Mentum: Encrypted, Knowledge-Based Modalities

Unified low-energy communication have led to many theoretical advances, including linked lists and wide-area networks. Even though such a hypothesis at first glance seems unexpected, it fell in line with our expectations. In our research, we prove the development of von Neumann machines, demonstrates the intuitive importance of networking. Here, we examine how robots can be applied to the extensive unification of Byzantine fault tolerance and superblocks

Implementation of the StandingTall programme to prevent falls in older people:a process evaluation protocol

INTRODUCTION: One in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally. METHODS AND ANALYSIS: This project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. TRIAL REGISTRATION NUMBER: ACTRN12619001329156

Implementation of the StandingTall programme to prevent falls in older people: A process evaluation protocol

Introduction One in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally. Methods and analysis This project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months. Ethics and dissemination Ethical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. Trial registration number ACTRN12619001329156

Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy

Autosomal dominant variants in LDB3 (also known as ZASP), encoding the PDZ-LIM domain-binding factor, have been linked to a late onset phenotype of cardiomyopathy and myofibrillar myopathy in humans. However, despite knockout mice displaying a much more severe phenotype with premature death, bi-allelic variants in LDB3 have not yet been reported. Here we identify biallelic loss-of-function variants in five unrelated cardiomyopathy families by next-generation sequencing. In the first family, we identified compound heterozygous LOF variants in LDB3 in a fetus with bilateral talipes and mild left cardiac ventricular enlargement. Ultra-structural examination revealed highly irregular Z-disc formation, and RNA analysis demonstrated little/no expression of LDB3 protein with a functional C-terminal LIM domain in muscle tissue from the affected fetus. In a second family, a homozygous LDB3 nonsense variant was identified in a young girl with severe early-onset dilated cardiomyopathy with left ventricular non-compaction; the same homozygous nonsense variant was identified in a third unrelated female infant with dilated cardiomyopathy. We further identified homozygous LDB3 frameshift variants in two unrelated probands diagnosed with cardiomegaly and severely reduced left ventricular ejection fraction. Our findings demonstrate that recessive LDB3 variants can lead to an early-onset severe human phenotype of cardiomyopathy and myopathy, reminiscent of the knockout mouse phenotype, and supporting a loss of function mechanism

The clinical and genetic spectrum of autosomal-recessive TOR1A-related disorders.

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5) is a rare neurodevelopmental disorder arising from biallelic variants in TOR1A, a gene that in the heterozygous state is associated to torsion dystonia-1 (DYT1 or DYT-TOR1A), an early-onset dystonia with reduced penetrance. While 15 individuals with TOR1A-AMC5 have been reported (less than 10 in detail), a systematic investigation of the full disease-associated spectrum has not been conducted. Here, we assess the clinical, radiological and molecular characteristics of 57 individuals from 40 families with biallelic variants in TOR1A. Median age at last follow-up was 3 years (0-24 years). Most individuals presented with severe congenital flexion contractures (95%) and variable developmental delay (79%). Motor symptoms were reported in 79% and included lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism was an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Survival was 71% with higher mortality in males. Death occurred at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum (72%), foci of signal abnormality in the subcortical and periventricular white matter (55%), diffuse white matter volume loss (45%), mega cisterna magna (36%) and arachnoid cysts (27%). The molecular spectrum included 22 distinct variants, defining a mutational hotspot in the C-terminal domain of the Torsin-1A protein. Genotype-phenotype analysis revealed an association of missense variants in the 3-helix bundle domain to an attenuated phenotype, while missense variants near the Walker A/B motif as well as biallelic truncating variants were linked to early death. In summary, this systematic cross-sectional analysis of a large cohort of individuals with biallelic TOR1A variants across a wide age-range delineates the clinical and genetic spectrum of TOR1A-related autosomal-recessive disease and highlights potential predictors for disease severity and survival

Implementation of a digital exercise programme in health services to prevent falls in older people.

Background: StandingTall uses eHealth to deliver evidence-based balance and functional strength exercises. Clinical trials have demonstrated improved balance, reduced falls and fall-related injuries and high adherence. This study aimed to evaluate the implementation of StandingTall into health services in Australia and the UK.Methods:Two hundred and forty-six participants (Australia, n = 184; UK, n = 62) were recruited and encouraged to use StandingTall for 2 h/week for 6-months. A mixed-methods process evaluation assessed uptake and acceptability of StandingTall. Adherence, measured as % of prescribed dose completed, was the primary outcome.Results: The study, conducted October 2019 to September 2021 in Australia and November 2020 to April 2022 in the UK, was affected by COVID-19. Participants’ mean age was 73 ± 7 years, and 196 (81%) were female. Of 129 implementation partners (e.g. private practice clinicians, community exercise providers, community service agencies) approached, 34% (n = 44) agreed to be implementation partners. Of 41 implementation partners who referred participants, 15 (37%) referred ≥5. Participant uptake was 42% (198/469) with mean adherence over 6 months being 41 ± 39% of the prescribed dose (i.e. 39 ± 41 min/week) of exercise. At 6 months, 120 (76%) participants indicated they liked using StandingTall, 89 (56%) reported their balance improved (moderately to a great deal better) and 125 (80%) rated StandingTall as good to excellent. For ongoing sustainability, health service managers highlighted the need for additional resources.Conclusions: StandingTall faced challenges in uptake, adoption and sustainability due to COVID-19 and a lack of ongoing funding. Adherence levels were lower than the effectiveness trial, but were higher than other exercise studies. Acceptance was high, indicating promise for future implementation, provided sufficient resources and support are made available

TOXICOLOGICAL PROFILING OF METHANOLIC AND AQUEOUS EXTRACTS OF AMORPHOPHALLUS COMMUTATUS VAR. WAYANADENSIS - ENDANGERED MEDICINAL PLANT IN RODENT MODELS

Objective: Amorphophallus commutatus var. wayanadensis (ACW) is exclusive endemic of Wayanad has been used among the traditional medicinal healers of tribal communities of Wayanad for the treatment of various ailments. Our aim of the study is to evaluate the toxicity profile of ACW is by acute and sub-acute in rodents.  Methods: In acute toxicity studies, mice were orally administered of single doses of 1000 and 2000mg/kg of methanolic and aqueous extract and sub-acute toxicity studies were performed by administration of 200 and 400mg/kg orally for 28 days. Results: In acute toxicity studies, administration of methanolic and aqueous extract didn't observe any signs of mortality or toxicity upto 2000mg/kg body weight. No significant change in the physical, biochemical, hematological and histopathology analysis were observed for methanolic and aqueous extracts by sub-acute toxicity studies. Conclusion: The methanolic and aqueous extract of Amorphophallus commutatus var. wayanadensis is relatively safe for long term oral administration fulfilling the basic priority for its use in traditional medicinal therapies

The Introductory Management Course: Taking Theory Application One Step Further

Undergraduate students, particularly those with little work experience, have difficulty making the transition from the more abstract concepts found in texts and lectures to the more practical aspects of real-life situations. Case analysis is often used to increase student skills in applying theories to specific situations. A method is proposed which takes the application of theory one step further: students are required to analyze a case analyze their operation in a functioning organization. Experience has shown that this technique helps students to internalize concepts and develop a workable set of skills which they can then use in other situations

Vitamin B6 requirements of patients on chronic peritoneal dialysis

Vitamin B6 requirements of patients on chronic peritoneal dialysis. Patients with chronic renal failure often develop vitamin B6 deficiency, which is of clinical concern because the multiorgan system manifestations are similar to those of uremia. Vitamin B6 deficiency in hemodialysis patients has been previously studied, but the need for daily pyridoxine supplementation in patients on chronic peritoneal dialysis (CPD) remains unclear. Therefore, we studied a group of 11 stable patients, nine on CAPD and two CCPD, to test for vitamin B6 deficiency and to establish daily requirements. Adequacy of vitamin B6 nutrition was assessed by measurement of plasma and dialysate effluent total vitamin B6 and pyridoxal 5′-phosphate (PLP), the latter using a very sensitive modification of the tyrosine apodecarboxylase enzyme assay. After four weeks without vitamin B6 supplements on a diet containing 1.3 ± 0.2mg vitamin B6/day (7.7 ± 1.2 µmol/day), all patients had subnormal plasma PLP levels, 16 ± 3nmol/liter (nml 40 to 60), seven having a severe deficiency (≤20nmol/liter). Plasma total vitamin B6 levels (which includes non-PLP forms of the vitamin) were normal in all patients at baseline, 116 ± 29nmol/liter. Peritoneal losses were small, 8 ± 2nmol PLP/day and 545 ± 61nmol total vitamin B6/day. Supplementation with 5mg/day oral pyridoxine HCl for up to 16 weeks adequately repleted eight patients (65 ± 7nmol PLP/L), while three patients required 10mg/day to achieve normal plasma PLP levels. During three episodes of peritonitis, dialysate losses of PLP did not increase. These data indicate that in these CPD patients: (1) dietary intake of vitamin B6 is inadequate to prevent significant deficiency; (2) low plasma PLP levels may be caused by impaired phosphorylation of precursor forms or increased degradation of PLP, not by the negligible losses into peritoneal dialysate; and (3) 10mg of daily oral pyridoxine hydrochloride supplementation restores plasma PLP levels to normal and is the recommended dose for these patients