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PURPOSE: To describe and evaluate a novel method to determine the validity of measurements made using cycle-by-cycle (CxC) recording techniques in patients with advanced retinal degenerations (RD) having low-amplitude flicker electroretinogram (ERG) responses. METHODS: The method extends the original CxC recording algorithm introduced by Sieving et al., retaining the original recording setup and the preliminary analysis of raw data. Novel features include extended use of spectrum analysis, reduction of errors due to known sources, and a comprehensive statistical assessment using three different tests. The method was applied to ERG recordings from seven patients with RD and two patients with CNGB3 achromatopsia. RESULTS: The method was implemented as a Windows application to processes raw data obtained from a commercial ERG system, and it features a computational toolkit for statistical assessment of ERG recordings with amplitudes as low as 1 µV, commonly found in advanced RD patients. When recorded using conditions specific for eliciting cone responses, none of the CNGB3 patients had a CxC validated response, indicating that no signal artifacts were present with our recording conditions. A comparison of the presented method with conventional 30 Hz ERG was performed. Bland-Altman plots indicated good agreement (mean difference, -0.045 µV; limits of agreement, 0.193 to -0.282 µV) between the resulting amplitudes. Within-session test-retest variability was 15%, comparing favorably to the variability of standard ERG amplitudes. CONCLUSIONS: This novel method extracts highly reliable clinical recordings of low-amplitude flicker ERGs and effectively detects artifactual responses. It has potential value both as a cone outcome variable and planning tool in clinical trials on natural history and treatment of advanced RDs.

Purpose – Substantial changes in the education system and the shift to online classes during the lockdown have raised teachers’ attention to the idea of practicing cooperative learning in online environments. Cooperative learning activities enhance academic skills if designed effectively. This study aims to explore students’ attitudes toward cooperative learning in online learning environments. Design/methodology/approach – This study is a descriptive study. A survey was administered to 50 graduate and postgraduate students of English as a Foreign Language. Findings – Results indicated that the students had positive attitudes toward the integration of cooperative tasks in online environments. They also revealed no significant differences in the attitudes toward cooperative learning based on the students’ level (i.e. undergraduate or postgraduate) and that the students preferred small groups. Originality/value – Cooperative learning is a widely researched topic, especially in higher education. However, most of the previous studies reported results of the implementation of cooperative learning in traditional classrooms. This study aimed to fill this gap by examining the impact of online tools on cooperative learning.

Abstract In many industrialised countries, sodium intake exceeds the nutritional guidelines. High sodium intake has been associated with health problems, such as arterial hypertension and, consequently, a higher health risk of cardiovascular disease. The aim of this study was to evaluate overall quality of salamis with reduced sodium content by analysing aldehydes, proteolysis, and lipolysis, as well as to verify the correlation between sensory acceptance and volatile compounds. Four formulations were prepared replacing NaCl by a mixture of KCI and CaCl2. Two controls, one with a high level and the other with a low NaCl level were also included in the study. Water activity and pH levels were monitored in all samples. Volatile compounds were measured, in particular, hexanal, 2,4-decadienal and 3-methylbutanal. Finally, a sensory acceptance test was carried out using potential consumers. The results highlighted a relation between aldehyde concentration and sensory acceptance, hexanal/3-methybutanal ratio, that may be a marker of partial NaCl substitution in salami. Thus, our results may be used to guide the use of NaCl substitution by KCl/CaCl2 in terms of volatile compounds. Graphical Abstract

Background: The aim of the study was to investigate a series of complete blood cell count-based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC and PD-L1 < 50% who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78–10.82 vs. 3.31; IQR: 2.15–4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82–21.20 vs. 9.20; IQR: 7.45–11.20, p = 0.013), and systemic inflammation index (SII, median: 1395; IQR: 929–3334 vs. 945; IQR: 552–1373, p = 0.025), but only NLR and NMR remained independently associated with clinical response in multivariate logistic regression. In the univariate analysis, white blood cells (OR:1.2202; 95% CI: 1.0339–1.4400, p = 0.019), neutrophils (OR:1.2916; 95% CI: 1.0692–1.5604, p = 0.008), NLR (OR:1.3601: 95% CI: 1.0949–1.6896, p = 0.005) and NMR (OR:1.2159; 95% CI: 1.00396–1.4221, p = 0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR, and MLR were independently associated with survival; NLR, at a cut-off value of 4.0, showed the better AUC (0.749) in predicting OS. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy.

Abstract Background Different professionals working in healthcare organizations (e.g., physicians, veterinarians, pharmacists, biologists, engineers, etc.) must be able to properly manage scarce resources to meet increasingly complex needs and demands. Due to the lack of specific courses in curricular university education, particularly in the field of medicine, management training programs have become an essential element in preparing health professionals to cope with global challenges. This study aims to examine factors influencing the effectiveness of management training programs and their outcomes in healthcare settings, at middle-management level, in general and by different groups of participants: physicians and non-physicians, participants with or without management positions. Methods A survey was used for gathering information from a purposive sample of professionals in the healthcare field attending management training programs in Italy. Factor analysis, a set of ordinal logistic regressions and an unpaired two-sample t-test were used for data elaboration. Results The findings show the importance of diversity of pedagogical approaches and tools and debate, and class homogeneity, as effectiveness factors. Lower competencies held before the training programs and problems of dialogue and discussion during the course are conducive to innovative practice introduction. Interpersonal and career outcomes are greater for those holding management positions. Conclusions The study reveals four profiles of participants with different gaps and needs. Training programs should be tailored based on participants’ profiles, in terms of pedagogical approaches and tools, and preserve class homogeneity in terms of professional backgrounds and management levels to facilitate constructive dialogue and solution finding approach.

Abstract African swine fever virus (ASFV) causes a devastating disease affecting domestic and wild pigs. ASF was first introduced in Sardinia in 1978 and until 2019 only genotype I isolates were identified. A remarkable genetic stability of Sardinian ASFV isolates was described, nevertheless in 2019 two wild boar isolates with a sustained genomic deletion (4342 base pairs) were identified (7303WB/19, 7212WB/19). In this study, we therefore performed in vitro experiments with monocyte-derived macrophages (moMФ) to unravel the phenotypic characteristics of these deleted viruses. Both 7303WB/19 and 7212WB/19 presented a lower growth kinetic in moMФ compared to virulent Sardinian 26544/OG10, using either a high (1) or a low (0.01) multiplicity of infection (MOI). In addition, flow cytometric analysis showed that both 7303WB/19 and 7212WB/19 presented lower intracellular levels of both early and late ASFV proteins. We subsequently investigated whether deleted virus variants were previously circulating in wild boars in Sardinia. In the four years preceding the last genotype I isolation (February 2015–January 2019), other eight wild boar isolates were collected, all belonging to p72 genotype I, B602L subgroup X, but none of them presented a sustained genomic deletion. Overall, we observed the deleted virus isolates in Sardinia only in 2019, at the end of a strong eradication campaign, and our data suggest that it might possess an attenuated phenotype in vivo. A better understanding of ASFV evolution in endemic territories might contribute to development of effective control measures against ASF.

The green oak leaf roller moth, Tortrix viridana, is one of the main defoliators of deciduous oaks in the Mediterranean region. Although aerial applications of Btk-based insecticides represent the most effective method to control the larval populations of this pest at a large spatial scale, the optimal time window for sprayings has not yet been defined. Accordingly, experimental trials were conducted in a Quercus pubescens forest district in Sardinia (Italy) involving both large-scale aerial treatments and small-scale applications from the ground. The aim of our work was to study how different larval development stages and/or sprouting phenological phases of the host trees affect Btk efficacy. Aerial sprayings were conducted in 2003 and 2004 in two different areas of about 300 ha, selected according to altitude and exposure to simulate three different application timings against different larval instars and sprouting phenological phases. From-the-ground applications were carried out in 2021 in a Q. pubescens forest stand by applying Btk-based insecticides at different timings, and the overall Q. pubescens phenological stage and the distribution of T. viridana larval development stages were assessed accordingly. The effectiveness of Btk applications was evaluated by estimating larval mortality 7, and 14 days after aerial applications, and 7, 14 and 21 days after ground applications. Defoliation due to T. viridana was also evaluated at the end of larval development in all years. In both 2003 and 2004, the average larval mortality due to Btk exceeded 80 % two weeks after aerial applications across all application timings. Damage caused by T. viridana varied with Btk application timing, with the later applications showing a higher defoliation than other timings. In ground application experiments, larval mortality significantly increased when Btk was sprayed against a larval population primarily composed of IV instars, which were feeding on sprouts with leaves that were spread out and had not fully developed internodes, thus resulting in a significative reduction of insect damage. Our findings indicate that, in accordance with the strict synchrony between the larval development and the oak flushing, the optimal timing for Btk application against T. viridana can be defined based on the bud burst phenological phase. In particular, the prevalence of sprout with expanding leaf surface allowing insecticidal droplet interception and the simultaneous presence of susceptible larval instars (within the IV), resulted in an increased treatment efficacy.

A pessoa que busca por um atendimento em psicologia tenciona diminuir algum sofrimento psíquico que esteja passando. Ultimamente, com a força das redes sociais mostrando relatos autobiográficos de autistas adultos, houve identificação de muitas pessoas que passaram a se questionar se eram autistas diante do intenso sofrimento vivido ao longo da vida. A categorização diagnóstica do Transtorno do Espectro do Autismo (TEA) vem sendo discutida de forma mais consistente a partir da publicação do DSM-5, em 2013, quando quadros clínicos infantis relacionados ao neurodesenvolvimento foram entendidos como um continuum. Com isso, abriu-se uma ampla discussão acerca do psicodiagnóstico em adultos. O presente trabalho visa compartilhar a experiência clínica da primeira autora em encontros dialógicos com adultos que suspeitavam serem autistas e buscavam um diagnóstico. A investigação clínica seguiu o método fenomenológico, que valoriza as vivências como fenômenos que podem revelar a estrutura constitutiva da pessoa; e a abordagem humanista de encontros relacionais em que se prioriza a dialogicidade para se aproximar do fenômeno investigado. Para tanto, iniciou-se um processo de avaliação psicológica compreensiva, colaborativa e interventiva para atender a dois interesses principais: a construção e refinamento de um raciocínio clínico e a ampliação do conhecimento de si por parte da pessoa atendida. Na experiência clínica, nota-se a possibilidade da (re)constituição e (res)significação de si para além do diagnóstico. Mais do que oferecer o diagnóstico, espera-se proporcionar uma atenção psicológica clínica eticamente condizente com a singularidade da experiência subjetiva.

BackgroundShared biological factors may play a role in both the cognitive deficits and the increased prevalence of metabolic syndrome observed in individuals with Schizophrenia (SCZ). These factors could entail disturbances in tryptophan (Trp) to both melatonin (MLT) and kynurenine (Kyn) metabolic pathways, as well as inflammation and alterations in the gut microbiome composition.MethodsThe present research project aims to investigate this hypothesis by recruiting 170 SCZ patients from two different recruitment sites, assessing their cognitive functions and screening for the presence of metabolic syndrome. Additionally, we plan to assess the impact of a 3-month cognitive remediation therapy on 30 of these patients. We will analyze clinical data alongside serum biomarkers and gene expression related to the Trp- to MLT and Kyn metabolic pathways, markers of inflammatory and composition of the gut microbiome. The association between Trp-MLT-Kyn levels, expression levels of selected genes, inflammatory markers and clinical phenotypes will be analyses in the context of general linear models.DiscussionThis project has the potential to identify some typical SCZ symptomatic clusters that will be more stringently associated with variations in the Trp-MLT-Kyn/inflammatory system and with a better response to cognitive remediation therapy. Moreover, in a future perspective, it may highlight a group of patients who may benefit from a pharmacological treatment aiming at reinstating the physiological Trp to MLT and Kyn system. Therefore, it has the potential to move research toward a personalized approach for SCZ management.

Previous studies indicated atypical Theory of Mind (ToM) abilities in individuals with autism spectrum disorder (ASD) at different ages. However, research focused on adolescents with ASD is still rare. This study aims to fill the gaps in the literature, by investigating ToM abilities in adolescents with ASD and in a group of typically developing ones. We applied the Theory of Mind Assessment Scale (Th.o.m.a.s.), a semi-structured interview that allows a multi-dimensional measurement of ToM, including different perspectives (first/s-order, first/third-person, egocentric/allocentric), various mental states (emotions, desires, beliefs) and metacognitive abilities related with mental states (awareness, relation, and strategies). The results indicated that ToM develops atypically in ASD, with strengths and weaknesses. First, participants with ASD were comparable to controls in some specific ToM aspects, i.e., third-person ToM, both from an egocentric and an allocentric perspective. However, they were significantly weaker in attributing an understanding of the mental states of others, both in first- and second-order ToM scenarios. Second, they showed the same level of awareness about mental states as controls, but they were significantly weaker in conceptualizing the relationship between mental states and behavior. Also, they found it very difficult to think about possible strategies that they or others might employ to realize desires and needs. Finally, they performed similarly to controls in understanding emotions, while they poorly understood desires and beliefs. These results point out the distinctive characteristics of ToM development in individuals with ASD, with important implications for individualized interventions.

Soil nematodes are among the most significant soil-dwelling organisms in forest ecosystems. However, the factors that shape the distribution of soil nematodes are still not well explored. Therefore, we collected soil samples from 20 forest sites along the eastern transect of China and sequenced 18S rRNA V9 region to reveal the biodiversity of soil nematodes. Our study found that soil nematode richness is higher in temperate mixed needleleaf and broadleaf forests compared with the other four vegetation regions. Soil physiochemical properties overrode climatic factors to be the primary drivers of soil nematode richness and community composition. Importantly, the soil nematode richness significantly enhanced ecosystem multifunctionality, especially bacterial biomass and enzyme activities, with a determination coefficient (r2) of 0.23, suggesting that soil nematodes played essential roles in the forest ecosystem.

The data model is a critical component of an Adaptive Web System (AWS). The major goals of such a data model are describing the application domain of the AWS and capturing data about the user in order to support the “adaptation effect”. There have been many proposals for data models, principally based on knowledge representation, machine learning, logic and reasoning, and, recently, ontologies. These models are focused on the implementation of the core layer of AWS, that is realizing the adaptation of contents and presentations of the system, but sometimes they are poor with respect to the application domain design. In this paper, we present an extension of the state-of-the-art XML Adaptive Hypermedia Model (XAHM), Object-Oriented XAHM (OO-XAHM) that supports the application domain modeling using an object-oriented approach. We also provide the formal definition of the model, its description via Unified Modeling Language (UML), and its implementation using XML Schema. Finally, we provide a complete case study that focuses the attention on the well-known Italian archaeological site Pompeii.

Arab learners of English often face challenges when it comes to correctly pronouncing English consonant clusters. To address these difficulties, technology-driven methods can be employed to enhance the acquisition of proper English consonant cluster pronunciation. This research endeavor aimed to assess the impact of web-based pronunciation training on the articulation of consonant clusters. The research followed an experimental design, involving fifty-eight Saudi learners of English as a foreign language (EFL) who were enrolled at a public university in Saudi Arabia. These participants were randomly divided into two groups. The experimental group received a list of words containing consonant clusters to practice using YouGlish as a resource. Meanwhile, the control group was instructed to listen to the instructor's pronunciation and then practice producing the words with consonant clusters. The outcomes demonstrated a significant improvement in the production of words with consonant clusters among the experimental group, attributed to the utilization of web-based pronunciation training. These findings hold promise for the field of language learning, highlighting the effectiveness of web-based pronunciation training as a valuable tool for teaching second language pronunciation.

Abstract Background Treatment options available for meningoencephalitis of unknown origin (MUO) in dogs are suboptimal, and currently, no single treatment protocol appears to be superior. Objectives Compare neurological deterioration rates at 7 days between dogs with MUO treated with corticosteroids alone or combined with cytosine arabinoside (CA) continuous rate infusion (CRI) and compare clinical deterioration and survival at 30 and 100 days. Animals Sixty‐nine dogs with magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) features or both compatible with MUO. Methods Parallel, blinded, randomized controlled trial. Simple randomization into 2 treatment groups: 4 mg/kg/day prednisolone (or dexamethasone equivalent) for 2 days or 200 mg/m2 CA CRI over 8 hours plus 2 mg/kg/day prednisolone. Blinding of the treatment protocol was carried out using reversible redaction of clinical records, and treatment failure was defined as deterioration of neurological assessment or death. Using intention‐to‐treat analysis, proportions failing treatment at 7, 30, and 100 days were compared using Fisher's exact test. All‐cause mortality at 100 days was compared using Kaplan‐Meier survival curves. Results Thirty‐five dogs were allocated to corticosteroid only, and 34 dogs were allocated to combined CA CRI and corticosteroid. Proportions failing treatment at 7, 30, and 100 days were 7/35 (20%), 9/35 (26%), and 15/35 (43%) in the corticosteroid‐only group and 8/34 (24%), 11/34 (32%), and 23/34 (68%) in the corticosteroid and CA CRI group. All‐cause mortality at 100 days was not significantly different between groups (P = .62). Clinically relevant treatment‐related adverse effects were not observed. Conclusions and Clinical Importance We found no difference in outcome between corticosteroid monotherapy and combined cytarabine CRI and corticosteroid therapy at 7, 30, and 100 days after diagnosis in dogs with MUO.

Abstract Evaluating potential routes of invasion of pathogens and vectors of sanitary importance is essential for planning and decision-making at multiple scales. An effective tool are process-explicit models that allow coupling environmental, demographic and dispersal information to evaluate population growth and range dynamics as a function of the abiotic conditions in a region. In this work we simulate multiple dispersal/invasion routes in Mexico that could be taken by ambrosia beetles and a specific symbiont, Harringtonia lauricola, responsible for a severe epiphytic of Lauraceae in North America. We used Xyleborus bispinatus Eichhoff 1868 as a study subject and estimated its demography in the laboratory in a temperature gradient (17, 20, 26, 29, 35 °C), which we then used to parameterize a process-based model to estimate its metapopulation dynamics. The maximum intrinsic growth rate of X. bispinatus is 0.13 with a thermal optimum of 26.2 °C. The models suggest important regions for the establishment and dispersal the states of Veracruz, Chiapas and Oaxaca (high host and secondary vectors diversity), the Isthmus of Tehuantepec (connectivity region), and Michoacán and Jalisco (important avocado plantations). The use of hybrid process-based models is a promising tool to refine the predictions applied to the study of biological invasions and species distributions.

Individuals suffering from diverse neuropsychiatric and neurodegenerative disorders often have comparable symptoms, which may underline the implication of shared hereditary influences and the same biological processes. Lysophosphatidic acid (LPA) is a bioactive phospholipid and a crucial regulator of the development of adult neuronal systems; hence, it may play an important role in the onset of certain diseases such as Alzheimer’s, Parkinson’s disease, and schizophrenia. During development, LPA signaling regulates many cellular processes such as proliferation, survival, migration, differentiation, cytoskeleton reorganization, and DNA synthesis. So far, six lysophosphatidic acid receptors that respond to LPA have been discovered and categorized based on their homology. Despite the abundance of evidence relating LPA cellular activities to different pathological conditions, little is known about the involvement of LPA in the field of neuropsychiatric and neurodegenerative diseases. The purpose of this review is to define LPA activities related to the illnesses stated above in order to better understand these pathologies and provide future novel treatment strategies based on the latest data.

Abstract Academic social contexts and educational beliefs may influence teaching practices and teaching intentions. Insight into such beliefs represents an important source of information for medical schools to improve the quality of teaching and to guide content of faculty development programs. The aim of this study was to explore beliefs about teaching among prospective clinical teachers at a newly established medical school in Southern Switzerland and to estimate the relationship between these beliefs and intention to commit to teaching in the newly established medical curriculum using Fishbein’s integrative model of behaviour prediction. We targeted a purposive sample of physicians working in hospital departments potentially involved in the clinical immersion of medical students enrolled in the program. We designed a cross-sectional quantitative study using an online questionnaire. The questionnaire included both items developed by the authors and items belonging to a previously validated questionnaire. Participants showed a high intention to commit to teaching in the newly established curriculum. We found that self-efficacy beliefs and two sets of behavioural beliefs, namely perceived importance and expectations, had a positive correlation with the intention to commit. On the other hand, we pointed out a number of normative beliefs that in the long run could hinder the maintenance of this commitment, which should be addressed both at the levels of both faculty development and institutional policy rules. Our study also highlights the importance of reinforcing teachers’ perceived self-efficacy in providing clinical supervision, strengthening their perceived importance of the clinical supervision, and incentivising the commitment of teachers by ensuring they have protected time to devote to this activity.

AbstractBackground In-flight medical emergencies (IMEs) are expected to increase as air travel normalized in the post-COVID-19 era. However, few studies have examined health professions students’ preparedness to respond to such emergencies. Therefore, this study aimed to investigate medical students’ knowledge, confidence, and willingness to assist during an IME in their internship program.Methods This cross-sectional survey utilized an online, self-administered questionnaire-based survey targeted at medical students at two medical colleges in Saudi Arabia. The questionnaire comprised three parts: sociodemographic characteristics, knowledge about aviation medicine (10 items), and confidence (7 items)/willingness (4 items) to assist during an IME. Odds Ratios (OR) and 95% Confidence Intervals (95%CI) were computed to detect potential associations between the knowledge levels and the other independent variables. Responses to confidence and willingness questions were scored on a 5-point Likert scale.Results Overall, 61.4% of participants had inadequate knowledge scores for providing care during an IME, and the proportion of participants did not differ between those who had or had not attended life support courses (60.4% vs. 66.7%, p > 0.99). Only frequency of air travel ≥ two times per year was associated with higher odds of adequate knowledge score [OR = 1.89 (95%CI 1.14–3.17), p = 0.02]. In addition, 93.3% of the participants had low, 6.3% had moderate, and 0.8% had high willingness scores, while 86.3% had low, 12.2% had moderate, and 1.5% had high confidence scores. There were no differences in the proportion of participants with low, moderate, and high willingness or confidence scores by attendance in life support courses.Conclusion Even though over 8 in 10 students in our study had previously attended life support courses, the overwhelming majority lacked the knowledge, confidence, and willingness to assist. Our study underscores the importance of teaching medical students about IMEs and their unique challenges before entering their 7th-year mandatory general internship.

IntroductionThe current investigation presents a two-fold approach to rediscovering the potential of Sonchus asper as a wild edible plant, both in its raw extract form and as a nanoformulated product. Furthermore, the study aimed to promote the valorization of traditional dishes and contribute to biodiversity conservation and sustainable use of S. asper, thus enhancing economic profits.MethodsLiquid chromatography-mass spectrometry analyses were conducted to characterize the metabolite profile of the raw and cooked leaf extracts, and the extract from discarded leaves. The antioxidant activity, the hypoglycaemic effect and the incorporation into liposomes were evaluated.Results38 compounds and 6 essential amino acids were identified. The incorporation into liposomes maximized the health-promoting properties for potential pharmaceutical or food applications.DiscussionThe commercialization of S. asper could: (i) contribute to improving the well-being of rural and urban communities, being S. asper a wild edible plant available at low cost, environmentally friendly, resilient, and adaptable; (ii) generate landowner economic returns.

Thyroid nodules in children are less common than in adults but they are approximately two- to three-fold more likely to be malignant in children. Among thyroid nodular diseases, Plummer's adenoma occurs very rarely in pediatrics, and currently, there is no literature providing evidence of this diagnosis in patients with Prader–Willi syndrome (PWS). We report the case of a 9-year-old Caucasian boy affected by PWS presenting with a rapidly growing palpable mass in the thyroid lodge associated with subclinical hyperthyroidism. Laboratory and other examinations (thyroid ultrasound, fine-needle aspiration of the nodule, and scintigraphy) were strongly suggestive for Plummer's adenoma; therefore, the patient underwent left hemithyroidectomy surgery, and anatomo-pathological examination confirmed the diagnosis. Our case describes the first evidence of an isolated follicular adenoma in children with PWS. Surgery is the only therapeutic option in younger children. Further evidence is needed to assess the possible correlation between these two conditions and the existence of potential risk factors.

In the last years, olive pomace, a by-product of olive oil extraction, has shown great interest. The work aims to valorize the olive pomace of two Sardinian olive cultivars, Bosana and Semidana, by incorporating them into the formulation of functional baked products to improve their nutritional value. The freeze-dried pomace of the two varieties has been used to substitute the type 00 flour in percentages of 1, 2, and 3% (w/w). The olive pomace was characterized by macro-composition analysis, while the bread samples were characterized for their proximate, physical, technological, sensory characteristics and shelf life. The specific volume of fortified samples decreased significantly compared to the control, while antioxidant activity, and nutritional parameters were significantly improved using olive pomace. Moreover, fortified samples showed a reduction of browning and whiteness indices with respect to control. Textural profile analysis showed a firmer product, compared to the control, with higher levels of olive pomace which also positively affected the cell size distribution in the crumb. Sensorially, consumers were mostly appealed by the 1% levels of substitution of olive pomace, in particular that of the Bosana. Hardness of all samples increased significantly along 7 days of storage thus resulting in a shelf life of less than 3 days. Therefore, it can be concluded that the incorporation of olive pomace, especially at low levels (1%), into white bread significantly improves the nutritional and sensorial quality of bread without significantly affecting its technological properties.

Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work, we show through over 45 μs of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how this glycan’s structural role changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2), and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha, and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.

Objective While the Gulf Cooperation Council (GCC) countries have demonstrated a strong commitment to strengthening primary healthcare (PHC), the costs of delivering these services in this region remain relatively unexplored. Understanding the costs of PHC delivery is essential for effective resource allocation and health system efficiency.Design We used an ingredient-based method to estimate the cost of delivering a selection of services at PHC facilities in the six GCC countries in 2019. Services were categorised into eight programmes: immunisation; non-communicable diseases (NCDs); oral and dental care; child health; nutrition; mental health; reproductive, maternal, neonatal and child health and general practice. The cost estimation focused on two key ingredients: the costs of drugs and supplies and the healthcare workforce cost. The coverage rates of specific types of health services, including screening and mental health services, were also estimated. Data for the analysis were obtained from ministries of health, health statistics reports, online databases, national surveys and scientific literature.Results The estimated costs of delivering the selected services at public PHC facilities in the six GCC countries totalled US$5.7 billion in 2019, representing 0.34% of the combined 2019 GDP. The per capita costs varied from US$69 to US$272. General practice and NCD programmes constituted 79% of the total costs modelled while mental health ranged between 0.0% and 0.3%. Over 8 million individuals did not receive NCD screening services, and over 30 million did not receive needed mental health services in public PHC facilities across the region.Conclusions To our knowledge, this is the first study to estimate the costs of services delivered at PHC facilities in the GCC countries. Identifying the main cost drivers and the services which individuals did not receive can be used to help strengthen PHC to improve efficiency and scale up needed services for better health outcomes.