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Scientific Reports Jun 2024Hereditary spastic paraplegias are a diverse group of degenerative disorders that are clinically categorized as isolated; with involvement of lower limb spasticity, or...
Hereditary spastic paraplegias are a diverse group of degenerative disorders that are clinically categorized as isolated; with involvement of lower limb spasticity, or symptomatic, where spastic paraplegia is complicated by further neurological features. We sought to identify the underlying genetic causes of these disorders in the participating patients. Three consanguineous families with multiple affected members were identified by visiting special schools in the Punjab Province. DNA was extracted from blood samples of the participants. Exome sequencing was performed for selected patients from the three families, and the data were filtered to identify rare homozygous variants. ExomeDepth was used for the delineation of the copy number variants. All patients had varying degrees of intellectual disabilities, poor speech development, spasticity, a wide-based gait or an inability to walk and hypertonia. In family RDHR07, a homozygous deletion involving multiple exons and introns of SPG11 (NC000015.9:g.44894055_449028del) was found and correlated with the phenotype of the patients who had spasticity and other complex movement disorders, but not those who exhibited ataxic or indeterminate symptoms as well. In families ANMD03 and RDFA06, a nonsense variant, c.985C > T;(p.Arg329Ter) in DDHD2 and a frameshift insertion‒deletion variant of AP4B1, c.965-967delACTinsC;p.(Tyr322SerfsTer14), were identified which were homozygous in the patients while the obligate carriers in the respective pedigrees were heterozygous. All variants were ultra-rare with none, or very few carriers identified in the public databases. The three loss of function variants are likely to cause nonsense-mediated decay of the respective transcripts. Our research adds to the genetic variability associated with the SPG11 and AP4B1 variants and emphasizes the genetic heterogeneity of hereditary spastic paraplegia.
Topics: Humans; Male; Female; DNA Copy Number Variations; Pedigree; Spastic Paraplegia, Hereditary; Exons; Child; Adolescent; Adult; Exome Sequencing; Child, Preschool; Adaptor Protein Complex 4; Consanguinity; Homozygote; Phenotype; Young Adult; Proteins
PubMed: 38906889
DOI: 10.1038/s41598-024-64922-8 -
The Lancet. Digital Health Jul 2024The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major... (Review)
Review
The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community.
Topics: Humans; Information Dissemination; Neuroimaging; Brain
PubMed: 38906618
DOI: 10.1016/S2589-7500(24)00069-4 -
PloS One 2024In Ontario, despite the increasing prevalence of Parkinson's disease (PD), barriers to access-to-care for people with Parkinson's disease (PwP) and their caregivers are...
In Ontario, despite the increasing prevalence of Parkinson's disease (PD), barriers to access-to-care for people with Parkinson's disease (PwP) and their caregivers are not well understood. The objective of this study is to examine spatial patterns of health care utilization among PwP and identify factors associated with PD-related health care utilization of individuals in Ontario. We employed a retrospective, population-based study design involving administrative health data to identify PwP as of March 31, 2018 (N = 35,482) using a previously validated case definition. An enhanced 2-step floating catchment area method was used to measure spatial accessibility to PD care and a descriptive spatial analysis was conducted to describe health service utilization by geographic area and specialty type. Negative binomial regression models were then conducted to identify associated geographic, socioeconomic, comorbidity and demographic factors. There was marked spatial variability in PD-related service utilization, with neurology and all provider visits being significantly higher in urban areas (CMF>1.20; p<0.05) and family physician visits being significantly higher (CMF >1.20; p<0.05) in more rural areas and remote areas. More frequent visits to family physicians were associated with living in rural areas, while less frequent visitation was associated with living in areas of low spatial accessibility with high ethnic concentration. Visits to neurologists were positively associated with living in areas of high spatial accessibility and with high ethnic concentration. Visits to all providers were also positively associated with areas of high spatial accessibility. For all outcomes, less frequent visits were found in women, older people, and those living in more deprived areas as years living with PD increased. This study demonstrates the importance of geographic, socioeconomic and individual factors in determining PwP's likelihood of accessing care and type of care provided. Our results can be expected to inform the development of policies and patient care models aimed at improving accessibility among diverse populations of PwP.
Topics: Humans; Parkinson Disease; Ontario; Female; Male; Aged; Patient Acceptance of Health Care; Middle Aged; Retrospective Studies; Aged, 80 and over; Health Services Accessibility; Adult; Rural Population; Socioeconomic Factors
PubMed: 38905210
DOI: 10.1371/journal.pone.0305062 -
Noise & HealthExcessive noise levels may decrease patients' sleep quality and increase the risk of sleep disorders in patients. Given that only a few studies have been conducted on...
BACKGROUND
Excessive noise levels may decrease patients' sleep quality and increase the risk of sleep disorders in patients. Given that only a few studies have been conducted on noise levels and sleep quality in hospitalized patients, this study investigated the effects of different noise environments on polysomnographic parameters and sleep in hospitalized patients. It also analyzed the factors associated with patients' sleep quality.
METHODS
A sample of 244 cases of hospitalized patients were retrospectively selected from March 2020 to March 2023. A total of 122 patients without ward noise reduction treatment were set as the control group. A total of 122 patients who were treated with ward noise reduction were set as the observation group. The polysomnographic monitoring parameters and sleep conditions levels were compared between the two groups, after which logistic regression was used to analyze the relevant factors that affected patients' sleep.
RESULTS
The incidence of noise level, rapid eye movement stage (R) phase proportion, nonrapid eye movement stage 1 (N1) phase proportion, and poorer sleep quality all had higher levels in the control group than in the observation group. In comparison, nonrapid eye movement stage 2 (N2) phase proportion, total sleep time (TST), and sleep efficiency (SE) were all lower than those in the observation group (P < 0.05). Regression analysis revealed that the need for surgery, having diabetes mellitus, higher noise level and low N2 percentage levels were all associated factors affecting the sleep quality of patients.
CONCLUSION
Environments with higher levels of noise can lead to patients' poorer sleep quality. Thus, it is necessary to actively implement noise management measures to avoid higher noise levels and maintain good sleep quality among patients.
Topics: Humans; Male; Female; Polysomnography; Noise; Middle Aged; Sleep Quality; Retrospective Studies; Adult; Aged; Hospitalization
PubMed: 38904810
DOI: 10.4103/nah.nah_12_24 -
International Journal of Occupational... Jun 2024Both physical and psychosocial risk factors contributing to musculoskeletal disorders occur in the professional nursing group, and previous literature suggested that...
OBJECTIVES
Both physical and psychosocial risk factors contributing to musculoskeletal disorders occur in the professional nursing group, and previous literature suggested that their interaction may increase the risk of musculoskeletal pain among nurses. The aim of the study was to examine perceived workload and stress as well as physical findings and musculoskeletal complaints in nurses.
MATERIAL AND METHODS
The participants consisted of 42 female nurses, age range 23-60 years. They marked on a pain drawing the site/sites that was/were painful at the moment of testing, its duration and intensity. Thereafter they were examined using the movement and respiration domains from the Global Physiotherapy Examination (GPE). Furthermore, a subjective workload measure was made using the paper version of the and stress was assessed using the .
RESULTS
Almost the entire study group declared that pain experienced in at least 1 location was chronic, i.e., had lasted ≥1 year (97%). The most frequent locations of pain were low back (22.4%) and cervical/head (21.6%) regions. In the GPE, most scores indicated restricted and reduced movement, with the subdomain flexibility having the highest deviation from the predefined standard. Furthermore, the results indicated hampered respiration, especially visible in standing position. Out of all workload scores, the highest was obtained for temporal demand. Perceived stress level was found to be moderate and significantly associated to chronic chest/ thoracic pain. Interestingly, the compression of thorax test positively correlated with mental (r = 0.42, p < 0.05) and physical demand (r = 0.35, p < 0.05), whereas the elbow drop test and temporal demand correlated negatively (r = -0.37, p < 0.05).
CONCLUSIONS
To sum up, the majority of nurses participating in this study had long-lasting pain and limited flexibility of the body and hampered respiration, which both may enhance intensity of experienced musculoskeletal pain. Int J Occup Med Environ Health. 2024;37(3).
PubMed: 38904294
DOI: 10.13075/ijomeh.1896.02389 -
BMJ Open Jun 2024Workplace stigmatisation and discrimination are significant barriers to accessing employment opportunities, reintegration and promotion in the workforce for people with...
Anticipated and experienced stigma and discrimination in the workplace among individuals with major depressive disorder in 35 countries: qualitative framework analysis of a mixed-method cross-sectional study.
OBJECTIVES
Workplace stigmatisation and discrimination are significant barriers to accessing employment opportunities, reintegration and promotion in the workforce for people with mental illnesses in comparison to other disabilities. This paper presents qualitative evidence of anticipated and experienced workplace stigma and discrimination among individuals with major depressive disorder (MDD) in 35 countries, and how these experiences differ across countries based on their Human Development Index (HDI) level.
DESIGN
Mixed-method cross-sectional survey.
PARTICIPANTS, SETTING AND MEASURES
The qualitative data were gathered as part of the combined European Union Anti-Stigma Programme European Network and global International Study of Discrimination and Stigma Outcomes for Depression studies examining stigma and discrimination among individuals with MDD across 35 countries. Anticipated and experienced stigma and discrimination were assessed using the Discrimination and Stigma Scale version 12 (DISC-12). This study used responses to the open-ended DISC-12 questions related to employment. Data were analysed using the framework analysis method.
RESULTS
The framework analysis of qualitative data of 141 participants identified 6 key 'frames' exploring (1) participants reported experiences of workplace stigma and discrimination; (2) impact of experienced workplace stigma and discrimination; (3) anticipated workplace stigma and discrimination; (4) ways of coping; (5) positive work experiences and (6) contextualisation of workplace stigma and discrimination. In general, participants from very high HDI countries reported higher levels of anticipated and experienced discrimination than other HDI groups (eg, less understanding and support, being more avoided/shunned, stopping themselves from looking for work because of expectation and fear of discrimination). Furthermore, participants from medium/low HDI countries were more likely to report positive workplace experiences.
CONCLUSIONS
This study makes a significant contribution towards workplace stigma and discrimination among individuals with MDD, still an under-researched mental health diagnosis. These findings illuminate important relationships that may exist between countries/contexts and stigma and discrimination, identifying that individuals from very high HDI countries were more likely to report anticipated and experienced workplace discrimination.
Topics: Humans; Cross-Sectional Studies; Depressive Disorder, Major; Social Stigma; Male; Female; Adult; Workplace; Middle Aged; Employment; Qualitative Research; Social Discrimination; Young Adult; Surveys and Questionnaires
PubMed: 38904137
DOI: 10.1136/bmjopen-2023-077528 -
Frontiers in Psychiatry 2024Unexplained physical signs and symptoms represent a significant portion of patient presentations in acute care settings. Even in cases where a patient presents with a...
Optimizing outcomes when treating functional neurological disorder in acute care settings: case reports depicting the value of diagnostic precision and timely and appropriate psychological interventions using an interdisciplinary framework.
INTRODUCTION
Unexplained physical signs and symptoms represent a significant portion of patient presentations in acute care settings. Even in cases where a patient presents with a known medical condition, functional or somatic symptoms may complicate the diagnostic and treatment processes and prognostic outcome. One umbrella category for neurologically related somatic symptoms, functional neurological disorder (FND), presents as involuntary neurological symptoms incompatible with another medical condition. Symptoms may include weakness and/or paralysis, movement disorders, non-epileptic seizures, speech or visual impairment, swallowing difficulty, sensory disturbances, or cognitive symptoms (1). While FND presents as neuropsychiatric, providers commonly report feeling hesitant to diagnose these disorders. Inexperience or lack of appropriate education on relevant research regarding evidence-based practices or standard of practice (SOP) may result in over- or underperforming diagnostic workups and consultations, utilizing inappropriate medications, and failing to offer evidence-based psychological interventions. Being mindful of these challenges when treating patients presenting with functional symptoms in acute care settings can help to support and protect the patients and care team and appropriately control healthcare costs.
METHODS
The University of Alabama at Birmingham Medical Center identified cases representing categories of quality and safety problems that arise in treating FND in acute care settings. Patients signed a consent form to participate in the case report. The case information for each was presented without identifying information.
DISCUSSION
The cases highlight potential challenges when caring for patients presenting with FND in acute care settings. The challenges covered include over- or underutilization of diagnostic workups and consultation, over- or underutilization of psychopharmacological medications, and over- or undertreating a medical condition when a functional symptom is present. In each case, these lapses and errors caused the patient distress, additional treatments, care delays, and delayed symptom remission. Additionally, these challenges have direct and indirect fiscal costs, which can be mitigated with the appropriate education and training, resources, and protocols. Hospitals can benefit from system-wide SOP to improve the identification and management of FND to prevent harm to patients. An SOP commonly presents to specific specialties and ensures the appropriate diagnostic workup, consultations, and timely evidence-based interventions.
PubMed: 38903638
DOI: 10.3389/fpsyt.2024.1288828 -
Frontiers in Neuroscience 2024VPS13A disease and Huntington's disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms,...
VPS13A disease and Huntington's disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms, neuropathological features, and cellular dysfunctions with selective degeneration of the medium spiny neurons of the striatum. However, their etiology is different. VPS13A disease is caused by a mutation in the VPS13A gene leading to a lack of protein in the cells, while HD is due to an expansion of CAG repeat in the huntingtin (Htt) gene, leading to aberrant accumulation of mutant Htt. Considering the similarities of both diseases regarding the selective degeneration of striatal medium spiny neurons, the involvement of VPS13A in the molecular mechanisms of HD pathophysiology cannot be discarded. We analyzed the VPS13A distribution in the striatum, cortex, hippocampus, and cerebellum of a transgenic mouse model of HD. We also quantified the VPS13A levels in the human cortex and putamen nucleus; and compared data on mutant Htt-induced changes in VPS13A expression from differential expression datasets. We found that VPS13A brain distribution or expression was unaltered in most situations with a decrease in the putamen of HD patients and small mRNA changes in the striatum and cerebellum of HD mice. We concluded that the selective susceptibility of the striatum in VPS13A disease and HD may be a consequence of disturbances in different cellular processes with convergent molecular mechanisms already to be elucidated.
PubMed: 38903599
DOI: 10.3389/fnins.2024.1394478 -
Frontiers in Neurology 2024-related disorders (-RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the gene. Dyskinetic crises, marked by...
BACKGROUND
-related disorders (-RD) encompass a diverse spectrum of neurodevelopmental and movement disorders arising from variants in the gene. Dyskinetic crises, marked by sudden and intense exacerbations of abnormal involuntary movements, present a significant challenge in -RD.
OBJECTIVES
This study aimed to establish a standardized framework for understanding dyskinetic crises, addressing crucial aspects such as definition, triggers, diagnostic criteria, complications, and management strategies.
METHODS
A Delphi consensus process was conducted involving international experts in -RD. The panel of thirteen experts participated in three voting rounds, discussing 90 statements generated through a literature review and clinical expertise.
RESULTS
Consensus was achieved on 31 statements, defining dyskinetic crises as abrupt, paroxysmal episodes involving distinct abnormal movements in multiple body regions, triggered by emotional stress or infections. Dyskinetic crises may lead to functional impairment and complications, emphasizing the need for prompt recognition. While individualized pharmacological recommendations were not provided, benzodiazepines and clonidine were suggested for acute crisis management. Chronic treatment options included tetrabenazine, benzodiazepines, gabapentin, and clonidine. Deep brain stimulation should be considered early in the treatment of refractory or prolonged dyskinetic crisis.
CONCLUSION
This consensus provides a foundation for understanding and managing dyskinetic crises in -RD for clinicians, caregivers, and researchers. The study emphasizes the importance of targeted parental and caregiver education, which enables early recognition and intervention, thereby potentially minimizing both short- and long-term complications. Future research should concentrate on differentiating dyskinetic crises from other neurological events and investigating potential risk factors that influence their occurrence and nature. The proposed standardized framework improves clinical management, stakeholder communication, and future -RD research.
PubMed: 38903163
DOI: 10.3389/fneur.2024.1403815 -
MedRxiv : the Preprint Server For... May 2024Deep brain stimulation is a viable and efficacious treatment option for dystonia. While the internal pallidum serves as the primary target, more recently, stimulation of...
Deep brain stimulation is a viable and efficacious treatment option for dystonia. While the internal pallidum serves as the primary target, more recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its complex surroundings have not been studied in depth. Indeed, multiple historical targets that have been used for surgical treatment of dystonia are directly adjacent to the STN. Further, multiple types of dystonia exist, and outcomes are variable, suggesting that not all types would profit maximally from the exact same target. Therefore, a thorough investigation of the neural substrates underlying effects on dystonia symptoms is warranted. Here, we analyze a multi-center cohort of isolated dystonia patients with subthalamic implantations ( = 58) and relate their stimulation sites to improvement of appendicular and cervical symptoms as well as blepharospasm. Stimulation of the ventral oral posterior nucleus of thalamus and surrounding regions was associated with improvement in cervical dystonia, while stimulation of the dorsolateral STN was associated with improvement in limb dystonia and blepharospasm. This dissociation was also evident for structural connectivity, where the cerebellothalamic, corticospinal and pallidosubthalamic tracts were associated with improvement of cervical dystonia, while hyperdirect and subthalamopallidal pathways were associated with alleviation of limb dystonia and blepharospasm. Importantly, a single well-placed electrode may reach the three optimal target sites. On the level of functional networks, improvement of limb dystonia was correlated with connectivity to the corresponding somatotopic regions in primary motor cortex, while alleviation of cervical dystonia was correlated with connectivity to the recently described 'action-mode' network that involves supplementary motor and premotor cortex. Our findings suggest that different types of dystonia symptoms are modulated via distinct networks. Namely, appendicular dystonia and blepharospasm are improved with modulation of the basal ganglia, and, in particular, the subthalamic circuitry, including projections from the primary motor cortex. In contrast, cervical dystonia was more responsive when engaging the cerebello-thalamo-cortical circuit, including direct stimulation of ventral thalamic nuclei. These findings may inform DBS targeting and image-based programming strategies for patient-specific treatment of dystonia.
PubMed: 38903109
DOI: 10.1101/2024.05.24.24307896