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Background: CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. Methods and Results: We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. Conclusions: The present study highlights the importance of considering the investigation of the CACNA1C gene in children’s neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder.

Plexiform fibromyxoma (PF), also referred to as plexiform angiomyxoid myofibroblast tumor, is an exceedingly rare mesenchymal neoplasm primarily affecting the stomach. Herein, we present a case of PF diagnosed in a 71-year-old male with a history of lung cancer, initially suspected to have a gastrointestinal stromal tumor (GIST) of the stomach, who subsequently underwent subtotal gastrectomy. The histopathological and molecular features of the tumor, including mutations in ABL1, CCND1, CSF1R, FGFR4, KDR, and MALAT1-GLI1 fusion, are elucidated and discussed in the context of diagnostic, prognostic, and therapeutic considerations.

Background: The COVID-19 pandemic has been a health emergency with a significant impact on the world due to its high infectiousness. The disease, primarily identified in the lower respiratory tract, develops with numerous clinical symptoms affecting multiple organs and displays a clinical finding of anosmia. Several authors have investigated the pathogenetic mechanisms of the olfactory disturbances caused by SARS-CoV-2 infection, proposing different hypotheses and showing contradictory results. Since uncertainties remain about possible virus neurotropism and direct damage to the olfactory bulb, we investigated the expression of SARS-CoV-2 as well as ACE2 receptor transcripts in autoptic lung and olfactory bulb tissues, with respect to the histopathological features. Methods: Twenty-five COVID-19 olfactory bulbs and lung tissues were randomly collected from 200 initial autopsies performed during the COVID-19 pandemic. Routine diagnosis was based on clinical and radiological findings and were confirmed with post-mortem swabs. Real-time RT-PCR for SARS-CoV-2 and ACE2 receptor RNA was carried out on autoptic FFPE lung and olfactory bulb tissues. Histological staining was performed on tissue specimens and compared with the molecular data. Results: While real-time RT-PCR for SARS-CoV-2 was positive in 23 out of 25 lung samples, the viral RNA expression was absent in olfactory bulbs. ACE2-receptor RNA was present in all tissues examined, being highly expressed in lung samples than olfactory bulbs. Conclusions: Our finding suggests that COVID-19 anosmia is not only due to neurotropism and the direct action of SARS-CoV-2 entering the olfactory bulb. The mechanism of SARS-CoV-2 neuropathogenesis in the olfactory bulb requires a better elucidation and further research studies to mitigate the olfactory bulb damage associated with virus action.

Melanins are complex, polymeric pigments with interesting properties like UV-light absorbance ability, metal ion chelation capacity, antimicrobial action, redox behaviors, and scavenging properties. Based on these characteristics, melanins might be applied in different industrial fields like food packaging, environmental bioremediation, and bioelectronic fields. The actual melanin manufacturing process is not environmentally friendly as it is based on extraction and purification from cuttlefish. Synthetic melanin is available on the market, but it is more expensive than animal-sourced pigment and it requires long chemical procedures. The biotechnological production of microbial melanin, instead, might be a valid alternative. Streptomycetes synthesize melanins as pigments and as extracellular products. In this review, the melanin biotechnological production processes by different Streptomyces strains have been revised according to papers in the literature. The different fermentation strategies to increase melanin production such as the optimization of growth conditions and medium composition or the use of raw sources as growth substrates are here described. Diverse downstream purification processes are also reported as well as all the different analytical methods used to characterize the melanin produced by Streptomyces strains before its application in different fields.

IntroductionDespite proven efficacy, HPV vaccination coverage is still suboptimal. Factors influencing vaccination uptake are education attainment, socio-economic position, and knowledge about HPV. This study aimed to assess HPV vaccination uptake and its correlates among medical students and identify logistic-organizational barriers, knowledge, and attitudes with regard towards HPV vaccination to improve current public health vaccination strategies. Medical students, with their acquired biological knowledge, were selected as a low-risk groups for HPV vaccination uptake. This cross-sectional study was conducted using a validated questionnaire.MethodsStudents in their the first 3 years of study students were preferentially invited. Eventually, the invitation was extended to every medical student. Logistic multivariable regression was used to assess determinants of HPV vaccination uptake. Additional analysis explored determinants of knowledge of and attitude toward HPV vaccination. Finally, a sensitive analysis was conducted to further assess the effect of knowledge and attitude on the HPV vaccination rate.ResultsA total of 882 medical students participated, with 74.5% enrolled in the first 3 years of their training. HPV vaccination uptake was 55.5%, ranging from 78.5% for females to 16.5% for males. Male sex and increasing age were consistently associated with a lower vaccination uptake (males sex: OR 0.03, CI 0.02–0.05; age: OR 0.77, CI 0.68–0.88), whereasilst progress in their academic career was associated with a to higher likelihood of being vaccinated (6th year: OR 3.45, CI 1.24–9.57). These associations were confirmed when considering the knowledge of and attitude towards HPV. Additionally also, an active outreach from healthcare institutions was associated with a higher likelihood of receiving HPV vaccination (OR 1.70, CI 1.09–2.65.ConclusionHPV vaccination in medical students was higher than in the general population; however, it was still suboptimal. An active and up-to-date call strategy and extending the free-of-charge offer are essential measures for to improvinge vaccination uptake. The findings support the need to improve public health strategies and increase awareness and knowledge ofregarding HPV vaccination.

IntroductionPsychological distress may result in impairment and difficulty understanding oneself and others. Thus, addressing metacognitive issues in psychotherapy may improve psychopathology in adolescents and young adults (AYAs). We aimed to compare metacognitive interpersonal therapy (MIT)-informed psychotherapy with other treatment-as-usual (TAU) therapies.MethodsWe administered the Global Assessment of Functioning (GAF) scale, the Clinical Global Impressions–Severity (CGI-S) scale, and the Brief Psychiatric Rating Scale (BPRS) at baseline (BL) and at treatment termination (the endpoint was at 6 months and any last results obtained before that term were carried forward in analyzes). Patients received concomitant psychiatric and psychological treatment.ResultsSixty AYAs were involved in the study. There was a significant reduction in symptomatology after the intervention. Twelve patients (17%) dropped out; treatment adherence was 83%. In the MIT group, 2 patients dropped out (11%), and in the TAU group, 9 patients dropped out (19%). All scales showed a significant reduction in symptoms between baseline (BL) and the 6-month endpoint: GAF (χ2 = 6.61, p

IntroductionThe dramatic increase in multidrug-resistance of Clostridioides difficile isolates has led to the search for new complementary medicines against C. difficile infection (CDI). In this study, we aimed to examine the inhibitory effects of hydroethanolic extract of Mentha longifolia L. (ETOH-ML) on the growth of C. difficile RT001 and its toxigenic cell-free supernatant (Tox-S)-induced inflammation and apoptosis.MethodsThe active phytochemical components of ETOH-ML were detected using GC and HPLC. The antimicrobial properties of the extract were examined against C. difficile RT001. Furthermore, cell viability and cytotoxicity of Caco-2 and Vero cells treated with various concentrations of ETOH-ML, Tox-S of C. difficile RT001, and their combination were assessed. Anti-inflammatory and anti-apoptotic activities of ETOH-ML were explored in Tox-S stimulated Caco-2 cells using RT-qPCR.ResultsBased on our results, rosmarinic acid was the main phytochemical component of ETOH-ML. The extract showed significant antimicrobial activity against C. difficile RT001 by agar dilution and broth microdilution methods. Moreover, ETOH-ML at concentrations of

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

Patients with Parkinson’s disease (PD), often elderly with various comorbidities, may require a continuous intestinal infusion of carbidopa/levodopa gel by the placement of a percutaneous endoscopic gastrostomy (PEG) with a jejunal tube (PEG-J) to improve their motor outcome and quality of life. However, it is unclear what is the best procedural sedation protocol for PEG-J procedures. Fifty patients with PD and indication for PEG-J procedure (implantation, replacement, removal) underwent, from 2017 to 2022, a sedation protocol characterized by premedication with atropine (0.01 mg/Kg i.v.), midazolam (0.015–0.03 mg/Kg i.v.) and induction with bolus propofol (0.5–1 mg/Kg i.v.) as well as, finally, sedation with continuous infusion propofol (2–5 mg/Kg/h i.v.) by Target Controlled Infusion (TCI) technique. Ninety-eight per cent of patients experienced no intraprocedural or peri-procedural adverse events. All the procedures were technically successful. A good discharge time was recorded. The vital parameters recorded during the procedure did not vary significantly. A PEG-J procedure conducted within 30 min showed a significant advantage over end-tidal carbon dioxide (EtCO2). Indeed, the latter showed some predictive behavior (OR: 1.318, 95% CI 1.075–1.615, p = 0.008). In the real world, this sedation protocol showed a good safety and effectiveness profile, even with reduced doses of midazolam and a TCI propofol technique in moderate sedation.

Abstract Background Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels. Methods In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality. Results 142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3–2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3–2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR − 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43–150), no patients required hemodialysis and 2 patients died due to non-cardiac causes. Conclusions In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function. Trial registration: The study was registered at Clinicaltrials.gov (NCT04766008). Graphical Abstract

The ranking pipelines of modern search platforms commonly exploit complex machine-learned models and have a significant impact on the query response time. In this paper, we discuss several techniques to speed up the document scoring process based on large ensembles of decision trees without hindering ranking quality. Specifically, we study the problem of document early exit within the framework of a cascading ranker made of three components: 1) an efficient but sub-optimal ranking stage; 2) a pruner that exploits signals from the previous component to force the early exit of documents classified as not relevant; and 3) a final high-quality component aimed at finely ranking the documents that survived the previous phase. To maximize speedup and preserve effectiveness, we aim to increase the accuracy of the pruner in identifying non-relevant documents without early exiting documents that are likely to be ranked among the final top- $k$ results. We propose an in-depth study of heuristic and machine-learning techniques for designing the pruner. While the heuristic technique only exploits the score/ranking information supplied by the first sub-optimal ranker, the machine-learned solution named LEAR uses these signals as additional features along with those representing query-document pairs. Moreover, we study alternative solutions to implement the first ranker, either a small prefix of the original forest or an auxiliary machine-learned ranker explicitly trained for this purpose. We evaluated our techniques through reproducible experiments using publicly available datasets and state-of-the-art competitors. The experiments confirm that our early-exit strategies achieve speedups ranging from $3\times $ to $10\times $ without statistically significant differences in effectiveness.

Abstract Colorectal cancer (CRC) is the third most revalent type of cancer in the world and the second most common cause of cancer death (about 1 million per year). Historically, natural compounds and their structural analogues have contributed to the development of new drugs useful in the treatment of various diseases, including cancer. Essential oils are natural odorous products made up of a complex mixture of low molecular weight compounds with recognized biological and pharmacological properties investigated also for the prevention and treatment of cancer. The aim of this paper is to highlight the possible role of essential oils in CRC, their composition and the preclinical studies involving them. It has been reviewed the preclinical pharmacological studies to determine the experimental models used and the anticancer potential mechanisms of action of natural essential oils in CRC. Searches were performed in the following databases PubMed/Medline, Web of science, TRIP database, Scopus, Google Scholar using appropriate MeSH terms. The results of analyzed studies showed that EOs exhibited a wide range of bioactive effects like cytotoxicity, antiproliferative, and antimetastatic effects on cancer cells through various mechanisms of action. This updated review provides a better quality of scientific evidence for the efficacy of EOs as chemotherapeutic/chemopreventive agents in CRC. Future translational clinical studies are needed to establish the effective dose in humans as well as the most suitable route of administration for maximum bioavailability and efficacy. Given the positive anticancer results obtained from preclinical pharmacological studies, EOs can be considered efficient complementary therapies in chemotherapy in CRC.

Abstract Bone marrow mesenchymal stem cells (BM-MSCs) exhibit multiple abnormalities in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), including reduced proliferative and clonogenic capacity, altered morphology, impaired immunoregulatory properties and capacity to support hematopoiesis. Here, we investigated expression of the FOXM1 gene, a transcription factor driving G2/M gene expression, in BM-MSCs isolated from patients with MDS and AML, de novo and therapy-related, compared to BM-MSCs isolated from healthy donors (HD). We observed a statistically significant downregulation of FOXM1 expression in BM-MSCs isolated from MDS and AML patients, as compared to controls. In parallel, expression of FOXM1 mitotic targets (CCNB1, CDC20, PLK1 and NDC80) was suppressed in patients’ BM-MSCs, as compared to HD. No differences in the expression of FOXM1 and its mitotic targets were observed in BM-mononuclear cells from the different sources. From a functional standpoint, silencing of FOXM1 mRNA in healthy MSC induced a significant decrease in the expression of its targets. In this line, healthy MSC silenced for FOXM1 showed an impaired ability to support hematopoiesis in vitro. These findings suggest that deregulation of FOXM1 may be involved in the senescent phenotype observed in MSC derived from myeloid neoplasms.

Abstract Desmodium adscendens (Sw.) DC. is a plant of the Fabaceae family especially rich in flavonoids but also in alkaloids, terpenoids, steroids, phenols, phenylpropanoids, glycosides, and volatiles. This herb has been traditionally used in numerous countries all over the world for its pharmacological and biological properties (i.e., it has been used for the treatment of diarrheas, fever, epilepsy, asthma, leishmaniasis, gastroduodenal ulcer, diabetes, hepatic diseases, etc.). Given the wide uses of D. adscendens, this review summarizes all recent data on D. adscendens evaluating its phytochemistry as well as its ethno‐traditional and pharmacological properties. In addition, an association between the phytocompounds of this plant and its potential mechanism of action in cell and animal models has been investigated, focusing with a special emphasis on human experiments.

The field of supramolecular peptides self-assembly has undergone outstanding growth since the early 1990s after the serendipitously discovery by Shuguang Zhang of an ionic self-complementary peptide as a repeating segment in a yeast protein. From then on, the field expanded at an accelerating pace and these self-assembled materials have become an integral part of a broad plethora of designer supramolecular nanomaterials useful for different applications ranging from 3D tissue cell cultures, regenerative medicine, up to optoelectronics. However, the supramolecular peptide based-nanomaterials available thus far for regenerative medicine still lack the dynamic complexity found in the biological structures that mediate regeneration. Indeed, self-assembling peptide (SAPs) suffer from poor mechanical stability, losing mechanical properties at low strains. Just like the extracellular matrix (ECM) of living systems, the chemical structure of the SAP-biomaterials should concurrently contain non-covalent and covalent bonds, bringing, respectively, infinite and finite lifetimes of interactions to obtain a reversibly dynamic matrix. In this review, will be highlighted the major advantages and current limitations of SAP-based biomaterials, and it will be discussed the most widely used strategies for precisely tune their mechanical properties (stiffness, resilience, strain-failure, stress resistance), describing recent and promising approaches in tissue engineering, regenerative medicine, and beyond.

Abstract The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P

The use of innovative approaches to elucidate the pathophysiological mechanisms of autoimmune diseases, as well as to further study of the factors which can have either a positive or negative effect on the course of the disease, is essential. In this line, the development of new molecular techniques and the creation of the Human Genome Program have allowed access to many more solutions to the difficulties that exist in the identification and characterization of the microbiome, as well as changes due to various factors. Such innovative technologies can rekindle older hypotheses, such as molecular mimicry, allowing us to move from hypothesis to theory and from correlation to causality, particularly regarding autoimmune diseases and dysbiosis of the microbiota. For example, Prevotella copri appears to have a strong association with rheumatoid arthritis; it is expected that this will be confirmed by several scientists, which, in turn, will make it possible to identify other mechanisms that may contribute to the pathophysiology of the disease. This article seeks to identify new clues regarding similar correlations between autoimmune activity and the human microbiota, particularly in relation to qualitative and quantitative microbial variations therein.

Green roofs have been widely recognized as sustainable nature-based solutions to mitigate floods in urban areas, which, in the last decades, are increasing due to the combination of intense worldwide urbanization and climate change. Besides flood mitigation, green roofs provide additional benefits for the urban environment (e.g., reducing the urban heat island and ensuring energy saving for the underneath building). Moreover, green roofs facilitate the increase of urban biodiversity, attracting different species of small animals, and upgrade the city aesthetic value. Among the different types of green roofs, multilayer blue-green roofs present an additional layer to store water during rainfall events. As part of the Polder Roof field lab project, prototypes of multilayer blue-green roof developed by the Dutch company Metropolder were installed in four Italian cities: Cagliari, Palermo, Perugia, and Viterbo. The four prototypes and the experimental set up are described and the potential benefits of this innovative solution are discussed. Preliminary analyses, from December 2020 to December 2021, enable to estimate runoff reduction and thermal properties of multilayer blue-green roofs, underlying the high potential of this nature-based solution, which allows to retain most of the rainfall events and to mitigate the daily temperature variability. HIGHLIGHTS Description of multilayer blue-green roofs installed in four Italian cities.; Analysis of the multilayer blue-green roof retention capacity.; Analysis of the multilayer blue-green roof thermal insultation properties.;

Therapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases. Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic work-up and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MNs patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MNs patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific. In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment and disease that allow planning treatments with an optimal risk/benefit ratio.

Eating disorders (ED) are serious disorders characterized by an alteration of eating habits and excessive concern about weight and body shapes (Fairburn, 2002), accompanied by significant impairment inequality of life, high mortality rates and serious organic consequences (Jenkins et al., 2011; Treasure et al., 2015; 2020). Although evidence-based psychological therapies for nonunderweight ED presentations such as cognitive behavioral therapy for eating disorders (CBT-ED) are widely available, there is substantial scope for improvements, particularly in terms of efficacy and adherence. One option is to develop interventions to address elements of pathology not fully addressed by existing empirical supported treatments, such as incorporating techniques aimed at addressing interpersonal problems and personality disorder features into existing treatment delivery. We adapted Metacognitive Interpersonal Therapy, a psychological intervention supported by evidence for treating personality disorders and integrated it with existing CBT techniques for eating disorders (MIT-ED). MIT-ED targets aspects of ED that are not included in the transdiagnostic CBT-E model such as poor metacognition, or maladaptive interpersonal schemas. This is a pre-registered (Protocol number: 0000781) pilot randomized clinical trial aimed at assessing acceptability and feasibility of MIT-ED and establishing preliminary evidence of effectiveness for future larger studies. Twenty patients (10 in each arm) will be randomized to 20 sessions of individual psychotherapy, either MIT-ED or CBTE. Repeated follow-ups will be collected up to 24 months. Participants are recruited at a private outpatient clinic for ED treatment. Acceptability will be assessed via session attendance, completion rates and preliminary outcomes. The primary outcome is ED pathology assessed with the Eating Disorder Examination Questionnaire-6. Other ED outcomes assessed will be eating disorder attitudes, clinical impairment and binge eating pathology. Secondary treatment outcomes are anxiety, depression, and global symptomatology. We will also assess emotional awareness, emotion regulation and therapeutic alliance. Based on previous studies of MIT for personality disorders we hypothesize that MIT-ED will be acceptable to patients, evidenced by high treatment adherence and retention. We hypothesize that MIT-ED will be associated with reductions in eating disorder pathology, at least equivalent to CBT-E. Results will be used to inform the study design, sampling, likely effect sizes and choice of outcome measures for future larger trials of MIT-ED in ED samples.

Hericium erinaceus, berberine, and quercetin are effective in experimental colitis. It is unknown whether they can ameliorate inflammatory bowel diseases in humans. This ex vivo study aimed to evaluate the anti-inflammatory potential of a nutraceutical compound of HBQ-Complex® (H. erinaceus, berberine, and quercetin), biotin, and niacin in inflammatory bowel disease patients. Tissue specimens were obtained either from Normal-Appearing Mucosa (NAM) or from Inflamed Mucosa (IM) in 20 patients with inflammatory bowel disease. mRNA and protein expression of COX-2, IL-10, and TNF-α were determined in NAM and IM biopsy samples (T0). IM samples were then incubated in HBQ-Complex® (with the addition of niacin and biotin), and COX-2, IL-10, and TNF-α tissue levels were evaluated at 120 minutes (T1) and 180 minutes (T2). Incubation with this compound resulted in a progressive decrease in gene and protein COX-2 and TNF-α expression at T1/T2 in the IM. IL-10 showed an opposite trend, with a progressive increase of mRNA and protein expression over the same time window. HBQ-Complex® (with the addition of niacin and biotin) decreased the expression of proinflammatory cytokines at the mRNA and protein levels in IBD tissue. On the contrary, mRNA and protein expression of the anti-inflammatory cytokine IL-10 showed a progressive increase.

IntroductionIn Europe, there is still suboptimal tetanus, diphtheria, and acellular pertussis (Tdap) booster coverage. This study aimed to assess coverage status, knowledge, and attitude on Tdap vaccination in healthcare workers (HcWs) of the University Hospital “Federico II” in Naples, Southern Italy, in 2022, to improve current vaccination strategies.MethodsA cross-sectional study was conducted using a validated anonymous questionnaire. Knowledge and attitude were measured as scores. Multivariable logistic and linear regression models were employed to identify correlates of Tdap booster and knowledge and attitude toward the vaccination, as appropriate. Models were controlled for age, sex, profession, department, and job seniority.ResultsA total of 206 questionnaires were administered among HcWs, and 143 (69.4%) were medical doctors. In total, 71 (34.47%) HcWs received the Tdap booster. Those who have worked 5–9 years at the hospital had a 78% lower likelihood of being vaccinated with the Tdap booster (5–9 years—OR: 0.22, CI: 0.06 | 0.85) as compared with newly hired HcWs. No differences in the average knowledge score were found. Other healthcare workers had a lower attitude as compared to medical doctors (Other—Coef. −2.15; CI: −4.14 | −0.15) and, as compared with those who worked in a clinical department, those who worked in a diagnostic–therapeutic department or medical management had 3.1 and 2.0 lower attitude scores, on average, respectively (diagnostic–therapeutic—Coef. −3.12, CI: −5.13 | −1.12; public health—Coef. −1.98, CI: −3.41 | −0.56).DiscussionThe study findings support the necessity to implement public health strategies and improve knowledge and attitude toward vaccinations and specifically highlight the importance of Tdap booster every 10 years as a prevention tool to protect high-risk populations.

The esophagus undergoes shrinkage after resection and fixation. The surgical in situ margin is greater than the specimen margin, measured by the pathologist. The length of disease‐free margins is critical to therapeutic planning. We propose specimen fixing to avoid discrepancies between the operative finding and the pathological result.

IntroductionMedullary thyroid cancer (MTC) is a rare type of neuroendocrine tumor that produces a hormone called calcitonin (CT). Thyroidectomy is the preferred treatment for MTC, as chemotherapy has been shown to have limited effectiveness. Targeted therapy approaches are currently being used for patients with advanced, metastatic MTC. Several studies have identified microRNAs, including miR-21, as playing a role in the development of MTC. Programmed cell death 4 (PDCD4) is a tumor suppressor gene that is an important target of miR-21. Our previous research has shown that high levels of miR-21 are associated with low PDCD4 nuclear scores and high CT levels. The aim of this study was to investigate the potential of this pathway as a novel therapeutic target for MTC.MethodsWe used a specific process to silence miR-21 in two human MTC cell lines. We studied the effect of this anti-miRNA process alone and in combination with cabozantinib and vandetanib, two drugs used in targeted therapy for MTC. We analyzed the effect of miR-21 silencing on cell viability, PDCD4 and CT expression, phosphorylation pathways, cell migration, cell cycle, and apoptosis.ResultsSilencing miR-21 alone resulted in a reduction of cell viability and an increase in PDCD4 levels at both mRNA and protein levels. It also led to a reduction in CT expression at both mRNA and secretion levels. When combined with cabozantinib and vandetanib, miR-21 silencing did not affect cell cycle or migration but was able to enhance apoptosis.ConclusionSilencing miR-21, although not showing synergistic activity with TKIs (tyrosine kinase inhibitors), represents a potential alternative worth exploring as a therapeutic target for MTC.

Summary: Background: The objective of this study is to investigate the trends of exposure and burden attributable to the four main metabolic risk factors, including high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high body-mass index (BMI), and high low-density lipoproteins cholesterol (LDL) in North Africa and the Middle East from 1990 to 2019. Methods: The data were retrieved from Global Burden of Disease Study 2019. Summary exposure value (SEV) was used for risk factor exposure. Burden attributable to each risk factor was incorporated in the population attributable fraction to estimate the total attributable deaths and disability-adjusted life-years (DALYs). Findings: While age-standardized death rate (ASDR) attributable to high-LDL and high-SBP decreased by 26.5% (18.6–35.2) and 23.4% (15.9–31.5) over 1990–2019, respectively, high-BMI with 5.1% (−9.0–25.9) and high-FPG with 21.4% (7.0–37.4) change, grew in ASDR. Moreover, age-standardized DALY rate attributed to high-LDL and high-SBP declined by 30.2% (20.9–39.0) and 25.2% (16.8–33.9), respectively. The attributable age-standardized DALY rate of high-BMI with 8.3% (−6.5–28.8) and high-FPG with 27.0% (14.3–40.8) increase, had a growing trend. Age-standardized SEVs of high-FPG, high-BMI, high-SBP, and high-LDL increased by 92.4% (82.8–103.3), 76.0% (58.9–99.3), 10.4% (3.8–18.0), and 5.5% (4.3–7.1), respectively. Interpretation: The burden attributed to high-SBP and high-LDL decreased during the 1990–2019 period in the region, while the attributable burden of high-FPG and high-BMI increased. Alarmingly, exposure to all four risk factors increased in the past three decades. There has been significant heterogeneity among the countries in the region regarding the trends of exposure and attributable burden. Urgent action is required at the individual, community, and national levels in terms of introducing effective strategies for prevention and treatment that account for local and socioeconomic factors. Funding: Bill & Melinda Gates Foundation.

Psychotropic drugs and benzodiazepines are nowadays among the primary substances of abuse. This results in a large and constant release into aquatic environments where they have potentially harmful effects on non-target organisms and, eventually, human health. In the last decades, evidence has been collected on the possible interference of benzodiazepines with reproductive processes, but data are few and incomplete. In this study, the possible negative influence of delorazepam on fertilization and embryo development has been tested in Paracentrotus lividus, a key model organism in studies of reproduction and embryonic development. Sperm, eggs, or fertilized eggs have been exposed to delorazepam at three concentrations: 1 μg/L (environmentally realistic), 5 μg/L, and 10 μg/L. Results indicate that delorazepam reduces the fertilizing capacity of male and female gametes and interferes with fertilization and embryo development. Exposure causes anatomical anomalies in plutei, accelerates/delays development, and alters the presence and distribution of glycoconjugates such as N-Acetyl-glucosamine, α-linked fucose, and α-linked mannose in both morulae and plutei. These results should attract attention to the reproductive fitness of aquatic species exposed to benzodiazepines and pave the way for further investigation of the effects they may exert on human fertility. The presence of benzodiazepines in the aquatic environment raises concerns about the reproductive well-being of aquatic species. Additionally, it prompts worries regarding potential impacts on human fertility due to the excessive use of anxiolytics.

Melanins are pigments employed in food, cosmetic, and textile industries, manufactured by extraction from cuttlefishes. Their biotechnological production by Streptomycetes, instead, has been poorly investigated so far. In this paper, for the first time, the strain Streptomyces nashvillensis DSM 40314 was tested as an extracellular melanin producer by investigating the influence of diverse temperatures (26, 28, and 30 °C) and pH values (6.0 and 7.0) on bacterial growth, melanin production, and on the activity of the secreted tyrosinase, the first enzyme of the pigment biosynthetic pathway. In physiological 96-h shake flask experiments, the optimal growth parameters resulted to be 28 °C and pH 7.0, at which a maximum biomass of 8.4 ± 0.5 gcdw/L, a melanin concentration of 0.74 ± 0.01 g/L (yield on biomass of 0.09 ± 0.01 g/gcdw and productivity of 0.008 ± 0.001 g/L/h), and a final tyrosinase activity of 10.1 ± 0.1 U/mL were reached. The produced pigment was purified from the broth supernatant with a two-step purification process (75.0 ± 2.0% of purity with 65.0 ± 5.0% of recovery) and tested for its chemical, antioxidant, and photoprotective properties. Finally, characterization by UV-visible and FT-IR spectroscopy, elemental analyses, and mono- and bi-dimensional NMR suggested the eumelanin-like nature of the pigment.

The field of supramolecular nanofiber-based hydrogels in biomedicine has witnessed remarkable growth over the past two decades [...]

Primary percutaneous coronary intervention (PCI) is the current class I therapeutic approach to treat acute ST-elevation myocardial infarction (STEMI). While primary PCI can restore adequate flow in the infarcted artery in the majority of cases, some patients experience the ‘no-reflow’ phenomenon, i.e., an abnormal myocardial reperfusion occurring even after the occluded coronary artery has been opened. No-reflow occurs when microvascular obstruction arises from embolization of thrombus or components of the atheromatous plaques. These embolic materials travel downstream within the infarct-related artery at time of primary PCI, leading to compromised blood flow. Currently, no expert consensus documents exist to outline an optimal strategy to prevent or treat no-reflow. Interventional cardiologists frequently employ intracoronary adenosine, calcium channel blockers, nicorandil, nitroprusside or glycoprotein IIb/IIIa inhibitors. However, evidence suggests that these interventions consistently enhance myocardial blood flow in only a specific subset of patients experiencing no-reflow. A recent and innovative therapeutic approach gaining attention is low-dose fibrinolysis during primary PCI, which offers the potential to augment coronary flow post-myocardial revascularization.

The automatic monitoring of activities in construction sites through the proper use of acoustic signals is a recent field of research that is currently in continuous evolution. In particular, the use of techniques based on Convolutional Neural Networks (CNNs) working on the spectrogram of the signal or its mel-scale variants was demonstrated to be quite successful. Nevertheless, the spectrogram has some limitations, which are due to the intrinsic trade-off between temporal and spectral resolutions. In order to overcome these limitations, in this paper, we propose employing the scalogramas a proper time–frequency representation of the audio signal. The scalogram is defined as the square modulus of the Continuous Wavelet Transform (CWT) and is known as a powerful tool for analyzing real-world signals. Experimental results, obtained on real-world sounds recorded in construction sites, have demonstrated the effectiveness of the proposed approach, which is able to clearly outperform most state-of-the-art solutions.

Although Jerusalem is one of the most photographed places in the world, few works have focused on the existence of its former 800-year-old Maghrebi Quarter, located in the shadow of the Western Wall. Founded in 1193 by Saladin’s son, al-Afdal ‘Ali to house Muslim pilgrims from North Africa (today Morocco, Algeria, Tunisia, and Libya), the Quarter was razed by Israeli bulldozers on the night of 10–11 June 1967’. Its 1,000 or so inhabitants were forced to flee within hours. Silenced by the occupation of East Jerusalem as part of the Six-Day War, the existence of the Maghrebi Quarter faded behind the walls of history. This research paper describes how 55 years after its razing, the selection of a corpus of archives, combined with 3D technology and Interprofessional collaborations between historians and 3D designers enable making a forgotten history accessible again. Beyond a discussion on methods and technical process, this research paper aims to highlight the potential applications of the data set and the 3D model not only for scholarly research but also for pedagogical purposes, for instance.

Abstract Background and aims In order to systematically review the latest evidence on anesthesia, intraoperative neurologic monitoring, postoperative heparin reversal, and postoperative blood pressure management for carotid endarterectomy. The present review is based on a single chapter of the Italian Health Institute Guidelines for diagnosis and treatment of extracranial carotid stenosis and stroke prevention. Methods and results A systematic article review focused on the previously cited topics published between January 2016 and October 2020 has been performed; we looked for both primary and secondary studies in the extensive archive of Medline/PubMed and Cochrane library databases. We selected 14 systematic reviews and meta-analyses, 13 randomized controlled trials, 8 observational studies, and 1 narrative review. Based on this analysis, syntheses of the available evidence were shared and recommendations were indicated complying with the GRADE-SIGN version methodology. Conclusions From this up-to-date analysis, it has emerged that any type of anesthesia and neurological monitoring method is related to a better outcome after carotid endarterectomy. In addition, insufficient evidence was found to justify reversal or no-reversal of heparin at the end of surgery. Furthermore, despite a low evidence level, a suggestion for blood pressure monitoring in the postoperative period was formulated.

Cholangiocarcinoma (CCA) is a rare cancer originating from the biliary epithelium and accounts for about 3% of all gastrointestinal malignancies. Unfortunately, the majority of patients are not eligible for surgical resection at the time of diagnosis, because of the locally advanced stage or metastatic disease. The overall survival time of unresectable CCA is generally less than 1 year, despite current chemotherapy regimens. Biliary drainage is often required as a palliative treatment for patients with unresectable CCA. Recurrent jaundice and cholangitis tend to occur because of reobstruction of the biliary stents. This not only jeopardizes the efficacy of chemotherapy, but also causes significant morbidity and mortality. Effective control of tumor growth is crucial for prolonging stent patency and consequently patient survival. Recently, endobiliary radiofrequency ablation (ERFA) has been experimented as a treatment modality to reduce tumor mass, and delay tumor growth, extending stent patency. Ablation is accomplished by means of high-frequency alternating current which is released from the active electrode of an endobiliary probe placed in a biliary stricture. It has been shown that tumor necrosis releases intracellular particles which are highly immunogenic and activate antigen-presenting cells, enhancing local immunity directed against the tumor. This immunogenic response could potentially enhance tumor suppression and be responsible for improved survival of patients with unresectable CCA who undergo ERFA. Several studies have demonstrated that ERFA is associated with an increased median survival of approximately 6 months in patients with unresectable CCA. Furthermore, recent data support the hypothesis that ERFA could ameliorate the efficacy of chemotherapy administered to patients with unresectable CCA, without increasing the risk of complications. This narrative review discusses the results of the studies published in recent years and focuses on the impact that ERFA could have on overall survival of patients with unresectable cholangiocarcinoma.

ObjectiveThe inverse relationships between chronic disease multimorbidity and health-related quality of life (HRQoL) have been well-documented in the literature. However, the mechanism underlying this relationship remains largely unknown. This is the first study to look into the potential role of functional limitation as a mediator in the relationship between multimorbidity and HRQoL.MethodsThis study utilized three recent waves of nationally representative longitudinal Household, Income, and Labor Dynamics in Australia (HILDA) surveys from 2009 to 2017 (n = 6,814). A panel mediation analysis was performed to assess the role of functional limitation as a mediator in the relationship between multimorbidity and HRQoL. The natural direct effect (NDE), indirect effect (NIE), marginal total effect (MTE), and percentage mediated were used to calculate the levels of the mediation effect.ResultsThis study found that functional limitation is a significant mediator in the relationship between multimorbidity and HRQoL. In the logistic regression analysis, the negative impact of multimorbidity on HRQoL was reduced after functional limitation was included in the regression model. In the panel mediation analysis, our results suggested that functional limitation mediated ~27.2% (p < 0.05) of the link between multimorbidity and the composite SF-36 score for HRQoL. Functional limitation also mediated the relationship between the number of chronic conditions and HRQoL for each of the eight SF-36 dimensions, with a proportion mediated ranging from 18.4 to 28.8% (p < 0.05).ConclusionFunctional status has a significant impact on HRQoL in multimorbid patients. Treatment should concentrate on interventions that improve patients' functioning and mitigate the negative effects of multimorbidity.

This study aims to assess the relationship between nutritional status and cognitive decline in a population of non-institutionalized elderly patients evaluated in a geriatric outpatient setting. Data from 144 patients admitted to the general geriatric outpatient services of Luigi Vanvitelli University Hospital (Naples, Italy) and San Felice a Cancello Hospital (San Felice a Cancello, Italy) were collected between January 1 and December 31, 2017. Cognitive function was evaluated through the mini-mental state examination and nutritional status was assessed through mini nutritional assessment. Logistic regression was used to assess the association between clinical characteristics and nutritional status, and it is reported as unadjusted, adjusted for age and sex, and adjusted for other potential confounding factors. In the unadjusted model, poor nutritional status was associated with a worse cognitive deficit (odds ratio (OR)=2.36; 95% confidence interval (CI)=1.77-3.55). The association remained significant after adjusting for age and sex (OR=2.36; 95% CI=1.77-3.55) and in the fully adjusted model (OR=2.92; 95% CI=1.90-5.64). In patients with dementia, malnutrition represents a significant burden that grows heavier as the disease progresses.

Background: Disasters are severely impactful events with the potential to provide injuries or death, destroy properties, and put in danger the mental health of people exposed to them. People who are particularly involved in disasters are first responders. In this work, we will focus on a specific type of first responder, i.e., cultural heritage clinicians who have the responsibility to preserve, protect, and recover cultural heritage from damage. Aims: This review aims to discuss the mental health risks for first responders after disasters, with a specific focus on cultural heritage first responders. Methods: Studies had to be: 1) in English; 2) on adults; 3) original studies or clinical trials; 4) related to the mental health of participants; 5) published in peer-reviewed journals. Exclusion criteria were: 1) being written in languages different from English; 2) being conducted on adolescents/children; 3) not being related to the mental health of participants; 4) being a book/report/summary; 5) not being a clinical trial; 6) not being peer-reviewed. The search was run throughout PsycInfo, PsycArticles, and Medline on the 1st of April 2022 on articles published between 2012 and 2022 by using these keywords: natural disasters or tsunamis or floods or drought or wildfire or earthquake or tornado or hurricane or snowstorm AND first responders or firefighters or paramedics or police or emergency services or emergency medical services AND mental health or mental illness or mental disorder or psychiatric illness. Results: First responders are at risk of depression, anxiety, sleep disturbances, alcohol/substance abuse, and suicide ideation. Currently, there are no studies on mental health risks for cultural heritage first responders. There are some training programs designed for first responders in emergencies. Recent results seem to confirm their usefulness for first responders, leading us to suggest their application also for cultural heritage first responders. Conclusion: Further studies should explore the psychological impact of cultural heritage first responders, as well as the effect that psychological training can have on them.

Phytates are a type of organophosphorus compound produced in terrestrial ecosystems by plants. In plant feeds, phytic acid and its salt form, phytate, account for 60%–80% of total phosphorus. Because phytate is a polyanionic molecule, it can chelate positively charged cations such as calcium, iron, and zinc. Due to its prevalence in vegetal tissues and the fact that people consume plants, phytate was first considered a potential health benefit. This updated review aims to summarize the current data on the results of clinical trials of phytates on human health, highlighting both beneficial and undesirable effects. To obtain these updated data, published papers in electronic databases such as PubMed/MedLine, TRIP database, Wiley, Google Scholar, Baidu, and Scopus were searched. Study results have shown that phytate can have beneficial health effects such as antioxidant, anticancer potential and reduction of pathological calcifications in blood vessels and organs; but also, negative effects by reducing the absorption of minerals important for maintaining the homeostasis of the human body. According to these recent results derived from recent clinical studies, phytates may be a potential natural source for health benefits. To improve clinical efficacy and human health benefits, further dose-response studies are needed to determine effective therapeutic doses and potential interactions with conventional drugs.

Summary: Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods: In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings: In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1–9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3–25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation: There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained. Funding: Bill & Melinda Gates Foundation.

Abstract Background Among athletes, bodybuilders are more predisposed to the use of dietary supplements (DS) and hormones (H) to increase in adaptations to physical training and performance. The purpose of the study was to identify social, psychological, and organisational factors that are associated with the use of food supplements and hormones in young bodybuilders of the metropolitan area of Naples. Methods 107 athletes, practicing bodybuilding, were consecutively recruited in 30 gyms, randomly selected in the metropolitan area of Naples. Athletes were administered an anonymous questionnaire. The questionnaire consists of 5 sections (socio-demographic, frequency and reasons for bodybuilding, knowledge, attitudes and behaviours). Descriptive statistics were performed using T-test and Chi-square statistics. A score was created for knowledge, attitudes, behaviours. Multivariable logistic regression models were employed to assess association between each score and the use of DS and H. Statistical analyses were carried out using STATA 15. Results 81.31% of the subjects reported to use DS while 35.51% H. Females are less likely to practise bodybuilding frequently than males (OR 0.18 (95% CI 0.05–0.69), p = 0.01). Subjects who have attended high school or university have a lower probability of taking DS (OR 0.17 (95% CI 0.04–0.65), p = 0.01). H users also use supplements more frequently (OR 61.21 (95% CI 3.99–939.31), p

Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March – May 2020, “period 1”), and then again between May and June (“period 2”) and June and July 2020 (“period 3”). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries’ first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic “normal” by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries.

ObjectiveTo provide estimates on the regional and national burden of tracheal, bronchus, and lung (TBL) cancer and its attributable risk factors from 1990 to 2019 in the North Africa and Middle East (NAME) region.Methods and materialsThe Global Burden of Disease (GBD) 2019 data were used. Disability-adjusted life years (DALYs), death, incidence, and prevalence rates were categorized by sex and age groups in the NAME region, in 21 countries, from 1990 to 2019. Decomposition analysis was performed to calculate the proportion of responsible factors in the emergence of new cases. Data are presented as point estimates with their 95% uncertainty intervals (UIs).ResultsIn the NAME region, TBL cancer caused 15,396 and 57,114 deaths in women and men, respectively, in 2019. The age-standardized incidence rate (ASIR) increased by 0.7% (95% UI -20.6 to 24.1) and reached 16.8 per 100,000 (14.9 to 19.0) in 2019. All the age-standardized indices had a decreasing trend in men and an increasing trend in women from 1990 to 2019. Turkey (34.9 per 100,000 [27.6 to 43.5]) and Sudan (8.0 per 100,000 [5.2 to 12.5]) had the highest and lowest age-standardized prevalence rates (ASPRs) in 2019, respectively. The highest and lowest absolute slopes of change in ASPR, from 1990 to 2019, were seen in Bahrain (-50.0% (-63.6 to -31.7)) and the United Arab Emirates (-1.2% (-34.1 to 53.8)), respectively. The number of deaths attributable to risk factors was 58,816 (51,709 to 67,323) in 2019 and increased by 136.5%. Decomposition analysis showed that population growth and age structure change positively contributed to new incident cases. More than 80% of DALYs could be decreased by controlling risk factors, particularly tobacco use.ConclusionThe incidence, prevalence, and DALY rates of TBL cancer increased, and the death rate remained unchanged from 1990 to 2019. All the indices and contribution of risk factors decreased in men but increased in women. Tobacco is still the leading risk factor. Early diagnosis and tobacco cessation policies should be improved.

Through adaptive optics (AO) imaging with the SOUL+LUCI instrument at the Large Binocular Telescope we were able to resolve, for the first time, individual stars in the gas-rich galaxy DDO68 C. This system was already suggested to be interacting with the extremely metal-poor dwarf DDO68, but its nature has remained elusive so far because of the presence of a bright foreground star close to its line of sight that hampers a detailed study of its stellar population and distance. In our study, we turned this interloper star into an opportunity to have a deeper insight on DDO68 C, using it as a guide star for the AO correction. Although the new data do not allow for a direct distance measurement through the red giant branch tip method, the combined analysis of the resolved-star color–magnitude diagram, of archival GALEX far-UV and near-UV photometry, and of H α data provides a self-consistent picture in which DDO68 C is at the same ∼13 Mpc distance as its candidate companion DDO68. These results indicate that DDO68 is a unique case of a low-mass dwarf, less massive than the Magellanic Clouds, interacting with three satellites (DDO68 C and two previously confirmed accreting systems), providing useful constraints on cosmological models and a potential explanation for its anomalous extremely low metallicity.

Bromelain is a key enzyme found in pineapple (Ananas comosus (L.) Merr.); a proteolytic substance with multiple beneficial effects for human health such as anti-inflammatory, immunomodulatory, antioxidant and anticarcinogenic, traditionally used in many countries for its potential therapeutic value. The aim of this updated and comprehensive review focuses on the potential anticancer benefits of bromelain, analyzing the cytotoxic, apoptotic, necrotic, autophagic, immunomodulating, and anti-inflammatory effects in cancer cells and animal models. Detailed information about Bromelain and its anticancer effects at the cellular, molecular and signaling levels were collected from online databases such as PubMed/MedLine, TRIP database, GeenMedical, Scopus, Web of Science and Google Scholar. The results of the analyzed studies showed that Bromelain possesses corroborated pharmacological activities, such as anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair. Nonetheless, bromelain clinical studies are scarce and still more research is needed to validate the scientific value of this enzyme in human cancer diseases.

BackgroundMany European Health Systems are implementing or increasing levels of cost-sharing for medicine in response to the growing constrains on public spending on health despite their negative impact on population health due to delay in seeking care.ObjectiveThis study aims to examine the relationships between multimorbidity (two or more coexisting chronic diseases, CDs), complex multimorbidity (three or more CDs impacting at least three different body systems), and out-of-pocket expenditure (OOPE) for medicine across European nations.MethodsThis study utilized data on participants aged 50 years and above from two recent waves of the Survey of Health, Aging, and Retirement in Europe conducted in 2013 (n = 55,806) and 2015 (n = 51,237). Pooled cross-sectional and longitudinal study designs were used, as well as a two-part model, to analyse the association between multimorbidity and OOPE for medicine.ResultsThe prevalence of multimorbidity was 50.4% in 2013 and 48.2% in 2015. Nearly half of those with multimorbidity had complex multimorbidity. Each additional CD was associated with a 34% greater likelihood of incurring any OOPE for medicine (Odds ratio = 1.34, 95% CI = 1.31–1.36). The average incremental OOPE for medicine was 26.4 euros for each additional CD (95% CI = 25.1–27·7), and 32.1 euros for each additional body system affected (95% CI 30.6–33.7). In stratified analyses for country-specific quartiles of household income the average incremental OOPE for medicine was not significantly different across groups.ConclusionBetween 2013 and 2015 in 13 European Health Systems increased prevalence of CDs was associated with greater likelihood of having OOPE on medication and an increase in the average amount spent when one occurred. Monitoring this indicator is important considering the negative association with treatment adherence and subsequent effects on health.