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Purpose To understand the role of the mitochondrial oxodicarboxylate carrier (SLC25A21) in the development of spinal muscular atrophy-like disease. Methods We identified a novel pathogenic variant in a patient by whole-exome sequencing. The pathogenicity of the mutation was studied by transport assays, computer modeling, followed by targeted metabolic testing and in vitro studies in human fibroblasts and neurons. Results The patient carries a homozygous pathogenic variant c.695A>G; p.(Lys232Arg) in the SLC25A21 gene, encoding the mitochondrial oxodicarboxylate carrier, and developed spinal muscular atrophy and mitochondrial myopathy. Transport assays show that the mutation renders SLC25A21 dysfunctional and 2-oxoadipate cannot be imported into the mitochondrial matrix. Computer models of central metabolism predicted that impaired transport of oxodicarboxylate disrupts the pathways of lysine and tryptophan degradation, and causes accumulation of 2-oxoadipate, pipecolic acid, and quinolinic acid, which was confirmed in the patient’s urine by targeted metabolomics. Exposure to 2-oxoadipate and quinolinic acid decreased the level of mitochondrial complexes in neuronal cells (SH-SY5Y) and induced apoptosis. Conclusion Mitochondrial oxodicarboxylate carrier deficiency leads to mitochondrial dysfunction and the accumulation of oxoadipate and quinolinic acid, which in turn cause toxicity in spinal motor neurons leading to spinal muscular atrophy–like disease.

Aim  To describe a spectrum of intracerebral large artery disease in Aicardi–Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1. Method  We used clinical and radiological description and molecular analysis. Results  Five individuals (three males, two females) were identified as having biallelic mutations in SAMHD1 and a cerebral arteriopathy in association with peripheral vessel involvement resulting in chilblains and ischaemic ulceration. The cerebral vasculopathy was primarily occlusive in three patients (with terminal carotid occlusion and basal collaterals reminiscent of moyamoya syndrome) and aneurysmal in two. Three of the five patients experienced intracerebral haemorrhage, which was fatal in two individuals. Post‐mortem examination of one patient suggested that the arteriopathy was inflammatory in origin. Interpretation  Mutations in SAMHD1 are associated with a cerebral vasculopathy which is likely to have an inflammatory aetiology. A similar disease has not been observed in patients with mutations in AGS1 to AGS4, suggesting a particular role for SAMHD1 in vascular homeostasis. Our report raises important questions about the management of patients with mutations in SAMHD1.

Focal status epilepticus in POLG ‐related mitochondrial disease is highly refractory to pharmacological agents, including general anesthesia. We report the challenges in managing a previously healthy teenager who presented with de novo epilepsia partialis continua and metabolic stroke resulting from the homozygous p.Ala467Thr POLG mutation, the most common pathogenic variant identified in the Caucasian population. We applied transcranial direct current stimulation ( tDCS ; 2 mA; 20 min) daily as an adjunctive therapy because her focal seizures failed to respond to five antiepileptic drugs at maximal doses. The electrical and clinical seizures stopped after 3 days of tDCS . The second course of tDCS was administered for 14 days when the focal seizures re‐emerged a month later. The patient tolerated the procedure well. Following 4 months of hospitalization and prolonged community rehabilitation, our patient has now returned to full‐time education with support, and there is no report of cognitive deficit. We have demonstrated the safety and efficacy of tDCS in treating refractory focal motor seizures caused by mitochondrial disease.

The test will require your complete and undivided attention for this two hour period, something most of us are not accustomed to. [...] the challenge is just not being good in computers... the real challenge is to be focused, concentrated and quick while answering the questions on a computer.

Waste recycling is one of the key aspects in current day studies to boost the country’s circular economy. Recycling wood from construction and demolished structures and combining it with plastics forms wood-polymer composites (WPC) which have a very wide scope of usage. Such recycled composites have very low environmental impact in terms of abiotic potential, global warming potential, and greenhouse potential. Processing of WPCs can be easily done with predetermined strength values that correspond to its end application. Yet, the usage of conventional polymer composite manufacturing techniques such as injection molding and extrusion has very limited scope. Many rheological characterization techniques are being followed to evaluate the influence of formulation and process parameters over the quality of final WPCs. It will be very much interesting to carry out a review on the material formulation of WPCs and additives used. Manufacturing of wood composites can also be made by using bio-based adhesives such as lignin, tannin, and so on. Nuances in complete replacement of synthetic adhesives as bio-based adhesives are also discussed by various researchers which can be done only by complete understanding of formulating factors of bio-based adhesives. Wood composites play a significant role in many non-structural and structural applications such as construction, floorings, windows, and door panels. The current review focuses on the processing of WPCs along with additives such as wood flour and various properties of WPCs such as mechanical, structural, and morphological properties. Applications of wood-based composites in various sectors such as automotive, marine, defense, and structural applications are also highlighted in this review.

This work is intended to understand the variation of pressure and flow at the pump inlet of liquid rocket engine. The opening and closure of the valve upstream of the pump features complex phenomenon. The opening and  closing of the valve cause pressure and flow variations at the pump inlet which may lead to combustion instabilities in combustion chamber of engine, hydraulic transients in feedlines, and off-design operation of turbo-pumps which are fundamental to the efficient testing and operation of engine. A numerical model to predict the pressure and flow transients across a control valve for different rate of opening in fluid feed systems has been developed using first-order finite difference technique. In case of flow in pipes, the velocity and pressure is governed by momentum and continuity equations. A computer code for the prediction of fluid transients is developed based on method of characteristics for one-dimensional fluid flow in pipelines and compared with test data for validation. The control valve is considered to be in-line with the feed line and modeled based on the valve coefficient vs. percent opening of valve. This model can subsequently be used to predict the effect of opening/closing time of the valve on pressure surges across the control valve and corresponding flow rate in the feedline for different opening of the valve.

Vigna stipulacea (Lam.) Kuntz., commonly known as Minni payaru is an underutilized legume species and has a great potential to be utilized as food crop. To evaluate and select the best germplasm to be harnessed in the breeding programme, we assessed the genetic diversity of V . stipulacea (94 accessions) conserved in the Indian National Genebank, based on morphological traits and microsatellite markers. Significant variation was recorded for the morphological traits studied. Euclidean distance using UPGMA method grouped all accessions into two major clusters. Accessions were identified for key agronomic traits such as, early flowering (IC331436, IC251436, IC331437); long peduncle length (IC553518, IC550531, IC553557, IC553540, IC550532, IC553564); and more number of seeds per pod (IC553529, IC622865, IC622867, IC553528). To analyse the genetic diversity among the germplasm 33 SSR primers were used anda total of 116 alleles were detected. The number of alleles varied from two to seven, with an average of 3.52 per loci. The polymorphic information content values varied from 0.20 to 0.74, with a mean of 0.40. The high number of alleles per locus and the allelic diversity in the studied germplasm indicated a relatively wider genetic base of V . stipulacea . Phylogenetic analysis clustered accessions into seven clades. Population structure analysis grouped them into five genetic groups, which were partly supported by PCoA and phylogenetic tree. Besides, PCoA and AMOVA also decoded high genetic diversity among the V . stipulacea accessions. Thus, morphological and microsatellite markers distinguished V . stipulacea accessions and assessed their genetic diversity efficiently. The identified promising accessions can be utilized in Vigna improvement programme through introgression breeding and/or can be used for domestication and enhanced utilization of V . stipulacea .

The All India Difficult Airway Association (AIDAA) guidelines for management of the unanticipated difficult airway in adults provide a structured, stepwise approach to manage unanticipated difficulty during tracheal intubation in adults. They have been developed based on the available evidence; wherever robust evidence was lacking, or to suit the needs and situation in India, recommendations were arrived at by consensus opinion of airway experts, incorporating the responses to a questionnaire sent to members of the AIDAA and the Indian Society of Anaesthesiologists. We recommend optimum pre-oxygenation and nasal insufflation of 15 L/min oxygen during apnoea in all patients, and calling for help if the initial attempt at intubation is unsuccessful. Transnasal humidified rapid insufflations of oxygen at 70 L/min (transnasal humidified rapid insufflation ventilatory exchange) should be used when available. We recommend no more than three attempts at tracheal intubation and two attempts at supraglottic airway device (SAD) insertion if intubation fails, provided oxygen saturation remains ≥ 95%. Intubation should be confirmed by capnography. Blind tracheal intubation through the SAD is not recommended. If SAD insertion fails, one final attempt at mask ventilation should be tried after ensuring neuromuscular blockade using the optimal technique for mask ventilation. Failure to intubate the trachea as well as an inability to ventilate the lungs by face mask and SAD constitutes 'complete ventilation failure', and emergency cricothyroidotomy should be performed. Patient counselling, documentation and standard reporting of the airway difficulty using a 'difficult airway alert form' must be done. In addition, the AIDAA provides suggestions for the contents of a difficult airway cart.