Search

The rising prevalence and legalisation of cannabis worldwide have underscored the need for a comprehensive understanding of its biological impact, particularly on mental health. Epigenetic mechanisms, specifically DNA methylation, have gained increasing recognition as vital factors in the interplay between risk factors and mental health. This study aimed to explore the effects of current cannabis use and high-potency cannabis on DNA methylation in two independent cohorts of individuals experiencing first-episode psychosis (FEP) compared to control subjects. The combined sample consisted of 682 participants (188 current cannabis users and 494 never users). DNA methylation profiles were generated on blood-derived DNA samples using the Illumina DNA methylation array platform. A meta-analysis across cohorts identified one CpG site (cg11669285) in the CAVIN1gene that showed differential methylation with current cannabis use, surpassing the array-wide significance threshold, and independent of the tobacco-related epigenetic signature. Furthermore, a CpG site localised in the MCUgene (cg11669285) achieved array-wide significance in an analysis of the effect of high-potency (THC = > 10%) current cannabis use. Pathway and regional analyses identified cannabis-related epigenetic variation proximal to genes linked to immune and mitochondrial function, both of which are known to be influenced by cannabinoids. Interestingly, a model including an interaction term between cannabis use and FEP status identified two sites that were significantly associated with current cannabis use with a nominally significant interaction suggesting that FEP status might moderate how cannabis use affects DNA methylation. Overall, these findings contribute to our understanding of the epigenetic impact of current cannabis use and highlight potential molecular pathways affected by cannabis exposure.

BackgroundShoe inserts, orthopaedic shoes, ankle-foot orthoses (AFOs) are important devices in Charcot-Marie-Tooth disease (CMT) management, but data about use, benefits and tolerance are scanty.MethodsWe administered to Italian CMT Registry patients an online ad hoc questionnaire investigating use, complications and perceived benefit/tolerability/emotional distress of shoe inserts, orthopaedic shoes, AFOs and other orthoses/aids. Patients were also asked to fill in the Quebec User Evaluation of Satisfaction with assistive Technology questionnaire, rating satisfaction with currently used AFO and related services.ResultsWe analysed answers from 266 CMT patients. Seventy per cent of subjects were prescribed lower limb orthoses, but 19% did not used them. Overall, 39% of subjects wore shoe inserts, 18% orthopaedic shoes and 23% AFOs. Frequency of abandonment was high: 24% for shoe inserts, 28% for orthopaedic shoes and 31% for AFOs. Complications were reported by 59% of patients and were more frequently related to AFOs (69%). AFO users experienced greater emotional distress and reduced tolerability as compared with shoe inserts (p<0.001) and orthopaedic shoes (p=0.003 and p=0.045, respectively). Disease severity, degree of foot weakness, customisation and timing for customisation were determinant factors in AFOs’ tolerability. Quality of professional and follow-up services were perceived issues.ConclusionsThe majority of CMT patients is prescribed shoe inserts, orthopaedic shoes and/or AFOs. Although perceived benefits and tolerability are rather good, there is a high rate of complications, potentially inappropriate prescriptions and considerable emotional distress, which reduce the use of AFOs. A rational, patient-oriented and multidisciplinary approach to orthoses prescription must be encouraged.

Background: The link between cannabis use and schizophrenia is well-established in epidemiological studies, especially among adolescents with early-onset use. However, this association in rodent models is less clear. This meta-analysis examined the effects of adolescent cannabinoid exposure on distinct schizophrenia-like behaviours in rodents and how experimental variations influence outcomes. Methods: Following a pre-registered protocol (CRD42022338761), we searched PubMed, Ovid Medline, Embse and APA PsychInfo for English-language original studies until May 2024. We synthesised data from experiments on schizophrenia-like behaviour in rats and mice after repeated peri-pubertal (onset between P23-P45) cannabinoid exposure. Risk of bias was assessed using the SYRCLE’s tool. Results: We included 359 experiments from 108 articles across 9 behavioural tests. We found meta-analytic evidence supporting that CB1R agonists, both natural and synthetic, elicited broad schizophrenia-like behavioural alterations, including impaired working memory [g= −0.56; (CI: −0.93, −0.18)], novel object recognition [g= −0.66; (CI: −0.97, −0.35)], novel object location recognition [g= −0.70; (CI: −1.07, −0.33]), social novelty preference [g= −0.52; (CI: −0.93, −0.11)], social motivation [g= −0.21; (CI: −0.42, −0.00)], pre-pulse inhibition [g= −0.43; (CI: −0.76, −0.10)], and sucrose preference [g= −0.87; (CI: −1.46, −0.27)]. By contrast, effects on novelty-induced locomotion were negligible. Subgroup analyses revealed similar effects across sexes and species. Substantial variance in the protocols and moderate-to-high heterogeneity in behavioural outcomes were observed. We found CBD may enhance fear memory recall, but data was limited. Discussion: This is the first meta-analysis to comprehensively assess the link between cannabinoids and schizophrenia-like behaviours in rodents. Our results support epidemiological links between early cannabis use and schizophrenia-like phenotypes, confirming the utility of animal models. Standardising protocols will optimise models to strengthen reproducibility and comparisons, our work provides a framework for refining rodent models to elucidate biological pathways linking cannabis and schizophrenia.

Purpose All-terrain vehicles (ATVs) pose a significant risk for morbidity and mortality amongst children. We hypothesize that current vague legislation regarding helmet use impacts injury patterns and outcomes in pediatric ATV accidents.Methods The institutional trauma registry was queried for pediatric patients involved in ATV accidents from 2006 to 2019. Patient demographics and helmet wearing status were identified in addition to patient outcomes, such as injury pattern, injury severity score, mortality, length of stay, and discharge disposition. These elements were analyzed for statistical significance.Results 720 patients presented during the study period, which were predominantly male (71%, n = 511) and less than 16 years old (76%, n = 543). Most patients were not wearing a helmet (82%, n = 589) at time of injury. Notably, there were 7 fatalities. A lack of helmet use is positively associated with head injury (42% vs 23%, P< .01), intracranial hemorrhage (15% vs 7%, P= .03), and associated with lower Glasgow Coma Scale (13.9 vs 14.4, P< .01). Children 16 years and older were least likely to wear a helmet and most likely to incur injuries. Patients over 16 years had longer lengths of stay, higher mortality, and higher need for rehabilitation.Conclusion Not wearing a helmet is directly correlated with injury severity and concerning rates of head injury. Children 16 years and older are at greatest risk for injury, but younger children are still at risk. Stricter state laws regarding helmet use are necessary to reduce pediatric ATV-related injury burden.Level of Evidence level III retrospective comparative study

Disorganization is a crucial domain in affective psychoses. However, it has received poor research attention, especially at the illness onset. The aims of this study were: (a) to monitor the longitudinal course of disorganization in young people with first episode affective psychosis (FEAP) across 2 years of follow-up, and (b) to investigate any relevant correlation of disorganized symptoms with psychopathology, functioning and the specific treatment elements of an “Early Intervention in Psychosis” (EIP) protocol along the follow-up period.

Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethylpackage and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p= <0.001; abuse: OR = 2.16; p< 0.001; neglect: OR = 2.27; p= <0.001). None of the CpG sites significantly mediated the adversity-psychosis association after Bonferroni correction (p< 8.1 × 10−8). However, 28, 34 and 29 differentially methylated probes associated with 21, 27, 20 genes passed a less stringent discovery threshold (p< 5 × 10−5) for composite, abuse and neglect respectively, with a lack of overlap between abuse and neglect. These included genes previously associated to psychosis in EWAS studies, such as PANK1, SPEG TBKBP1, TSNARE1 or H2R. Downstream gene ontology analyses did not reveal any biological pathways that survived false discovery rate correction. Although at a non-significant level, DNAm changes in genes previously associated with schizophrenia in EWAS studies may mediate the CA-psychosis association. These results and associated involved processes such as mitochondrial or histaminergic disfunction, immunity or neural signalling requires replication in well powered samples. The lack of overlap between mediating genes associated with abuse and neglect suggests differential biological trajectories linking CA subtypes and psychosis.

Previous researchers have argued that material objects reproduce institutional logics on the basis of their durability, immutability and mobility. In this paper we analyse material objects that secure logics not because they reveal meanings and significations, but because they allow individuals and groups to confront the mystery of institutional values. Drawing on extensive historical sources, we analyse a small material object, a book entitled The Spiritual Exercises, and investigate the institutionalization of a practice for discovering what cannot be rendered material, the ineffable mystery of God’s will, as key component of the Jesuit beliefs system. We argue that religious logics require objects that present, rather than resolve, the mystery of institutional values. We extend the literature on institutional logics by considering how mystery enables institutions and their logics to embrace difference, adapt and endure for centuries. Our paper shows that institutional values and goods are ontologically mysterious no-things, ready to be interrogated through objects and procedural logics.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting 5%of the elderly population. Currently, the diagnosis of PD is mainly based on clinical features and no definitive diagnostic biomarkers have been identified. The discovery of biomarkers at the earliest stages of PD is of extreme interest. This review focuses on the current findings in the field of circulating non-coding RNAs in PD. We briefly describe the more established circulating biomarkers in PD and provide a more thorough review of non-coding RNAs, in particular microRNAs, long non-coding RNAs and circular RNAs, differentially expressed in PD, highlighting their potential for being considered as biomarkers for diagnosis. Together, these studies hold promise for the use of peripheral biomarkers for the diagnosis of PD.

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2Aand transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

ABSTRACTIntroductionChimeric antigen receptor (CAR)-T-cell therapy is a new treatment for patients with hematologic malignancies in which other therapies have failed.Areas coveredThe review provides an overview for recognizing and managing the most acute toxicities related to CAR-T cells.Expert opinionThe development of immune-mediated toxicities is a common challenge of CAR-T therapy. The mechanism that determines this toxicity is still unclear, although an unfavorable tumor microenvironment and a pro-inflammatory state put patients at risk. The monitoring, diagnosis, and treatment of post-CAR-T toxicities must be determined and based on international guidelines and internal clinical practice. It is urgent to identify biomarkers that can identify patients at greater risk of developing complications. The adoption of consistent grading criteria is necessary to improve toxicity management strategies continually. The first-line therapy consists of supportive care and treatment with tocilizumab or corticosteroids. An early start of cytokine blockade therapies could mitigate toxicity. The plan will include cytokine release prophylaxis, a risk-adapted treatment, prevention of on-target/off-tumor effect, and a switch on/off CAR-T approach.

Purpose: Financial and nonfinancial disclosures are still anchored to conventional notions of transparency, whereby corporations “push” information out to various stakeholders. Such information is now “pulled” from various sources and addresses aspects of corporate behavior that go well beyond those envisioned by the disclosure framework. This shift makes notions of values, measurement and accountability more fragmented, complex and difficult. The paper aims to bring the accounting scholarly debate back to what and how transparency can be achieved especially in relation to issues of social inequality and sustainability. Design/methodology/approach: After an analysis of the limitations of current approaches to disclosure, the paper proposes a shift toward normative policies that profit of years of critique of positivism. Findings: Drawing on the notion of value-added, the paper ends with a new income statement design, labeled as Value-Added Statement for Nature, which recognizes Nature as a further stakeholder and forces human stakeholders to give voice, or at least acknowledge the lack of voice, for non-human actors. Originality/value: The author proposes a shift in the perspective, practice and institutional arrangements in which disclosure occurs. Measurement and transparency need to happen in communication exercises, which do not presuppose what needs to be made transparent once and for good but define procedures on how to make fragmented, complex, multiple and volatile notions of value transparent. Income statements and accounting more in general is to be reconceived as a platform where stakeholders will have to continuously negotiate what counts as the common good in the interest of all, including Nature.

Previous studies showed that lifestyle behaviors (cigarette smoking, alcohol, coffee) are inversely associated with Parkinson’s disease (PD). The prodromal phase of PD raises the possibility that these associations may be explained by reverse causation. To examine associations of lifestyle behaviors with PD using two-sample Mendelian randomisation (MR) and the potential for survival and incidence-prevalence biases. We used summary statistics from publicly available studies to estimate the association of genetic polymorphisms with lifestyle behaviors, and from Courage-PD (7,369 cases, 7,018 controls; European ancestry) to estimate the association of these variants with PD. We used the inverse-variance weighted method to compute odds ratios (ORIVW) of PD and 95%confidence intervals (CI). Significance was determined using a Bonferroni-corrected significance threshold (p = 0.017). We found a significant inverse association between smoking initiation and PD (ORIVWper 1-SD increase in the prevalence of ever smoking = 0.74, 95%CI = 0.60–0.93, p = 0.009) without significant directional pleiotropy. Associations in participants ≤67 years old and cases with disease duration ≤7 years were of a similar size. No significant associations were observed for alcohol and coffee drinking. In reverse MR, genetic liability toward PD was not associated with smoking or coffee drinking but was positively associated with alcohol drinking. Our findings are in favor of an inverse association between smoking and PD that is not explained by reverse causation, confounding, and survival or incidence-prevalence biases. Genetic liability toward PD was positively associated with alcohol drinking. Conclusions on the association of alcohol and coffee drinking with PD are hampered by insufficient statistical power.

Visual organizational research has burgeoned over the past decade. Despite an initially hesitant engagement with visuality in organization and management studies, it is now only proper to speak of a ‘visual turn’ in this domain of scholarly inquiry. We wish to take the opportunity provided by the Perspectivesformat to engage with prominent work published in Organization Studies, in appreciation of the diversity of approaches to the visual in organizational research, and highlight some generative tensions across this body of work. In particular, we have scrutinized six articles based on their treatment of signification(how the visual mode enables meaning-making and meaning-sharing in and around organizations), manifestation(how visual organizational artefacts and their properties relate to affordances) and implication(how visualization practices produce organizational outcomes). Inspired by the frictions and gaps across these articles, we developed three distinct perspective shiftsthat highlight the importance of the invisible, the immaterial and the performance withinvisualization. We conclude with a comparative matrix that maps different conceptualizations of visualization, and suggest opportunities for future research based on how we see the field of visual organizational studies evolving.

Graphical Abstract:

The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes1,2. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPTmRNA internal ribosome entry site3. MAPTencodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules. Hyperphosphorylated, aggregation-prone tau forms the hallmark inclusions of tauopathies4. Mutations in MAPTcause familial frontotemporal dementia, and common variations forming the MAPTH1 haplotype are a significant risk factor in many tauopathies5and Parkinson’s disease. Notably, expression of MAPT-AS1 or minimal essential sequences from MAPT-AS1 (including MIR) reduces—whereas silencing MAPT-AS1 expression increases—neuronal tau levels, and correlate with tau pathology in human brain. Moreover, we identified many additional NATs with embedded MIRs (MIR-NATs), which are overrepresented at coding genes linked to neurodegeneration and/or encoding IDPs, and confirmed MIR-NAT-mediated translational control of one such gene, PLCG1. These results demonstrate a key role for MAPT-AS1 in tauopathies and reveal a potentially broad contribution of MIR-NATs to the tightly controlled translation of IDPs6, with particular relevance for proteostasis in neurodegeneration.

Background: Pain is a common symptom in oncologic patients and its management is generally guided with reference to pain individually perceived by patients and expressed through self-reported scales. However, the utility of these tools is limited as it strongly depends on patients’ opinions. For this reason, more objective instruments are desirable. Objective: In this overview, scientific articles indicating potential markers to be used for pain management in cancer were collected and discussed. Methods: Research was performed on principal electronic scientific databases by using the words “pain”, “cancer”, “markers” and “biomarkers” as the main keywords, and findings describing potential biomarkers for the management of cancer pain were reported. Results: Studies on pain markers not specific for cancer typology (inflammatory, genetic markers predicting response to analgesic drugs, neuroimaging markers) and pain markers for specific types of cancer (bone cancer, breast cancer, lung cancer, head and neck cancer, prostate cancer, cancer in pediatrics) have been presented and commented on. Conclusion: This overview supports the view of the involvement of inflammatory mediators in the mechanisms underlying cancer pain. Only a small amount of data from research up till today is available on markers that can help in the management of pain, except for pro-inflammatory cytokines and other inflammatory indexes such as C-reactive protein (CRP). However, biomarkers are a promising strategy useful to predict pain intensity and to objectively quantify analgesic response in guiding decisions regarding individual-tailored treatments for cancer patients.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n= 2883), and their unaffected siblings (n= 2271), compared to controls (n= 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = –0.45 to –0.73, p< 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = –0.14 to –0.33, p< 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = –0.88 to –0.60, p< 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = –0.13 to –0.38, p< 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = –0.21 to –0.43, p< 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

The contribution of ribosome heterogeneity and ribosome-associated proteins to the molecular control of proteomes in health and disease remains unclear. Here, we demonstrate that survival motor neuron (SMN) protein—the loss of which causes the neuromuscular disease spinal muscular atrophy (SMA)—binds to ribosomes and that this interaction is tissue-dependent. SMN-primed ribosomes are preferentially positioned within the first five codons of a set of mRNAs that are enriched for translational enhancer sequences in the 5′ untranslated region (UTR) and rare codons at the beginning of their coding sequence. These SMN-specific mRNAs are associated with neurogenesis, lipid metabolism, ubiquitination, chromatin regulation and translation. Loss of SMN induces ribosome depletion, especially at the beginning of the coding sequence of SMN-specific mRNAs, leading to impairment of proteins that are involved in motor neuron function and stability, including acetylcholinesterase. Thus, SMN plays a crucial role in the regulation of ribosome fluxes along mRNAs encoding proteins that are relevant to SMA pathogenesis.

ABSTRACTSocial media have become a common way for people to express their personal viewpoints, including sentiments about health topics. We present the results of an opinion mining analysis on vaccination performed on Twitter from September 2016 to August 2017 in Italy. Vaccine-related tweets were automatically classified as against, in favor or neutral in respect of the vaccination topic by means of supervised machine-learning techniques. During this period, we found an increasing trend in the number of tweets on this topic. According to the overall analysis by category, 60% of tweets were classified as neutral, 23% against vaccination, and 17% in favor of vaccination. Vaccine-related events appeared able to influence the number and the opinion polarity of tweets. In particular, the approval of the decree introducing mandatory immunization for selected childhood diseases produced a prominent effect in the social discussion in terms of number of tweets. Opinion mining analysis based on Twitter showed to be a potentially useful and timely sentinel system to assess the orientation of public opinion toward vaccination and, in future, it may effectively contribute to the development of appropriate communication and information strategies.

The RNA-binding protein LIN28B regulates developmental timing and determines stem cell identity by suppressing the let-7family of microRNAs. Postembryonic reactivation of LIN28Bimpairs cell commitment to differentiation, prompting their transformation. In this study, we assessed the extent to which ectopic lin28bexpression modulates the physiological behavior of neural crest cells (NCC) and governs their transformation in the trunk region of developing embryos. We provide evidence that the overexpression of lin28binhibits sympathoadrenal cell differentiation and accelerates NCC migration in two vertebrate models, Xenopus leavisand Danio rerio. Our results highlight the relevance of ITGA5and ITGA6in the LIN28B-dependent regulation of the invasive motility of tumor cells. The results also establish that LIN28Boverexpression supports neuroblastoma onset and the metastatic potential of malignant cells through let-7a-dependent and let-7a-independent mechanisms.

Epitranscriptomic mRNA modifications affect gene expression, with their altered balance detected in various cancers. YTHDF proteins contain the YTH reader domain recognizing the m6A mark on mRNA and represent valuable drug targets. Crystallographic structures have been determined for all three family members; however, discrepancies are present in the organization of the m6A-binding pocket. Here, we present new crystallographic structures of the YTH domain of YTHDF1, accompanied by computational studies, showing that this domain can exist in different stable conformations separated by a significant energetic barrier. During the transition, additional conformations are explored, with peculiar druggable pockets appearing and offering new opportunities for the design of YTH-interfering small molecules.

Disorganization is a crucial domain in affective psychoses. However, it has received poor research attention, especially at the illness onset. The aims of this study were: (a) to monitor the longitudinal course of disorganization in young people with first episode affective psychosis (FEAP) across 2 years of follow-up, and (b) to investigate any relevant correlation of disorganized symptoms with psychopathology, functioning and the specific treatment elements of an “Early Intervention in Psychosis” (EIP) protocol along the follow-up period.

The transmission of infectious agents within healthcare settings is a priority public health problem. Although the main burden of healthcare-associated infections is commonly caused by Gram-negative bacteria and fungi, vaccine-preventable diseases represent an additional infectious risk for patients attending healthcare facilities. Hepatitis B, rotavirus gastroenteritis, influenza, measles, pertussis and pneumococcal and meningococcal invasive bacterial infections still represent a threat, notwithstanding the presence of universal vaccination programs. For this reason, healthcare worker immunization is an important strategy to limit the risk of vaccine-preventable diseases in such a fragile population.

Sexuality in the elderly is related to psycho-physical well-being. Aim of this study was to analyze the correlation between sexual health, thyroid hormones, cognitive functions, and physical fitness in elderly population. Fifty-one fit adults were recruited (age: 71.9 ± 5.3 years, 26 females and 25 males). Sexuality was evaluated using the Changes in Sexual Functioning Questionnaire-short form (CSFQ-14) and the Sexual Attitude Scale (SAS). Thyroid function was assessed by measuring serum TSH, FT3, and FT4. Cognitive functions and depressive symptoms were evaluated by the Mini Mental State Examination (MMSE) test and Geriatric Depression Scale (GDS) scores. Subjects’ physical fitness was evaluated using the following tests: Short Physical Performance Battery (SPPB), Handgrip test (HG), Timed Up and Go test (TUG), and 2-Minute step test (ST). CSFQ-14 positively correlated with MMSE (p< 0.05) and negatively with GDS (p< 0.05), while thyroid function was not correlated with sexuality, in both genders. A negative relationship between FT4 vs. weight, FT3 vs. HG and FT3/FT4 ratio vs. ST were found (p= 0.05) in females, while in males, it occurred for TSH vs. TUG (p< 0.05); a positive relationship existed in females between FT4 vs. ST (p< 0.05). Finally, CSFQ-14 was significantly correlated with SPPB (p< 0.05), CST, TUG, and ST (p< 0.01), in both genders. We demonstrated a strict relationship between active sexuality, preserved cognitive function and appropriate physical fitness in elderly subjects, independently from gender. Our preliminary data suggest that in elderly fit population, peripheral thyroxin deiodination may be a useful predictor of better physical performance and more successful aging.

ABSTRACTIntroduction: Salivary gland cancers (SGCs) are a rare and heterogeneous group of malignant tumors arising from either major or minor salivary glands. Among SGCs patients, adenoid cystic carcinoma (ACC) is the most frequent histotype and its genetic aberrations are well known even though they are generally uncommon. Non-ACC subtypes are rarer and more heterogeneous than ACC from a histological and genomic point of view. In non-ACC, some altered molecular pathways [e.g. BRAF or RET mutations, Androgen Receptor (AR)] are potentially targetable with specific drugs.Areas covered: A literature search was performed to summarize the main druggable genomic aberrations involving non-ACC SGCs. An overview of the genomics of non-ACC salivary gland malignancies is discussed. We describe the pattern of potentially targetable genomic alterations in non-ACC salivary gland malignancies according to their frequency rather than to the single non-ACC histotype.Expert opinion/commentary: The genetic profiling through in-depth molecular analyses [e.g. Next-generation sequencing (NGS)] is advised in all patients affected by recurrent and/or metastatic non-ACC SGCs to find any potentially druggable target. Some histotypes may carry driving mutations that must be investigated and defined. For the rare cancers, access to a referral center is recommended to optimize the management of these patients.

Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder.

RNA-binding proteins (RBPs) are pleiotropic factors that control the processing and functional compartmentalization of transcripts by binding primarily to mRNA untranslated regions (UTRs). The competitive and/or cooperative interplay between RBPs and an array of coding and noncoding RNAs (ncRNAs) determines the posttranscriptional control of gene expression, influencing protein production. Recently, a variety of well-recognized and noncanonical RBP domains have been revealed by modern system-wide analyses, underlying an evolving classification of ribonucleoproteins (RNPs) and their importance in governing physiological RNA metabolism. The possibility of targeting selected RNA–protein interactions with small molecules is now expanding the concept of protein “druggability,” with new implications for medicinal chemistry and for a deeper characterization of the mechanism of action of bioactive compounds. Here, taking SF3B1, HuR, LIN28, and Musashi proteins as paradigmatic case studies, we review the strategies applied for targeting RBPs, with emphasis on the technological advancements to study protein–RNA interactions and on the requirements of appropriate validation strategies to parallel high-throughput screening (HTS) efforts.

RNA-binding proteins (RBPs) are pleiotropic factors that control the processing and functional compartmentalization of transcripts by binding primarily to mRNA untranslated regions (UTRs). The competitive and/or cooperative interplay between RBPs and an array of coding and noncoding RNAs (ncRNAs) determines the posttranscriptional control of gene expression, influencing protein production. Recently, a variety of well-recognized and noncanonical RBP domains have been revealed by modern system-wide analyses, underlying an evolving classification of ribonucleoproteins (RNPs) and their importance in governing physiological RNA metabolism. The possibility of targeting selected RNA–protein interactions with small molecules is now expanding the concept of protein “druggability,” with new implications for medicinal chemistry and for a deeper characterization of the mechanism of action of bioactive compounds. Here, taking SF3B1, HuR, LIN28, and Musashi proteins as paradigmatic case studies, we review the strategies applied for targeting RBPs, with emphasis on the technological advancements to study protein–RNA interactions and on the requirements of appropriate validation strategies to parallel high-throughput screening (HTS) efforts.

Since the economic crisis of 2008 were growth in health spending has reached unsustainable levels many countries have reduced public spending on health but it is now rising again in Italy (OECD, 2017). This study proposes a new way to use the official indicators for healthcare monitoring in order to assesses the impact by the reform of the Italian National Health Service on the equity access to health care service. A preliminary analysis was performed in order to evaluate geographical hospital resource allocation taking into account both the amount of resources and the intensity of care needed. A second analysis, performed using a two-stage least squares (2SLS) regression model, was addressed to explain geographic lifespan differences between Italian regions. In conclusion, this study attempts to provide an alternative reading to “sector studies”, to highlight more clearly the extent of the “healthcare mobility” phenomenon and the role of the supply structure as a driver of this phenomenon.

ABSTRACTThe decline in children’s vaccination coverage and the resurgence of preventable infectious diseases draw attention to parents’ vaccine hesitancy. Our study introduces two validated tools to independently assess vaccine hesitancy and health literacy among parents with school-age children. We developed a Vaccine Confidence Index (VCI) from 10 Likert items, exploring their relationships through exploratory and confirmatory factor analyses. We modified the IMETER (Italian medical term recognition test) to measure health literacy. We assessed the internal consistency of the modified IMETER and the 10 Likert items using Cronbach’s alpha test (α) and McDonald’s omega total coefficient (ω) with good results (ω = 0.92, α = 0.90; ω = 0.87, α = 0.82 respectively). We used these tools within a questionnaire conducted on 743 parents recruited from pediatric clinic waiting rooms in Italy, collecting demographic data, information sources on vaccines and vaccine-preventable diseases knowledge. The VCI resulting from factor analyses consisted of six items on a ten-point Likert scale, reflecting the ratio of positive to negative items. The survey revealed significant variations in the VCI according to individual features such as education, use of social networks, or Health institutions as sources of information. Multivariate logistic regression identified an association between vaccine intention and the VCI. Health literacy was functional for 91.2% of participants, but knowledge about vaccine-preventable diseases was generally low. The VCI showed no significant association with health literacy and vaccine-preventable diseases knowledge. The VCI and the modified IMETER effectively assess vaccination attitude and health literacy, offering valuable public health tools for tailoring vaccination campaigns to hesitant population subgroups.

Background

Borderline Personality Disorder (BPD) is under-investigated in First Episode Psychosis (FEP). BPD psychotic manifestations and mood changes are also difficult to differentiate from first episode affective psychosis. The aim of this study was to compare sociodemographic and clinical features between FEP patients with BPD vs. Bipolar Disorder (BD) or Major Depressive Disorder (MDD) both at baseline and across a 2-year follow-up period.