Dyschromatosis Universalis Hereditaria.

Dyschromatosis universalis hereditaria (DUH) is a rare pigmentary genodermatosis usually inherited in autosomal dominant fashion characterized by multiple pinpoint to pea-sized hypo- and hyper-pigmented macules arranged in reticulate pattern that develops within the first few years of life. An 11 years old boy presented with multiple gradually progressive asymptomatic hypopigmented macules on hyperpigmented background on trunk, extremities and face since 2 years of age. Family history was absent. Punch biopsies revealed increased number of melanocytes in the epidermis with basal cell vacuolar alteration and pigmentary incontinence and perivascular infiltration by lymphocytes and melanophages in the dermis. We herein present a sporadic case of dyschromatosis universalis hereditaria.

Thirty-Day Mortality for Proximal Femoral Fractures Treated at a U.K. Elective Center with a Site-Streaming Policy During the COVID-19 Pandemic.

COVID-19 led to the reconfiguration of U.K. orthopaedic trauma services because surgical capacity was threatened in acute centers. We report the 30-day mortality of proximal femoral fractures in older adults treated at an elective orthopaedic center. METHODS: Patients >60 years old who presented with a proximal femoral fracture to any of 4 sites in the regional trauma network were transferred to our elective center for emergency surgery. Care was modeled according to the National Institute for Health and Care Excellence guidelines, and efforts were made to treat all patients within 36 hours. Data were collected prospectively, and mortality outcomes were recorded. RESULTS: Of the 192 patients who presented to the elective orthopaedic center, 167 were treated there. The median age of the latter patients was 88 years (interquartile range, 83 to 79 years). The median Charlson Comorbidity Index was 4 (interquartile range, 4 to 6). The median time from emergency department admission to surgical treatment was 24.5 hours (interquartile range, 18.8 to 34.7 hours). The 30-day rate of mortality was 10.2%. A total of 29 (17.4%) tested positive for COVID-19 during their admission, of whom 10 died, for a case-fatality rate of 34.5%. There were no significant differences in age (p = 0.33) or Charlson Comorbidity Index (p = 0.13) between patients who tested positive and those who did not. There was no significant difference in age between those who tested positive and died and those who tested positive and did not die (p = 0.13), but there was a significant difference in Charlson Comorbidity Index between those subgroups (p = 0.03). CONCLUSIONS: During a pandemic, an elective orthopaedic center can be reconfigured to a surgical center for older patients with proximal femoral fractures with acceptable health-care quality outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Association between vestibular function and rotational spatial orientation perception in older adults.

BACKGROUND: Spatial orientation is a complex process involving vestibular sensory input and possibly cognitive ability. Previous research demonstrated that rotational spatial orientation was worse for individuals with profound bilateral vestibular dysfunction. OBJECTIVE: Determine whether rotational and linear vestibular function were independently associated with large amplitude rotational spatial orientation perception in healthy aging. METHODS: Tests of rotational spatial orientation accuracy and vestibular function [vestibulo-ocular reflex (VOR), ocular and cervical vestibular evoked myogenic potentials (VEMP)] were administered to 272 healthy community-dwelling adults participating in the Baltimore Longitudinal Study of Aging. Using a mixed model multiple linear regression we regressed spatial orientation errors on lateral semicircular canal function, utricular function (ocular VEMP), and saccular function (cervical VEMP) in a single model controlling for rotation size, age, and sex. RESULTS: After adjusting for age, and sex, individuals with bilaterally low VOR gain (ß= 20.9, p = 0.014) and those with bilaterally absent utricular function (ß= 9.32, p = 0.017) made significantly larger spatial orientation errors relative to individuals with normal vestibular function. CONCLUSIONS: The current results demonstrate for the first time that either bilateral lateral semicircular canal dysfunction or bilateral utricular dysfunction are associated with worse rotational spatial orientation. We also demonstrated in a healthy aging cohort that increased age also contributes to spatial orientation ability.

Saccular function is associated with both angular and distance errors on the triangle completion test.

OBJECTIVE: The present study was designed to determine whether healthy older adults with age-related vestibular loss have deficits in spatial navigation. METHODS: 154 adults participating in the Baltimore Longitudinal Study of Aging were tested for semicircular canal, saccular, and utricular function and spatial navigation ability using the blindfolded Triangle Completion Test (TCT). Multiple linear regression was used to investigate the relationships between each measure of vestibular function and performance on the TCT (angular error, end point error, and distance walked) while controlling for age and sex. RESULTS: Individuals with abnormal saccular function made larger angular errors (ß = 4.2°, p < 0.05) and larger end point errors (ß = 13.6 cm, p < 0.05). Independent of vestibular function, older age was associated with larger angular (ß's = 2.2-2.8°, p's < 0.005) and end point errors (ß's = 7.5-9.0 cm, p's < 0.005) for each decade increment in age. CONCLUSIONS: Saccular function appears to play a prominent role in accurate spatial navigation during a blindfolded navigation task. SIGNIFICANCE: We hypothesize that gravitational cues detected by the saccule may be integrated into estimation of place as well as heading direction.

Community-dwelling adults with a history of falling report lower perceived postural stability during a foam eyes closed test than non-fallers.

Perceived postural stability has been reported to decrease as sway area increases on firm surfaces. However, changes in perceived stability under increasingly challenging conditions (e.g., removal of sensory inputs) and the relationship with sway area are not well characterized. Moreover, whether perceived stability varies as a function of age or history of falls is unknown. Here we investigate how perceived postural stability is related to sway area and whether this relationship varies as a function of age and fall history while vision and proprioceptive information are manipulated. Sway area was measured in 427 participants from the Baltimore Longitudinal Study of Aging while standing with eyes open and eyes closed on the floor and a foam cushion. Participants rated their stability [0 (completely unstable) to 10 (completely stable)] after each condition, and reported whether they had fallen in the past year. Perceived stability was negatively associated with sway area (cm2) such that individuals who swayed more felt less stable across all conditions (ß = - 0.53, p < 0.001). Perceived stability decreased with increasing age (ß = - 0.019, p < 0.001), independent of sway area. Fallers had a greater decline in perceived stability across conditions (F = 2.76, p = 0.042) compared to non-fallers, independent of sway area. Perceived postural stability declined as sway area increased during a multisensory balance test. A history of falling negatively impacts perceived postural stability when vision and proprioception are simultaneously challenged. Perceived postural stability may provide additional information useful for identifying individuals at risk of falls.

Reduced vestibular function is associated with longer, slower steps in healthy adults during normal speed walking.

BACKGROUND: Vestibular signals contribute to balance and walking. With aging, vestibular function declines and gait speed decreases. Vestibular loss contributes to decreasing gait speed, but this influence could be linked to spatial and/or temporal aspects of gait. We investigated the relationship between vestibular function (semicircular canal and otolith function) and spatial and temporal gait parameters in a cohort of adults. METHODS: 113 community-dwelling healthy adults (mean age 72.2 (14.6) years) participating in the Baltimore Longitudinal Study of Aging were tested. Horizontal semicircular canal (SCC) function was evaluated using quantitative vestibulo-ocular reflex gain. Otolith function was measured with cervical and ocular vestibular evoked myogenic potentials. Gait kinematics were collected during normal speed walking. Multiple linear regressions examined the association between spatial and temporal gait parameters and SCC and otolith function separately, controlling for age, gender, height, and either cadence (for spatial gait outcomes) or stride length (for temporal gait outcomes) to account for gait speed effects. RESULTS: Vestibular SCC function was significantly associated with both spatial and temporal gait parameters. Every 0.1 decrease in SCC function resulted in longer stride length (ß = -.04 m, p = 0.004), longer stance time (ß = 15.8 ms, p < 0.003), and a slower cadence (ß = -2.1 steps/minute, p < 0.001). Otolith function was not associated with any gait parameter. CONCLUSIONS: Reduced horizontal SCC function was associated with longer, slower steps in a cohort of healthy adults. These results indicate that vestibular signals contribute to specific spatial and temporal aspects of gait thought to contribute to upright balance.

Multifarious applications of atomic force microscopy in forensic science investigations.

Forensic science is a wide field comprising of several subspecialties and uses methods derived from natural sciences for finding criminals and other evidence valid in a legal court. A relatively new area; Nano-forensics brings a new era of investigation in forensic science in which instantaneous results can be produced that determine various agents such as explosive gasses, biological agents and residues in different crime scenes and terrorist activity investigations. This can be achieved by applying Nanotechnology and its associated characterization techniques in forensic sciences. Several characterization techniques exist in Nanotechnology and nano-analysis is one such technique that is used in forensic science which includes Electron microscopes (EM) like Transmission (TEM) and Scanning (SEM), Raman microscopy (Micro -Raman) and Scanning Probe Microscopes (SPMs) like Atomic Force Microscope (AFM). Atomic force microscopy enables surface characterization of different materials by examining their morphology and mechanical properties. Materials that are immeasurable such as hair, body fluids, textile fibers, documents, polymers, pressure sensitive adhesives (PSAs), etc. are often encountered during forensic investigations. This review article will mainly focus on the use of AFM in the examination of different evidence such as blood stains, forged documents, human hair samples, ammunitions, explosives, and other such applications in the field of Forensic Science.

LC-MS/MS Validation Analysis of Trastuzumab Using dSIL Approach for Evaluating Pharmacokinetics.

Quantitative targeted proteomics based approaches deploy state-of-the-art Liquid chromatography tandem mass spectrometry LC-MS technologies and are evolving as a complementary technique to standard ligand-binding based assays. Advancements in MS technology, which have augmented the specificity, selectivity and sensitivity limits of detection and freedom from antibody generation, have made it amicable towards various clinical applications. In our current work, a surrogate peptide based quantitative proteomics assessment is performed by selecting specific signature peptides from the complementary determining region CDR region of trastuzumab (Herclon®, Roche products in India). We developed a double Stable Isotope Label (dSIL) approach by using two different surrogate peptides to evaluate the proteolytic digestion efficiency and accurate quantification of the target analyte peptide of Herclon® in human serum. Method validation experiments were meticulously performed as per bioanalytical method validation guidelines. The dSIL approach, using an LC-MS/MS based quantification assay demonstrated good linearity over a range of 5-500 µg/mL of Herclon®, and validation experimental data is in compliance with bioanalytical regulatory guidelines.

Cyclodextrin based ternary system of modafinil: Effect of trimethyl chitosan and polyvinylpyrrolidone as complexing agents.

Modafinil is an approved drug for the treatment of narcolepsy and have a strong market presence in many countries. The drug is widely consumed for off-label uses and currently listed as a restricted drug. Modafinil has very low water solubility. To enhance the aqueous solubility of modafinil by the formation of a ternary complex with Hydroxypropyl-ß-cyclodextrin and two hydrophilic polymers was the main objective of the present study. Pyrrolidone (PVP K30) and a water soluble chitosan derivative, trimethyl chitosan (TMC) were studied by solution state and solid state characterization methods for their discriminatory efficiency in solubility enhancement of modafinil. Phase solubility study depicted the highest complexation efficiency (2.22) of cyclodextrin derivative in the presence of TMC compared to the same in the presence of PVP K30 (0.08) and in the absence of any polymer (0.92). FT-IR analysis of binary and ternary complex expressed comparable contribution of both polymers in formation of inclusion complex. The thermal behaviour of binary and ternary complex, involving individual polymers disclosed the influence of TMC on polymorphism of the drug. DSC study revealed efficiency of TMC to prevent conversion of metastable polymorphic form to stable polymorphic form. Ternary complex, involving TMC enhanced water solubility of the drug 1.5 times more compared to the binary complex of the drug whereas PVP K30 reduced the Solubility.

Intra-articular and portal infiltration versus wrist block for analgesia after arthroscopy of the wrist: a prospective RCT.

Wrist block has been used to provide pain relief for many procedures on the hand and wrist but its role in arthroscopy of the wrist remains unexplored. Chondrotoxicity has been a concern with the intra-articular infiltration of local anaesthetic. We aimed to evaluate and compare the analgesic effect of portal and wrist joint infiltration with a wrist block on the pain experienced by patients after arthroscopy of the wrist. A prospective, randomised, double-blind trial was designed and patients undergoing arthroscopy of the wrist under general anaesthesia as a day case were recruited for the study. Levo-bupivacaine was used for both techniques. The effects were evaluated using a ten-point visual analogue scale, and the use of analgesic agents was also compared. The primary outcomes for statistical analyses were the mean pain scores and the use of analgesia post-operatively. A total of 34 patients (63% females) were recruited to the portal and joint infiltration group and 32 patients (59% males) to the wrist block group. Mean age was 40.8 years in the first group and 39.7 years in the second group (p > 0.05). Both techniques provided effective pain relief in the first hour and 24 hours post-operatively but wrist block gave better pain scores at bedtime on the day of surgery (p = 0.007) and at 24 hours post-operatively (p = 0.006). Wrist block provides better and more reliable analgesia in patients undergoing arthroscopy of the wrist without exposing patients to the risk of chondrotoxicity.

Chitosan as a suitable nanocarrier material for anti-Alzheimer drug delivery.

Chitosan, a biocompatible natural polysaccharide is frequently reported carrier material in targeted drug delivery to treat neurodegenerative disorders. Chitosan and its biodegradable products exert its bioactivities on nerve cells and blood brain barrier at the molecular level, which are beneficial in anti-Alzheimer therapy. Flexibility of surface modification, the ability to get attached with varieties of ligand molecules and the formation of the stable nano complex in physiological condition make chitosan an adorable material for delivery of anti-Alzheimer drugs and siRNA to the brain. The success rate of nose to brain delivery of anti-Alzheimer drugs enhances when chitosan used as a carrier material. This review covers direct and indirect anti-Alzheimer effects of chitosan, surface modification strategies to augment permeation from the blood-brain barrier structure, different ligands reported for brain targeting of chitosan nanoparticles containing anti Alzheimer drugs, blood compatibility and widely utilized chitosan nanoparticle fabrication techniques. Key intellectual claims are also condensed through patents to appraise chitosan as an attractive polymer for brain targeted nanoformulation which is currently facing oversight by regulatory agencies and manufacturers.

Development of forced degradation and stability indicating studies of drugs-A review.

Forced degradation is a degradation of new drug substance and drug product at conditions more severe than accelerated conditions. It is required to demonstrate specificity of stability indicating methods and also provides an insight into degradation pathways and degradation products of the drug substance and helps in elucidation of the structure of the degradation products. Forced degradation studies show the chemical behavior of the molecule which in turn helps in the development of formulation and package. In addition, the regulatory guidance is very general and does not explain about the performance of forced degradation studies. Thus, this review discusses the current trends in performance of forced degradation studies by providing a strategy for conducting studies on degradation mechanisms and also describes the analytical methods helpful for development of stability indicating method.

Development of forced degradation and stability indicating studies of drugs-A review / 药物分析学报

Forced degradation is a degradation of new drug substance and drug product at conditions more severe than accelerated conditions. It is required to demonstrate specificity of stability indicating methods and also provides an insight into degradation pathways and degradation products of the drug substance and helps in elucidation of the structure of the degradation products. Forced degradation studies show the chemical behavior of the molecule which in turn helps in the development of formulation and package. In addition, the regulatory guidance is very general and does not explain about the performance of forced degradation studies. Thus, this review discusses the current trends in performance of forced degradation studies by providing a strategy for conducting studies on degradation mechanisms and also describes the analytical methods helpful for development of stability indicating method.

Labeling of nucleosides with fluorescamine and detection by spectrofluorometer for End Stage Renal Disease.

Nucleosides are characterized as biomarkers in AIDS, Alzheimer, tumor, breast cancer and various malignant diseases. In the present work a direct method for the detection of nucleosides (adenosine, cytidine, uridine and guanosine) from urine samples has been developed. Nucleosides represent the extent of damage in genetic material, analysis of nucleosides by ultrasonic assisted microextraction effectively eliminates the interfering constituent of urine. This has made it a highly selective and sensitive method to analyze the nucleosides with a lower limit of detection 0.220 µmol/L and Limit of quantitation 0.660 µmol/L. The method has been validated with good linearity and correlation of coefficients of the calibration curves was higher than 0.997. The coefficients were in the range of 0.11-16.92% (inter-day) and 0.38-16.43% (intra-day), respectively.

Simultaneous monitoring of selective serotonin reuptake inhibitors in human urine, plasma and oral fluid by reverse-phase high performance liquid chromatography.

A simple and rapid reverse-phase high-performance liquid chromatography method is developed for the simultaneous determination of selective serotonin reuptake inhibitors (sertraline, citalopram, paroxetine and fluoxetine) in urine, plasma and oral fluid. Separation was performed on a Crestpack-18 column (4.6 × 250 mm × 5 µ) within 17.5 min. The mobile phase was composed of water (50 mL) [with glacial acetic acid (0.15 mL) + triethyl amine (0.30 mL)]-acetonitrile (40 mL)-methanol (10 mL), delivered isocratically (0.6 mL/min) at 270 nm. Liquid-liquid extraction was performed for isolation of analytes from biofluids. The developed methodology was validated in terms of sensitivity, linearity, accuracy, precision, stability and selectivity. The calibration curves were linear in the range of 5-1,000 ng/mL for all the compounds in three matrices, with coefficients of determination between 0.9991 to 0.9998. The average extraction recoveries for all the four analytes were above 90%. The limits of detection and limits of quantification were in the ranges of 0.02-1.20 and 0.12-2.51 ng/mL, respectively. The intra-day and inter-day variation coefficients were less than 8.0 and 11%, respectively. Moreover, the results were compared statistically for each analyte in three matrices and found to be equivalent, which signifies the absence of matrix effect. Thus, the method can be applied for the determination of selective serotonin reuptake inhibitors in urine, plasma and oral fluid for routine therapeutic and toxicological screening.

Optical nanobiosensor: a new analytical tool for monitoring carboplatin-DNA interaction in vitro.

The interaction of DNA and Carboplatin was studied with DNA labeled gold nanoparticles (AuNPs) based optical nanobiosensor. Carboplatin, a cytotoxic drug, is responsible for producing nephrotoxicity at effective dose. Thus, we have developed optical nanobiosensor for monitoring carboplatin-DNA interaction based on Fluorescence Resonance Energy Transfer (FRET) phenomenon. Paracetamol, an analgesic agent, was used as controlled drug in this study. The DNA labeled AuNPs, exposed to carboplatin, a binding event among the DNA and carboplatin takes place, resulting in a conformational change within the biosensor complex which decreases the distance among the fluorescent molecules or the fluorescent/quencher molecules. As the carboplatin interact with DNA, an increase in fluorescence intensity was observed. So, the major difference in increased fluorescence intensity between carboplatin-DNA and paracetamol-DNA interaction shows significant observations. Results have demonstrated that Optical sensor is able to rapidly and effectively monitor carboplatin-DNA interaction with a detection limit up to 0.45 µg/ml. This suggests that the developed optical nanobiosensor was ideal for monitoring Drug-DNA interaction studies while performing combinatorial synthesis for new drug development.

Impact of metabolic syndrome on re-stenosis development: role of drug-eluting stents.

Metabolic syndrome (MetS) is defined as a cluster of numerous cardiovascular risk factors, which encompasses obesity, dyslipidaemia, insulin resistance and hypertension. Patients with MetS are more prone to developing cardiovascular events than other patients. To date, several approaches such as physical exercise, dietary control and invasive and non-invasive therapeutic interventions for dyslipidaemia, hypertension and insulin resistance have been used to manage MetS. However, there is a progressive elevation in the incidence of fatal and non-fatal cardiovascular events due to the increased prevalence of obesity and diabetes. Percutaneous coronary intervention has emerged over the last few years as an effective revascularisation strategy for those with coronary artery disease, in parallel with the development of effective anti-platelet medications and newer drug-eluting stents. In recent years, considerable research efforts have been undertaken to elucidate the pathophysiology of re-stenosis and develop strategies to prevent re-stenosis following percutaneous transluminal coronary angioplasty and stent implantation. Although the rate of stent re-stenosis and target-lesion revascularisation has been reduced, there is little information in the literature on the outcome of MetS in the pathophysiology of re-stenosis. In this review article, we summarise the recent development and progress on re-stenosis and the role of drug-eluting stents, particularly in MetS.

Solid lipid nanoparticles of a water soluble drug, ciprofloxacin hydrochloride.

The aim of this study was to understand and investigate the relationship between experimental factors and their responses in the preparation of ciprofloxacin hydrochloride based solid lipid nanoparticles. A quadratic relationship was studied by developing central composite rotatable design. Amount of lipid and drug, stirring speed and stirring time were selected as experimental factors while particle size, zeta potential and drug entrapment were used as responses. Prior to the experimental design, a qualitative prescreening study was performed to check the effect of various solid lipids and their combinations. Results showed that changing the amount of lipid, stirring speed and stirring time had a noticeable influence on the entrapment efficiencies and particle size of the prepared solid lipid nanoparticles. The particle size of a solid lipid nanoparticle was in the range of 159-246 nm and drug encapsulation efficiencies were marginally improved by choosing a binary mixture of physically incompatible solid lipids. Release of ciprofloxacin hydrochloride from solid lipid nanoparticle was considerably slow, and it shows Higuchi matrix model as the best fitted model. Study of solid lipid nanoparticle suggested that the lipid based carrier system could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release for water soluble actives.