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We recently described increased D- and L-serine concentrations in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, the post-mortem caudate-putamen of human Parkinson's disease (PD) brains and the cerebrospinal fluid (CSF) of de novo living PD patients. However, data regarding blood D- and L-serine levels in PD are scarce. Here, we investigated whether the serum profile of D- and L-serine, as well as the other glutamate N-methyl-D-aspartate ionotropic receptor (NMDAR)-related amino acids, (i) differs between PD patients and healthy controls (HC) and (ii) correlates with clinical-demographic features and levodopa equivalent daily dose (LEDD) in PD. Eighty-three consecutive PD patients and forty-one HC were enrolled. PD cohort underwent an extensive clinical characterization. Serum levels of D- and L-serine, L-glutamate, L-glutamine, L-aspartate, L-asparagine and glycine were determined using High Performance Liquid Chromatography. In age- and sex-adjusted analyses, no differences emerged in the serum levels of D-serine, L-serine and other NMDAR-related amino acids between PD and HC. However, we found that D-serine and D-/Total serine ratio positively correlated with age in PD but not in HC, and also with PD age at onset. Moreover, we found that higher LEDD correlated with lower levels of D-serine and the other excitatory amino acids. Following these results, the addition of LEDD as covariate in the analyses disclosed a selective significant increase of D-serine in PD compared to HC (Δ ≈ 38%). Overall, these findings suggest that serum D-serine and D-/Total serine may represent a valuable biochemical signature of PD.
Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Serina/metabolismo , Dopamina/metabolismo , Levodopa/uso terapêutico , Aminoácidos , Ácido Glutâmico , EnvelhecimentoRESUMO
Joubert syndrome (JS) is a recessively inherited congenital ataxia characterized by hypotonia, psychomotor delay, abnormal ocular movements, intellectual disability, and a peculiar cerebellar and brainstem malformation, the "molar tooth sign." Over 40 causative genes have been reported, all encoding for proteins implicated in the structure or functioning of the primary cilium, a subcellular organelle widely present in embryonic and adult tissues. In this paper, we developed an in vitro neuronal differentiation model using patient-derived induced pluripotent stem cells (iPSCs), to evaluate possible neurodevelopmental defects in JS. To this end, iPSCs from four JS patients harboring mutations in distinct JS genes (AHI1, CPLANE1, TMEM67, and CC2D2A) were differentiated alongside healthy control cells to obtain mid-hindbrain precursors and cerebellar granule cells. Differentiation was monitored over 31 days through the detection of lineage-specific marker expression by qRT-PCR, immunofluorescence, and transcriptomics analysis. All JS patient-derived iPSCs, regardless of the mutant gene, showed a similar impairment to differentiate into mid-hindbrain and cerebellar granule cells when compared to healthy controls. In addition, analysis of primary cilium count and morphology showed notable ciliary defects in all differentiating JS patient-derived iPSCs compared to controls. These results confirm that patient-derived iPSCs are an accessible and relevant in vitro model to analyze cellular phenotypes connected to the presence of JS gene mutations in a neuronal context.
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Anormalidades Múltiplas , Diferenciação Celular , Cerebelo , Cerebelo/anormalidades , Anormalidades do Olho , Células-Tronco Pluripotentes Induzidas , Doenças Renais Císticas , Neurônios , Retina , Retina/anormalidades , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Humanos , Anormalidades do Olho/genética , Anormalidades do Olho/patologia , Cerebelo/patologia , Cerebelo/metabolismo , Neurônios/metabolismo , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Retina/metabolismo , Doenças Renais Císticas/genética , Doenças Renais Císticas/patologia , Doenças Renais Císticas/metabolismo , Masculino , Feminino , Mutação/genética , Cílios/metabolismoRESUMO
BACKGROUND: Multiple sclerosis (MS) is frequently accompanied by comorbid conditions. OBJECTIVES: This study aimed to determine the prevalence of key comorbid conditions in people with multiple sclerosis (pwMS) and assess their impact on quality of life and work-related activities. METHODS: A cross-sectional study involving 755 pwMS from two third-level Italian MS centers was conducted. Comorbidities were identified from medical records, and quality of life was assessed using the EQ-5D-3L questionnaire. Work-related challenges were evaluated using the Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job). RESULTS: 53.8% of pwMS had at least one comorbidity. Hypertension, depression, and anxiety were the most prevalent. Comorbidity presence was associated with reduced quality of life scores in almost all EQ-5D-3L domains and greater job difficulties in all but one MSQ-Job domain. CONCLUSION: Comorbidities in pwMS are prevalent and have a profound influence on quality of life and work-related activities. This comprehensive study offers new insights into the role of comorbidities in MS within the Italian context, emphasizing the need for a multidisciplinary approach in MS management. Further research is crucial to deepen our understanding of these findings in the broader Italian MS community.
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Comorbidade , Esclerose Múltipla , Qualidade de Vida , Humanos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Adulto , Itália/epidemiologia , Depressão/epidemiologia , Ansiedade/epidemiologia , Emprego/estatística & dados numéricos , Hipertensão/epidemiologia , PrevalênciaRESUMO
BACKGROUND: Several studies suggested that SARS-CoV-2 was already spreading worldwide during the last months of 2019 before the first outbreak was detected in Wuhan, China. Lombardy (Northern Italy) was the first European region with sustained SARS-CoV-2 transmission and recent investigations detected SARS-CoV-2-RNA-positive patients in Lombardy since late 2019. METHODS: We tested for anti-SARS-CoV-2 IgG all serum samples available in our laboratory (N = 235, collected between March 2017 and March 2022) that we received within the framework of measles/rubella surveillance from measles and rubella virus-negative patients. RESULTS: Thirteen of 235 samples (5.5%) were IgG-positive. The positivity rate increased starting in 2019 and was significantly different from the expected false positive rate from 2019 onwards. Additionally, in 2019 the percentage of IgG-positive patients was significantly lower among SARS-CoV-2 RNA-negative patients (3/92) compared to SARS-CoV-2 RNA-positive patients (2/7, p = 0.04). The highest percentage of IgG positivity in the pre-pandemic period was recorded during the second half of 2019. This coincided with an increase in negativity for measles and a widening of the peak of the number of measles discarded cases per 100,000 inhabitants, indicating a higher-than-normal number of measles-negative patients experiencing fever and rash. This also coincided with the first patient positive for SARS-CoV-2 RNA (September 12th, 2019); this patient was also positive for anti-SARS-CoV-2 IgG and IgM. CONCLUSIONS: Although the number of samples was low and one cannot conclusively establish that the virus started circulating in Lombardy around September 2019, our findings should stimulate similar research investigating the possibility of undetected SARS-CoV-2 pre-pandemic circulation.
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COVID-19 , Sarampo , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , RNA Viral , Sarampo/diagnóstico , Sarampo/epidemiologia , Anticorpos Antivirais , Imunoglobulina G , Imunoglobulina MRESUMO
BACKGROUND: Comorbid conditions are common in people with multiple sclerosis (pwMS). They can delay diagnosis and negatively impact the disease course, progression of disability, therapeutic management, and adherence to treatment. OBJECTIVE: To quantify the economic impact of comorbidity in multiple sclerosis (MS), based on cost-of-illness estimates made using a bottom-up approach. METHODS: A retrospective study was carried out in two northern Italian areas. The socio-demographic and clinical information, including comorbidities data, were collected through ad hoc anonymous self-assessment questionnaire while disease costs (direct and indirect costs of disease and loss of productivity) were estimated using a bottom-up approach. Costs were compared between pwMS with and without comorbidity. Adjusted incremental costs associated with comorbidity were reported using generalized linear models with log-link and gamma distributions or two-part models. RESULTS: 51.0% of pwMS had at least one comorbid condition. Hypertension (21.0%), depression (15.7%), and anxiety (11.7%) were the most prevalent. PwMS with comorbidity were more likely to use healthcare resources, such as hospitalizations (OR = 1.21, p < 0.001), tests (OR = 1.59, p < 0.001), and symptomatic drugs and supplements (OR = 1.89, p = 0.012), and to incur non-healthcare costs related to investment (OR = 1.32, p < 0.001), transportation (OR = 1.33, p < 0.001), services (OR = 1.33, p < 0.001), and informal care (OR = 1.43, p = 0.16). Finally, they experienced greater productivity losses (OR = 1.34, p < 0.001) than pwMS without comorbidity. The adjusted incremental annual cost per patient due to comorbidity was 3,106.9 (13% of the overall costs) with MS disability found to exponentially affect annual costs. CONCLUSION: Comorbidity has health, social, and economic consequences for pwMS.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Qualidade de Vida , Estudos Retrospectivos , Comorbidade , Efeitos Psicossociais da Doença , Custos de Cuidados de SaúdeRESUMO
SUMMARY: Professional exposure to benzene has been extensively investigated by occupational medicine, leading to strict regulation of exposure threshold values. However, the petrochemical industry utilizes many chemical substances, whose exposure, without effective control and mitigation actions, could influence the health status over time. The aim of this narrative review is to describe health status of petrochemical workers related to occupational exposures, inquiring literature from 1980 to present. We used the PubMed and Web of Science search engines. As regards non-neoplastic diseases, despite heterogeneous prevalence estimates, we could say that standardized mortality rate (SMR) for hypertension, hypercholesterolemia and diabetes does not increase overall, compared to reference populations; a possible explanation may be the "healthy worker effect". Attention should be paid to color disperception and respiratory symptoms, due to toxic or irritating substances exposure. Studies concerning neoplastic pathology have mainly investigated mortality outcomes, finding no increase in cancer, except for melanoma or other skin cancers and leukemia. As regards the former, however, it is not excluded that other risk factors may contribute (e.g. UV rays in offshore workers), while for leukemia, only the most recent studies have analyzed various subtypes of hematopoietic tumors, highlighting a possible risk for the development of myelodysplastic syndrome. The risk of pleural mesothelioma was also increased, likely due to asbestos exposures, while the risk of death from prostate cancer remains controversial.
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Leucemia , Mesotelioma , Doenças Profissionais , Exposição Ocupacional , Petróleo , Masculino , Humanos , Petróleo/toxicidade , Exposição Ocupacional/efeitos adversos , Nível de Saúde , Leucemia/complicações , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologiaRESUMO
BACKGROUND: During the COVID-19 pandemic, the health care workers (HCWs) at the frontline have been largely exposed to infected patients, running a high risk of being infected by the SARS-CoV-2 virus.Since limiting transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in health care setting is crucial to avoid the community spread of SARS-CoV-2, we want to share our experience as an early hit hospital where standard infection control practices have been conscientiously applied and effective. We believe that our example, as first and hardest hit country, might be a warning and aid not only for those who have been hit later, but also for a second fearful wave of contagion. In addition, we want to offer an insight on modifiable risk factors for HWs-related infection. METHODS: Demographic, lifestyle, work-related and comorbidities data of 1447 HCWs, which underwent a nasopharyngeal swab for SARS-CoV-2, were retrospectively collected. For the 164 HCWs positive for SARS-CoV-2, data about safety in the workplace, symptoms and clinical course of COVID-19 were also collected. Cumulative incidence of SARS-CoV-2 infection was estimated. Risk factors for SARS-CoV-2 infection were assessed using a multivariable Poisson regression. RESULTS: The cumulative incidence of SARS-CoV-2 infection among the screened HCWs was 11.33% (9.72-13.21). Working in a COVID-19 ward, being a former smoker (versus being a person who never smoked) and BMI was positively associated with SARS-CoV-2 infection, whereas being a current smoker was negatively associated with this variable. CONCLUSIONS: Assuming an equal accessibility and proper use of personal protective equipment of all the HCWs of our Hospital, the great and more prolonged contact with COVID-19 patients remains the crucial risk factor for SARS-CoV-2. Therefore, increased and particular care needs to be focused specifically on the most exposed HCWs groups, which should be safeguarded. Furthermore, in order to limit the risk of asymptomatic spread of SARS-CoV-2 infection, the HCWs mild symptoms of COVID-19 should be considered when evaluating the potential benefits of universal staff testing.
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COVID-19/epidemiologia , Recursos Humanos em Hospital , Adulto , Índice de Massa Corporal , COVID-19/diagnóstico , COVID-19/prevenção & controle , Teste de Ácido Nucleico para COVID-19 , Feminino , Humanos , Incidência , Controle de Infecções , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Encaminhamento e Consulta , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , FumarRESUMO
BACKGROUND: The increasing multiple sclerosis (MS) prevalence is varying across the macroscopic regional areas. Only few studies have explored the microscopic geographic variation of MS prevalence, which could highlight MS spatial clusters. OBJECTIVE: In this ecological study, we aimed to estimate 2016 MS prevalence in the province of Pavia (Northern Italy) and to describe MS risk geographical variation across small area units, compared to the year 2000. METHODS: Bayesian models were fit to estimate area-specific MS relative risks. The mean of the posterior marginal distribution of relative risks differences for each area were used to describe the risk variation. RESULTS: The 2016 overall prevalence was 169.4 per 100,000 inhabitants (95% CI 158.8-180.6). The Bayesian mapping of MS showed some clusters of higher and lower disease prevalence. Furthermore, several municipalities located in the north part of the province were more at risk with respect to the year 2000. CONCLUSIONS: The current MS prevalence sets the province of Pavia among high-risk areas and, compared with the previous prevalence estimate (86 per 100,000 in year 2000), indicates an increased MS risk. The Bayesian mapping highlighted area with a significantly higher/lower MS risk where to investigate etiologic hypotheses based on environmental and genetic exposures.
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Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Idoso , Teorema de Bayes , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
SUMMARY: Background. Interruptions occurring during the drug preparation and administration have a documented effect on patients' safety. However, literature has paid little attention to show how the introduction of a set of standardized organizational interventions, based on the combination of the current evidence, could reduce the number of interruptions occurring during drug therapy management. For this reason, this study used the most recent evidence to combine a set of standardized organizational interventions, and it was aimed to assess the effect of those interventions on the number of interruptions occurring during drug therapy management (Hypothesis a) and the overall duration of the therapy administration (Hypothesis b). Methods. A quasi-experimental study was performed, using pre- and a post- organizational implementation data collections in a single Italian center. The data collections were related to the interruptions and 40 shifts were randomly selected for both pre- and post-phase, respectively on December 2016 and February 2017. The standardized organizational interventions were implemented using the current evidence on this topic. Results. The standardized organizational interventions decreased the interruptions in the post-implementation phase, but those had not an effect on the duration of the therapy administration. Conclusions. This study represented an updated evidence, which describes the effect of a standardized and evidence-based set of organisational interventions' implementation on drug therapy management. Our results suggest a number of hints for managers and future researches. Managers should keep into account the usefulness of those interventions, while future researches with experimental designs are needed to provide harder evidence on this topic.
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Tratamento Farmacológico/enfermagem , Erros de Medicação/prevenção & controle , Conduta do Tratamento Medicamentoso/normas , Recursos Humanos de Enfermagem Hospitalar/organização & administração , Tratamento Farmacológico/normas , Feminino , Hospitais/normas , Humanos , Itália , Masculino , Recursos Humanos de Enfermagem Hospitalar/normas , Segurança do Paciente/normas , Gestão da Segurança/organização & administraçãoRESUMO
OBJECTIVES: to evaluate time and spatial distribution of hospitalization due to neurological diseases in the province of Pavia (Lombardy Region, Northern Italy). DESIGN: ecological study. SETTING AND PARTICIPANTS: the study was performed on aggregate data of people residing in the province of Pavia in the period 2005-2014. MAIN OUTCOME MEASURES: hospital discharge records of neurological diseases and raw and standardized hospitalization rates. RESULTS: hospitalization due to neurological diseases in the Province of Pavia showed a slight decreasing trend in time. For the year 2014, the spatial analysis of hospitalizations highlights excesses of risk in the Lomellina district, both in males and in females. CONCLUSION: spatial analysis confirms previous results on specific neurological diseases and suggests more detailed analysis on hospitalization excesses in Lomellina area.
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Hospitalização/estatística & dados numéricos , Doenças do Sistema Nervoso/epidemiologia , Idoso , Estudos Epidemiológicos , Feminino , Humanos , Itália/epidemiologia , MasculinoRESUMO
AIM: Even though a standard clinical definition for an apparent life-threatening event (ALTE) was established more than two decades ago, the specific International Classification of Disease (ICD) code was firstly included only in 2012. This study estimated the incidence of ALTEs in Northern Italy, together with features and risk factors. METHODS: We used the Lombardy Region Hospital Discharge Records (HDR) database to estimate the cumulative incidence for ALTE during 2002-2006 and drew up a risk profile by comparing cases with and without ALTE who were followed in infancy. RESULTS: There were 246 infants registered in the HDR with ALTE putative diagnostic codes, suggesting a cumulative incidence of 4.1 per 1000 live births in the study area. Of the 148 cases with clinical co-morbidities, 31% had gastroesophageal reflux and 7% had acute respiratory infections. We analysed follow-up data from 15 ALTE cases and 1619 healthy infants and found that the significant risk factors were gastroesophageal reflux and a family history of sudden death. CONCLUSION: We established the regional incidence of ALTE and found risk factors in infants considered healthy in the first week of life and without pathological perinatal conditions. The systematic use of the specific ALTE ICD code (R68.13, ICD-10-CM) and common knowledge about ALTE diagnostic guidelines are clearly needed.
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Doenças do Recém-Nascido/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Music therapy (MT) interventions are aimed at creating and developing a relationship between patient and therapist. However, there is a lack of validated observational instruments to consistently evaluate the MT process. AIM: The purpose of this study was the validation of Music Therapy Session Assessment Scale (MT-SAS), designed to assess the relationship between therapist and patient during active MT sessions. METHODS: Videotapes of a single 30-min session per patient were considered. A pilot study on the videotapes of 10 patients was carried out to help refine the items, define the scoring system and improve inter-rater reliability among the five raters. Then, a validation study on 100 patients with different clinical conditions was carried out. The Italian MT-SAS was used throughout the process, although we also provide an English translation. RESULTS: The final scale consisted of 7 binary items accounting for eye contact, countenance, and nonverbal and sound-music communication. In the pilot study, raters were found to share an acceptable level of agreement in their assessments. Explorative factorial analysis disclosed a single homogeneous factor including 6 items (thus supporting an ordinal total score), with only the item about eye contact being unrelated to the others. Moreover, the existence of 2 different archetypal profiles of attuned and disattuned behaviours was highlighted through multiple correspondence analysis. CONCLUSIONS: As suggested by the consistent results of 2 different analyses, MT-SAS is a reliable tool that globally evaluates sonorous-musical and nonverbal behaviours related to emotional attunement and empathetic relationship between patient and therapist during active MT sessions.
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Musicoterapia/métodos , Musicoterapia/estatística & dados numéricos , Relações Profissional-Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Comunicação não Verbal , Projetos Piloto , Psicometria , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340 controls. Association analyses were performed using the PLINK program, and pathway analyses were performed using the MAGENTA software. We identified multiple signals within the HLA region and conditioning studies suggested that a few of them contributed independently to the strong association of the HLA locus with APS3v. Outside the HLA region, variants in GPR103, a gene not suggested by previous studies of APS3v, T1D, or AITD, showed genome-wide significance (p < 5 × 10(-8)). In addition, a locus on 1p13 containing the PTPN22 gene showed genome-wide significant associations. Pathway analysis demonstrated that cell cycle, B-cell development, CD40, and CTLA-4 signaling were the major pathways contributing to the pathogenesis of APS3v. These findings suggest that complex mechanisms involving T-cell and B-cell pathways are involved in the strong genetic association between AITD and T1D.
Assuntos
Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Poliendocrinopatias Autoimunes/genética , Tireoidite Autoimune/genética , Linfócitos B/imunologia , Antígenos CD40/genética , Antígeno CTLA-4/genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Desequilíbrio de Ligação/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Linfócitos T/imunologiaRESUMO
Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High-Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine, and D-serine, as well as their precursors L-glutamine, L-asparagine, and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle, and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty.
Assuntos
Biomarcadores , Disfunção Cognitiva , Idoso Fragilizado , Glicina , Serina , Humanos , Masculino , Idoso , Serina/sangue , Feminino , Glicina/sangue , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Idoso de 80 Anos ou mais , Fragilidade/sangueRESUMO
BACKGROUND: Generally infrequent, multiple sclerosis (MS) with late onset (LOMS) is characterized by an onset over the age of 50 and a mainly progressive course, while relapsing-remitting (RR) forms are less frequently observed and explored. This study aimed to characterize a large cohort of MS patients with RRMS at onset to assess the baseline factors related to the worst disability trajectories and explore the role of LOMS. METHODS: The data were extracted from the Italian MS Register (IMSR). Disability trajectories, defined using at least two and up to twenty expanded disability status scale (EDSS) assessments annually performed, were implemented using group-based trajectory models (GBTMs) to identify different groups with the same trajectories over time. MS profiles were explored using multinomial logistic regression. RESULTS: A total of 16,159 RR patients [1012 (6.26%) presented with LOMS] were analyzed. The GBTM identified four disability trajectories. The group with the most severe EDSS trend included 12.3% of the patients with a mean EDSS score > 4, which increased over time and exceeded 6 score. The group with medium severity EDSS trend comprised 21.9% of the patients and showed a change in EDSS > 3 scores over time. The largest group with 50.8% of patients reported a constant EDSS of 2 score. Finally, the benign group comprised 14.9% of the patients with a low and constant EDSS of 1 score over time. The probability of being in the worst groups increased if the patient was male; had LOMS or experienced brainstem, spinal, or supratentorial symptoms. CONCLUSIONS: Four MS severity profiles among RRMS patients in the IMSR have been reported, with LOMS being associated with a rapid worsening of EDSS scores. These findings have important implications for recognizing and managing how older age, aging, and age-related factors interact with MS and its evolution.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Masculino , Esclerose Múltipla/complicações , Progressão da Doença , Fatores Etários , Envelhecimento , Itália , Esclerose Múltipla Recidivante-Remitente/complicações , Avaliação da DeficiênciaRESUMO
Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⻹¹). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R.â=â0.923, 95% CI 0.860-0.991; pâ=â0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], pâ=â0.004; after eGFR adjustment: 0.89 [0.83-0.96], pâ=â0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
Assuntos
Pressão Sanguínea , Estudo de Associação Genômica Ampla/métodos , Hipertensão/genética , Uromodulina/genética , Idoso , Alelos , Cromossomos Humanos Par 16/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Genótipo , Taxa de Filtração Glomerular , Humanos , Hipertensão/fisiopatologia , Modelos Lineares , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Fatores de Risco , Análise de Sobrevida , Uromodulina/sangueRESUMO
BACKGROUND: Practicing on the human body was considered extremely relevant for health professionals' education, but a drastic reduction was observed due to an increase in alternative virtual and multimedia means, and, in Italy, also due to a lack of regulation. Italian Law 10/2020 regulates body donation for research and training through an advanced directive for post-mortem body donation. METHODS: A cross-sectional study was carried out to investigate the law knowledge and body donation perception of health students of any degree courses enrolled at the University of Pavia, Italy, in 2021, through ad hoc web questionnaire. RESULTS: 485 students participated to this survey; median age was of 21 years (25th-75th percentiles, 20-23), 73.2% were females, and 62.5% were medical students. Among them 14.9% knew the Italian law 10/2020. Age was the only variable associated with students' knowledge of the law. Further, 8.3% reported the current availability of cadaveric practice, 85.6% of health students acknowledged usefulness of cadaveric practice, with a significant difference between medical and non-medical students (71.4% vs 28.6%, p < 0.001). Overall, 59.7% would donate their body, rising to 62.7% with reference to specific law regulation, with 30.5% and 28.7% undecided, respectively. 51.3% of participants answered not practicing religious faith, 82.9% with Catholic families, without significance on the knowledge of the law. CONCLUSIONS: Poor knowledge of the law compared with great interest and acknowledged cadaveric practice usefulness highlighted the need for better information, especially among health students, where critical discussion could be more valuable. Then, there arises the urgent need to fill the gaps within university studies and syllabuses, to relaunch the central role that cadaveric practice and research had in the education of health professionals. Consequences on basic and specific health students' skills, on health education quality in general, and further on health professionals' expertise must be carefully considered.
Assuntos
Estudantes de Medicina , Obtenção de Tecidos e Órgãos , Feminino , Humanos , Adulto Jovem , Adulto , Masculino , Estudos Transversais , Inquéritos e Questionários , Itália , Cadáver , Percepção , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
Asbestos-related diseases still represent a major public health problem all over the world. Among them, malignant mesothelioma (MM) is a poor-prognosis cancer, arising from the serosal lining of the pleura, pericardium and peritoneum, triggered by asbestos exposure. Literature data suggest the key role of iron metabolism in the coating process leading to the formation of asbestos bodies, considered to be both protective and harmful. Two sample sets of individuals were taken into consideration, both residing in Broni or neighboring cities (Northwestern Italy) where an asbestos cement factory was active between 1932 and 1993. The present study aims to compare the frequency of six SNPs involved in iron trafficking, previously found to be related to protection/predisposition to MM after asbestos exposure, between 48 male subjects with documented asbestos exposure who died of MM and 48 male subjects who were exposed to asbestos but did not develop MM or other neoplastic respiratory diseases (Non-Mesothelioma Asbestos Exposed - NMAE). The same analysis was performed on 76 healthy male controls. The allelic and genotypic frequencies of a sub-group of 107 healthy Italian individuals contained in the 1000 genomes database were considered for comparison. PCR-multiplex amplification followed by SNaPshot mini-sequencing reaction was used. The findings presented in this study show that the allelic and genotypic frequencies for six SNP markers involved in iron metabolism/homeostasis and the modulation of tumor microenvironment are not significantly different between the two sample sets of MM and NMAE. Therefore, the SNPs here considered do not seem to be useful markers for individual susceptibility to mesothelioma. This finding is not in agreement with previous literature.
Assuntos
Amianto , Mesotelioma Maligno , Mesotelioma , Exposição Ocupacional , Masculino , Humanos , Polimorfismo de Nucleotídeo Único , Mesotelioma/genética , Amianto/efeitos adversos , Ferro/metabolismo , Homeostase , Microambiente TumoralRESUMO
The increasing demand for renewable energy production entails the development of novel green technologies, among them the use of biomass for energy generation. Industrial processes raise new issues regarding emerging risks for the health of people working in biogas plants and of nearby communities. The potential epidemiological and environmental impacts on human health related to biogas plants were assessed by means of a review of the available literature. Nineteen papers published between 2000 and 2022 were identified through electronic database search using search strings. The selected works are epidemiological studies and environmental monitoring studies, which aimed at investigating what are the health risk factors for biogas plant workers and for people living in the surrounding communities. The results of the epidemiological studies revealed a potential exposure to endotoxins and fungi that are associated with respiratory symptoms. Furthermore, the results from the environmental monitoring studies showed significant concentrations of particulate matter, microbial agents, endotoxins, and VOCs in occupational settings. In conclusion, the results of this literature review suggest that further analyses through an integrated approach combining environmental and health data are necessary for a comprehensive understanding of the potential risks associated with the uptake of biogas technology.
Assuntos
Biocombustíveis , Meio Ambiente , Humanos , Biomassa , Material Particulado , Monitoramento Ambiental , AnaerobioseRESUMO
Introduction: Italian administrative healthcare databases are frequently used for studies on real-world drug utilization. However, there is currently a lack of evidence on the accuracy of administrative data in describing the use of infusive antineoplastics. In this study, we used rituximab as a case study to investigate the validity of the regional administrative healthcare database of Tuscany (RAD) in describing the utilization of infusive antineoplastics. Methods: We identified patients aged 18 years or older who had received ≥1 rituximab administration between 2011 and 2014 in the onco-haematology ward of the University Hospital of Siena. We retrieved this information from the Hospital Pharmacy Database (HPD-UHS) and linked the person-level information to RAD. Patients who had received ≥1dispensing of rituximab, single administration episodes, and patients treated for non-Hodgkin Lymphoma (nHL) or Chronic Lymphocytic Leukemia (CLL) were identified in RAD and validated using HPD-UHS as the reference standard. We identified the indications of use using algorithms based on diagnostic codes (ICD9CM codes, nHL=200*, 202*; CLL=204.1). We tested 22 algorithms of different complexity for each indication of use and calculated sensitivity and positive predictive value (PPV), with 95% confidence intervals (95%CI), as measures of validity. Results: According to HPD-UHS, 307 patients received rituximab for nHL (N=174), CLL (N=21), or other unspecified indications (N=112) in the onco-haematology ward of the University Hospital of Siena. We identified 295 rituximab users in RAD (sensitivity=96.1%), but PPV could not be assessed due to missing information in RAD on dispensing hospital wards. We identified individual rituximab administration episodes with sensitivity=78.6% [95%CI: 76.4-80.6] and PPV=87.6% [95%CI: 86.1-89.2]. Sensitivity of algorithms tested for identifying nHL and CLL ranged from 87.7% to 91.9% for nHL and from 52.4% to 82.7% for CLL. PPV ranged from 64.7% to 66.1% for nHL and from 32.4% to 37.5% for CLL. Discussion: Our findings suggest that RAD is a very sensitive source of information for identifying patients who received rituximab for onco-haematological indications. Single administration episodes were identified with good-to-high accuracy. Patients receiving rituximab for nHL were identified with high sensitivity and acceptable PPV, while the validity for CLL was suboptimal.