments, guarantee subsampling accuracy at the micrometre scale granting access to individual components otherwise impossible to target: the achievable information yield makes even the smallest soil samples potential sources of pioneering discoveries. Yet, archaeological excavations are still the primary mode of retrieving new soil samples. We argue that, when dealing with archaeological sites that were excavated and partially musealised in the past, the exploration of related museum collections should be prioritized as perspective source of new study samples. Analysing old and potentially very informative samples, with an approach that we define as “Green Archaeology”, may represent a source of well-structured primary data as well as a means for planning new excavations, delivering novel discoveries while safeguarding site integrity and promoting Third Mission valorisation of sites and heritage dormant collections.

Abstract Novel technologies such as complex magnetic fields—CMFs represent an eco-sustainable proposal to counteract the infection associated to resistant microorganisms. The aim of this study was to evaluate the effect of two CMF programs (STRESS, ANTIBACTERIAL) against clinical antifungal resistant C. albicans also evaluating their uneffectiveness on gingival fibroblasts (hGFs). The STRESS program was more efficacious on C. albicans biofilm with up to 64.37% ± 10.80 of biomass and up to 99.19% ± 0.06 CFU/ml reductions in respect to the control also inducing an alteration of lipidic structure of the membrane. The MTT assay showed no CMFs negative effects on the viability of hGFs with a major ROS production with the ANTIBACTERIAL program at 3 and 24 h. For the wound healing assay, STRESS program showed the best effect in terms of the rate migration at 24 h, showing statistical significance of p

Agriculture is one of the most essential activities for humanity. Systems capable of automatically harvesting a crop using robots or performing a reasonable production estimate can reduce costs and increase production efficiency. With the advancement of computer vision, image processing methods are becoming increasingly viable in solving agricultural problems. Thus, this work aims to count green oranges directly from trees through video footage filmed in line along a row of orange trees on a plantation. For the video image processing flow, a solution was proposed integrating the YOLOv4 network with object-tracking algorithms. In order to compare the performance of the counting algorithm using the YOLOv4 network, an optimal object detector was simulated in which frame-by-frame corrected detections were used in which all oranges in all video frames were detected, and there were no erroneous detections. Being the scientific and technological innovation the possibility of distinguishing the green color of the fruits from the green color of the leaves. The use of YOLOv4 together with object detectors managed to reduce the number of double counting errors and obtained a count close to the actual number of oranges visible in the video. The results were promising, with an mAP50 of 80.16%, mAP50:95 of 53.83%, precision of 0.92, recall of 0.93, F1-score of 0.93, and average IoU of 82.08%. Additionally, the counting algorithm successfully identified and counted 204 oranges, closely approaching the actual count of 208. The study also resulted in a database with an amount of 644 images containing 43,109 orange annotations that can be used in future works.

The imbalance in skin microbiota is characterized by an increased number of pathogens in respect to commensal microorganisms. Starting from a skin microbiota collection, the aim of this work was to evaluate the possible role of Pomegranate (Punica granatum L.) Peel Extract (PPE) in restoring the skin microbiota balance acting on Staphylococcus spp. PPE was extracted following green methodology by using n-butane and the Dimethyl Ether (DME) solvents and analyzed for phytochemical composition and antimicrobial activity. The PPE antimicrobial action was evaluated against Gram +, Gram - bacteria and yeast reference strains and the most effective extract was tested against the main skin microbiota isolated strains. PPE extracted with DME showed the best antimicrobial action with MICs ranging from 1 to 128 mg/mL; the main active compounds were Catechin, Quercetin, Vanillic acid and Gallic acid. The PPE in DME anti-adhesive effect was examined against S. epidermidis and S. aureus mono and dual-species biofilm formation by biomass quantification and CFU/mL determination. The extract toxicity was evaluated by using Galleria mellonella larvae in vivo model. The extract displayed a significant anti-adhesive activity with a remarkable species-specific action at 4 and 8 mg/mL against S. epidermidis and S. aureus mono and dual-species biofilms. PPE in DME could represent an eco-sustainable non-toxic strategy to affect the Staphylococcal skin colonization in a species-specific way. The innovation of this work is represented by the reuse of food waste to balance skin microbiota.

Psychological theories of actual causation aim to characterizewhich of multiple causes of an event is singled out as the pri-mary cause. We present one such theory called the continu-ity account of actual causation. The continuity account treatsevents as changes of state in continuous time and traces a se-quence of stage changes backwards through time from an eventto its primary cause. The account is broadly compatible withthe physical process view of causation and we test it by ask-ing people to identify the primary cause of events occurring insimple physical systems. An initial experiment confirms thatroot causes are more likely to be chosen as primary causes thanare immediate causes. A second experiment demonstrates thatroot causes that have temporal continuity with the effect arepreferred even when probability raising accounts would pre-dict otherwise. The results of both experiments are consistentwith the continuity account, and suggest that inferences aboutchanges of state in continuous time may underpin an importantclass of actual causation judgments.

Recent studies indicate that mass concentration alone is not the best parameter to assess the toxicity and the health effects of particulate matter (PM). Indeed, the chemical composition of the particles plays an important role, and oxidative potential (OP) measurements are being proposed as an alternative way to assess toxicity. The European Union (EU) is currently proposing a draft of the new air quality directive which includes OP measurements but does not specify the methods and/or protocols of analysis. In this light, the purpose of this study was to evaluate the feasibility of two literature assays, namely ascorbic acid (AA) and dithiothreitol (DTT), for routine PM analysis by testing urban PM filters from a one-year sampling campaign conducted by ARPA Lombardia. Indoor PM samples were also tested to emphasize the importance of monitoring closed spaces in which people spend most of their time. Following the optimization of the DTT assay, both methods proved to be suitable for large-scale PM analysis. The results show that the oxidative strength of urban PM is constant throughout the year for the outdoor samples (OPAA: 0.067–0.39 nmol min−1 m−3; OPDTT: 0.033–0.109 nmol min−1 m−3), indicating the need for routine OP monitoring. Instead, indoor areas were characterized by particles with a lower oxidative capacity (OPAA: 5.40–24 pmol min−1 m−3; OPDTT: 9.7–32 pmol min−1 m−3), driven both by lower concentrations and a different chemical composition. All the data collected highlight the need to add this parameter as part of the chemical characterization of PM, moving in the same direction as the new EU air quality directive.

Headache is a frequent symptom among patients with hypermobility spectrum disorders. This mini review focuses specifically on a challenging aspect of headache evaluation in all patients, but especially those with hypermobility – the orthostatic headache. While the differential for an orthostatic headache is overall limited, patients with hypermobility disorders have risk factors for all of the most commonly encountered orthostatic headache disorders. The most common conditions to produce orthostatic headaches are discussed – spontaneous intracranial hypotension, cervicogenic headache, and postural orthostatic tachycardia syndrome. Less common etiologies of orthostatic headache pertinent to any patient are presented in table format.

ABSTRACT Objectives: to develop a responsive website focused on treatment adherence for adult users living with HIV. Methods: technological study conducted between August and October 2020, in the light of Pierre Lévy’s theoretical-philosophical framework, using the Double Diamond Process methodology associated with the five stages of The Elements of User Experience framework. Results: it was developed the responsive website Positive Care (Positive o Cuidado), composed of an initial presentation screen and 13 other screens named: Family Health and You; Undetectable = Untransmissible; Antiretroviral Drugs; Routine Tests; Vaccination; Antiretroviral Delivery; Drug Interactions; Combined Prevention; Support Services; Healthy Life; Family and Reproductive Planning; Covid 19; and Questions, Curiosities, and Myths. Final Considerations: the responsive website was developed based on the software design and programming process and has requirements/functionalities with the potential to strengthen the collective intelligence about HIV and, consequently, to promote treatment adherence by its users.

Abstract Iron homeostasis and dyserythropoiesis are poorly investigated in pyruvate kinase deficiency (PKD), the most common glycolytic defect of erythrocytes. Herein, we studied the main regulators of iron balance and erythropoiesis, as soluble transferrin receptor (sTfR), hepcidin, erythroferrone (ERFE), and erythropoietin (EPO), in a cohort of 41 PKD patients, compared with 42 affected by congenital dyserythropoietic anemia type II (CDAII) and 50 with hereditary spherocytosis (HS). PKD patients showed intermediate values of hepcidin and ERFE between CDAII and HS, and clear negative correlations between log-transformed hepcidin and log-EPO (Person’s r correlation coefficient = − 0.34), log-hepcidin and log-ERFE (r = − 0.47), and log-hepcidin and sTfR (r = − 0.44). sTfR was significantly higher in PKD; EPO levels were similar in PKD and CDAII, both higher than in HS. Finally, genotype–phenotype correlation in PKD showed that more severe patients, carrying non-missense/non-missense genotypes, had lower hepcidin and increased ERFE, EPO, and sTFR compared with the others (missense/missense and missense/non-missense), suggesting a higher rate of ineffective erythropoiesis. We herein investigated the main regulators of systemic iron homeostasis in the largest cohort of PKD patients described so far, opening new perspectives on the molecular basis and therapeutic approaches of this disease.

Purpose: A case of a patient receiving warfarin for pulmonary embolism (PE) concomitantly with rifampin for treatment of active pulmonary tuberculosis (PTB) is presented. A successful clinical intervention whereby the patient achieved therapeutic anticoagulation after switching to an alternative rifamycin antibacterial, rifabutin, is described. Summary: The drug-drug interaction between warfarin and rifampin is well known and documented. However, to our knowledge, no case reports of the interaction between warfarin and rifabutin have been published, and literature describing this interaction is lacking. We describe the case of a 27-year-old African American female referred to a pharmacist-managed anticoagulation clinic for treatment of PE with warfarin. The patient was also being treated for active tuberculosis with rifampin, isoniazid, pyrazinamide, and ethambutol. Warfarin was initiated and over the course of 1 month was continuously increased to a total weekly dose (TWD) of 140 mg without ever achieving the target international normalized ratio (INR) of 2 to 3. In an attempt to reach the target INR, rifampin was switched to rifabutin to minimize the drug-drug interaction with warfarin. Six days after this switch, the target INR was achieved with a lower warfarin TWD of 115 mg. Rifabutin interacts with warfarin to a lesser degree than rifampin and may be considered as an alternative in patients taking warfarin who require treatment with a rifamycin. Conclusion: For patients in whom therapeutic anticoagulation with warfarin has been difficult, the use of rifabutin may be considered in place of rifampin when the concomitant use of a rifamycin is required.

We investigated by targeted next generation sequencing the genetic bases of hereditary spherocytosis in 25 patients and compared the molecular results with the biochemical lesion of RBC membrane obtained by SDS-PAGE analysis. The HS diagnosis was based on available guidelines for diagnosis of congenital hemolytic anemia, and patients were selected because of atypical clinical presentation or intra-family variability, or because presented discrepancies between laboratory investigation and biochemical findings. In all patients but 5 we identified pathogenic variants in SPTA1, SPTB, ANK1, SLC4A1, EPB42 genes able to justify the clinical phenotype. Interestingly, a correspondence between the biochemical lesion and the molecular defect was identified in only 11/25 cases, mostly with band 3 deficiency due to SLC4A1 mutations. Most of the mutations in SPTB and ANK1 gene didn’t hesitate in abnormalities of RBC membrane protein; conversely, in two cases the molecular lesion didn’t correspond to the biochemical defect, suggesting that a mutation in a specific cytoskeleton protein may result in a more complex RBC membrane damage or suffering. Finally, in two cases the HS diagnosis was maintained despite absence of both protein defect and molecular lesion, basing on clinical and family history, and on presence of clear laboratory markers of HS. The study revealed complex relationships between the primary molecular lesion and the final effect in the RBC membrane cytoskeleton, and further underlines the concept that there is not a unique approach to the diagnosis of HS.