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A light-driven metal-free protocol for the synthesis of sulfone-containing indoles under mild conditions is reported. Specifically, the process is driven by the photochemical activity of halogen-bonded complexes formed upon complexation of a sacrificial donor, namely 1,4-diazabicyclo[2.2.2]octane (DABCO), with α-iodosulfones. The reaction provides a variety of densely functionalized products in good yields (up to 96% yield). Mechanistic investigations are reported. These studies provide convincing evidences for the photochemical formation of reactive open-shell species.

Silent nociceptors remained enigmatic ever since they were first described decades ago. Here, Nees. et al. show that inflammation-induced upregulation of TMEM100 unsilences silent nociceptors, which triggers secondary mechanical pain hypersensitivity.

Abstract Traumatic brain injury is common, and often results in debilitating consequences. Even mild traumatic brain injury leaves approximately 20% of patients with symptoms that persist for months. Despite great clinical need there are currently no approved pharmaceutical interventions that improve outcomes after traumatic brain injury. Increased understanding of the endocannabinoid system in health and disease has accompanied growing evidence for therapeutic benefits of Cannabis sativa. This has driven research of Cannabis’ active chemical constituents (phytocannabinoids), alongside endogenous and synthetic counterparts, collectively known as cannabinoids. Also of therapeutic interest are other Cannabis constituents, such as terpenes. Cannabinoids interact with neurons, microglia, and astrocytes, and exert anti-inflammatory and neuroprotective effects which are highly desirable for the management of traumatic brain injury. In this review, we comprehensively appraised the relevant scientific literature, where major and minor phytocannabinoids, terpenes, synthetic cannabinoids, and endogenous cannabinoids were assessed in TBI, or other neurological conditions with pathology and symptomology relevant to TBI, as well as recent studies in preclinical TBI models and clinical TBI populations.

This study investigated the effect of five in-house cooking methods (grilling, oven-cooking, frying, microwaving, and boiling) on lipid content and fatty acid composition in red mullet ( Mullus barbatus ). Moreover, the nutritional quality of the lipid fraction was evaluated by determining a number of lipid nutritional quality indices (LNQI). Moisture content of red mullet decreased after cooking, with the exception of boiled fish, while the lipid content significantly increased after microwave treatment and frying. After the latter, a ten-fold increase in lipid content was noted compared to fresh fish (from 2.1 to 21.1 g/100 g wet matter). All cooking methods caused significant changes in the fatty acid (FA) profile of M. barbatus . The content of saturated fatty acids (SFA) varied significantly between raw and cooked fish with the lowest values determined for fried sample. Monounsaturated fatty acid (MUFA) content increased after oven cooking and frying, while polyunsaturated fatty acid (PUFA) content showed an opposite trend. The eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) were the dominant fatty acids among n 3 acids in all samples. EPA+DHA contribution in total FAs was significantly lower in the samples after oven cooking (19.6% total FAs) and frying (4.99% total FAs) than in the raw (25.5% of total FAs) fish. The n 3/ n 6 ratio (range 1.25–3.65) decreased significantly after cooking; however, it remained above the recommended values for a healthy human nutrition (1:5). The PUFA/SFA ratio was between 0.69 in fried and 1.02 in boiled fish, both being greater than those recommended by the WHO/FAO [2003]. Atherogenicity index value decreased significantly after the cooking particularly in fried fish. The polyene index (PI), as a measure of PUFA damage, was in the range of 0.42–1.18. Although all cooking methods affected the FA profile, based on LNQI, it can be concluded that barbecue-grilling and boiling were the best cooking methods for healthy eating, due to their lowest effect on essential FAs.

A series of CoPd/KIT-6 bimetallic catalysts with various Co:Pd molar ratios at different calcination temperatures were prepared and used for the direct synthesis of H2O2 from H2 and O2. These catalysts were characterized by nitrogen adsorption–desorption, low and wide-angle X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), elemental mapping and energy-dispersive X-ray (EDX) methods. It was found that the particle size, electronic interactions, morphology, and textural properties of these catalysts as well as their catalytic activity in the reaction of H2 with O2 were affected by Co addition and different calcination temperatures. Also, the results showed that while the H2O2 selectivity depends on Pd2+ species, the H2 conversion is related to Pd0 active sites. Among these catalysts, CoPd/KIT-6 calcined at 350 °C (CoPd/KIT-350 catalyst) showed the best catalytic activity with 50% of H2O2 selectivity and 51% conversion of H2.

There has been little innovation in identifying novel insulin sensitizers. Metformin, developed in the 1920s, is still used first for most Type 2 diabetes patients. Mice with genetic reduction of p52Shc protein have improved insulin sensitivity and glucose tolerance. By high-throughput screening, idebenone was isolated as the first small molecule 'Shc Blocker'. Idebenone blocks p52Shc's access to Insulin Receptor to increase insulin sensitivity. In this work the avidity of 34 novel idebenone analogs and 3 metabolites to bind p52Shc, and to block the interaction of p52Shc with the Insulin receptor was tested. Our hypothesis was that if an idebenone analog bound and blocked p52Shc's access to insulin receptor better than idebenone, it should be a more effective insulin sensitizing agent than idebenone itself. Of 34 analogs tested, only 2 both bound p52Shc more tightly and/or blocked the p52Shc-Insulin Receptor interaction more effectively than idebenone. Of those 2 only idebenone analog #11 was a superior insulin sensitizer to idebenone. Also, the long-lasting insulin-sensitizing potency of idebenone in rodents over many hours had been puzzling, as the parent molecule degrades to metabolites within 1 h. We observed that two of the idebenone's three metabolites are insulin sensitizing almost as potently as idebenone itself, explaining the persistent insulin sensitization of this rapidly metabolized molecule. These results help to identify key SAR = structure-activity relationship requirements for more potent small molecule Shc inhibitors as Shc-targeted insulin sensitizers for type 2 diabetes.

Nanoporous (NP) gold, the most extensively studied and efficient NP metal, possesses exceptional properties that make it highly attractive for advanced technological applications. Notably, its remarkable catalytic properties in various significant reactions hold enormous potential. However, the exploration of its catalytic activity in the degradation of water pollutants remains limited. Nevertheless, previous research has reported the catalytic activity of NP Au in the degradation of methyl orange (MO), a toxic azo dye commonly found in water. This study aims to investigate the behavior of nanoporous gold in MO solutions using UV-Vis absorption spectroscopy and high-performance liquid chromatography. The NP Au was prepared by chemical removal of silver atoms of an AuAg precursor alloy prepared by ball milling. Immersion tests were conducted on both pellets and powders of NP Au, followed by examination of the residual solutions. Additionally, X-ray photoelectron spectroscopy and electrochemical impedance measurements were employed to analyze NP Au after the tests. The findings reveal that the predominant and faster process involves the partially reversible adsorption of MO onto NP Au, while the catalytic degradation of the dye plays a secondary and slower role in this system.

Oral tongue squamous-cell carcinoma (OTSCC) is the most prevalent malignancy in the head and neck region. Lymphatic spread, particularly to cervical lymph nodes, significantly impacts 5-year survival rates, emphasizing the criticality of precise staging. Metastatic cervical lymph nodes can decrease survival rates by 50%. Yet, elective neck dissection (END) in T1–2 cN0 patients proves to be an overtreatment in around 80% of cases. To address this, sentinel lymph node biopsy (SLNB) was introduced, aiming to minimize postoperative morbidity. This study, conducted at the ENT and Maxillofacial Surgery department of the Istituto Nazionale Tumori in Naples, explores SLNB’s efficacy in early-stage oral tongue squamous-cell carcinoma (OTSCC). From January 2020 to January 2022, 122 T1/T2 cN0 HNSCC patients were enrolled. Radioactive tracers and lymphoscintigraphy identified sentinel lymph nodes, aided by a gamma probe during surgery. Results revealed 24.6% SLN biopsy positivity, with 169 SLNs resected and a 21.9% positivity ratio. The study suggests SLNB’s reliability for T1-2 cN0 OTSCC patient staging and early micrometastasis detection.

The RAS is a hormonal system playing a pivotal role in the control of blood pressure and electrolyte homeostasis, the alteration of which is associated with different pathologies, including acute respiratory distress syndrome (ARDS). As such, it is not surprising that a number of studies have attempted to elucidate the role and balance of the renin–angiotensin system (RAS) in COVID-19. In this review article, we will describe the evidence collected regarding the two main enzymes of the RAS (i.e., ACE and ACE2) and their principal molecular products (i.e., AngII and Ang1-7) in SARS-CoV-2 infection, with the overarching goal of drawing conclusions on their possible role as clinical markers in association with disease severity, progression, and outcome. Moreover, we will bring into the picture new experimental data regarding the systemic activity of ACE and ACE2 as well as the concentration of AngII and Ang1-7 in a cohort of 47 COVID-19 patients hospitalized at the IRCCS Sacro Cuore-Don Calabria Hospital (Negrar, Italy) between March and April 2020. Finally, we will discuss the possibility of considering this systemic pathway as a clinical marker for COVID-19.

Background/Objectives: Pathogenic variants in the deleted in colorectal cancer gene (DCC), encoding the Netrin-1 receptor, may lead to mirror movements (MMs) associated with agenesis/dysgenesis of the corpus callosum (ACC) and cognitive and/or neuropsychiatric issues. The clinical phenotype is related to the biological function of DCC in the corpus callosum and corticospinal tract development as Netrin-1 is implicated in the guidance of developing axons toward the midline. We report on a child with a novel inherited, monoallelic, pathogenic variant in the DCC gene. Methods: Standardized measures and clinical scales were used to assess psychomotor development, communication and social skills, emotional and behavioural difficulties. MMs were measured via the Woods and Teuber classification. Exome sequencing was performed on affected and healthy family members. Results: The patient’s clinical presentation during infancy consisted of paroxysmal dystonic posturing when asleep, mimicking nocturnal leg cramps. A brain magnetic resonance imaging (MRI) showed complete ACC. He developed typical upper limb MMs during childhood and a progressively evolving neuro-phenotype with global development delay and behavioural problems. We found an intrafamilial clinical variability associated with DCC mutations: the proband’s father and uncle shared the same DCC variant, with a milder clinical phenotype. The atypical early clinical presentation of the present patient expands the clinical spectrum associated with DCC variants, especially those in the paediatric age. Conclusions: This study underlines the importance of in-depth genetic investigations in young children with ACC and highlights the need for further detailed analyses of early motor symptoms in infants with DCC mutations.

BackgroundHepatitis E virus (HEV) infection is a common cause of acute clinical hepatitis worldwide and is emerging as a disease in Argentina. It is primarily transmitted through contaminated water and food, following the fecal-oral route. Furthermore, is a zoonotic disease with swine as the primary reservoir. Prevalence of HEV infection in humans in several regions of Argentina remains unknown.Objectives(i) Determine the seroprevalence of HEV among the human population in Tandil, Buenos Aires, Argentina; (ii) Evaluate its association with demographic, socioeconomic and other risk exposures variables, and (iii) Describe and analyze spatial patterns related to HEV infection.MethodsFrom August 2020 to July 2021, serum samples were collected from 969 individuals aged 1–80 years. Seroprevalence and 95% Confidence Interval was determined. To assess the factors associated with the presence of anti-HEV antibodies, associations between the variables and seropositivity were evaluated through bivariate and multivariate analysis. Spatial scanning for clusters of positivity was carried out. Factors associated with these clusters were also assessed.ResultsAnti-HEV antibodies were detected in 4.64% (IC 95% 3.27–6.02) of samples. Dark urine was associated with seropositivity (p = 0.02). Seropositivity was linked with the presence of natural water courses near their households (p = 0.02); the age (p = 0.04); and previous travel to Europe (p = 0.04). A spatial cluster of low rates of HEV seropositivity was detected, with greater distance of the households to water courses associated to the cluster, and male sex inversely associated to it.Discussion and conclusionThis study is the first study to investigate the prevalence of HEV in the population from Tandil, Buenos Aires, Argentina. Considering HEV infection in the differential diagnosis in individuals presenting acute hepatitis is highlighted. The incorporation of HEV testing into blood screening policies should be mandatory. Factors related to the infection and spatial patterns of high and low risk were determined, and should be considered when implementing specific preventive measures.

Abstract The manipulation of carbon nitride (CN) structures is one main avenue to enhance the activity of CN‐based photocatalysts. Increasing the efficiency of photocatalytic heterogeneous materials is a critical step toward the realistic implementation of sustainable schemes for organic synthesis. However, limited knowledge of the structure/activity relationship in relation to subtle structural variations prevents a fully rational design of new photocatalytic materials, limiting practical applications. Here, the CN structure is engineered by means of a microwave treatment, and the structure of the material is shaped around its suitable functionality for Ni dual photocatalysis, with a resulting boosting of the reaction efficiency toward many CX (X = N, S, O) couplings. The combination of advanced characterization techniques and first‐principle simulations reveals that this enhanced reactivity is due to the formation of carbon vacancies that evolve into triazole and imine N species able to suitably bind Ni complexes and harness highly efficient dual catalysis. The cost‐effective microwave treatment proposed here appears as a versatile and sustainable approach to the design of CN‐based photocatalysts for a wide range of industrially relevant organic synthetic reactions.

ObjectiveSome salivary proteins seem to be differently abundant among caries-free (CF) and caries-affected (CA) individuals, but previous results are contradictory precluding that definitive conclusion be drawn. A pooled analysis of the available evidence may provide more robust data on identifying oral cavity protein patterns among CF and CA individuals. This systematic review and meta-analysis (PROSPERO CRD42021269079) aimed to compare the oral cavity protein abundance among caries-free and caries-affected individuals.MethodsThis study was conducted following PRISMA guidelines. PubMed, Embase, and Web of Science databases were systematically assessed (up to February 2023) to retrieve clinical studies written in English, German, or in Latin-based languages that compared the oral cavity protein abundance among CF and CA individuals. Data extraction and methodological quality assessment (NIH guidelines) were independently performed by two investigators. Qualitative synthesis was performed from all included studies and meta-analysis was performed using a random-effects model with inverse variance for studies that reported the concentration of proteins or enzymatic activity. Standardized mean difference (SMD) with respective 95% confidence interval (CI) were calculated for each outcome.ResultsA total of 90 studies (two cohort and 88 cross-sectional designs) of more than 6,000 participants were selected for data extraction, being the quality of evidence graded as “fair” for most of them. The oral cavity of CF individuals presented lower total protein concentration [SMD = 0.37 (95% CI: 0.07–0.68; 18 studies)], lower total antioxidant capacity [SMD = 1.29 (95% CI: 0.74–1.85); 17 studies], and lower carbonic anhydrase activity [SMD = 0.83 (95% CI: 0.58–1.09); three studies], whereas CA individuals presented lower carbonic anhydrase concentration [SMD = −0.66 (95% CI: −1.00 to −0.32); three studies], urease [SMD = −0.95 (IC 95%: −1.72 to −0.17); four studies], and arginine deiminase system [SMD = −2.07 (95% CI: −3.53 to −0.62); three studies] activities. Antimicrobial peptides, secretory immunoglobulin-A concentrations and alpha-amylase activity were similar among individuals.ConclusionDifferences on oral cavity protein abundance were observed among CF and CA individuals. These data indicate some protein patterns for the oral health and dental caries conditions. Even when statistically significant, some of the results were not very consistent. Cohort studies need to be conducted to validate these results.

Abstract Lecythis tuyrana is an endemic tree in the Magdalena River basin in Colombia with unexplored forestry, nutraceutical, medicinal and nutritional potential. In the nursery, two experiments on the production of L. tuyrana seedling were evaluated. In the first experiment, three container volumes and the absence or presence (3 g L-1) of a controlled-release fertilizer (CRF) were evaluated. The use of tube trays (700 cm3) and CRF significantly increased the height, biomass, and Dickson quality index of the seedlings (between 28 to 61 %) compared to those not fertilized. In the second experiment the light acclimation of seedlings was evaluated in two environments: full sun at 50% and 100%. There were no changes in photosynthetic rates when the seedlings were kept in the shade for longer, but there was a lesser accumulation of biomass. A light intensity of approximately 1 600 µmol m-2 s-1 is considered optimal for L. tuyrana seedling.

Background Despite advances, blood oxygen level-dependent (BOLD) cardiac MRI for myocardial perfusion is limited by inadequate spatial coverage, imaging speed, multiple breath holds, and imaging artifacts, particularly at 3.0 T. Purpose To develop and validate a robust, contrast agent-unenhanced, free-breathing three-dimensional (3D) cardiac MRI approach for reliably examining changes in myocardial perfusion between rest and adenosine stress. Materials and Methods A heart rate-independent, free-breathing 3D T2 mapping technique at 3.0 T that can be completed within the period of adenosine stress (≤4 minutes) was developed by using computer simulations, ex vivo heart preparations, and dogs. Studies in dogs were performed with and without coronary stenosis and validated with simultaneously acquired nitrogen 13 (13N) ammonia PET perfusion in a clinical PET/MRI system. The MRI approach was also prospectively evaluated in healthy human volunteers (from January 2017 to September 2017). Myocardial BOLD responses (MBRs) between normal and ischemic myocardium were compared with mixed model analysis. Results Dogs (n = 10; weight range, 20-25 kg; mongrel dogs) and healthy human volunteers (n = 10; age range, 22-53 years; seven men) were evaluated. In healthy dogs, T2 MRI at adenosine stress was greater than at rest (mean rest vs stress, 38.7 msec ± 2.5 [standard deviation] vs 45.4 msec ± 3.3, respectively; MBR, 1.19 ± 0.08; both, P < .001). At the same conditions, mean rest versus stress PET perfusion was 1.1 mL/mg/min ± 0.11 versus 2.3 mL/mg/min ± 0.82, respectively (P < .001); myocardial perfusion reserve (MPR) was 2.4 ± 0.82 (P < .001). The BOLD response and PET MPR were positively correlated (R = 0.67; P < .001). In dogs with coronary stenosis, perfusion anomalies were detected on the basis of MBR (normal vs ischemic, 1.09 ± 0.05 vs 1.00 ± 0.04, respectively; P < .001) and MPR (normal vs ischemic, 2.7 ± 0.08 vs 1.7 ± 1.1, respectively; P < .001). Human volunteers showed increased myocardial T2 at stress (rest vs stress, 44.5 msec ± 2.6 vs 49.0 msec ± 5.5, respectively; P = .004; MBR, 1.1 msec ± 8.08). Conclusion This three-dimensional cardiac blood oxygen level-dependent (BOLD) MRI approach overcame key limitations associated with conventional cardiac BOLD MRI by enabling whole-heart coverage within the standard duration of adenosine infusion, and increased the magnitude and reliability of BOLD contrast, which may be performed without requiring breath holds. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.

The increasing wealth of truck global positioning system (GPS) data has broadened the opportunities for understanding freight logistics activities and enhancing research capabilities to real-world case studies. A very important piece of information from the planning and regulatory perspective concerns the occurrence and location of rest stops. In this study, we propose a data-driven unsupervised machine learning method to impute truck stop events by using a Continuous Hidden Markov Model (CHMM). Specifically, we estimate the joint probability distribution of a mixture of multivariate Gaussian densities, whose parameters depend on the latent states of a Markov chain. Each density represents a cluster of stops that are identified not only from their spatial proximity but also from their temporal proximity as the clustering of the rest stops depends on latent states that are conditional on expected times retrieved from the observed data. In this study, we applied the proposed method to a database containing more than 71 million GPS records of Australian trucks, and we particularly aimed to identify rest stops based on a list of features related to the locations and the load of the trucks. The results showed that the CHMM could account for the location proximity for different activities of truck drivers, and they were validated against complementary data on truck loads and land use by using a stratified sampling technique. Validation results indicated that 94.1% of the rest stops were correctly identified, and highlighted the advantage of the proposed approach without any requirement of labelled data, driver logbook or complimentary survey.

El colesteatoma es una masa de apariencia blanda, comprimible y asociada principalmente a la hipoacusia. Su diagnóstico se realiza mediante otoscopia, pero si el examen físico no es concluyente se deben realizar estudios radiológicos. Su presentación es infrecuente; así, la incidencia de colesteatoma adquirido por cada año en Colombia es de 3/100000 niños y 9,2/100000 adultos. Es importante en las valoraciones que cada personal de salud lo pueda reconocer y derivar, permitiendo realizar de forma temprana la intervención quirúrgica que eviten cuadros clínicos invasivos que pueden aumentar la posibilidad de complicaciones. Nuestro objetivo fue describir la importancia del colesteatoma con sus implicaciones clínicas en los diferentes pacientes con patología auditiva, lo que permite hacer entender la importancia del diagnóstico oportuno. Se realizó una búsqueda de literatura en las bases de datos de PubMed y Scielo, orientada hacia artículos actualizados y relevantes en inglés y español, publicados en los últimos 5 años. Se analizó la relación entre hipoacusia y colesteatoma, su importancia médica, implicaciones y abordaje terapéutico. Los diferentes estudios evidencian la presencia de colesteatoma e hipoacusia unilateral, en algunos casos la presentación clínica se asociada a patologías sindrómicas. En esta patología el tratamiento es quirúrgico, con una previa valoración que establezca el tipo de intervención, adicionalmente, el seguimiento postquirúrgico es obligatorio en todos los pacientes. En conclusión, el colesteatoma es una causa de la hipoacusia, especialmente entre la población pediátrica, la cual debe ser diagnosticada de forma oportuna con el objeto de permitir una valoración especializada que ofrezca un tratamiento quirúrgico de acuerdo al compromiso anatómico y la individualización del paciente.

A new biocomposite material based on polylactic acid (PLA) with meshes of Yanchama fibers is introduced. This bio-based composite was fabricated by compression molding and film-staking process. This new biocomposite material was tested by tensile tests in different directions and was numerically simulated. The composite was simulated as an elastic orthotropic material. The nine constants of elastic orthotropic behavior are calculated from modules of Young measured experimentally. The experiment results and simulations are the same. The results show that the mechanical behavior of the PLA-Yanchama composite under different load solicitudes can be predicted if it is simulated as an orthotropic elastic material.

Abstract Studies reporting vaccine effectiveness against COVID-19 outcomes concentrate mainly on estimates of one single type of vaccine and variant, seldom considering waning effects. We aimed to estimate the effectiveness of the overall COVID-19 vaccination programme implemented in the Apulia region of Italy at preventing SARS-CoV-2 infections, COVID-19-related hospital admissions and deaths during alpha and delta variant dominant periods. We conducted a retrospective cohort study using electronic health records of persons 16 years and older resident in the Apulia region, assessing the effectiveness of the combined use of BNT162b2, mRNA-1273, ChAdOx1-S and Ad26.COV2.S vaccines against confirmed COVID-19 infections, hospitalisations and deaths, for fully and partially vaccinated persons as well as by time since vaccination and variants. Cox regression models yielding hazard ratios were used to calculate the overall vaccination programme effectiveness. From 1 January to 1 December 2021, we included 3,530,967 eligible persons in the cohort, of whom 2,770,299 were fully vaccinated and 158,313 were COVID-19 positive at the end of the study period. The effectiveness of the programme over the entire study period for fully vaccinated persons against COVID-19 infection, hospitalisation and death were 87.69% (CI95% 87.73–88.18), 94.08% (93.58–94.54) and 95.95% (CI95% 95.26–96.54), respectively. The effectiveness against COVID-19 infection of fully vaccinated subjects during the alpha and delta period was respectively 88.20% (CI95% 87.60–99.78) and 59.31% (CI95% 57.91–60.67), against hospitalisation 93.89% (CI95% 92.67–94.90) and 88.32% (CI95% 86.50–89.90) and against death 93.83% (CI95% 91.65–95.45) and 85.91 (CI95% 79.98–90.09). The waning effects of the programme regarding COVID-19 infection during the delta period were stronger than for alpha, with 75.85% (CI95% 74.38–77.24) effectiveness after 1–2 months and 8.35% (CI95% 3.45–13.01) after 5–6 months after full vaccination. The effectiveness against hospitalisation and death during the delta period waned rapidly and at 7–8-months after the full vaccination respectively decreased to 27.67% (CI95% 7.48–43.45) and 48.47 (CI95% 53.97–34.82). Our study suggests that the COVID-19 vaccination program in Apulia was strongly protective against COVID-19 infection, hospitalisation, and death due to alpha as well as delta variants, although its effectiveness is reduced over time.