The Molecular Impact of Glucosylceramidase Beta 1 (Gba1) in Parkinson's Disease: a New Genetic State of the Art.

Parkinson's disease (PD) is a neurodegenerative disorder affecting 2-3% of those aged over 65, characterized by motor symptoms like slow movement, tremors, and muscle rigidity, along with non-motor symptoms such as anxiety and dementia. Lewy bodies, clumps of misfolded proteins, contribute to neuron loss in PD. Mutations in the GBA1 gene are considered the primary genetic risk factor of PD. GBA1 mutations result in decreased activity of the lysosomal enzyme glucocerebrosidase (GCase) resulting in α-synuclein accumulation. We know that α-synuclein aggregation, lysosomal dysfunction, and endoplasmic reticulum disturbance are recognized factors to PD susceptibility; however, the molecular mechanisms connecting GBA1 gene mutations to increased PD risk remain partly unknown. Thus, in this narrative review conducted according to a systematic review method, we aimed to present the main contributions arising from the molecular impact of the GBA1 gene to the pathogenesis of PD providing new insights into potential impacts for advances in the clinical care of people with PD, a neurological disorder that has contributed to the substantial increase in the global burden of disease accentuated by the aging population. In summary, this narrative review highlights the multifaceted impact of GBA1 mutations in PD, exploring their role in clinical manifestations, genetic predispositions, and molecular mechanisms. The review emphasizes the importance of GBA1 mutations in both motor and non-motor symptoms of PD, suggesting broader therapeutic and management strategies. It also discusses the potential of CRISPR/Cas9 technology in advancing PD treatment and the need for future research to integrate these diverse aspects for improved diagnostics and therapies.

Onychomycosis in patients with multiple sclerosis: prevalence, clinical description, mycological, and dermoscopic study in a Mexican population.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease related to HLA-DR8. Susceptibility to onychomycosis has been found in Mexican mestizos with HLA-DR8. The frequency of onychomycosis in this neurological disease is unknown. OBJECTIVES: To determine the frequency of onychomycosis and its clinical, mycological, and dermoscopic characteristics in patients with MS in comparison with the general population. METHODS: Observational, cross-sectional, case-control study in patients with MS from October 2017 to February 2018. Age, gender, MS type, and time of progression from diagnosis to date and baseline treatment were collected after signed informed consent. A neurological exploration and clinical examination of fingernails and toenails for onychomycosis was conducted. Mycological and dermoscopic studies of the infected nails were performed on patients with clinical diagnosis of onychomycosis. A healthy control group was taken for each case (1:1), paired by age and gender. RESULTS: The frequency of onychomycosis in patients with MS was higher than the healthy population (32% vs. 26%, P = 0.509). A higher frequency of non-dermatophyte fungi was found, although it was not statistically significant. The clinical manifestations and dermoscopic findings in patients with MS and onychomycosis were similar to those of the general population. CONCLUSION: The frequency of onychomycosis in patients with MS is slightly higher than that of the general population. A possible association of HLA-DR8 as a susceptibility factor for onychomycosis is proposed. The etiology of opportunistic fungi in MS patients with onychomycosis may be related to immunosuppressive treatment.

Public health in the field and the emergency operations center: methods for implementing real-time onsite syndromic surveillance at large public events.

OBJECTIVE: To develop an onsite syndromic surveillance system for the early detection of public health emergencies and outbreaks at large public events. METHODS: As the third largest public health jurisdiction in the United States, Maricopa County Department of Public Health has worked with academic and first-response partners to create an event-targeted syndromic surveillance (EVENTSS) system. This system complements long-standing traditional emergency department-based surveillance and provides public health agencies with rapid reporting of possible clusters of illness. RESULTS: At 6 high profile events, 164 patient reports were collected. Gastrointestinal and neurological syndromes were most commonly reported, followed by multisyndromic reports. Neurological symptoms were significantly increased during hot weather events. The interview rate was 2 to 7 interviews per 50 000 people per hour, depending on the ambient temperature. Discussion Study data allowed an estimation of baseline values of illness occurring at large public events. As more data are collected, prediction models can be built to determine threshold levels for public health response. CONCLUSIONS: EVENTSS was conducted largely by volunteer public health graduate students, increasing the response capacity for the health department. Onsite epidemiology staff could make informed decisions and take actions quickly in the event of a public health emergency.

Evaluation of a hepatitis A immunization program.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of a hepatitis A vaccine requirement targeted at child-care center attendees 2-5 years of age in Maricopa County, AZ. A case-control study conducted before implementation in 1997 found that individuals with hepatitis A were 6 times more likely to have worked in or attended a child-care center than were matched controls, and 40% of hepatitis A cases were attributable to attending or working in a child-care center. METHODS: A case-control study was conducted postimplementation in 1999. Cases were individuals reported to surveillance staff between August 1, 1999 and April 30, 2000. Cases were included if they met the Centers for Disease Control and Prevention hepatitis A surveillance case definition. Each case (n = 72) was matched to 2 controls (n = 144) based on age and neighborhood. RESULTS: Cases were more likely to have had contact with a hepatitis A case [odds ratio (OR), 7.04; 95% confidence interval (CI), 1.96, 25.31] than were their matched controls in the unadjusted analysis. Individuals with direct contact with a child-care center (OR 0.221; CI 0.05, 0.99) were protected against disease. In the multivariate analysis, contact with a hepatitis A case (OR 5.63; CI 1.22, 25.91) was significantly associated with disease, and the protective effect of education (OR 0.19; CI 0.06, 0.60) remained significant. CONCLUSION: The results of this study suggest the vaccination requirement had some impact on the epidemiology of hepatitis A in Maricopa County. The risk associated with child-care centers seen in the 1997 study is no longer significantly associated with hepatitis A disease.

The validity of chief complaint and discharge diagnosis in emergency department-based syndromic surveillance.

OBJECTIVE: Emergency department (ED)-based syndromic surveillance systems are being used by public health departments to monitor for outbreaks of infectious diseases, including bioterrorism; however, few systems have been validated. The authors evaluated a "drop-in" syndromic surveillance system by comparing syndrome categorization in the ED with chief complaints and ED discharge diagnoses from medical record review. METHODS: A surveillance form was completed for each ED visit at 15 participating Arizona hospitals between October 27 and November 18, 2001. Each patient visit was assigned one of ten clinical syndromes or "none." For six of 15 EDs, kappa statistics were used to compare syndrome agreement between surveillance forms and syndrome categorization with chief complaint and ED discharge diagnosis from medical record review. RESULTS: Overall, agreement between surveillance forms and ED discharge diagnoses (kappa = 0.55; 95% confidence interval [CI] = 0.52 to 0.59) was significantly higher than between surveillance forms and chief complaints (kappa = 0.48; 95% CI = 0.44 to 0.52). Agreement between chief complaints and ED discharge diagnoses was poor for respiratory tract infection with fever (kappa = 0.33; 95% CI = 0.27 to 0.39). Furthermore, pediatric chief complaints showed lower agreement for respiratory tract infection with fever when compared with adults (kappa = 0.34 [95% CI = 0.20 to 0.47] vs. kappa = 0.44 [95% CI = 0.28 to 0.59], respectively). CONCLUSIONS: In general, this syndromic surveillance system classified patients into appropriate syndrome categories with fair to good agreement compared with chief complaints and discharge diagnoses. The present findings suggest that use of ED discharge diagnoses, in addition to or instead of chief complaints, may increase surveillance validity for both automated and drop-in syndromic surveillance systems.