Development of Time Measuring Technique to Measure the Shock Speed during the Propagation in the Free Atmosphere

In the study of wave propagation in the free atmosphere, it is desirable to obtain time measurements to an accuracy of microsecond level. An experiment has been conducted to measure the wave speed during the propagation in the free atmosphere by the present technique. Due to sudden rupture of the diaphragm for the chamber pressure of 4.2 kg/cm2 and a wave generating in a shock tube travels with subsonic speed and the measured incident wave Mach number is 0.8 which leaves the shock tube in the free atmosphere. The measured travelling time of the incident wave to travel 61.5 cm distance in the shock tube is 2200 μsec and the same technique can apply to measure the shock wave speed. Several trigger points are installed at the exit of the shock tube in the open atmosphere to measure the strength of the wave propagation. It is observed that the wave strength decreases during the wave propagation in free atmosphere. Due to spherical expansion behind the wave, the pressure across the wave decreases. A numerical simulation is also conducted on supersonic shock wave to determine the shock speed and the travelling time in the free atmosphere. The pressures across shock wave at different locations of the shock wave are determined by solving the Euler equations and the simulation results indicate that the shock speed decreases during the propagation in the free atmosphere. In both experimental and numerical results, it is observed that the strength of the wave propagation in the free atmosphere decreases continuously due to spherical expansion.  The present technique can also be used to measure the supersonic jet velocity, the velocity of bullet and any particle velocity in subsonic or supersonic ranges

Urothelial carcinoma of urinary bladder with histologic grading: a study in a tertiary care hospital, Bangladesh

Background: Urinary bladder cancer is one of the most common forms of all cancers in the world.  It is the ninth leading cause of death from cancer among men. The incidence of urinary bladder cancer in Bangladesh is increasing day by day. The aim of the study was to evaluate different clinic-pathological parameters of urothelial carcinoma of urinary bladder with the grade of the tumor. Methods: This study was a cross sectional study done over a period of two years, from March 2018 to February 2020 at the department of pathology, Dhaka medical college, Dhaka. Total 73 samples were collected, fixed overnight in 10% buffered formalin and stained with hematoxylin and eosin staining. Pathological grading was confirmed and different clinic-pathological parameters were evaluated. Results: Most of the cases (22 cases, 30.1%) were found in the fifth decade (51-60). Mean age of the patients was found to be 60.85 (±12.72) years, 58 (79.5%) cases were male and 15 (20.5%) cases were female with male to female ratio of 3.9:1. Most of the cases (49 cases, 67.1%) were smokers. Most common clinical presentation was hematuria (91.8% cases), most frequent tumor location was the lateral wall of the urinary bladder and 75.3% cases were reported as high-grade urothelial carcinoma. Conclusions: Different clinic-pathological parameters with histologic grading were evaluated in this study which may have a significant impact in epidemiology, diagnosis and assessment of biological behavior of urothelial carcinoma

Attenuated variants of Lesch-Nyhan disease

Lesch–Nyhan disease is a neurogenetic disorder caused by deficiency of the enzyme hypoxanthine–guanine phosphoribosyltransferase. The classic form of the disease is described by a characteristic syndrome that includes overproduction of uric acid, severe generalized dystonia, cognitive disability and self-injurious behaviour. In addition to the classic disease, variant forms of the disease occur wherein some clinical features are absent or unusually mild. The current studies provide the results of a prospective and multi-centre international study focusing on neurological manifestations of the largest cohort of Lesch–Nyhan disease variants evaluated to date, with 46 patients from 3 to 65 years of age coming from 34 families. All had evidence for overproduction of uric acid. Motor abnormalities were evident in 42 (91%), ranging from subtle clumsiness to severely disabling generalized dystonia. Cognitive function was affected in 31 (67%) but it was never severe. Though none exhibited self-injurious behaviours, many exhibited behaviours that were maladaptive. Only three patients had no evidence of neurological dysfunction. Our results were compared with a comprehensive review of 78 prior reports describing a total of 127 Lesch–Nyhan disease variants. Together these results define the spectrum of clinical features associated with hypoxanthine–guanine phosphoribosyltransferase deficiency. At one end of the spectrum are patients with classic Lesch–Nyhan disease and the full clinical phenotype. At the other end of the spectrum are patients with overproduction of uric acid but no apparent neurological or behavioural deficits. Inbetween are patients with varying degrees of motor, cognitive, or behavioural abnormalities. Recognition of this spectrum is valuable for understanding the pathogenesis and diagnosis of all forms of hypoxanthine–guanine phosphoribosyltransferase deficiency

Involuntary Thumb Flexion on Neurological Examination: An Unusual Form of Upper Limb Dystonia in the Faroe Islands

Background: The prevalence of dystonia varies worldwide. A prior report suggested a high prevalence of focal dystonia in the Faroese population, possibly reflecting a founder effect. During standardized neurological examination as part of an ongoing neuroepidemiologic study in the Faroe Islands, we noted an unusual phenomenon of thumb flexion during repetitive hand movements in a subset of subjects and sought to define its phenomenology. Methods: We requested commentary from a panel of dystonia experts regarding the phenomenology of the movements. These experts reviewed the videotaped neurological examination. Results: Among the experts, dystonia was the leading diagnosis. Alternate causes were considered, but deemed less likely. Discussion: Diagnosis of dystonia requires careful clinical assessment and consideration of associated features. We report a novel form of dystonia, not previously described to our knowledge, in this isolated population. Further studies of dystonia prevalence in the Faroe Islands are merited to characterize its burden in this population and its specific clinical characteristics

Reduced levels of dopamine and altered metabolism in brains of HPRT knock-out rats: a new rodent model of Lesch-Nyhan Disease

Lesch-Nyhan disease (LND) is a severe neurological disorder caused by loss-of-function mutations in the gene encoding hypoxanthine phosphoribosyltransferase (HPRT), an enzyme required for efficient recycling of purine nucleotides. Although this biochemical defect reconfigures purine metabolism and leads to elevated levels of the breakdown product urea, it remains unclear exactly how loss of HPRT activity disrupts brain function. As the rat is the preferred rodent experimental model for studying neurobiology and diseases of the brain, we used genetically-modified embryonic stem cells to generate an HPRT knock-out rat. Male HPRT-deficient rats were viable, fertile and displayed normal caged behaviour. However, metabolomic analysis revealed changes in brain biochemistry consistent with disruption of purine recycling and nucleotide metabolism. Broader changes in brain biochemistry were also indicated by increased levels of the core metabolite citrate and reduced levels of lipids and fatty acids. Targeted MS/MS analysis identified reduced levels of dopamine in the brains of HPRT-deficient animals, consistent with deficits noted previously in human LND patients and HPRT knock-out mice. The HPRT-deficient rat therefore provides a new experimental platform for future investigation of how HPRT activity and disruption of purine metabolism affects neural function and behaviour

Research Priorities in Limb and Task-Specific Dystonias

Dystonia, which causes intermittent or sustained abnormal postures and movements, can present in a focal or a generalized manner. In the limbs, focal dystonia can occur in either the upper or lower limbs and may be task-specific causing abnormal motor performance for only a specific task, such as in writer’s cramp, runner’s dystonia, or musician’s dystonia. Focal limb dystonia can be non-task-specific and may, in some circumstances, be associated with parkinsonian disorders. The true prevalence of focal limb dystonia is not known and is likely currently underestimated, leaving a knowledge gap and an opportunity for future research. The pathophysiology of focal limb dystonia shares some commonalities with other dystonias with a loss of inhibition in the central nervous system and a loss of the normal regulation of plasticity, called homeostatic plasticity. Functional imaging studies revealed abnormalities in several anatomical networks that involve the cortex, basal ganglia, and cerebellum. Further studies should focus on distinguishing cause from effect in both physiology and imaging studies to permit focus on most relevant biological correlates of dystonia. There is no specific therapy for the treatment of limb dystonia given the variability in presentation, but off-label botulinum toxin therapy is often applied to focal limb and task-specific dystonia. Various rehabilitation techniques have been applied and rehabilitation interventions may improve outcomes, but small sample size and lack of direct comparisons between methods to evaluate comparative efficacy limit conclusions. Finally, non-invasive and invasive therapeutic modalities have been explored in small studies with design limitations that do not yet clearly provide direction for larger clinical trials that could support new clinical therapies. Given these gaps in our clinical, pathophysiologic, and therapeutic knowledge, we have identified priorities for future research including: the development of diagnostic criteria for limb dystonia, more precise phenotypic characterization and innovative clinical trial design that considers clinical heterogeneity, and limited available number of participants

The Dystonia Coalition: A multicenter network for clinical and translational studies

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition is a consortium of investigators that was established to address these challenges. Since 2009, the Dystonia Coalition has encouraged collaboration by engaging 56 sites across North America, Europe, Asia, and Australia. Its emphasis on collaboration has facilitated establishment of international consensus for the definition and classification of all dystonias, diagnostic criteria for specific subtypes of dystonia, standardized evaluation strategies, development of clinimetrically sound measurement tools, and large multicenter studies that document the phenotypic heterogeneity and evolution of specific types of dystonia