PRICKLE1-related early onset epileptic encephalopathy

The PRICKLE1 (Prickle Planar Cell Polarity Protein 1-MIM 608500) gene is involved in different phases of human development. The related diseases include autosomal recessive progressive myoclonus epilepsy - ataxia syndrome, neural tube defects associated with heterozygous mutations, agenesis of corpus callosum, polymicrogyria, and autistic spectrum disorder. Reported here is a young boy with a new variant (NM_153026.2:c.820G>A, p.Ala274Thr) presenting with an early infantile epileptic encephalopathy with developmental arrest

Technological, nutritional and sensory properties of pasta fortified with agro-industrial by-products: a review

Reducing food waste is a priority to move towards more sustainable food systems. Since agro-food byproducts are often rich in healthy compounds, such as fibre, phytochemicals, protein, fatty acids, vitamins and minerals, the waste valorisation could move through their transformation into ingredients useful for the formulation of functional foods. Pasta is a staple food widely consumed all over the world representing an optimal carrier for nutrients delivery. The incorporation of ingredients of a high added value obtained by agro-industrial by-products in pasta can improve its nutritional value and provides several health benefits. At the same time, the inclusion of new ingredients could modify the physical, chemical and textural properties determining the change of the organoleptic characteristics of fortified pasta, affecting its acceptability. Thus, the preparation of new pasta formulations with high nutritional properties, good technological and sensory characteristics represents a challenge for the food industry

Clinical variability at the mild end of BRAT1-related spectrum: Evidence from two families with genotype–phenotype discordance

Biallelic mutations in the BRAT1 gene, encoding BRCA1-associated ATM activator 1, result in variable phenotypes, from rigidity and multifocal seizure syndrome, lethal neonatal to neurodevelopmental disorder, and cerebellar atrophy with or without seizures, without obvious genotype-phenotype associations. We describe two families at the mildest end of the spectrum, differing in clinical presentation despite a common genotype at the BRAT1 locus. Two siblings displayed nonprogressive congenital ataxia and shrunken cerebellum on magnetic resonance imaging. A third unrelated patient showed normal neurodevelopment, adolescence-onset seizures, and ataxia, shrunken cerebellum, and ultrastructural abnormalities on skin biopsy, representing the mildest form of NEDCAS hitherto described. Exome sequencing identified the c.638dup and the novel c.1395G>A BRAT1 variants, the latter causing exon 10 skippings. The p53-MCL test revealed normal ATM kinase activity. Our findings broaden the allelic and clinical spectrum of BRAT1-related disease, which should be suspected in presence of nonprogressive cerebellar signs, even without a neurodevelopmental disorder

The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons.

Midbrain dopaminergic (mDA) neurons are diverse in their projection targets, effect on behavior, and susceptibility to neurodegeneration. Little is known about the molecular mechanisms establishing this diversity during development. We show that the transcription factor BCL11A is expressed in a subset of mDA neurons in the developing and adult murine brain and in a subpopulation of pluripotent-stem-cell-derived human mDA neurons. By combining intersectional labeling and viral-mediated tracing, we demonstrate that Bcl11a-expressing mDA neurons form a highly specific subcircuit within the murine dopaminergic system. In the substantia nigra, the Bcl11a-expressing mDA subset is particularly vulnerable to neurodegeneration upon α-synuclein overexpression or oxidative stress. Inactivation of Bcl11a in murine mDA neurons increases this susceptibility further, alters the distribution of mDA neurons, and results in deficits in skilled motor behavior. In summary, BCL11A defines mDA subpopulations with highly distinctive characteristics and is required for establishing and maintaining their normal physiology

Whole mitochondrial genome sequencing provides new insights into the phylogeography of loggerhead turtles (Caretta caretta) in the Mediterranean Sea

Population structure and phylogeography of the loggerhead sea turtle (Caretta caretta) have so far been assessed mainly by mitochondrial DNA (mtDNA) single-gene sequencing studies. However, phylogenetic relationships amongst matrilines, genetic characterisation of rookeries and mixed-stock analyses have suffered from the limited resolution obtained by comparison of relatively short sequences such as from the mtDNA control region. Whole mitogenome sequencing can significantly improve population genetics, particularly in marine organisms showing female natal philopatry. Despite mitogenomics becoming increasingly common in biodiversity monitoring and conservation, only a few complete mitogenomes are available for C. caretta. In this study, we sequenced the complete mtDNA of 61 loggerhead turtles sampled between 2008 and 2021 along the Italian coastline and central Mediterranean Sea. We assigned complete mtDNA haplotypes to dead embryos and bycatch samples, and introduced a first nomenclature for loggerhead mitogenomes. Analysis of mtDNA diversity, Maximum Parsimony and Bayesian phylogenetic reconstruction allowed improved resolution of lineages with respect to studies reporting on partial mtDNA control region sequence comparisons, and we were able to further inform previous analyses on loggerhead ancestry based on control region haplogroups. Overall, whole mitogenome analysis has potential for considerable improvement of evolutionary history and phylogeographic investigations as well as mixed-stock surveys of loggerhead turtles

Development and characterization of phytosterol-enriched oil microcapsules for foodstuff application

Phytosterols are lipophilic compounds contained in plants and have several biological activities. The use of phytosterols in food fortification is hampered due to their high melting temperature, chalky taste, and low solubility in an aqueous system. Also, phytosterols are easily oxidized and are poorly absorbed by the human body. Formulation engineering coupled with microencapsulation could be used to overcome these problems. The aim of this study was to investigate the feasibility of encapsulating soybean oil enriched with phytosterols by spray-drying using ternary mixtures of health-promoting ingredients, whey protein isolate (WPI), inulin, and chitosan as carrier agents. The effect of different formulations and spray-drying conditions on the microencapsules properties, encapsulation efficiency, surface oil content, and oxidation stability were studied. It was found that spherical WPI-inulin-chitosan phytosterol-enriched soybean oil microcapsules with an average size below 50 μm could be produced with good encapsulation efficiency (85%), acceptable level of surface oil (11%), and water activity (0.2–0.4) that meet industrial requirements. However, the microcapsules showed very low oxidation stability with peroxide values reaching 101.7 meq O2/kg of oil just after production, and further investigations and optimization are required before any industrial application of this encapsulated system

A model of collaboration: the Academic Practice Council.

If the profession of nursing is to survive in the changing health care delivery system, new models of collaboration between nursing education and nursing practice must be developed. Nursing is both an academic discipline and a practice profession. The historic dissonance between education and practice has never served the profession of nursing; the pressing challenge is to blend one with the other now. In an effort to respond to the demands of the discipline and profession of nursing, an academic institution and a health care delivery system developed a model of interagency collaboration. This article addresses historical perspectives, and evolution, structure, activities, evaluation, and future plans to the Academic Practice Council

The "Time and Change" test: An appropriate method to detect cognitive decline in the elderly

The Time and Change (T&C) test is an easy and time-saving test validated for the detection of dementia. Our aim was to determine how geriatric features like depression, disability, and comorbidity are able to influence the result of the T&C and, consequently, to decide whether it could be a reliable screening test for cognitive impairment in the elderly. A total of 220 participants (mean age = 75.8 +/- 9.6 years, 63.7% females) underwent the T&C, Mini-Mental State Examination, and the Clock Drawing Test; Activities of Daily Living, Instrumental Activities of Daily Living, comorbidity, and depression were also evaluated. Time and Change-positive participants were older, had poorer cognitive tests, and had higher levels of disability and comorbidity than participants testing negative. Multivariate analysis showed that cognitive impairment and comorbidity were the only features that influenced the T&C, regardless of age, education, disability, and depression. We conclude that the T&C should be implemented in primary care because it quickly identifies elderly patients with cognitive impairment who need a more accurate evaluation

Specificity and total positive rate of head-up, tilt testing potentiated with sublingual nitroglycerin in older patients with unexplained syncope.

The aim of this study was to assess the specificity and total positive rate of head-up tilt testing (HUTT) potentiated with sublingual nitroglycerin in detecting the vasovagal origin of unexplained syncope in the elderly, since the diagnostic value of this non-invasive test has not yet been proven in this age group. In a period of 3 years, 128 elderly patients (mean age 71.6 +/-5.1 years, 50% males) with syncope of unknown origin, and 101 control subjects matched for age and gender were tilted upright to 60 degrees for 45 minutes. If syncope did not occur, sublingual nitroglycerin (0.4 mg) was administered, and observation Was continued for 20 minutes. The positive response was defined as the reproduction of syncope or pre-syncope according to VASIS definition. During the unmedicated phase, syncope occurred in 26 patients (20.3%) and in no members of the control group. After nitroglycerin, 53 patients (41.4%) and 2 control subjects (2%) displayed syncope. The total positive rate of the test Was 61.8% With a specificity of 98.0%. In conclusion, HUTT potentiated with sublingual nitroglycerin provides an adequate specificity and total positive rate in old patients with unexplained syncope; therefore it can be proposed as a useful diagnostic tool to detect the vasovagal origin of syncope not only in middle but also in advanced age