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.

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.

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.

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.

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.

Shaped focal plane detectors for particle concentration and mean size observations.

We describe a method of designing shaped focal plane detectors for achieving a range of objectives in measurement of particles suspended in a fluid. These detectors can be designed to measure the total concentration in a wide size range (e.g. 200:1) or concentration in a size sub-range (e.g. 63

Empirical forward scattering phase functions from 0.08 to 16 deg. for randomly shaped terrigenous 1-21 microm sediment grains.

We present in-water forward scattering phase functions covering the angle range 0.08 to 16 degrees for 19 narrow-sized dispersions of randomly shaped sediment grains. These dispersions cover particle size range from 1 to 20 microns. These phase functions offer a realistic alternative to Mie theory. Qualitatively, (i) the magnitude of phase functions at the smallest angles for equal size spheres and randomly shaped particles are nearly equal; (ii) the oscillations predicted by Mie theory for spheres disappear for random shaped grains, and (iii) the tendency of phase functions of large spheres to merge at large angles is also seen with randomly shaped grains. The data are also provided in tabulated form.

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.

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.

Chirality--a new era of therapeutics.

To develop the newer pharmaceuticals and to spur the strong growth, being a general property of 'handedness', chirality plays a major role. The Easson-Stedman principle shows the differences in the biological activity between enantiomers resulted from selective reactivity of one enantiomer with its receptor. It helps to improve the pharmacokinetic properties and to remove undesirable side effects by virtue of the unique activity of enantiomers. Racemic switching and marketing drug combinations are used as tools for drug life-cycle management and to redevelop racemic mixtures as single enantiomers.

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.

Dynamic instability at liquid/vapor interface far from equilibrium.

Attempt has been made to elucidate the mechanism of electric potential oscillations at oil-aqueous solution interface involving adsorption at oil-vapor interface on a semi-theoretical basis. The mechanism stipulates adsorption of ammonia, amines and pheromones at the liquid-vapor interface followed by transfer of ions through membrane-aqueous solution interface and subsequent interaction of ammonium (amine) ions and carbocations from pheromones with diffusing halide ions from the bulk. Relationship of the above mechanism with sensing mechanism of smell by olfactory nerves has also been pointed out.

The distribution of bone islands and juxta-articular bone cysts in the growing hand.

Bone islands and juxta-articular bone cysts are relatively common incidental findings when X-rays are taken for other purposes. We have identified that the incidence of bone islands in the hands of asymptomatic children between the ages of 5 and 13 years is 3.8% and the incidence of cysts in the same population is 2.8%. Bone islands were most common in the scaphoid, whilst juxta-articular bone cysts were most common in the capitate. The age at which they appear has not been reported previously. This study first identifies their presence in the hands of children of age 10 years and 2 months (bone islands) and 10 years 0 months (juxta-articular bone cysts). Most of the lesions were already present on the first radiograph taken. New bone islands appeared in five cases between the ages of 13 years and 1 month and 15 years and 3 months. New juxta-articular bone cysts were observed to appear in five cases between the ages of 10 years 10 months and 15 years 0 months. No island or cyst changed in size during the review period.

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.

Chiral chromatographic separation of beta-blockers.

A novel amide based chiral stationary phase m-[(+)-alpha-methyl benzyl carboxamide] XAD-4 has been synthesized by covalently linking R(+)-1-phenylethylamine to chloroformoyl Amberlite XAD-4 under weak alkaline conditions. The synthesized resin has been primarily characterized by m.p., elemental analysis and FT-IR and 13C NMR spectra. beta-Blockers viz. atenolol, metoprolol, and propranolol were successfully separated into their enantiomers using a mixture of sodium acetate-acetic acid buffer (pH 4.1):acetonitrile (4:6, v/v) solution using the synthesized resin. Hydrogen bonding and pi-pi interactions are supposed to be the major analyte-chiral stationary phase interactions.

Low dose naltrexone therapy in multiple sclerosis.

The use of low doses of naltrexone for the treatment of multiple sclerosis (MS) enjoys a worldwide following amongst MS patients. There is overwhelming anecdotal evidence, that in low doses naltrexone not only prevents relapses in MS but also reduces the progression of the disease. It is proposed that naltrexone acts by reducing apoptosis of oligodendrocytes. It does this by reducing inducible nitric oxide synthase activity. This results in a decrease in the formation of peroxynitrites, which in turn prevent the inhibition of the glutamate transporters. Thus, the excitatory neurotoxicity of glutamate on neuronal cells and oligodendrocytes via activation of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid class of glutamate receptor is prevented. It is crucial that the medical community respond to patient needs and investigate this drug in a clinical trial.

Cell-cycle kinetics and VSV-G pseudotyped retrovirus-mediated gene transfer in blood-derived CD34+ cells.

As hematopoietic stem and progenitor cells have a low mitotic index, we have quantitated the impact of cytokine combinations on cell cycling of CD34+ cells and, using VSV-G pseudotyped retroviral vectors, correlated our findings with ex vivo gene transfer. We tested nine different combinations of cytokines for induction of human peripheral blood CD34+ cells into cell cycle over 72 hours. Using the 5-bromodeoxyuridine-Hoechst 33258 (BrdU-Hoechst) assay, we measured the cell-cycle kinetics. The combinations of cytokines tested that were most efficient in inducing the CD34+ cells into cycle were stem cell factor (SCF) plus one of the following: interleukin-1 (IL-1), IL-3, granulocyte colony-stimulating factor (G-CSF). The maximum numbers of cells in S+G2M phase were observed after 48 hours of culture. At least 35 +/- 5% of the CD34+ cells remained quiescent in the first G0/G1 phase, however, no matter which cytokine combination was used. Cell-cycle analysis of the CD34+CD38- subset by 7-amino actinomycin D staining did not detect cycling cells during 72 hours of culture with any of the cytokines tested. To investigate whether the cells could be infected by the VSV-G pseudotyped virus containing the neomycin phospho-transferase gene (neo), we exposed CD34+ cells to the virus for 7-8 hours after 0, 36, and 48 hours of cytokine stimulation. Total CD34+ cells and the CD34+CD38- subset were analyzed by polymerase chain reaction (PCR) for reverse-transcribed viral DNA of the neomycin resistance gene (RT-neoDNA). Immediately after exposure to the virus, RT-neoDNA was detectable in CD34+ cells that have been cultured with or without cytokines for 36 to 48 hours. Forty-eight hours postinfection, however, RT-neoDNA could be detected only with cytokine combinations that induced mitosis of the CD34+ cells, consistent with the requirement for mitotic activity for retroviral integration. Similar experiments performed with the 34+CD38- subset showed that RT-reoDNA could not be detected at any time point. Thus, postinfection RT-neoDNA could be immediately detected in noncycling CD34+ cells but not in CD34+CD38- cells. These results suggest during short-term liquid culture, there may be blocks for reverse transcription of retroviral RNA in CD34+CD38-cells in addition to the lack of mitotic activity.

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.