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Intro: The ongoing outbreak of Monkeypoxvirus (MPXV) turned the spotlight back on zoonotic poxviruses (ZPs). MPXV, Cowpoxvirus (CPXV) and Vaccinia Virus (VV) are the zoonotic species belonging to the Orthopoxvirus (OPXV) genus in the Poxviridae family. The diagnostics currently available are designed for specialised laboratories and are unsuitable for field and point of care use. Here we present a sensitive and specific low-tech workflow for the rapid identification of ZPs. Methods: An isothermal (Hyperfluux) multiple dye assay, targeting the OPXV RNA Polimerase (RPO) was designed and validated. Analytical sensitivity was assessed by using both a sintetic dsDNA fragment and MPXV field samples. Standards were assigned to absolute values by using digital PCR and a probe- based assay. LOD was estimated by fitting a probit regression model with a prediction level of 95% after running a negative sample and 5 low positive samples in 5 replicates. Specificity was assessed by using bacterial and viral DNA from herpesviruses, zoonotic parapoxviruses and orthopoxviruses. For field applications, Xample Prep tool was employed to treat MPXV clinical samples prior amplification; the results were then compared to those obtained with DNAs extracted with standard method. Findings: The assay resulted highly sensitive with estimated LOD of 18,6 DNA copies/μl and rapid being performed in 35 minutes overall from samples to results. Only Zoonotic OPXV DNA was amplified showing a high specificity and comparable results were obtained from purified viral DNA and Xample Prep treated samples. Discussion: For its performances, rapidity, thermostable reagents, and ability to efficiently amplify clinical samples, without prior DNA extraction, the assay is suitable for use in low-resource settings, in the field and in community clinics. Conclusion: Besides clinical applications, to allow proper patients' management, the availability of such a diagnostic workflow can be critical to understand the real incidence and prevalence of zoonotic OPXV among humans and animal reservoirs.

Chikungunya is a mosquito-borne infection of humans, and its diffusion has increased worldwide. In 2007 an outbreak occurred in Italy. In this study, the antibody response of 133 patients followed up starting from the acute phase of infection was investigated. Antibody titres were periodically scored up to 1 year since the infection: 82.7% of the IgM antibody disappeared within 12 months, and the IgG response lasted longer than 12 months. Nevertheless, the IgG mean titre was lower in 95.5% of patients at the end of follow-up, thus suggesting a decrease within a relatively short period.

The high heterogeneity of some residual biomasses makes rather difficult their energy use and standardisation is a key aspect for these fuel products. Torrefaction is an interesting process used to improve the quality of ligno-cellulosic biomasses and to achieve standardisation. In the present study torrefaction has been employed on residues and by-products deriving from sunflower production chain, in particular sunflower stalks and oil press cake. The thermal behaviour of materials has been studied at first by thermo-gravimetric analysis in order to identify torrefaction temperatures range. Different residence time and torrefaction temperatures have been employed in a bench top torrefaction reactor afterwards. Analyses of raw and torrefied materials have been carried out to assess the influence of the process. As a consequence of torrefaction, the carbon and ash contents increase while the volatilisation range is reduced making the material more stable and standardised. Mass yield, energy yield and energy densification reach values of about 60 %, 80 % and 1.33 for sunflower stalks and 64 %, 85 % and 1.33 for sunflower oil press cake respectively. As highlighted by results, torrefaction is more interesting for sunflower stalks than oil cake and husks because of the different starting characteristics. Untreated oil cake and husks already show a good high heating value and the eventual torrefaction should be mild. On the contrary for sunflower stalks the process is more useful and could be more severe.

Abstract Robust biomarkers for anti-epileptic drugs (AEDs) activity in the human brain are essential to increase the probability of successful drug development. The frequency analysis of electroencephalographic (EEG) activity, either spontaneous or evoked by transcranial magnetic stimulation (TMS-EEG) can provide cortical readouts for AEDs. However, a systematic evaluation of the effect of AEDs on spontaneous oscillations and TMS-related spectral perturbation (TRSP) has not yet been provided. We studied the effects of Lamotrigine, Levetiracetam, and of a novel potassium channel opener (XEN1101) in two groups of healthy volunteers. Levetiracetam suppressed TRSP theta, alpha and beta power, whereas Lamotrigine decreased delta and theta but increased the alpha power. Finally, XEN1101 decreased TRSP delta, theta, alpha and beta power. Resting-state EEG showed a decrease of theta band power after Lamotrigine intake. Levetiracetam increased theta, beta and gamma power, while XEN1101 produced an increase of delta, theta, beta and gamma power. Spontaneous and TMS-related cortical oscillations represent a powerful tool to characterize the effect of AEDs on in vivo brain activity. Spectral fingerprints of specific AEDs should be further investigated to provide robust and objective biomarkers of biological effect in human clinical trials.

Abstract Objective Transcranial magnetic stimulation (TMS) produces characteristic deflections in the EEG signal named TMS‐evoked EEG potentials (TEPs), which can be used to assess drug effects on cortical excitability. TMS can also be used to determine the resting motor threshold (RMT) for eliciting a minimal muscle response, as a biomarker of corticospinal excitability. XEN1101 is a novel potassium channel opener undergoing clinical development for treatment of epilepsy. We used TEPs and RMT to measure the effects of XEN1101 in the human brain, to provide evidence that XEN1101 alters cortical excitability at doses that might be used in future clinical trials. Methods TMS measurements were incorporated in this Phase I clinical trial to evaluate the extent to which XEN1101 modulates TMS parameters of cortical and corticospinal excitability. TEPs and RMT were collected before and at 2‐, 4‐, and 6‐hours post drug intake in a double‐blind, placebo‐controlled, randomized, two‐period crossover study of 20 healthy male volunteers. Results Consistent with previous TMS investigations of antiepileptic drugs (AEDs) targeting ion channels, the amplitude of TEPs occurring at early (15–55 msec after TMS) and at late (150–250 msec after TMS) latencies were significantly suppressed from baseline by 20 mg of XEN1101. Furthermore, the RMT showed a significant time‐dependent increase that correlated with the XEN1101 plasma concentration. Interpretation Changes from baseline in TMS measures provided evidence that 20 mg of XEN1101 suppressed cortical and corticospinal excitability, consistent with the effects of other AEDs. These results support the implementation of TMS as a tool to inform early‐stage clinical trials.

Homer Legacy software is a well-known software for simulation of small hybrid systems that can be used for both design and research. This dataset is a set of files generated by Homer Legacy bringing the simulation results of hybrid energy systems over the last seven years, as a consequence of the research work led by Dr. Alexandre Beluco, Federal University of Rio Grande do Sul, in southern Brazil. The data correspond to twelve papers published in the last seven years. Two of them describe hydro PV hybrid systems with photovoltaic panels operating on the water surface of reservoirs. One of these twelve papers suggests the modeling of hydropower plants with reservoirs and the other the modeling of pumped hydro storage, and a third still uses these models in a place that could receive both the two types of hydroelectric power plant. The other simulated hybrid systems include wind turbines, diesel generators, batteries, among other components. This data article describes the files that integrate this dataset and the papers that have been published presenting the hybrid systems under study and discussing the results. The files that make up this dataset are available on Mendeley Data repository at https://doi.org/10.17632/ybxsttf2by.2.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a fast and minimally invasive methodology with a crucial impact on patients’ management. It has an important and established role in the diagnosis and staging of mediastinal and abdominal malignancies, but little is discussed in the literature on the usefulness of this technique in the diagnosis of infectious diseases. In the current report, we present three different cases where EUS was essential for reaching the diagnosis of tuberculosis and paracoccidiodomicosis in cases otherwise seen as malignant. In conclusion, EUS was successful not only in obtaining enough cells for morphological analysis, but also for the production of cell blocks and assessment of the presence of the microorganisms by special stains. EUS allied to fine needle biopsy was an important tool in determining diagnoses of enlarged lymph nodes, revealing the diagnosis of infectious diseases in cases otherwise seen as malignant. The wide use of this methodology in cases such as those reported here cannot only rule out malignancy, but also aid critically ill patients by installing early proper therapy without the need for aggressive interventions.

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants (ECs), whose presence in the environment is of increasing concern due to their widespread use and possible detrimental effects on wildlife and humans. These chemicals may present multiple hazardous properties such as environmental persistence, toxicity, high mobility, and the potential for bioaccumulation. In this study, extended bibliographic research was conducted to characterize the removal efficiency (RE) of PPCPs in wastewater treatment plants (WWTPs) considering different technologies. Measured values of RE were collected from the literature or calculated for 251 compounds. The molecular structure of the 245 PPCPs were used as the input to generate predictions of multiple properties using several QSAR tools, such as the OECD Toolbox, OPERA, EPI Suite™, and QSAR-ME Profiler. These predictions were compared to regulatory thresholds to identify hazardous chemicals and to screen persistent, mobile and toxic (PMT) or persistent, bioaccumulative and toxic (PBT) substances. Finally, chemicals were prioritized by combining values of RE and QSAR predictions for multiple properties. A total of 16 out of the 245 molecules were prioritized as the most hazardous compounds to the aquatic environment and, among these, six were associated with potential risk due to their exposure concentrations reported in the literature.

Arboviral diseases are a growing global health concern. Pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) can underlie encephalitis due to West Nile virus (WNV) (∼40% of patients) and tick-borne encephalitis (TBE, due to TBE virus [TBEV]) (∼10%). We report here that these auto-Abs can also underlie severe forms of rarer arboviral infections. Auto-Abs neutralizing high concentrations of IFN-α2, IFN-β, and/or IFN-ω are present in the single case of severe Powassan virus (POWV) encephalitis studied, two of three cases of severe Usutu virus (USUV) infection studied, and the most severe of 24 cases of Ross River virus (RRV) disease studied. These auto-Abs are not found in any of the 137 individuals with silent or mild infections with these three viruses. Thus, auto-Abs neutralizing type I IFNs underlie an increasing list of severe arboviral diseases due to Flaviviridae (WNV, TBEV, POWV, USUV) or Togaviridae (RRV) viruses transmitted to humans by mosquitos (WNV, USUV, RRV) or ticks (TBEV, POWV)., (© 2024 Gervais et al.)

Background: Despite its wide diffusion in surgical procedures, very few experiences are reported so far about the possible applications of remote proctoring (RP) in structural heart interventions., Aims: Our aim was to demonstrate the feasibility, safety, and efficacy of RP during transcatheter edge-to-edge repair using a mixed reality-based head-mounted display (HMD)., Methods: Two users (a doctor and a proctor), wearing HMDs, were connected through a 5G network, allowing them to share audio and video signals. During the procedure, the proctor was located in a contiguous room, without any direct connection with the operator. The primary endpoint was noninferiority of HMD-mediated interaction if compared with direct in-person interaction. It was assessed using an operator-proctor interaction test based on six questions asked by the doctor to the proctor on six key procedural steps., Results: Between September 2021 and April 2022, nine patients were enrolled in the study (15 clips delivered). The primary endpoint was reached in 9/15 clips implanted (60%). The first three failures were due to a chat software problem, and the others were linked with a 5G network malfunction. However, the HMD and its mixed reality tools were well tolerated by the operators, and no interference with the procedure was registered in any of the cases., Conclusions: In our experience, RP during structural heart interventions is feasible and efficacious. Wearing the HMD is comfortable and does not affect safety and effectiveness of interventional procedures. However, especially if considering a wide geographic use of this tool, a stable internet connection is imperative., (© 2024 Wiley Periodicals LLC.)

Background: SARS-CoV-2 is responsible for the ongoing global pandemic, and the continuous emergence of novel variants threatens fragile populations, such as immunocompromised patients. This subgroup of patients seems to be seriously affected by intrahost viral changes, as the pathogens, which are keen to cause replication inefficiency, affect the impaired immune system, preventing efficient clearance of the virus. Therefore, these patients may represent an optimal reservoir for the development of new circulating SARS-CoV-2 variants. The following study aimed to investigate genomic changes in SARS-CoV-2-positive immunocompromised patients over time., Methods: SARS-CoV-2-positive nasopharyngeal swabs were collected at different time points for each patient (patient A and patient B), extracted and then analyzed through next-generation sequencing (NGS). The resulting sequences were examined to determine mutation frequencies, describing viral evolution over time., Case Presentation: Patient A was a 53-year-old patient with onco-hematological disease with prolonged infection lasting for 51 days from May 28th to July 18th, 2022. Three confirmed SARS-CoV-2-positive samples were collected on May 28th, June 15th and July 4th. Patient B was 75 years old and had onco-hematological disease with prolonged infection lasting for 146 days. Two confirmed positive SARS-CoV-2 samples were collected at the following time points: May 21st and August 18th., Conclusion: Heat map construction provided evidence of gain and/or loss of mutations over time for both patients, suggesting within-host genomic evolution of the virus. In addition, mutation polymorphisms and changes in the SARS-CoV-2 lineage were observed in Patient B. Sequence analysis revealed high mutational pattern variability, reflecting the high complexity of viral replication dynamics in fragile patients., (© 2024. The Author(s).)

Purpose: To evaluate if background parenchymal enhancement (BPE) on contrast-enhanced mammography (CEM), graded according to the 2022 CEM-dedicated Breast Imaging Reporting and Data System (BI-RADS) lexicon, is associated with breast density, menopausal status, and age., Methods: This bicentric retrospective analysis included CEM examinations performed for the work-up of suspicious mammographic findings. Three readers independently and blindly evaluated BPE on recombined CEM images and breast density on low-energy CEM images. Inter-reader reliability was estimated using Fleiss κ. Multivariable binary logistic regression was performed, dichotomising breast density and BPE as low (a/b BI-RADS categories, minimal/mild BPE) and high (c/d BI-RADS categories, moderate/marked BPE)., Results: A total of 200 women (median age 56.8 years, interquartile range 50.5-65.6, 140/200 in menopause) were included. Breast density was classified as a in 27/200 patients (13.5%), as b in 110/200 (55.0%), as c in 52/200 (26.0%), and as d in 11/200 (5.5%), with moderate inter-reader reliability (κ = 0.536; 95% confidence interval [CI] 0.482-0.590). BPE was minimal in 95/200 patients (47.5%), mild in 64/200 (32.0%), moderate in 25/200 (12.5%), marked in 16/200 (8.0%), with substantial inter-reader reliability (κ = 0.634; 95% CI 0.581-0.686). At multivariable logistic regression, premenopausal status and breast density were significant positive predictors of high BPE, with adjusted odds ratios of 6.120 (95% CI 1.847-20.281, p = 0.003) and 2.416 (95% CI 1.095-5.332, p = 0.029) respectively., Conclusion: BPE on CEM is associated with well-established breast cancer risk factors, being higher in women with higher breast density and premenopausal status., (© 2024. Italian Society of Medical Radiology.)

Oropouche fever is caused by Oropouche virus (OROV), transmitted primarily through the bite of infected midges, particularly of the genus Culicoides . The virus is mainly circulating in Central and South America where several countries reported an ongoing outbreak. We report here two imported cases of OROV infection identified in Italy, late May-early June 2024. These cases indicate that in the shadow of a massive dengue outbreak in the Americas, the Oropouche outbreak might be more widespread than previously estimated.

Aligner orthodontics has gained significant popularity as an alternative to traditional braces because of its aesthetic appeal and comfort. The biomechanical principles that underlie aligner orthodontics play a crucial role in achieving successful outcomes. The biomechanics of aligner orthodontics revolve around controlled force application, tooth movement, and tissue response. Efficient biomechanics in aligner orthodontics involves consideration of attachment design and optimized force systems. Attachments are tooth-colored shapes bonded to teeth, aiding in torque, rotation, and extrusion movements. Optimized force systems ensure that forces are directed along the desired movement path, reducing unnecessary strain on surrounding tissues. Understanding and manipulating the biomechanics of aligner orthodontics is essential for orthodontists to achieve optimal treatment outcomes. This approach requires careful treatment planning, considering the mechanics required for each patient's specific malocclusion. As aligner orthodontics continues to evolve, advances in material science and treatment planning software contribute to refining biomechanical strategies, enhancing treatment efficiency, and expanding the scope of cases that can be successfully treated with aligners., (Copyright © 2023 World Federation of Orthodontists. Published by Elsevier Inc. All rights reserved.)

In the mid-1990s, the identification of BRCA1/2 genes for breast cancer susceptibility led to testing breast MRI accuracy in screening women at increased risk. From 2000 onwards, ten intraindividual comparative studies showed the marked superiority of MRI: the sensitivity ranged 25-58% for mammography, 33-52% for ultrasound, 48-67% for mammography plus ultrasound, and 71-100% for MRI; specificity 93-100%, 91-98%, 89-98%, and 81-98%, respectively. Based on the available evidence, in 2006-2007, the UK National Institute for Clinical Excellence and the American Cancer Society recommended MRI screening of high-risk women, followed by other international guidelines. Despite evidence-based medicine ideally requiring randomised controlled trials (RCTs) for policy changes regarding screening procedures, breast MRI for high-risk screening was adopted in many countries worldwide. In 2019, the results of the "DENSE" RCT were published in favour of breast MRI screening of women with extremely dense breasts compared to mammography alone, showing a reduction of more than 80% of the interval cancer rate in women who attended MRI screening. Even though international recommendations in favour of this practice were issued, substantial obstacles still prevent health systems from adopting breast MRI for screening women with extremely dense breasts. A paradox is evident: we adopted a screening procedure without evidence from RCTs, and now that we have this level-1 evidence for the same procedure, we fail to do so. This critical review tries to explain the differences between the two cases, as examples of the complex pathways of translating radiological research into everyday practice.Critical relevance statement The high-level evidence in favour of breast MRI screening of women with extremely dense breasts is failing to persuade policy makers to translate this into clinical practice.Key points• Breast MRI screening of high-risk women was adopted on basis of the evidence provided by test accuracy comparative studies showing an MRI performance greatly superior to that of mammography.• Breast MRI screening of women with extremely dense breasts has not been adopted although the evidence of a large reduction in interval cancer rate from a RCT.• We illustrate the differences between the two cases, as an example of the complex ways of translation of radiological research in clinical practice according to the EBM theory., (© 2024. The Author(s).)

The COVID-19 pandemic led to a surge of critically ill patients and a sudden increase in the need for oxygen treatment worldwide. Pre-existing gaps in oxygen systems became apparent, and governments, multilateral agencies, and other partners scrambled to increase the production, supply, and use of oxygen to meet this need. The importance of an oxygen ecosystem that is appropriate for the local context became clear. This review describes strategies for oxygen ecosystems in middle-income countries, with specific experiences from Lebanon, following the authors' extensive assessment of the country's oxygen ecosystem, on behalf of the government and UNICEF. In the assessment, fifteen governmental hospitals were visited and evaluated using the UNICEF Oxygen System Planning Tool, discussions were held with key stakeholders, and documents were reviewed. An optimal oxygen ecosystem needs to take into consideration the production of oxygen and delivery to facilities, the maintenance system within facilities, and the clinical use of oxygen. Lebanon, a lower-middle income country in the Middle East, is contending with an extensive economic crisis affecting the health system. Eighteen recommendations for strengthening the oxygen ecosystem in Lebanon that are relevant for other middle-income countries include the establishment of a National Oxygen Committee, installation of additional oxygen plants, strengthened systems for maintenance and electricity supply, increased production, procurement and supply chain resilience, improved training and human resources, the use of data collection and regular information to guide the ecosystem, and integration of oxygen into the rest of the health system., Competing Interests: TB, CG, GR, HT, AD, MM, and RS are either employed by UNICEF or have received consultancy fees from UNICEF for the submitted work. TB declares personal fees from the World Bank, USAID, and the Wellcome Trust, all outside the submitted work. NH is employed by the Ministry of Public Health, Government of Lebanon., (Copyright © 2024 Tim Baker et al.)

Post-bariatric hypoglycaemia (PBH) is a metabolic complication of bariatric surgery (BS), consisting of low post-prandial glucose levels in patients having undergone bariatric procedures. While BS is currently the most effective and relatively safe treatment for obesity and its complications, the development of PBH can significantly impact patients' quality of life and mental health. The diagnosis of PBH is still challenging, considering the lack of definitive and reliable diagnostic tools, and the fact that this condition is frequently asymptomatic. However, PBH's prevalence is alarming, involving up to 88% of the post-bariatric population, depending on the diagnostic tool, and this may be underestimated. Given the prevalence of obesity soaring, and an increasing number of bariatric procedures being performed, it is crucial that physicians are skilled to diagnose PBH and promptly treat patients suffering from it. While the milestone of managing this condition is nutritional therapy, growing evidence suggests that old and new pharmacological approaches may be adopted as adjunct therapies for managing this complex condition., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: Carboplatin is still the cornerstone of the first-line treatment in advanced Epithelial Ovarian Cancer (aEOC) management and the clinical response to platinum-derived agents remains the major predictor of long-term outcomes., Patient and Methods: We aimed to identify the best treatment of the aEOC in terms of efficacy and safety, considering all treatment phases. A systematic literature search has been done to compare all treatments in aEOC population. Randomized trials with available survival and safety data published in the 2011-2022 timeframe were enclosed. Only trials reporting the BRCA or HRD (Homologous Recombination Deficiency) status were considered., Data Extraction and Synthesis: A ranking of treatment schedules on the progression-free survival (PFS) endpoint was performed. The random-effect model was used to elaborate and extract data. The Network Meta-Analysis (NMA) by Bayesian model was performed by STATA v17. Data on PFS were extracted in terms of Hazard ratio with relative confidence intervals., Results: This NMA involved 18 trials for a total of 9105 patients. Within 12 treatment groups, we performed 3 different sensitivity analyses including "all comers" Intention to Treat (ITT) population, BRCA-mutated (BRCAm), and HRD subgroups, respectively. Considering the SUCRA-reported cumulative PFS probabilities, we showed that in the ITT population, the inferred best treatment was niraparib plus bevacizumab with a SUCRA of 96.7. In the BRCAm subgroup, the best SUCRA was for olaparib plus chemotherapy (96,9). The HRD population showed an inferred best treatment for niraparib plus bevacizumab (SUCRA 98,4). Moreover, we reported a cumulative summary of PARPi toxicity, in which different 3-4 grade toxicity profiles were observed, despite the PARPi "class effect" in terms of efficacy., Conclusions: Considering all aEOC subgroups, the best therapeutical option was identified as PARPi plus chemotherapy and/or antiangiogenetic agents, suggesting the relevance of combinatory approaches based on molecular profile. This work underlines the potential value of "chemo-free" regimens to prolong the platinum-free interval (PFI)., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Reactions capable of transposing the oxidation levels of adjacent carbon atoms enable rapid and fundamental alteration of a molecule's reactivity. Herein, we report the 1,2-transposition of the carbon atom oxidation level in cyclic and acyclic tertiary amides, resulting in the one-pot synthesis of 1,2- and 1,3-oxygenated tertiary amines. This oxidation level transfer was facilitated by the careful orchestration of an iridium-catalyzed reduction with the functionalization of transiently formed enamine intermediates. A novel 1,2-carbonyl transposition is described, and the breadth of this redox transposition strategy has been further explored by the development of aminoalcohol and enaminone syntheses. The diverse β-functionalized amine products were shown to be multifaceted and valuable synthetic intermediates, accessing challenging biologically relevant motifs.

Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis., (© 2023 Gervais et al.)

In the present study, the antiviral activity of cannabinoids isolated from Cannabis sativa L. was assessed in vitro against a panel of SARS-CoV-2 variants, indicating cannabidiolic acid (CBDA) was the most active. To overcome the instability issue of CBDA, its methyl ester was synthesized and tested for the first time for its antiviral activity. CBDA methyl ester showed a neutralizing effect on all the SARS-CoV-2 variants tested with greater activity than the parent compound. Its stability in vitro was confirmed by ultra-high-performance liquid chromatography (UHPLC) analysis coupled with high-resolution mass spectrometry (HRMS). In addition, the capacity of both CBDA and its derivative to interact with the virus spike protein was assessed in silico . These results showed that CBDA methyl ester can be considered as a lead compound to be further developed as a new effective drug against COVID-19 infection.

Background: The optimal strategy for the treatment of recurrent and/or advanced endometrial cancer is still undefined. Recently, despite the lack of any predictive biomarker, the combination of pembrolizumab with lenvatinib has improved survival outcomes. We here report the long-term management of lung toxicity in a patient with endometrial cancer, and we critically review the current therapeutic options for this disease., Results: A patient with heavily pretreated endometrial cancer took pembrolizumab plus lenvatinib for 1 year, achieving a persistent partial response with a time to treatment failure of 18 months, despite relevant lung toxicity that did not affect the remarkable overall clinical benefit. A systematic review of this combination underlines the efficacy outcome despite toxicity. Interestingly, the literature review on lung toxicity suggested the role of anti-angiogenetic agents in the pathogenesis of lung cavitation, probably related to direct treatment activity, and disclosed a potential radiological sign predictive of the activity of anti-angiogenetic agents., Conclusion: We underline the efficacy of pembrolizumab plus lenvatinib in the current treatment landscape of endometrial cancer, underscoring the relevance of a correct management of toxicity., 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 © 2023 Staropoli, Salvino, Falcone, Farenza, Costa, Rossini, Manti, Crispino, Riillo, Ciliberto, Arbitrio, Tassone and Tagliaferri.)

Usutu virus (USUV) is an arthropod-borne flavivirus emerged in Africa in 1950s and in Eruope in 1990s causing a massive number of birds' deaths. The role of USUV as human pathogen has been only recently hypothesized and cases of USUV infection in humans remain limited and often related to immunocompromised subjects. Herein, we report a case of USUV meningoencephalitis infection in an immunocompromised patient with no history of previous flavivirus infection. The infection due to USUV evolved rapidly since hospital admission thus resulting fatal in few days after symptoms onset and, although not proven, a suspected bacteria co-infection has been hypothesized. Based on these findings, we suggested that when USUV meningoencephalitis is suspected in countries endemic, careful attention should be applied to neurological syndromes during summer months especially among immunocompromised patients., (© 2023. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

Several reports have indicated that SARS-CoV-2 infection displays unexpected mild clinical manifestations in people with cystic fibrosis (pwCF), suggesting that CFTR expression and function may be involved in the SARS-CoV-2 life cycle. To evaluate the possible association of CFTR activity with SARS-CoV-2 replication, we tested the antiviral activity of two well-known CFTR inhibitors (IOWH-032 and PPQ-102) in wild type (WT)-CFTR bronchial cells. SARS-CoV-2 replication was inhibited by IOWH-032 treatment, with an IC 50 of 4.52 μM, and by PPQ-102, with an IC 50 of 15.92 μM. We confirmed this antiviral effect on primary cells (MucilAir TM wt-CFTR) using 10 μM IOWH-032. According to our results, CFTR inhibition can effectively tackle SARS-CoV-2 infection, suggesting that CFTR expression and function might play an important role in SARS-CoV-2 replication, revealing new perspectives on the mechanisms governing SARS-CoV-2 infection in both normal and CF individuals, as well as leading to potential novel treatments.

The West Nile Virus (WNV) and Sindbis virus (SINV) are avian-hosted mosquito-borne zoonotic viruses that co-circulate in some geographical areas and share vector species such as Culex pipiens and Culex torrentium . These are widespread in Europe, including northern parts and Finland, where SINV is endemic, but WNV is currently not. As WNV is spreading northwards in Europe, we wanted to assess the experimental vector competence of Finnish Culex pipiens and Culex torrentium mosquitoes to WNV and SINV in different temperature profiles. Both mosquito species were found susceptible to both viruses and got infected via infectious blood meal at a mean temperature of 18 °C. WNV-positive saliva was detected at a mean temperature of 24 °C, whereas SINV-positive saliva was detected already at a mean temperature of 18 °C. Cx . torrentium was found to be a more efficient vector for WNV and SINV over Cx . pipiens . Overall, the results were in line with the previous studies performed with more southern vector populations. The current climate does not seem optimal for WNV circulation in Finland, but temporary summertime transmission could occur in the future if all other essential factors are in place. More field data would be needed for monitoring and understanding the northward spreading of WNV in Europe.

We herein report a waste minimization protocol for the β-azidation of α,β-unsaturated carbonyl compounds using TMSN 3 . The selection of the appropriate catalyst ( POLITAG-M-F ), in combination with the reaction medium, resulted in enhanced catalytic efficiency and a low environmental footprint. The thermal and mechanical stability of the polymeric support allowed us to recover the POLITAG-M-F catalyst for up to 10 consecutive runs. The CH 3 CN:H 2 O azeotrope has a 2-fold positive effect on the process, increasing the efficiency of the protocol and minimizing waste generation. Indeed, the azeotropic mixture, used as a reaction medium and for the workup procedure, was recovered by distillation, leading to an easy and environmentally friendly procedure for product isolation in high yield and with a low E-factor. A comprehensive evaluation of the environmental profile was performed by the calculation of different green metrics (AE, RME, MRP, 1/SF) and a comparison with other literature available protocols. A flow protocol was defined to scale-up the process, and up to 65 mmol of substrates were efficiently converted with a productivity of 0.3 mmol/min., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Monkeypox infection is a zoonosis first described in humans in 1970 in Congo. While previously manifesting in small, confined outbreaks, the disease is rapidly spreading globally. The aim of this study was to investigate microbiological samples (skin, rectal, and oropharyngeal swab samples and plasma and urine samples) that can help in adequate diagnostic, therapeutic, and prognostic management. We present 30 laboratory-confirmed monkeypox patients with peculiar clinical and virological features admitted to the Sexually Transmitted Diseases Centre of Sant' Orsola Hospital, University of Bologna, in the period between 20 June and 10 August 2022. Demographic, anamnestic, and clinical data were obtained, and microbiological samples were collected and analyzed by real-time PCR to detect the presence of monkeypox virus (MPXV) DNA. All monkeypox patients were adult men who have sex with men (MSM) (mean age, 37.5 years). Nonskin samples were collected from 29 patients during the acute phase of the infection. The detection rates of MPXV DNA in plasma, urine, and oropharyngeal swab samples (82.3%, 64.7%, and 75.0%, respectively) were highest in samples collected 4 to 6 days after symptom onset. The presence of MPXV in plasma and urine samples was analyzed 11 to 38 days after symptom onset to monitor viral shedding duration. Interestingly, MPXV DNA was detected in a urine sample collected on day 21 in one patient. Prolonged positivity in urine after the clinical recovery suggests a potential source of infection by contamination of wastewater and sewage and transmission to possible animal reservoirs and highlights the need for further investigations on nonskin samples to extend and more adequately standardize the patient isolation period.

Objective: There is a lack of information about the normal trend of C-reactive protein (CRP) blood levels in the postoperative days after gynecological benign surgery. We investigated the impact of different surgical techniques on CRP trend. We performed a comparative analysis between a CRP and white blood cell (WBC) trend in postoperative monitoring., Methods: We studied 207 surgical patients for benign gynecological pathology. We analyzed CRP and WBC levels after surgery in the total number of women and separately by approaches., Results: CRP mean log scores showed a typical behavior. Moreover, results from chi-square test underline that the proportion of women with this result is independent from the type of surgery they underwent. Log score mean values of CPR differed between all groups and between times. No difference in the mean number of white cells between the second and the third day was found, as observed for CRP., Conclusions: Our study shows a trend reference model in postoperative monitoring of patients with benign gynecological surgery. The comparative analysis between the CRP and WBC trend in the postoperative days provided us data demonstrating the superiority of CRP in postsurgical patient outcomes monitoring., (© 2022 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Introduction: Temporary anchorage devices represent a fundamental tool to reliably manage orthodontic anchorage in several conditions. One of the most recent application is represented by the combination of aligners with TADs to simplify specific movements such as posterior intrusion, anterior intrusion, molars distalization. The objective of this case report is to show a novel technique called "G-block" to manage posterior anchorage with a hybrid approach combining aligners and TADs., Materials and Methods: This case report shows a Class II malocclusions (end to end relationship) with increased overjet and incisors proclination treated with aligners and maxillary distalization approach. To manage the posterior anchorage after second molar distalization and to avoid the use of Class II elastics, TADs (Spider Pin 1.3mm×10mm) were inserted into the interradicular space between the maxillary first and second molars following second molar distalization. The mini screws were used to provide both direct and indirect anchorage. The second molars were connected to the TAD by means of a 0.18 SS wire embedded in the attachment and blocked to the head of the mini-screw for indirect anchorage, while an elastic chain connecting the TADs to the buttons bonded to the first molars and premolars provided direct anchorage during first molar and premolar distalization., Results: A solid bilateral Class I occlusion was achieved with a normal overjet and overbite. The dental arches were well aligned and leveled with good intra-arch symmetry and regular arch forms. Final cephalometric analysis showed a significant change in upper incisor proclination (15̊ reduction) while maintaining correct torque control and a significant change in molar relationship. The aesthetic analysis showed an improvement in lip competence and incisor exposure., Conclusion: The use of TADs for posterior anchorage after maxillary molar distalization with aligners, could represent an effective solution to easily manage the posterior anchorage reducing the need for patient's compliance in using elastics and in particular simplifying the posterior teeth movements by coupling the force expressed from the aligners with the force expressed by the auxiliary system., (Copyright © 2022 CEO. Published by Elsevier Masson SAS. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen responsible for pandemic coronavirus disease 2019 (COVID-19). It is a highly contagious virus which primarily affects the respiratory tract, nevertheless, the lungs are not the only target organs of the virus. The intestinal tract could represent an additional tropism site for SARS-CoV-2. Several observations have collectively suggested that enteric infections can occur in COVID-19 patients. However, the detection of viral RNA in gastrointestinal (GI) tissue samples has not been adequately investigated and results are conflicting., Aim: To detect the presence of SARS-CoV-2 RNA in intestinal mucosa samples and to evaluate histological features., Methods: The COVID-19 patients hospitalized at an Italian tertiary hospital from April 2020 to March 2021 were evaluated for enrollment in an observational, monocentric trial. The study population was composed of two groups of adult patients. In the first group (biopsy group, 30 patients), patients were eligible for inclusion if they had mild to moderate disease and if they agreed to have a rectal biopsy; in the second group (surgical specimen group, 6 patients), patients were eligible for inclusion if they underwent intestinal resection during index hospitalization. Fifty-nine intestinal mucosal samples were analyzed., Results: Viral RNA was not detectable in any of the rectal biopsies performed (0/53). Histological examination showed no enterocyte damage, but slight edema of the lamina propria with mild inflammatory lymphoplasmacytic infiltration. There was no difference in inflammatory infiltrates in patients with and without GI symptoms. SARS-CoV-2 RNA was detected in fecal samples in 6 cases out of 14 cases examined (42.9%). In the surgical specimen group, all patients underwent emergency intestinal resection. Viral RNA was detected in 2 surgical specimens of the 6 examined, both of which were from patients with active neoplastic disease. Histological examination also pointed out abundant macrophages, granulocytes and plasma cells infiltrating the muscular layer and adipose tissue, and focal vasculitis., Conclusion: Mild-moderate COVID-19 may not be associated with rectal infection by the virus. More comprehensive autopsies or surgical specimens are needed to provide histological evidence of intestinal infection., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: This is a proof of concept, as a pilot study, with the aim to evaluate continuous glucose monitoring metrics (CGM) in subjects with type 2 diabetes (T2DM), treated with nutritional therapy and metformin, before and after testosterone replacement therapy (TRT)., Methods: In this longitudinal observational study, subjects affected by T2DM and starting TRT for documented ED and hypogonadism were enrolled. All subjects mounted a CGM system during the v0 visit, one week before the beginning of the TRT (week-1), during v2, four weeks after the start of TRT (week 4), and v4 (week 12). CGM was worn for about 144 h after each visit., Results: A total of seven patients, referring to our clinic for erectile dysfunction (ED), were studied (aged 63.3 ± 2.3 years). Mean (± standard deviation) total testosterone level was 2.3 ± 0.6 ng/mL at baseline. After TRT, total testosterone level was 4.6 ± 3.04 ng/mL at week 4 and 3.93 ± 4.67 ng/mL at week 12. No significant differences were observed in TIR, TAR, TBR, estimated HbA1c, AUC below, and AUC above limit during the intervention period., Conclusions: This is the first study evaluating the effects of TRT on daily glucose excursions in subjects with T2DM and hypogonadism. Though we did not find any significant difference in key CGM metrics during the 12 weeks of TRT, this study confirms the glycometabolic safety of the TRT even on the most novel standardized glycemic targets.

With the prevalence of obesity alarmingly increasing, it is of primary interest to identify those factors predicting the success of anti-obesity therapeutic strategies currently adopted in clinical practice, and in particular, those of bariatric procedures showing the greatest success in terms of weight loss and maintenance in both the short and long term. Given sex-related differences in psychosocial status, hormonal homeostasis, and body fat distribution, it is likely that the response to different weight management strategies differs by sex. The objective was to elucidate the effect of sex on different bariatric procedures' efficacy and safety outcomes. Searches of PubMed, Cochrane, and Embase databases were performed, followed by hand-searching of reference lists from all relevant articles. We included all the studies evaluating the effect of bariatric procedures on body mass index loss (BMIL), and/or percentage excess weight loss (%EWL), and/or percentage excess body mass index loss, and/or percentage of responders, and/or short-/long-term complications and co-morbidity resolution, broken down by sex. Twenty-seven studies with a total of 114,919 patients were included. Men were more likely to achieve greater BMIL, consistent with higher male baseline BMI, and women were 2.87 times more likely to be classified as weight responders (95% confidence interval [CI]: 1.90-4.34), as well as to perform better in terms of %EWL (95% CI: .13-.54). Upon subgroup analysis based on bariatric procedure, women were more likely to be successful in terms of %EWL upon bioenteric intragastric balloon (BIB) placement (.72, 95% CI: .42-1.02). There was no sex difference regarding investigated co-morbidity resolution (hypertension, diabetes, and obstructive sleep apnea syndrome) or occurrence of short-term complications, whereas women were more likely to develop long-term complications, with an odds ratio of 1.97 (95% CI: 1.57-2.49). Sex does not have a clear effect on efficacy outcomes of bariatric procedures. Differentiating by procedure, BIB may be more effective in women, although results are discordant based on the weight loss outcome considered. If the short-term postoperative complication rate is similar across both sexes, long-term complications occur more frequently in women. To clarify the real effect of sex on bariatric procedure-derived health benefits, it is crucial to report sex-stratified results in future studies, as well as evaluate body composition changes that go beyond simple body weight reduction., (Copyright © 2022 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: After the diagnosis of L-SIL, 77. 3% had a persistent infection and anomalous Pap Test results. Many of these patients had highlighted psychological consequences such as anxiety, hypochondria, fear of cancer, and sexual problems. Several studies suggested that the clearance of HR-HPV infection could be accelerated by cervical excisional procedures, especially in L-SIL. In consideration of the psychological implications for HPV infection and related dysplasia in patients with CIN1 at PAP-smear and HR-HPV positivity at least for 6 months, we decided to plan a prospective study where we tried to anticipate excisional cervical using a minimally invasive treatment: thin loop electrosurgical excision procedure (t-LEEP). This study aims to analyze the clearance of HR-HPV after 6 and 12 months, clinical outcomes related to t-LEEP, and the psycho-relational impact at 12 months after t-LEEP., Materials and Methods: We enrolled patients with the diagnosis of L-SIL at PAP-smear and HR-HPV positivity with a persistent CIN 1 (at least for 6 months), confirmed by cervical biopsy. All enrolled patients underwent t-LEEP. We followed prospectively and performed for all patients the HPV DNA test at 6 (T1) and 12 months (T2) and STAI-Y and FSFI scores at T0 and T2., Results: We prospectively enrolled 158 patients, 22 are excluded for the established criteria. Patients with HR-HPV and CIN 1 lesions treated with t-LEEP had an overall clearance of 83.8% at T2. In subgroups analysis at T2, we had a regression: in smoker 71.8%, in contraceptive users 69.5%, in patients aged <25 years 100%, aged 25-30 years 85%, aged 30-35 years 94.4%, aged 35-40 years 92%, and aged ≥40 years 89.1%, in HPV-16 96.4%, in HPV-53 89.5%, in HPV-18 87.5%, in HPV-31 86.6%, and in coinfected 3.5%. STAI-Y and FSFI after t-LEEP (T2) were statistically significant, reducing anxiety status and improving sexual function., Conclusion: Based on these results, the use of t-LEEP in patients with persistent CIN 1 and HPV-HR at least for 6 months could be useful for accelerating HPV-HR clearance, in particular, for a subpopulation patient with an increased risk of progression and/or patients with psychological and sexual consequences of carrying an HR-HPV infection., 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. The reviewer SL declared a past co-authorship with the authors to the handling editor., (Copyright © 2022 Plotti, Rossini, Ficarola, De Cicco Nardone, Montera, Guzzo, Luvero, Fabris, Angioli and Terranova.)

People with cystic fibrosis should be considered at increased risk of developing severe symptoms of COVID-19. Strikingly, a broad array of evidence shows reduced spread of SARS-CoV-2 in these subjects, suggesting a potential role for CFTR in the regulation of SARS-CoV-2 infection/replication. Here, we analyzed SARS-CoV-2 replication in wild-type and CFTR-modified human bronchial epithelial cell lines and primary cells to investigate SARS-CoV-2 infection in people with cystic fibrosis. Both immortalized and primary human bronchial epithelial cells expressing wt or F508del-CFTR along with CRISPR/Cas9 CFTR-ablated clones were infected with SARS-CoV-2 and samples were harvested before and from 24 to 72 h post-infection. CFTR function was also inhibited in wt-CFTR cells with the CFTR-specific inhibitor IOWH-032 and partially restored in F508del-CFTR cells with a combination of CFTR modulators (VX-661+VX-445). Viral load was evaluated by real-time RT-PCR in both supernatant and cell extracts, and ACE-2 expression was analyzed by both western blotting and flow cytometry. SARS-CoV-2 replication was reduced in CFTR-modified bronchial cells compared with wild-type cell lines. No major difference in ACE-2 expression was detected before infection between wild-type and CFTR-modified cells, while a higher expression in wild-type compared to CFTR-modified cells was detectable at 72 h post-infection. Furthermore, inhibition of CFTR channel function elicited significant inhibition of viral replication in cells with wt-CFTR, and correction of CFTR function in F508del-CFTR cells increased the release of SARS-CoV-2 viral particles. Our study provides evidence that CFTR expression/function is involved in the regulation of SARS-CoV-2 replication, thus providing novel insights into the role of CFTR in SARS-CoV-2 infection and the development of therapeutic strategies for COVID-19.

Background: Several studies have been proposed with the aim to demonstrate correlations between the dento-mandibular apparatus and the skeletal muscle system of the human body even in regions distant from the oral cavity. However, a definite conclusion cannot be drawn. The aim of this paper is to demonstrate a possible correlation between dental occlusion and sport performances in track and field athletes., Methods: Sixteen track and field athletes were enrolled for the study and were randomly divided in three groups: Untreated control group, Placebo group (with a lower plaque without occlusal coverage) and Treated group (with occlusal splint). Changes in sprint and jump performance were assessed on a weekly basis for 5 consecutive weeks, during which athletes had to wear oral devices, except for the first week of baseline, for at least 3 trainings lasting 2 hours per week . All participants performed the countermovement jump (CMJ), the drop jump (DJ), the 10m and 30m sprint tests, always on the same day on the week., Results: No statistically significant difference resulted between Control group and Placebo group and between Control group and Treated group. However, it was possible to observe a clinical improvement of measurements obtained, especially for CMJ, 10m and 30m sprint tests. No variation neither statistical neither clinical was observed in DJ test analysis., Conclusions: Even if statistically it was not possible to demonstrate an improvement in sport performance, most of the athlete analyzed showed better results during training session with occlusal splint compared to athlete without occlusal splint, in countermovement jump, in 10m and 30m sprint tests.