Combinations of Service Use Types of People With Early Cognitive Disorders

Objectives Understanding which persons most likely use particular combinations of service types is important as this could lead to a better understanding of care pathways. The aim of this study is to identify combinations of service use within a sample of community-dwelling people with mild cognitive impairment (MCI) and dementia and identify factors related to these service use combinations. Methods A latent class analysis performed at baseline on a merged dataset (n = 530) was used to classify care recipients based on following service use types: general practitioner visits, physiotherapist visits, hospital outpatient specialist visits, emergency room visits, hospital inpatient visits with stay over, day care visits, use of domestic homecare, use of personal homecare, and informal care on (instrumental) activities of daily living. Multinomial logistic regression was performed to identify factors associated with service use combinations using clinical characteristics of the care recipient and demographic characteristics of the care recipient and caregiver. Results Three service use classes were identified; a formal homecare class (10% of participants), an informal care class (46% of participants), and a low user class (44% of participants). Factors increasing the likelihood of being in the formal homecare class compared with the low service use class included a diagnosis of MCI or dementia, activities of daily living impairment, older age of the care recipient, and care recipient not living together with the caregiver. Conclusions Besides a diagnosis of MCI or dementia, other factors (activities of daily living impairment, age, and living situation) were associated with service use. We recommend using these factors alongside the diagnostic label for care indication

De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus

Subcellular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endosomal-lysosomal pathway remains largely unclear besides being involved in protein glycosylation. DHDDS encodes for the catalytic subunit (DHDDS) of the enzyme cis-prenyltransferase (cis-PTase), involved in dolichol biosynthesis and dolichol-dependent protein glycosylation in the endoplasmic reticulum. An autosomal recessive form of retinitis pigmentosa (retinitis pigmentosa 59) has been associated with a recurrent DHDDS variant. Moreover, two recurring de novo substitutions were detected in a few cases presenting with neurodevelopmental disorder, epilepsy, and movement disorder. We evaluated a large cohort of patients (n=25) with de novo pathogenic variants in DHDDS and provided the first systematic description of the clinical features and long-term outcome of this new neurodevelopmental and neurodegenerative disorder. The functional impact of the identified variants was explored by yeast complementation system and enzymatic assay. Patients presented during infancy or childhood with a variable association of neurodevelopmental disorder, generalized epilepsy, action myoclonus/cortical tremor, and ataxia. Later in the disease course they experienced a slow neurological decline with the emergence of hyperkinetic and/or hypokinetic movement disorder, cognitive deterioration, and psychiatric disturbances. Storage of lipidic material and altered lysosomes were detected in myelinated fibers and fibroblasts, suggesting a dysfunction of the lysosomal enzymatic scavenger machinery. Serum glycoprotein hypoglycosylation was not detected and, in contrast to retinitis pigmentosa and other congenital disorders of glycosylation involving dolichol metabolism, the urinary dolichol D18/D19 ratio was normal. Mapping the disease-causing variants into the protein structure revealed that most of them clustered around the active site of the DHDDS subunit. Functional studies using yeast complementation assay and in vitro activity measurements confirmed that these changes affected the catalytic activity of the cis-PTase and showed growth defect in yeast complementation system as compared with the wild-type enzyme and retinitis pigmentosa-associated protein. In conclusion, we characterized a distinctive neurodegenerative disorder due to de novo DHDDS variants, which clinically belongs to the spectrum of genetic progressive encephalopathies with myoclonus. Clinical and biochemical data from this cohort depicted a condition at the intersection of congenital disorders of glycosylation and inherited storage diseases with several features akin to of progressive myoclonus epilepsy such as neuronal ceroid lipofuscinosis and other lysosomal disorders

Correction: Involvement of phenoloxidase in browning during grinding of Tenebrio molitor larvae.

[This corrects the article DOI: 10.1371/journal.pone.0189685.]

Efficacy of a combined physical and occupational therapy intervention in patients with subacute neuralgic amyotrophy:A pilot study

<p>BACKGROUND: Neuralgic Amyotrophy (NA) is characterized by neuropathic pain, subsequent patchy paresis and possible sensory loss in the upper extremity. Many patients experience difficulties in performing activities of daily life and are unable to resume work. We developed a combined physical- and occupational therapy program for patients recovering from NA.</p><p>OBJECTIVE: Evaluation of the effectiveness of a multidisciplinary intervention program for patients with subacute NA.</p><p>METHODS: We performed a within subject proof-of-principle pilot study in eight patients with subacute NA. Patients followed 8 hours of physical and 8 hours of occupational therapy spread over a 16-week period. Primary outcome measures: The Canadian Occupational Performance Measure (COPM) and Shoulder Rating Questionnaire (SRQ). Secondary outcome measure: Disability of Arm Shoulder and Hand (DASH).</p><p>RESULTS: Improvements (mean (95% CI)) were found in the performance and satisfaction scores of the COPM +2.3 (0.9-3.7) and +1.4 (0.4-2.4) points, respectively and the SRQ +14.8 (7.4-22.0) points. The majority of patients (6 out of 8) also demonstrated improvements in the DASH.</p><p>CONCLUSION: The proposed physical and occupational therapy program, may be effective for patients with subacute NA, as demonstrated by improvements in activity, performance and participation.</p>

Effect of pH on specific oxidative enzyme activity (nmol mL^-1s^-1) of enzyme extracts from the larvae of <i>T</i>. <i>molitor</i> (A), <i>A</i>. <i>diaperinus</i> (B) and <i>H</i>. <i>illucens</i> (C).

<p>L-DOPA (red), L-DOPA+H₂O₂ (orange), L-dopamine (light blue), L-tyrosine (green) or ABTS (purple) were used as substrates and buffer (dark blue) as negative control (n = 2, error bars represent absolute deviation).</p

Color formation directly after grinding in MilliQ water and centrifugation of <i>T</i>. <i>molitor</i>, <i>A</i>. <i>diaperinus</i> and <i>H</i>. <i>illucens</i>.

<p>Color formation directly after grinding in MilliQ water and centrifugation of <i>T</i>. <i>molitor</i>, <i>A</i>. <i>diaperinus</i> and <i>H</i>. <i>illucens</i>.</p

AEC fractionation pattern (black line) at 214 nm for <i>T</i>. <i>molitor</i> (A) and <i>A</i>. <i>diaperinus</i> (B).

<p>The panels also report the increase of absorbance at 520 nm per day for each fraction, when assayed with L-DOPA (red) and L-tyrosine (green) (n = 2), error bars represent absolute deviation).</p

Overview of reactions between different enzymes and substrates which occur (+).

<p>Overview of reactions between different enzymes and substrates which occur (+).</p

Reaction products formed after incubation of pooled fractions T_I-V from <i>T</i>. <i>molitor</i> with substrates L-tyrosine and L-DOPA; + formed, × not found, = substrate constant, − substrates decreases, n/a not applicable.

<p>Reaction products formed after incubation of pooled fractions T_I-V from <i>T</i>. <i>molitor</i> with substrates L-tyrosine and L-DOPA; + formed, × not found, = substrate constant, − substrates decreases, n/a not applicable.</p