Microsecond Isomer at the N=20 Island of Shape Inversion Observed at FRIB.

Excited-state spectroscopy from the first experiment at the Facility for Rare Isotope Beams (FRIB) is reported. A 24(2)-µs isomer was observed with the FRIB Decay Station initiator (FDSi) through a cascade of 224- and 401-keV γ rays in coincidence with ^{32}Na nuclei. This is the only known microsecond isomer (1 µs≤T_{1/2}<1 ms) in the region. This nucleus is at the heart of the N=20 island of shape inversion and is at the crossroads of the spherical shell-model, deformed shell-model, and ab initio theories. It can be represented as the coupling of a proton hole and neutron particle to ^{32}Mg, ^{32}Mg+π^{-1}+ν^{+1}. This odd-odd coupling and isomer formation provides a sensitive measure of the underlying shape degrees of freedom of ^{32}Mg, where the onset of spherical-to-deformed shape inversion begins with a low-lying deformed 2^{+} state at 885 keV and a low-lying shape-coexisting 0_{2}^{+} state at 1058 keV. We suggest two possible explanations for the 625-keV isomer in ^{32}Na: a 6^{-} spherical shape isomer that decays by E2 or a 0^{+} deformed spin isomer that decays by M2. The present results and calculations are most consistent with the latter, indicating that the low-lying states are dominated by deformation.

Crossing N=28 Toward the Neutron Drip Line: First Measurement of Half-Lives at FRIB.

New half-lives for exotic isotopes approaching the neutron drip-line in the vicinity of N∼28 for Z=12-15 were measured at the Facility for Rare Isotope Beams (FRIB) with the FRIB decay station initiator. The first experimental results are compared to the latest quasiparticle random phase approximation and shell-model calculations. Overall, the measured half-lives are consistent with the available theoretical descriptions and suggest a well-developed region of deformation below ^{48}Ca in the N=28 isotones. The erosion of the Z=14 subshell closure in Si is experimentally confirmed at N=28, and a reduction in the ^{38}Mg half-life is observed as compared with its isotopic neighbors, which does not seem to be predicted well based on the decay energy and deformation trends. This highlights the need for both additional data in this very exotic region, and for more advanced theoretical efforts.

Addition of oral fexofenadine to topical therapy leads to a significantly greater reduction in the serum interleukin-31 levels in mild to moderate paediatric atopic dermatitis.

BACKGROUND: Recent evidence has suggested that oral antihistamines could have a beneficial role in atopic dermatitis (AD) because of their anti-inflammatory action. AIM: To evaluate the effectiveness of adding an oral second-generation, nonsedating, H1-receptor antihistamine (fexofenadine) to topical treatment in AD. METHODS: In this prospective randomized study, 50 patients with a diagnosis of mild to moderate AD were recruited and randomized into two groups: Group A was given appropriate topical treatment (topical tacrolimus 0.03-0.1% ointment once daily along with topical fluticasone propionate 0.05% cream once daily, as well as paraffin-based emollients) combined with oral fexofenadine, while Group B was given appropriate topical treatment only. Both groups received the respective treatments for 8 weeks. RESULTS: There was no significant difference between the two groups in terms of the SCORing Atopic Dermatitis and the 5-dimensions Itch Scale at any of the time points (Weeks 2, 4 and 8). However, in the fexofenadine group, the level of serum interleukin (IL)-31 decreased significantly from baseline to Week 8 of treatment. CONCLUSIONS: Although we could not conclusively confirm the clinical efficacy of adding oral fexofenadine to topical treatment in AD, serological evaluation indicates that fexofenadine treatment can lead to significant lowering of serum IL-31 levels in patients with AD.

Severe epidermolysis bullosa/Kindler syndrome-like phenotype of an autoinflammatory syndrome in a child.

A 5-year-old boy presented with generalized cutaneous erosions, severe scarring, depigmentation and contractures affecting major joints. The lesions had initially affected his ears, nose, feet, and the genital and ocular mucosa, leading to significant depigmentation, scarring, contractures and mutilation. The whole of the trunk and limbs were involved at the time of presentation, with the exception of some islands of spared skin on the proximal thighs, legs, nipples and external genitalia. Electron microscopy revealed a split in the sublamina densa with the absence of anchoring fibrils, suggestive of dystrophic epidermolysis bullosa (EB). Immunofluorescence antigen mapping demonstrated a broad reticulate pattern of staining with collagen IV, VII, and laminin 332 in the floor of the blister, suggestive of Kindler syndrome. Next-generation sequencing revealed a de novo heterozygous missense mutation (a variant of unknown significance) in exon 22 of the phospholipase-C gamma 2 gene (PLCG2), which resulted in a substitution of serine by asparagine at codon 798 (p.Asp798Ser), a result that was validated using Sanger sequencing. The child was diagnosed with PLCG2-associated antibody deficiency and immune dysregulation (PLAID)/autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) syndrome. The cutaneous and corneal erosions, inflammation and scarring of this magnitude, and the eventual result of death have not been described previously for the PLAID/APLAID spectrum previously. In conclusion, this was an unusual acquired autoinflammatory severe EB-like disease that may be associated with de novo PLCG2 mutation.

Assessment toolbox for Indian medical graduate competencies.

The new competency-based medical education curriculum for Bachelor of Medicine and Bachelor of Surgery is being implemented in a phased manner in medical colleges across India since the year 2019. The Graduate Medical Education Regulations enlist a total of 35 global competencies for the five roles expected of an Indian medical graduate, the roles being clinician, communicator, leader, professional, and life-long learner. Along with an effective implementation of the new curriculum, both in spirit and in action, it is imperative to assess the listed competencies. The new curriculum demands a more careful and mature selection of assessment tools, based on the competency and its expected level of achievement. It is these two variables that make choosing the right assessment method not just a matter of choice, but also of expertise. An array of tools in our armamentarium can sometimes separate confuse and the teachers. So, using the right tool, in the right context, at the right juncture, supplemented by other tools, and backed by constructive feedback, can help nurture the good intent ingrained in the competency-based curriculum. Hence, an attempt was made to compile an assessment toolbox for various global competencies. A PubMed, Science Direct and Google Scholar search, with relevant keywords was carried out. To the initially extracted 90,121 articles, limitations were applied, duplicates were removed and screening for assessment of global competencies and its attributes was done to select 232 articles. Finally, 31 articles were used for designing the proposed toolbox. Prioritization for the tools for the global competencies was based on thorough literature review and extensive discussion. The evolved assessment toolbox is presented in this article, which would help teachers pick the most useful methods of assessment for global competencies.

Blended programmatic assessment for competency based curricula.

The uncertainty in all spheres of higher education due to the COVID-19 pandemic has had an unprecedented impact on teaching-learning and assessments in medical colleges across the globe. The conventional ways of assessment are now neither possible nor practical for certifying medical graduates. This has necessitated thoughtful considerations in making adjustments to the assessment system, with most institutions transitioning to online assessments that so far have remained underutilized. Programmatic assessment encourages the deliberate and longitudinal use of diverse assessment methods to maximize learning and assessment and at present can be utilized optimally as it ensures the collection of multiple low-stake assessment data which can be aggregated for high-stake pass/fail decisions by making use of every opportunity for formative feedback to improve performance. Though efforts have been made to introduce programmatic assessment in the competency-based undergraduate curriculum, transitioning to online assessment can be a potential opportunity if the basic tenets of programmatic assessment, choice of online assessment tools, strategies, good practices of online assessments and challenges are understood and explored explicitly for designing and implementing online assessments. This paper explores the possibility of introducing online assessment with face-to-face assessment and structuring a blended programmatic assessment in competency-based medical education.

Paediatric morphoea: a holistic review. Part 2: diagnosis, measures of disease activity, management and natural history.

Paediatric morphoea is a debilitating fibrosing disorder of uncertain aetiology, affecting the skin and subcutaneous tissues. Defining optimum management strategies in paediatric morphoea remains an ongoing challenge, owing to the varied presentations and a relative paucity of paediatric-specific studies. We performed a literature search on PubMed, MEDLINE and Google Scholar, using keywords such as 'pediatric morphea', 'juvenile localised scleroderma' and 'juvenile systemic sclerosis'. Relevant studies, including randomized trials, reviews of standard current guidelines and original research articles, were selected and results analysed before summarizing them. In Part 1 of this review, we described the epidemiology, aetiopathogenesis and clinical classification; in this part, we discuss the diagnosis, markers of disease activity, management and natural history in paediatric morphoea.

Paediatric morphoea: a holistic review. Part 1: epidemiology, aetiopathogenesis and clinical classification.

Morphoea, also known as localized scleroderma, is a debilitating fibrosing disorder of uncertain aetiology, affecting the skin and subcutaneous tissues. Paediatric-onset disease is not uncommon and is associated with frequent relapses. The disease has complex pathogenetic mechanisms and multiple clinical subtypes, and affects children of all ages. Recent research has focused on elucidating the disease pathophysiology and identifying measures of disease activity. We performed a literature search on PubMed, MEDLINE and Google Scholar, using keywords such as 'pediatric morphea', 'juvenile localised scleroderma' and 'juvenile systemic sclerosis'. Relevant studies, including randomized trials, reviews of standard current guidelines and original research articles, were selected, and results were analysed before being summarized. In the first of this two-part review, we provide a bird's-eye view of the current literature concerning the epidemiology, aetiopathogenesis and clinical classification of paediatric morphoea; in Part 2, we review the diagnosis, markers of disease activity, management and natural history.

The power of subjectivity in competency-based assessment.

With the introduction of competency-based undergraduate curriculum in India, a paradigm shift in the assessment methods and tools will be the need of the hour. Competencies are complex combinations of various attributes, many of which being not assessable by objective methods. Assessment of affective and communication domains has always been neglected for want of objective methods. Areas like professionalism, ethics, altruism, and communication-so vital for being an Indian Medical Graduate, can be assessed longitudinally applying subjective means only. Though subjectivity has often been questioned as being biased, it has been proven time and again that a subjective assessment in expert hands gives comparable results as that of any objective assessment. By insisting on objectivity, we may compromise the validity of the assessment and deprive the students of enriched subjective feedback and judgement also. This review highlights the importance of subjective assessment in competency-based assessment and ways and means of improving the rigor of subjective assessment, with particular emphasis on the development and use of rubrics.

Investigation of high-frequency hearing loss and outer hair cell function of the cochlea in patients with psoriasis: a case-control study.

The inner ear can be the target of autoimmune attacks, and sensorineural hearing loss can occur as a complication in various non-organ-specific autoimmune diseases. The aim of this study was to compare cochlear functions and hearing evaluation in patients with psoriasis and controls. In total, 29 patients with psoriasis and 30 healthy controls (HCs) were included in the study. Pure-tone audiometry at 250, 500, 1000, 2000, 4000, 8000, 10 000, 12 000, 14 000 and 16 000 Hz was performed for patients as HCs, as were immittance measures including tympanometry, acoustic reflex and otoacoustic emission testing. There were statistically significant (P < 0.05) differences between patients and HCs for pure-tone thresholds at high frequencies, and for distortion product otoacoustic emission (DPOAE) responses and signal : noise ratio at all frequencies. In our study, based on DPOAE and audiological findings, there was damage to the outer hair cells of the cochlea, resulting in high-frequency hearing loss in patients with psoriasis.

An unusual case of reversible mild cognitive impairment.

Mild cognitive impairment (MCI) is cognitive dysfunction greater than expected for age and education in either a single cognitive domain or in multiple domains without impairment of activities of daily living. The present case report describes the case of an elderly male patient of 71 years who presented with MCI and was Venereal Disease Research Laboratory test reactive in serum. This was confirmed by Treponema pallidum Hemagglutination Assay. After a complete course of antibiotic therapy, his memory complaints disappeared completely. Though syphilis is termed as reversible dementia; to the best of our knowledge, this is the first case of MCI with reactive syphilis serology who responded to antimicrobial therapy.

Selection of indigenous Lactobacillus paracasei CD4 and Lactobacillus gastricus BTM 7 as probiotic: assessment of traits combined with principal component analysis.

AIMS: The population of the Himalayan region is known to consume a variety of fermented and nonfermented foods and as a result they have been benefited in terms of overall health, because of the associated beneficial microbes. Therefore, the focus of the present study was to identify new strains of lactic acid bacteria (LAB) from dairy products such as milk (cow, goat, buffalo) and fermented products (curd and buttermilk) with properties suitable for use as probiotic cultures. METHODS AND RESULTS: A total of 75 isolates tentatively identified as LAB from 100 samples were initially screened for production of ß-haemolysin as indicators of virulence which resulted in 38 isolates with no haemolytic activity. Further subtractive screening based on resistance to gastrointestinal tract barriers (acid and bile salts) resulted in the selection of the eight most promising strains. All these eight strains were resistant to pH 2·0, 1% bile concentration and pancreatin (1 mg l-1 ). Among the eight isolates, three isolates were identified as Brevibacillus thermoruber and the others as Brevibacillus aydinogluensis, Lactobacillus gastricus, L. paracasei, Enterococcus sp. Weisella confusa based on 16S rDNA region. Among these isolates, L. paracasei CD4 and L. gastricus BTM7 indicated maximum tolerance to simulated gastric environment. Both the isolates possessed highest score for cell surface hydrophobicity, cell autoaggregation, adherence to Caco-2 cell lines and antimicrobial activity against clinical isolates of Escherichia coli and Shigella sp. comparable to standard strain of Lactobacillus rhamnosus GG. Further principal component analysis and clustering analysis based on Euclidean Similarity index of probiotic characters revealed that L. paracasei strain CD4 and L. gastricus strain BTM7 were placed closest to reference strain L. rhamnosus GG and were therefore identified as most promising probiotic candidate cultures. CONCLUSIONS: These characteristics suggest that these strains could be excellent candidates for probiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Milk-based products serve as reservoir for bacterial species with probiotic attributes.

Demographics of tuberculosis of spine and factors affecting neurological improvement in patients suffering from tuberculosis of spine: a retrospective analysis of 312 cases.

OBJECTIVES: The purpose of the study was to study demographics of tuberculosis of spine and analyze factors that might affect neurological improvement in such patients. METHODS: Of the 638 suspected cases of spinal tuberculosis, 312 cases with confirmed diagnosis with at least 1-year follow-up were selected for retrospective analysis. Two hundred cases who presented with neurological deficit were further divided into three groups-completely improved, partially improved and no improvement according to American Spinal Injury Association impairment scale (AIS) grading. All continuous variables and categorical variables were compared across groups. RESULTS: A total of 209 (66.99%) patients had typical clinical presentation. A total of 264 (84.62%) had typical magnetic resonance imaging (MRI) presentation. Among 356 involved vertebrae, thoracic levels (T1-10) were most commonly affected in 163 (45.78%) followed by thoracolumbar (T11-L2) vertebrae in 98 (27.52%). In 250 patients (80.12%), disease was restricted to one or two adjoining vertebrae. At presentation, 112 (35.89%) patients were neurologically intact, whereas 97 (31%) were AIS D, 65 (20.83%) were AIS C, 8 (2.5%) were AIS B and 30 (9.61%) were AIS A. On statistical analysis, although three groups of patients with complete improvement, partial improvement and no improvement were similar in age, sex, radiological presentation, and co-morbidities and the presence of pulmonary tuberculosis, they were significantly different with regard to the levels of vertebral involvement, AIS grade at presentation, bladder and bowel involvement and its duration. CONCLUSIONS: In management of patients suffering from tuberculosis of spine, levels of vertebral involvement, AIS grade at presentation, bladder and bowel involvement and its duration significantly affect the final neurological improvement.

Retrospective analysis of spinal trauma in patients with ankylosing spondylitis: a descriptive study in Indian population.

OBJECTIVE: This study aims to understand the demographics, mode of trauma, hospital stay, complications, neurological improvement, mortality and expenditure incurred by Indian patients with spinal trauma and ankylosing spondylitis (AS). METHODS: Retrospective analysis of the patient data admitted to a tertiary referral hospital from 2008 to 2013 with the diagnosis of AS and spinal trauma was carried out. The variables studied were demographics, mode of trauma, neurological status, neurological improvement, involved vertebral level, duration of hospital stay, comorbid factors, expenditure and complications during the stay. RESULTS: Forty-six patients with diagnosis of AS with spine trauma were admitted over the last 5 years with a total of 52 fractures. All were male patients; 58.6% had injury because of trivial trauma and 78.2% patients presented with neurological injury. C5 C6, C6 C7, C7 D1 and D12 were the most common injured level. Fractures through intervertebral disc were most common in cervical spine. Of the patients, 52.7% had shown neurological improvement of at least grade 1(AIS). Mean expenditure of patient admitted with spinal cord injury (SCI) with AS is 7957 USD (United States dollar), which is around five times the per capita income in India (as per year 2013). CONCLUSION: Males with AS are much more prone to spinal fractures than females and its incidence may be higher than previously reported. Domestic falls are the most common mechanism of spinal trauma in this population. High velocity injuries are associated with complete SCI. The study reinforces the need for development of subsidized spinal care services for SCI management.

Type 2A Koebner phenomenon in vitiligo is distinct from other subtypes: observations from an Indian cohort.

BACKGROUND: Koebner phenomenon (KP) in vitiligo has been redefined and classified recently. OBJECTIVES: To study the clinical characteristics of various grades of KP. METHODS: In this prospective cross-sectional study, 202 patients with vitiligo were studied between January 2011 and December 2012 for the presence of KP. Based on the new Vitiligo European Task Force guidelines, KP was classified as type 1-3 and grades Ι-IV. Disease characteristics were studied in the various groups and subgroups based on the presence of KP. RESULTS: Koebner phenomenon was seen in 130 of 202 patients. The mean age of patients showing KP was 23.9 ± 13.6 years, compared with 19.3 ± 12.4 years for patients not showing KP (P = 0.02). The mean body surface area involved in the KP-positive group was 4.6 ± 5.6%, vs. 1.5 ± 1.1% in the KP-negative group (P = 0.001). Fifty-five patients experiencing KP received low-dose dexamethasone oral minipulse therapy compared with nine of those who did not (P = 0.01). Of the 130 patients with KP, grade Ι KP was seen in 32, grade II KP in 116, grade III KP in 22 and grade IV KP in 16. There was a significant difference between type 1 and type 2A KP, and between type 2A and type 2B KP. In contrast, type 1 and type 2B KP were found not to be significantly different and had a good degree of correlation. CONCLUSIONS: Patients with KP have a significantly higher age at onset, more extensive cutaneous involvement and are more likely to receive systemic steroids for disease control. Type 2A disease was found to be distinct from the other subtypes.

Caprine Toll-like receptor 8 gene sequence characterization reveals close relationships among ruminant species.

TLR8 mediates antiviral immunity by recognizing ssRNA viruses and triggers potent antiviral and antitumor immune responses. In this study, approximately 3.5 Kb nucleotide sequence data of caprine TLR8 gene were generated from one sample each of twelve different Indian goat breeds belonging to different geographical regions. Cloning and characterization of cDNA synthesized from RNA purified from goat spleen revealed TLR8 ORF to be of 3102 nucleotides long coding for 1033 amino acids similar to other ruminant species, that is sheep, buffalo and cattle. The sequence analysis at nucleotide level revealed goat TLR8 to be closer to buffalo sharing 99.6% homology, followed by cattle and sheep. Simple Modular Architecture Research Tool (SMART) used for the structural analysis of goat TLR8 showed the presence of 16 leucine-rich repeats (LRRs) along with single Toll/interleukin-1 receptor (TIR) domain. TIR domain when compared with other livestock species was found to be conserved in ruminant species goat, sheep, cattle and buffalo. The phylogenetic analysis also revealed grouping of all ruminant species together, goat being closer to buffalo followed by cattle and sheep. Total 4 polymorphic sites were observed in TLR8 gene of one specimen goat representing each of 12 different breeds studied, all of which were synonymous and present within the coding region. Of these 4 SNPs, two were in ectodomains, one in TIR domain and one was found to be present in transmembrane domain. PCR-RFLP genotyping of two of the SNPs indicated variations in allele frequencies among different goat breeds. The expression profiling in 13 tissues of goat showed maximum expression of TLR8 gene in kidney followed by spleen, lung and lymph node. Overall, our results indicate conservation of TLR8 gene among the ruminant species and low variation within Indian goat breeds.