A case report of children of the same family presenting with congenital cataract- as part of a rare genetic disorder—Sengers Syndrome

Sengers syndrome is a rare autosomal recessive mitochondrial disorder characterized by congenital cataract, hypertrophic cardiomyopathy, and mitochondrial myopathy. We report two siblings with known mutation for Sengers Syndrome (AGK gene mutation) who presented to us with cataract and hypertrophic cardiomyopathy. They have a deceased elder sibling who was operated for cataract earlier.     

Pangolin Indexing System: implications in forensic surveillance of large seizures

International Journal of Legal Medicine - Demand for pangolin scales in East Asia has increased dramatically in the past two decades, raising concern to the pangolin survival and bringing them to...     

Preparation and characterization of solid lipid nanoparticles-a review

In the present scenario, most of the developed and new discovered drugs are posing real challenge to the formulation scientists due to their poor aqueous solubility which in turn is responsible for poor bioavailability. One of the approach to overcome above problem is the packaging of the drug in to particulate carrier system. Among various carriers, lipid emerged as very attractive candidate because of its unique property of enhancing the bioavailability of poorly water soluble drugs. Solid lipid, one of the physical forms of lipid, is used to formulate nanoparticles, popularly known as Solid lipid nanoparticles (SLNs), as an alternative carrier system to emulsions, liposomes and polymeric micro- and nano-particles. SLNs combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews numerous production techniques for SLNs along with their advantages and disadvantages. Special attention is paid to the characterization of the SLNs by using various analytical tools. It also emphasizes on physical state of lipid (supercooled melts, different lipid modifications).     

Volumetric interpretation of protein adsorption: interfacial packing of protein adsorbed to hydrophobic surfaces from surface-saturating solution concentrations

The maximum capacity of a hydrophobic adsorbent is interpreted in terms of square or hexagonal (cubic and face-centered-cubic, FCC) interfacial packing models of adsorbed blood proteins in a way that accommodates experimental measurements by the solution-depletion method and quartz-crystal-microbalance (QCM) for the human proteins serum albumin (HSA, 66 kDa), immunoglobulin G (IgG, 160 kDa), fibrinogen (Fib, 341 kDa), and immunoglobulin M (IgM, 1000 kDa). A simple analysis shows that adsorbent capacity is capped by a fixed mass/volume (e.g. mg/mL) surface-region (interphase) concentration and not molar concentration. Nearly analytical agreement between the packing models and experiment suggests that, at surface saturation, above-mentioned proteins assemble within the interphase in a manner that approximates a well-ordered array. HSA saturates a hydrophobic adsorbent with the equivalent of a single square or hexagonally-packed layer of hydrated molecules whereas the larger proteins occupy two-or-more layers, depending on the specific protein under consideration and analytical method used to measure adsorbate mass (solution depletion or QCM). Square or hexagonal (cubic and FCC) packing models cannot be clearly distinguished by comparison to experimental data. QCM measurement of adsorbent capacity is shown to be significantly different than that measured by solution depletion for similar hydrophobic adsorbents. The underlying reason is traced to the fact that QCM measures contribution of both core protein, water of hydration, and interphase water whereas solution depletion measures only the contribution of core protein. It is further shown that thickness of the interphase directly measured by QCM systematically exceeds that inferred from solution-depletion measurements, presumably because the static model used to interpret solution depletion does not accurately capture the complexities of the viscoelastic interfacial environment probed by QCM.     

Volumetric interpretation of protein adsorption: Kinetics of protein-adsorption competition from binary solution

The standard solution-depletion method is implemented with SDS-gel electrophoresis as a multiplexing, separation-and-quantification tool to measure competition between two proteins (i and j) for adsorption to the same hydrophobic adsorbent particles (either octyl sepharose or silanized glass) immersed in binary-protein solutions. Adsorption kinetics reveals an unanticipated slow protein-size-dependent competition that controls steady-state adsorption selectivity. Two sequential pseudo-steady-state adsorption regimes (State 1 and State 2) are frequently observed depending on i, j solution concentrations. State 1 and State 2 are connected by a smooth transition, giving rise to sigmoidally-shaped adsorption-kinetic profiles with a downward inflection near 60 min of solution/adsorbent contact. Mass ratio of adsorbed i, j proteins (m_i/m_j) remains nearly constant between States 1 and 2, even though both m_i and m_j decrease in the transition between states. State 2 is shown to be stable for 24 h of continuous-adsorbent contact with stagnant solution whereas State 2 is eliminated by continuous mixing of adsorbent with solution. In sharp contrast to binary-competition results, adsorption to hydrophobic adsorbent particles from single-protein solutions (pure i or j) exhibits no detectable kinetics within the timeframe of experiment from either stagnant or continuously mixed solution, quickly achieving a single steady-state value in proportion to solution concentration. Comparison of binary competition between dissimilarly-sized protein pairs chosen to span a broad molecular-weight (MW) range demonstrates that selectivity between i and j scales with MW ratio that is proportional to protein-volume ratio (ubiquitin, Ub, MW = 10.7 kDa; human serum albumin, HSA, MW = 66.3 kDa; prothrombin, FII, 72 kDa; immunoglobulin G, IgG, MW = 160 kDa; fibrinogen, Fib, MW = 341 kDa). Results are interpreted in terms of a kinetic model of adsorption that has protein molecules rapidly diffusing into an inflating interphase that is spontaneously formed by bringing a protein solution into contact with a physical surface (State 1). State 2 follows by rearrangement of proteins within this interphase to achieve the maximum interphase concentration (dictated by energetics of interphase dehydration) within the thinnest (lowest volume) interphase possible by ejection of interphase water and initially-adsorbed proteins. Implications for understanding biocompatibility are discussed using a computational example relevant to the problem of blood–plasma coagulation.     

Early tracheostomy in closed head injuries: experience at a tertiary center in a developing country – a prospective study

Background

An important factor contributing to the high mortality in patients with severe head trauma is cerebral hypoxia. The mechanical ventilation helps both by reduction in the intracranial pressure and hypoxia. Ventilatory support is also required in these patients because of patient's inability to protect the airway, persistence of excessive secretions, and inadequacy of spontaneous ventilation. Prolonged endotracheal intubation is however associated with trauma to the larynx, trachea, and patient discomfort in addition to requirement of sedatives. Tracheostomy has been found to play an integral role in the airway management of such patients, but its timing remains subject to considerable practice variation. In a developing country like India where the intensive care facilities are scarce and rarely available, these critical patients have to be managed in high dependency cubicles in the ward, often with inadequately trained nursing staff and equipment to monitor them. An early tracheostomy in the selected group of patients based on Glasgow Coma Score(GCS) may prove to be life saving.Against this background a prospective study was contemplated to assess the role of early tracheostomy in patients with isolated closed head injury.

Methods

The series consisted of a cohort of 50 patients admitted to the surgical emergency with isolated closed head injury, that were not considered for surgery by the neuro-surgeon or shifted to ICU, but had GCS score of less than 8 and SAPS II score of more than 50. First 50 case records from January 2001 that fulfilled the criteria constituted the control group. The patients were managed as per ATLS protocol and intubated if required at any time before decision to perform tracheostomy was taken. These patients were serially assessed for GCS (worst score of the day as calculated by senior surgical resident) and SAPS scores till day 15 to chart any changes in their status of head injuries and predictive mortality. Those patients who continued to have a GCS score of <8 and SAPS score of >50 for more than 24 hours (to rule out concussion or recovery) underwent tracheostomy. All these patients were finally assessed for mortality rate and hospital stay, the statistical analysis was carried out using SPSS10 version. The final outcome (in terms of mortality) was analyzed utilizing chi-square test and p value <0.05 was considered significant.

Results

At admission both tracheostomy and non-tracheostomy groups were matched with respect to GCS score and SAPS score. The average day of tracheostomy was 2.18 ± 1.0038 days. The GCS scores on days 1, 2, 3, 4, 5, 10 between tracheostomy and non-tracheostomized group were comparable. However the difference in the GCS scores was statistically significant on day 15 being higher in the tracheostomy group.Thus early tracheostomy was observed to improve the mortality rate significantly in patients with isolated closed head injury

Conclusion

It may be concluded that early tracheostomy is beneficial in patients with isolated closed head injury which is severe enough to affect systemic physiological parameters, in terms of decreased mortality and intubation associated complications in centers where ICU care is not readily available. Also, in a selected group of patients, early tracheostomy may do away with the need for prolonged mechanical ventilation.     

‘Old Is Gold’: How Traditional Indian Dietary Practices Can Support Pediatric Diabetes Management

Nutrition is crucial for maintaining normal growth, development, and glycemic control in young people with diabetes (PwD). Undue restrictions cause nutrient deficiencies as well as poor adherence to meal plans. Widespread availability of low-cost, ultra-processed, and hyperpalatable food is further damaging. Most families struggle to find ways to provide nutritious, yet attractive, food with a low glycemic index (GI). India is one of the oldest continuous civilizations with a rich and diverse cultural and culinary heritage. Traditional dietary practices, including the centuries-old ‘Thali’ (meaning plate) concept, emphasize combinations (grains, lentils, vegetables, dairy, spices, prebiotics and probiotics, and fats) of local, seasonal, and predominantly plant-based ingredients. These practices ensure that all of the necessary food groups are provided and fit well with current evidence-based recommendations, including the International Society for Pediatric and Adolescent Diabetes (ISPAD) 2018 Guidelines. Techniques for the preparation, cooking, and preservation of food further impact the GI and nutrient availability. These practices benefit nutrient density, diet diversity, and palatability and thus improve adherence to meal plans and glycemic control. This narrative review describes the ancient wisdom, food composition, and culinary practices from across India which are still valuable today. These may be of benefit worldwide to improve glycemic control as well as quality of life, especially in PwD.     

In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease

IntroductionThe utility of [¹⁸F]FPBM [2-(2′-((dimethylamino)methyl)-4′-(3-[¹⁸F]-fluoropropoxy)phenylthio)benzenamine], a selective serotonin transporter (SERT) tracer, and [¹⁸F]AV-133 [(+)-2-Hydroxy-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizine], a selective vesicular monoamine transporter 2 (VMAT2) tracer, were tested in the 6-hydroxydopamine (6-OHDA) unilateral lesioned rat model.MethodsPositron emission tomography (PET) imaging of three 6-OHDA unilateral lesioned male Sprague Dawley rats (Rats 1–3) were performed with [¹⁸F]FPBM and [¹⁸F]AV-133 to examine whether changes in SERT and VMAT2 binding, respectively, could be detected in the brain. The brains of the three rats were then removed and examined by in vitro autoradiography with [¹⁸F]FPBM and the dopamine transporter ligand, [¹²⁵I]IPT [N-(3′-[¹²⁵I]-iodopropen-2′-yl)-2-beta-carbomethoxy-3-beta-(4-chloro phenyl) tropane, for confirmation. Biodistribution of [¹⁸F]FPBM in a separate group of p-chloroamphetamine (PCA) treated rats were also performed.ResultsPET image analysis showed varying levels of SERT binding reduction (Rat 1=-11%, Rat 2=-4%, Rat 3=-43%; n=2) and a clear and definitive loss of VMAT2 binding (Rat 1=-87%, Rat 2=-72%, and Rat 3=-91%; n=1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (p-chloroamphetamine) showed a significant reduction of [¹⁸F]FPBM uptake in the cortex and hypothalamus regions of the brain.ConclusionThe preliminary data suggest that [¹⁸F]FPBM and [¹⁸F]AV-133 may be useful for the examination of serotonergic and dopaminergic neuron integrity, respectively, in the living brain.