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1.
Vet Sci ; 11(3)2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38535839

ABSTRACT

Paratuberculosis (PTB) and tuberculosis (TB) are two mycobacterial diseases with a severe economic and health impact on domestic ruminants. The ante mortem diagnosis of PTB is hampered, among other factors, by the limited sensitivity of all the available diagnostic techniques. Since TB-infected goats subjected to the comparative intradermal tuberculin test (CITT) may experience a booster effect on their antibody titer and a potential enhancement to the sensitivity of humoral techniques for tuberculosis, in the present study we aimed to evaluate this diagnostic strategy on the humoral diagnosis of PTB in serum and milk samples collected from a caprine herd that was TB free and PTB infected. The results from 120 goats indicated a significant increase (p < 0.001) in the quantitative response detected using an ELISA technique, conducted using serum and milk samples taken 15 and 30 days after performing a CITT (day 0 of the study); although, it did not translate into a significant increase in the number of reactors during any of the testing events (0, 3,15, 30 and 60 days post-CITT). Additionally, the number of ELISA-positive animals was higher for the serum versus the milk samples at both 15 and 30 days post-CITT. The increase in the quantitative ELISA result suggested a diagnostic strategy that maximizes ELISA sensitivity, mainly using serum samples, in PTB-infected herds; although, it may depend on individual differences and the interpretation criteria.

2.
Heliyon ; 10(2): e24552, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38312573

ABSTRACT

Oat (Avena sativa) is a cereal grain rich in fibers, proteins, vitamins and minerals. Oats have been linked to several health benefits, such as lowering blood cholesterol levels, counteracting cardiovascular disease and regulating blood sugar levels. This study aimed to characterize two new oat lines with high ß-glucan content emanating from ethyl methyl sulphonate mutagenesis on the Lantmännen elite variety Belinda. Two of the mutated lines, and the mother variety Belinda, were profiled for ß-glucan, arabinoxylan, total dietary fiber and starch composition. In addition, total lipid and protein content, amino acid composition and ß-glucan molecular weights were analyzed. The high levels of ß-glucan resulted in a significant increase in total dietary fiber, but no correlation could be established between higher or lower levels of the assayed macromolecules, i.e., between arabinoxylan-, starch-, lipid- or protein levels in the mutated lines compared to the reference. The results indicate separate biosynthetic pathways for ß-glucans and other macromolecules and an independent regulation of the different polysaccharides studied. Therefore, ethyl methyl sulphonate mutagenesis can be used to increase levels of multiple macromolecules in the same line.

3.
BMC Health Serv Res ; 24(1): 152, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38291412

ABSTRACT

BACKGROUND: The number of patients depending on home mechanical ventilation (HMV) has increased substantially in Germany in recent years. These patients receive long-term care in different nursing facilities (nursing home, shared living community, private home). However, there are limited data available on the quality of care of HMV patients. The aim of the OVER-BEAS project was to identify quality indicators (QIs) of HMV care using an evidence-based approach. METHODS: A multidisciplinary board consisting of professionals and experts of HMV provision compiled a set of QIs between March and September 2019. In a structured, transparent process a set of QIs covering structures, processes and outcome of HMV patient's care were proposed and evaluated based on the best available evidence. QIs were defined as relevant, reliable and valid measurements of the quality of HMV care and furthermore to be comprehensive and applicable in practice. RESULTS: The experts proposed 40 QIs and consented a final set of 26 QIs. Based on the final set, questionnaires to document the QIs were developed: (1) to assess the quality and describe the structure of the nursing facility; and (2) to gather information on patient-related processes and outcomes. The feasibility of the questionnaires was tested in 5 nursing facilities treating HMV patients. The remarks from the nursing specialists were categorised in three groups: (1) term missing accuracy, (2) problem of understanding, and (3) not documented or documented elsewhere. Mean documentation time by the nursing specialists for one patient was 15 min. Based on this feedback, the questionnaires were finalised. CONCLUSIONS: We proposed a set of QIs relating to long-term HMV care and developed two questionnaires to collect this information. In a pilot study, we found the set of questionnaires to be feasible in assessing the quality of HMV care according to current evidence. The development of standardised evidence-based QIs to evaluate HMV care is a step towards implementing a standardised quality assurance program to document the quality of care of HMV patients.


Subject(s)
Quality Indicators, Health Care , Respiration, Artificial , Humans , Pilot Projects , Long-Term Care , Nursing Homes
4.
Front Public Health ; 11: 1238144, 2023.
Article in English | MEDLINE | ID: mdl-37732100

ABSTRACT

Background: At the beginning of the pandemic in 2020, healthcare assistants in general practices were confronted with numerous new challenges. The aim of the study was to investigate the stress factors of healthcare assistants in March/April 2020 as well as in the further course of the pandemic in 2020. Methods: From August to December 2020, 6,300 randomly selected healthcare assistants in four German states were invited to participate in the study. We performed a mixed methods design using semi-structured telephone interviews and a cross-sectional survey with quantitative and open questions. The feeling of psychological burden was assessed on a 6-point likert-scale. We defined stress factors and categorized them in patient, non-patient and organizational stress factors. The results of the three data sets were compared within a triangulation protocol. Results: One thousand two hundred seventy-four surveys were analyzed and 28 interviews with 34 healthcare assistants were conducted. Of the participants, 29.5% reported experiences of a very high or high feeling of psychological burden in March/April 2020. Worries about the patients' health and an uncertainty around the new disease were among the patient-related stress factors. Non-patient-related stress factors were problems with the compatibility of work and family, and the fear of infecting relatives with COVID-19. Organizational efforts and dissatisfaction with governmental pandemic management were reported as organizational stress factors. Support from the employer and team cohesion were considered as important resources. Discussion: It is necessary to reduce stress among healthcare assistants by improving their working conditions and to strengthen their resilience to ensure primary healthcare delivery in future health crises.


Subject(s)
COVID-19 , Family Practice , Humans , COVID-19/epidemiology , Pandemics , Cross-Sectional Studies , Allied Health Personnel
5.
Res Vet Sci ; 159: 72-80, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37087923

ABSTRACT

Persistence of bovine tuberculosis (bTB) in cattle herd remains a major challenge in disease elimination due to the ineffectual removal of all infected animals in a bTB breakdown. Characterization of herds with a higher probability of experiencing further bTB breakdowns can help to implement specific risk-based policies for disease control and eradication. Here, our aim was to identify herd- and breakdown-level risk factors in bTB infected herds in Castilla y Leon, Spain, associated with a decreased time to recurrence and an increased risk of recurrence using a mixed effects Cox proportional hazards model and a multivariable logistic regression model, respectively. Results revealed that location (province), herd size and number of incoming animals/contacts were good predictors of a decreased time to bTB recurrence and an increased risk of becoming a recurrent herd. Additionally, the duration of the previous outbreak and the number of IFN-γ herd-tests applied in it were associated with increased odds of (an early) recurrence. Risk factors identified here can be used for early identification of herds in which bTB eradication may be more challenging and that should thus be subjected to increased control efforts. The characterization of high-risk herds may help to minimize the risk of reinfection and emphasize early detection and removal of bTB positive animals in the herd.


Subject(s)
Cattle Diseases , Tuberculosis, Bovine , Cattle , Animals , Tuberculosis, Bovine/epidemiology , Tuberculosis, Bovine/diagnosis , Spain/epidemiology , Risk Factors , Logistic Models , Cattle Diseases/epidemiology
7.
Dev Med Child Neurol ; 65(2): 207-214, 2023 02.
Article in English | MEDLINE | ID: mdl-35723607

ABSTRACT

AIM: To evaluate early dystonic features in children and adolescents with SGCE-myoclonus-dystonia. METHOD: In this cross-sectional study, 49 patients (26 females and 23 males) with SGCE-myoclonus-dystonia (aged 15y 2mo, SD 12y) with childhood-onset (2y 10mo, SD 1y 10mo) dystonia were examined using a standardized video recorded protocol. Dystonia was rated using the Writer's Cramp and Gait Dystonia Rating Scales. Disability and impairment for handwriting and walking were also rated. RESULTS: Dystonia was present at rest (n=1), posture (n=12), and during specific motor tasks (n=45) such as writing (n=35), walking (n=23), and running (n=20). Most children reported disability while performing these tasks. Early dystonic patterns were identified for writer's cramp and gait dystonia, the latter named the 'circular shaking leg', 'dragging leg', and 'hobby-horse gait' patterns. Sensory tricks were used by five and eight children to improve dystonia and myoclonus during writing and walking respectively. The rating scales accurately measured the severity of action dystonia and correlated with self-reported disability. INTERPRETATION: Children with SGCE-myoclonus-dystonia show recognizable dystonic patterns and sensory tricks that may lead to an early diagnosis and timely therapeutic approach. Isolated writer's cramp is a key feature in childhood and should prompt SCGE analysis. The proposed action dystonia scales could be used to monitor disease course and response to treatment. WHAT THIS PAPER ADDS: Most children with SGCE-myoclonus-dystonia got writer's cramp and had walking and running dystonia. Writer's cramp was a key feature and should prompt SGCE genetic investigation. 'Circular shaking leg', 'dragging leg', and 'hobby-horse gait' were recognized as early gait patterns. Children used sensory tricks to improve myoclonus and dystonia, suggesting common pathophysiological mechanisms. Action dystonia rating scales are valid tools to assess severity in children.


Subject(s)
Dystonia , Dystonic Disorders , Movement Disorders , Myoclonus , Child , Female , Humans , Male , Cross-Sectional Studies , Dystonia/diagnosis , Dystonic Disorders/diagnosis , Myoclonus/diagnosis , Myoclonus/genetics , Sarcoglycans/genetics
8.
Epilepsia ; 64(2): 443-455, 2023 02.
Article in English | MEDLINE | ID: mdl-36318112

ABSTRACT

OBJECTIVE: Mutations in the genes encoding neuronal ion channels are a common cause of Mendelian neurological diseases. We sought to identify novel de novo sequence variants in cases with early infantile epileptic phenotypes and neurodevelopmental anomalies. METHODS: Following clinical diagnosis, we performed whole exome sequencing of the index cases and their parents. Identified channel variants were expressed in Xenopus oocytes and their functional properties assessed using two-electrode voltage clamp. RESULTS: We identified novel de novo variants in KCNA6 in four unrelated individuals variably affected with neurodevelopmental disorders and seizures with onset in the first year of life. Three of the four identified mutations affect the pore-lining S6 α-helix of KV 1.6. A prominent finding of functional characterization in Xenopus oocytes was that the channel variants showed only minor effects on channel activation but slowed channel closure and shifted the voltage dependence of deactivation in a hyperpolarizing direction. Channels with a mutation affecting the S6 helix display dominant effects on channel deactivation when co-expressed with wild-type KV 1.6 or KV 1.1 subunits. SIGNIFICANCE: This is the first report of de novo nonsynonymous variants in KCNA6 associated with neurological or any clinical features. Channel variants showed a consistent effect on channel deactivation, slowing the rate of channel closure following normal activation. This specific gain-of-function feature is likely to underlie the neurological phenotype in our patients. Our data highlight KCNA6 as a novel channelopathy gene associated with early infantile epileptic phenotypes and neurodevelopmental anomalies.


Subject(s)
Epilepsy , Neurodevelopmental Disorders , Humans , Epilepsy/genetics , Mutation/genetics , Seizures/genetics , Kv1.6 Potassium Channel/genetics
9.
Rev Esp Enferm Dig ; 115(2): 80-84, 2023 02.
Article in English | MEDLINE | ID: mdl-35607929

ABSTRACT

BACKGROUND AND AIMS: Minor nonspecific gastrointestinal subepithelial lesions (usually defined by the term 'tumor') are usually associated with a malignant illness and cancer. The aim of this study was to assess anxiety-distress and carcinophobia in patients referred to specialized monographic outpatient clinics for evaluation and treatment of this type of lesion. METHODS: Prospective, multicenter, cohort study. Specific self-reported questionnaires were used to report threatening life-experiences and to assess levels of distress (The Hospital Anxiety and Depression Scale) and cancer-related worries (The Cancer Worry Scale). RESULTS: Forty participants were included and analyzed at baseline. Pathologic and borderline anxiety were detected in 13% (5/40, 95%CI: 4-27%) and 35% (14/40, 95%CI: 21-52%) of participants, respectively, whereas, cancer-related worries (moderate to very high) were observed in 48% (19/40, 95%CI: 32-64%) of participants. Pathologic global distress was identified in 25% (10/40, 95%CI: 13-42%) of subjects. Higher educational level (university studies), a lack of lifetime psychiatric comorbidity and a lack of family history of cancer were associated with less anxiety, global distress and carcinophobia. CONCLUSIONS: Almost half of the patients diagnosed with a minor nonspecific gastrointestinal subepithelial lesion presented anxiety-distress and/or carcinophobia. Specific associations with anxiety-distress reaction and fears were detected.


Subject(s)
Anxiety , Neoplasms , Humans , Cohort Studies , Prospective Studies , Anxiety/complications , Comorbidity , Depression/epidemiology , Depression/complications
10.
Rev. esp. enferm. dig ; 115(2): 80-84, 2023. tab, graf
Article in English | IBECS | ID: ibc-215607

ABSTRACT

Background and Aims: Minor nonspecific gastrointestinal subepithelial lesions (usually defined by the term ‘tumor’) are usually associated with a malignant illness and cancer. The aim of this study was to assess anxiety-distress and carcinophobia in patients referred to specialized monographic outpatient clinics for evaluation and treatment of this type of lesion. Methods: Prospective, multicenter, cohort study. Specific self-reported questionnaires were used to report threatening life-experiences and to assess levels of distress (The Hospital Anxiety and Depression Scale) and cancer-related worries (The Cancer Worry Scale). Results: Forty participants were included and analyzed at baseline. Pathologic and borderline anxiety were detected in 13% (5/40, 95%CI: 4-27%) and 35% (14/40, 95%CI: 21-52%) of participants, respectively, whereas, cancer-related worries (moderate to very high) were observed in 48% (19/40, 95%CI: 32-64%) of participants. Pathologic global distress was identified in 25% (10/40, 95%CI: 13-42%) of subjects. Higher educational level (university studies), a lack of lifetime psychiatric comorbidity and a lack of family history of cancer were associated with less anxiety, global distress and carcinophobia. Conclusions: Almost half of the patients diagnosed with a minor nonspecific gastrointestinal subepithelial lesion presented anxiety-distress and/or carcinophobia. Specific associations with anxiety-distress reaction and fears were detected (AU)


Subject(s)
Humans , Male , Female , Aged , Phobic Disorders/diagnosis , Phobic Disorders/psychology , Neoplasms/diagnosis , Neoplasms/psychology , Anxiety/psychology , Cohort Studies , Prospective Studies , Self Report
11.
Mov Disord ; 37(11): 2197-2209, 2022 11.
Article in English | MEDLINE | ID: mdl-36054588

ABSTRACT

BACKGROUND AND OBJECTIVE: The objective of this study was to better delineate the genetic landscape and key clinical characteristics of complex, early-onset, monogenic hyperkinetic movement disorders. METHODS: Patients were recruited from 14 international centers. Participating clinicians completed standardized proformas capturing demographic, clinical, and genetic data. Two pediatric movement disorder experts reviewed available video footage, classifying hyperkinetic movements according to published criteria. RESULTS: One hundred forty patients with pathogenic variants in 17 different genes (ADCY5, ATP1A3, DDC, DHPR, FOXG1, GCH1, GNAO1, KMT2B, MICU1, NKX2.1, PDE10A, PTPS, SGCE, SLC2A1, SLC6A3, SPR, and TH) were identified. In the majority, hyperkinetic movements were generalized (77%), with most patients (69%) manifesting combined motor semiologies. Parkinsonism-dystonia was characteristic of primary neurotransmitter disorders (DDC, DHPR, PTPS, SLC6A3, SPR, TH); chorea predominated in ADCY5-, ATP1A3-, FOXG1-, NKX2.1-, SLC2A1-, GNAO1-, and PDE10A-related disorders; and stereotypies were a prominent feature in FOXG1- and GNAO1-related disease. Those with generalized hyperkinetic movements had an earlier disease onset than those with focal/segmental distribution (2.5 ± 0.3 vs. 4.7 ± 0.7 years; P = 0.007). Patients with developmental delay also presented with hyperkinetic movements earlier than those with normal neurodevelopment (1.5 ± 2.9 vs. 4.7 ± 3.8 years; P < 0.001). Effective disease-specific therapies included dopaminergic agents for neurotransmitters disorders, ketogenic diet for glucose transporter deficiency, and deep brain stimulation for SGCE-, KMT2B-, and GNAO1-related hyperkinesia. CONCLUSIONS: This study highlights the complex phenotypes observed in children with genetic hyperkinetic movement disorders that can lead to diagnostic difficulty. We provide a comprehensive analysis of motor semiology to guide physicians in the genetic investigation of these patients, to facilitate early diagnosis, precision medicine treatments, and genetic counseling. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Subject(s)
Chorea , Dystonia , Dystonic Disorders , Movement Disorders , Child , Humans , Hyperkinesis , Movement Disorders/genetics , Movement Disorders/diagnosis , Dystonic Disorders/genetics , Chorea/diagnosis , Chorea/genetics , Nerve Tissue Proteins , Forkhead Transcription Factors , Phosphoric Diester Hydrolases , Sodium-Potassium-Exchanging ATPase , GTP-Binding Protein alpha Subunits, Gi-Go/genetics
12.
Dev Med Child Neurol ; 64(6): 743-752, 2022 06.
Article in English | MEDLINE | ID: mdl-34988976

ABSTRACT

AIM: To correlate clinical, radiological, and biochemical features with genetic findings in children with bilateral basal ganglia lesions of unknown aetiology, and propose a diagnostic algorithm for early recognition. METHOD: Children with basal ganglia disease were recruited in a 2-year prospective multicentre study for clinical, biomarker, and genetic studies. Radiological pattern recognition was examined by hierarchical clustering analysis. RESULTS: We identified 22 genetic conditions in 30 out of 62 paediatric patients (37 males, 25 females; mean age at onset 2y, SD 3; range 0-10y; mean age at assessment 11y, range 1-25y) through gene panels (n=11), whole-exome sequencing (n=13), and mitochondrial DNA (mtDNA) sequencing (n=6). Genetic aetiologies included mitochondrial diseases (57%), Aicardi-Goutières syndrome (20%), and monogenic causes of dystonia and/or epilepsy (17%) mimicking Leigh syndrome. Radiological abnormalities included T2-hyperintense lesions (n=26) and lesions caused by calcium or manganese mineralization (n=9). Three clusters were identified: the pallidal, neostriatal, and striatal, plus the last including mtDNA defects in the oxidative phosphorylation system with prominent brain atrophy. Mitochondrial biomarkers showed poor sensitivity and specificity in children with mitochondrial disease, whereas interferon signature was observed in all patients with patients with Aicardi-Goutières syndrome. INTERPRETATION: Combined whole-exome and mtDNA sequencing allowed the identification of several genetic conditions affecting basal ganglia metabolism. We propose a diagnostic algorithm which prioritizes early use of next-generation sequencing on the basis of three clusters of basal ganglia lesions.


Subject(s)
Basal Ganglia Diseases , Mitochondrial Diseases , Autoimmune Diseases of the Nervous System , Basal Ganglia Diseases/diagnosis , Basal Ganglia Diseases/genetics , Child , Child, Preschool , DNA, Mitochondrial , Female , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging , Male , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/genetics , Mutation , Nervous System Malformations , Prospective Studies
13.
Seizure ; 92: 155-157, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34521063

ABSTRACT

Dravet syndrome (DS) is a severe infantile-onset epilepsy syndrome featuring drug resistant epilepsy, global developmental delay and intellectual disability. In addition to ataxia and progressive crouch gait, Parkinsonism has recently been reported as characteristic in young adults with DS. We describe 5 patients out of a series of 23 patients with DS who present between 12 and 24 months of age with repetitive episodes of eyelid closure, sometimes as fast as eye blinking or flickering. Consistent lack of any EEG correlate in serial video-EEG ruled out an epileptic origin. We propose that this movement disorder, namely 'eyelid stereotypies', might be an early motor trait of SCN1A-associated DS.


Subject(s)
Epilepsies, Myoclonic , Spasms, Infantile , Epilepsies, Myoclonic/complications , Epilepsies, Myoclonic/diagnosis , Epilepsies, Myoclonic/genetics , Eyelids , Humans , Mutation , NAV1.1 Voltage-Gated Sodium Channel/genetics , Young Adult
14.
Brain ; 144(9): 2659-2669, 2021 10 22.
Article in English | MEDLINE | ID: mdl-34415322

ABSTRACT

Phosphoinositides are lipids that play a critical role in processes such as cellular signalling, ion channel activity and membrane trafficking. When mutated, several genes that encode proteins that participate in the metabolism of these lipids give rise to neurological or developmental phenotypes. PI4KA is a phosphoinositide kinase that is highly expressed in the brain and is essential for life. Here we used whole exome or genome sequencing to identify 10 unrelated patients harbouring biallelic variants in PI4KA that caused a spectrum of conditions ranging from severe global neurodevelopmental delay with hypomyelination and developmental brain abnormalities to pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Functional analyses by western blotting and immunofluorescence showed decreased PI4KA levels in the patients' fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells. In conclusion, we report a novel severe metabolic disorder caused by PI4KA malfunction, highlighting the importance of phosphoinositide signalling in human brain development and the myelin sheath.


Subject(s)
Alleles , Genetic Variation/genetics , Hereditary Central Nervous System Demyelinating Diseases/genetics , Minor Histocompatibility Antigens/genetics , Neurodevelopmental Disorders/genetics , Phosphotransferases (Alcohol Group Acceptor)/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Hereditary Central Nervous System Demyelinating Diseases/diagnostic imaging , Humans , Infant , Infant, Newborn , Leukocytes, Mononuclear/physiology , Male , Neurodevelopmental Disorders/diagnostic imaging , Pedigree
15.
Hum Mutat ; 42(10): 1215-1220, 2021 10.
Article in English | MEDLINE | ID: mdl-34212451

ABSTRACT

De novo rare damaging variants in genes involved in critical developmental pathways, notably regulation of synaptic transmission, have emerged as a frequent cause of neurodevelopmental disorders (NDD). NDD show great locus heterogeneity and for many of the associated genes, there is substantial phenotypic diversity, including epilepsy, intellectual disability, autism spectrum disorder, movement disorders, and combinations thereof. We report two unrelated patients, a young girl with early-onset refractory epilepsy, severe disability, and progressive cerebral and cerebellar atrophy, and a second girl with mild dysmorphism, global developmental delay, and moderate intellectual disability in whom trio-based whole-exome sequencing analysis uncovered de novo missense variants in CHRM1. Biochemical analyses of one of the NDD-associated variants proved that it caused a reduction in protein levels and impaired cellular trafficking. In addition, the mutated receptor showed defective activation of intracellular signaling pathways. Our data strengthen the concept that brain-reduced muscarinic signaling lowers the seizure threshold and severely impairs neurodevelopment.


Subject(s)
Autism Spectrum Disorder , Epilepsy , Intellectual Disability , Neurodevelopmental Disorders , Epilepsy/genetics , Female , Humans , Intellectual Disability/genetics , Mutation , Neurodevelopmental Disorders/genetics , Receptor, Muscarinic M1/genetics , Receptors, Muscarinic/genetics
16.
PLoS One ; 16(5): e0251289, 2021.
Article in English | MEDLINE | ID: mdl-33974636

ABSTRACT

Chiari Malformation Type 1 (CM-1) is characterized by herniation of the cerebellar tonsils below the foramen magnum and the presence of headaches and other neurologic symptoms. Cranial bone constriction is suspected to be the most common biologic mechanism leading to CM-1. However, other mechanisms may also contribute, particularly in the presence of connective tissue disorders (CTDs), such as Ehlers Danlos Syndrome (EDS). Accumulating data suggest CM-1 with connective tissue disorders (CTD+) may have a different patho-mechanism and different genetic risk factors than CM-1 without CTDs (CTD-). To identify CM-1 genetic risk variants, we performed whole exome sequencing on a single large, multiplex family from Spain and targeted sequencing on a cohort of 186 unrelated adult, Caucasian females with CM-1. Targeted sequencing captured the coding regions of 21 CM-1 and EDS candidate genes, including two genes identified in the Spanish family. Using gene burden analysis, we compared the frequency of rare, functional variants detected in CM-1 cases versus publically available ethnically-matched controls from gnomAD. A secondary analysis compared the presence of rare variants in these genes between CTD+ and CTD- CM-1 cases. In the Spanish family, rare variants co-segregated with CM-1 in COL6A5, ADGRB3 and DST. A variant in COL7A1 was present in affected and unaffected family members. In the targeted sequencing analysis, rare variants in six genes (COL7A1, COL5A2, COL6A5, COL1A2, VEGFB, FLT1) were significantly more frequent in CM-1 cases compared to public controls. In total, 47% of CM-1 cases presented with rare variants in at least one of the four significant collagen genes and 10% of cases harbored variants in multiple significant collagen genes. Moreover, 26% of CM-1 cases presented with rare variants in the COL6A5 gene. We also identified two genes (COL7A1, COL3A1) for which the burden of rare variants differed significantly between CTD+ and CTD- CM-1 cases. A higher percentage of CTD+ patients had variants in COL7A1 compared to CTD+ patients, while CTD+ patients had fewer rare variants in COL3A1 than did CTD- patients. In summary, rare variants in several collagen genes are particularly frequent in CM-1 cases and those in COL6A5 co-segregated with CM-1 in a Spanish multiplex family. COL6A5 has been previously associated with musculoskeletal phenotypes, but this is the first association with CM-1. Our findings underscore the contribution of rare genetic variants in collagen genes to CM-1, and suggest that CM-1 in the presence and absence of CTD symptoms is driven by different genes.


Subject(s)
Arnold-Chiari Malformation/genetics , Collagen Type I/genetics , Collagen Type VII/genetics , Collagen Type VI/genetics , Adult , Child , Comorbidity , Family Health , Female , Genetic Variation , Humans , Male , Exome Sequencing
17.
Mol Neurobiol ; 58(8): 3938-3952, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33886091

ABSTRACT

Myoclonus-dystonia (MD) is a rare childhood-onset movement disorder, with an estimated prevalence of about 2 per 1,000,.000 in Europe, characterized by myoclonic jerks in combination with focal or segmental dystonia. Pathogenic variants in the gene encoding ε-sarcoglycan (SGCE), a maternally imprinted gene, are the most frequent genetic cause of MD. To date, the exact role of ε-sarcoglycan and the pathogenic mechanisms that lead to MD are still unknown. However, there are more than 40 reported isoforms of human ε-sarcoglycan, pointing to a complex biology of this protein. Additionally, some of these are brain-specific isoforms, which may suggest an important role within the central nervous system. In the present review, we aim to provide an overview of the current state of knowledge of ε-sarcoglycan. We will focus on the genetic landscape of SGCE and the presence and plausible role of ε-sarcoglycan in the brain. Finally, we discuss the importance of the brain-specific isoforms and hypothesize that SGCE may play essential roles in normal synaptic functioning and their alteration will be strongly related to MD.


Subject(s)
Dystonic Disorders/genetics , Dystonic Disorders/metabolism , Sarcoglycans/genetics , Sarcoglycans/metabolism , Amino Acid Sequence , Animals , Brain/metabolism , Brain/pathology , Dystonic Disorders/diagnosis , Humans , Protein Isoforms/genetics , Protein Isoforms/metabolism , Synapses/genetics , Synapses/metabolism , Synapses/pathology
19.
Psicooncología (Pozuelo de Alarcón) ; 18(1): 11-36, 09 abr. 2021. tab, ilus
Article in Spanish | IBECS | ID: ibc-225336

ABSTRACT

Introducción: La atención psicosocial de las personas con enfermedad oncológica y la familia debe formar parte de todo modelo integral de atención que pretenda reducir el impacto vital del cáncer. Las intervenciones psicosociales han probado su eficacia en la ayuda a pacientes y familiares para afrontar las situaciones de alta complejidad psicosocial emergentes a consecuencia de un diagnóstico de cáncer. Objetivo: Definir y explicar el modelo de Atención Psicosocial del Comité Psicosocial del Instituto Catalán de Oncología (ICO) utilizando criterios de vulnerabilidad, complejidad y derivación; enmarcado y basado en los valores del ICO (centrados en las necesidades de pacientes con cáncer y sus familias). Método: El modelo que se presenta en este documento consta de cinco pilares: 1) Principios de la Práctica Psicosocial en Oncología; 2) Áreas de actuación en la Atención Psicosocial del paciente con cáncer y la familia; 3) Cribado de malestar emocional y derivación del paciente con cáncer y la familia para una atención psicooncológica específica; 4) Comité Psicosocial: (objetivos; funciones; organización; composición; disciplinas participantes; criterios de derivación y niveles de complejidad; y procedimiento); y 5) Índice de productividad. Resultados: Pacientes y familiares atendidos por el CPS mostraron mejoría estadísticamente significativa en los niveles del malestar emocional, pasando de una media inicial de 8,12/10 (EVA/ENV) a una media 6,27/10 (EVA/ENV). Asimismo, se constata que las intervenciones derivadas del comité psicosocial redujeron el porcentaje de casos iniciales de alta complejidad, pasando de un 69,3% a un 49,3% (AU)


Introduction: Psychosocial care for cancer patients and their families should be part of all comprehensive model of care that aims to reduce the life impact of cancer. Psychosocial interventions have proven to be effective in helping patients and families to cope with the highly complex psychosocial situations that arise as a result of a cancer diagnosis. Aim: To define and explain the model of Psychosocial Care in the Psychosocial Committee of the Catalan Institute of Oncology (ICO) using criteria of vulnerability, complexity and referral; framed and based on the values of the ICO (focused on patients and family’s needs). Method: The model presented in this document consists of five pillars: 1) Principles of Psychosocial Practice in Oncology; 2) Areas of action in the Psychosocial Care of the cancer patient and family; 3) Screening for emotional distress and referral of the cancer patient and family for specific psycho-oncological care; 4) PsychosocialCommittee: (objectives; functions; organization; composition; participating disciplines; referral criteria and levels of complexity; and procedure); and 5) Productivity index. Results: Patients and relatives who were attended by the CPS showed statistically significant improvement in the levels of emotional distress, going from an initial mean of 8.12 / 10 (VAS / ENV) to a mean of 6.27 / 10 (VAS / ENV). It also shows that the interventions derived from the psychosocial committee reduced the percentage of initial cases of high complexity, from 69.3% to 49.3% (AU)


Subject(s)
Humans , Psychosocial Support Systems , Neoplasms/psychology , Psycho-Oncology , Academies and Institutes , Consensus , Spain
20.
Prev Vet Med ; 189: 105307, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33676325

ABSTRACT

Post-mortem inspection (PMI) of routinely slaughtered cattle in abattoirs is an extremely valuable tool for detecting bovine tuberculosis (bTB) infected herds that can supplement active surveillance activities. However, its true performance is difficult to assess due to the multiple factors that may affect it. Here, we determined relative efficiencies in the detection of bTB-compatible lesions and probabilities of subsequent laboratory confirmation of abattoirs located in Castilla y Leon, one of the regions with the largest cattle population in Spain, between 2010 and 2017. The slaughtered animal population was split based on the results of the ante-mortem tests (reactors or non-reactors), and two generalized linear multivariable mixed models were fitted to each subpopulation to calculate the risk of lesion detection and laboratory confirmation per abattoir while accounting for the effect of potential confounding variables. Throughout the 8-year period, ∼30,000 reactors and >2.8 million non-reactor animals in the ante-mortem tests were culled in the abattoirs under study. Bovine TB compatible lesions were detected in 4,710 (16%) reactors and 828 (0.03%) non-reactor animals, of which >95% were confirmed as infected through bacteriology. The probability of disclosure of bTB-like lesions was associated with the animal subpopulation, type of source unit, the herd size, the year of slaughter, the breed and age of the animal, and/or the season of slaughter. The probabilities of detection of bTB-like lesions varied largely depending on the abattoir in both subpopulations, ranging from 603 to 3,070 per 10,000 animals for the reactors and 0.2-16.1 per 10,000 animals for the non-reactor animals. Results obtained here will help to quantify the performance of PMI in abattoirs in Castilla y Leon and the between-abattoir variability, and to identify animals at increased risk of having bTB-like lesions detected during PMI based on animal- and farm-related factors.


Subject(s)
Abattoirs , Tuberculosis, Bovine , Animals , Cattle , Mycobacterium bovis , Risk Factors , Seasons , Spain/epidemiology , Tuberculosis, Bovine/diagnosis , Tuberculosis, Bovine/epidemiology
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