iIL13Pred: improved prediction of IL-13 inducing peptides using popular machine learning classifiers.

BACKGROUND: Inflammatory mediators play havoc in several diseases including the novel Coronavirus disease 2019 (COVID-19) and generally correlate with the severity of the disease. Interleukin-13 (IL-13), is a pleiotropic cytokine that is known to be associated with airway inflammation in asthma and reactive airway diseases, in neoplastic and autoimmune diseases. Interestingly, the recent association of IL-13 with COVID-19 severity has sparked interest in this cytokine. Therefore characterization of new molecules which can regulate IL-13 induction might lead to novel therapeutics. RESULTS: Here, we present an improved prediction of IL-13-inducing peptides. The positive and negative datasets were obtained from a recent study (IL13Pred) and the Pfeature algorithm was used to compute features for the peptides. As compared to the state-of-the-art which used the regularization based feature selection technique (linear support vector classifier with the L1 penalty), we used a multivariate feature selection technique (minimum redundancy maximum relevance) to obtain non-redundant and highly relevant features. In the proposed study (improved IL-13 prediction (iIL13Pred)), the use of the mRMR feature selection method is instrumental in choosing the most discriminatory features of IL-13-inducing peptides with improved performance. We investigated seven common machine learning classifiers including Decision Tree, Gaussian Naïve Bayes, k-Nearest Neighbour, Logistic Regression, Support Vector Machine, Random Forest, and extreme gradient boosting to efficiently classify IL-13-inducing peptides. We report improved AUC, and MCC scores of 0.83 and 0.33 on validation data as compared to the current method. CONCLUSIONS: Extensive benchmarking experiments suggest that the proposed method (iIL13Pred) could provide improved performance metrics in terms of sensitivity, specificity, accuracy, the area under the curve - receiver operating characteristics (AUCROC) and Matthews correlation coefficient (MCC) than the existing state-of-the-art approach (IL13Pred) on the validation dataset and an external dataset comprising of experimentally validated IL-13-inducing peptides. Additionally, the experiments were performed with an increased number of experimentally validated training datasets to obtain a more robust model. A user-friendly web server ( www.soodlab.com/iil13pred ) is also designed to facilitate rapid screening of IL-13-inducing peptides.

A single subset of dendritic cells controls the cytokine bias of natural killer T cell responses to diverse glycolipid antigens.

Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α(+) DEC-205(+) dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α(+) dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses.

A prospective real-world study evaluating serum levels of arginine and cysteine in women with chronic telogen effluvium: do we really need blanket prescription of amino acid supplementation?

Amino acids form a major component of hair fibres and are prescribed routinely in the form of nutritional supplements in patients with chronic telogen effluvium (CTE). Such a practice is based on assumption of a nutritional deficiency state in such patients. In this prospective study, we evaluated the serum levels of cysteine and arginine in 30 women with CTE and in healthy controls. We found no significant difference between the two groups in terms of serum arginine levels. Cysteine levels were higher in patients with CTE (P < 0.001). No correlation was found between levels of serum amino acids (cysteine and arginine) and either diet type (vegetarian or not) or body mass index, and no significant correlation between levels of the two amino acids and severity of disease. Our work suggests that arginine and cysteine deficiency is not present in women with CTE. Supplementation is unlikely to be of any benefit in nutrient-replete populations and only adds to the cost of therapy.

Adjunctive use of saturated solution of potassium iodide (SSKI) with liposomal amphotericin B (L-AMB) in mucormycosis achieves favorable response, shortened dose and duration of amphotericin: A retrospective study from a COVID-19 tertiary care center.

PURPOSE: Second wave of COVID-19 pandemic was associated with an unprecedented rise in cases of mucormycosis, treatment of which has been challenging owing to the availability and side effects associated with amphotericin. METHODS: All patients presenting with rhino-orbital cerebral mucormycosis (ROCM) following COVID-19 infection between April 2021 to June 2021 were included in this retrospective interventional study. Primary objective was to assess the clinical response with combination of intravenous liposomal amphotericin B (4-5 mg/kg/day) and saturated solution of potassium iodide (SSKI) given orally along with surgical debridement. RESULTS: Twenty-five patients of ROCM were treated with the regimen. Mean age and fasting blood sugar levels were 53.48 years and 239.64 mg/dL respectively. All patients had history of intake of steroids with a mean daily dose of 86.39 mg of prednisolone equivalent. 88% of patients had a "proven" diagnosis of mucormycosis. Cultures were positive in 52% of patients with Rhizopus arrhizus as the predominant species. The mean daily dose of amphotericin received was 268 mg/day with a mean duration of 9.52 days. Mean daily dose of SSKI was 2.57 g. 21 patients (84%) had stabilization of disease at week 8 and achieved cure at the end of treatment whereas the mortality rate was 16%. Factors that significantly affected outcome were eye and central nervous system (CNS) involvement on presentation. CONCLUSION: SSKI, with its remarkably low cost and safety profile, makes it a potential adjuvant drug that may help achieve the twin benefits of shortened duration and dose of LAMB.

Rab4A organizes endosomal domains for sorting cargo to lysosome-related organelles.

Sorting endosomes (SEs) are the regulatory hubs for sorting cargo to multiple organelles, including lysosome-related organelles, such as melanosomes in melanocytes. In parallel, melanosome biogenesis is initiated from SEs with the processing and sequential transport of melanocyte-specific proteins toward maturing melanosomes. However, the mechanism of cargo segregation on SEs is largely unknown. Here, RNAi screening in melanocytes revealed that knockdown of Rab4A results in defective melanosome maturation. Rab4A-depletion increases the number of vacuolar endosomes and disturbs the cargo sorting, which in turn lead to the mislocalization of melanosomal proteins to lysosomes, cell surface and exosomes. Rab4A localizes to the SEs and forms an endosomal complex with the adaptor AP-3, the effector rabenosyn-5 and the motor KIF3, which possibly coordinates cargo segregation on SEs. Consistent with this, inactivation of rabenosyn-5, KIF3A or KIF3B phenocopied the defects observed in Rab4A-knockdown melanocytes. Further, rabenosyn-5 was found to associate with rabaptin-5 or Rabip4/4' (isoforms encoded by Rufy1) and differentially regulate cargo sorting from SEs. Thus, Rab4A acts a key regulator of cargo segregation on SEs.This article has an associated First Person interview with the first author of the paper.

Iatrogenic Cushing's syndrome due to topical steroid abuse in a child with Psoriasis presenting as septicaemia.

Psoriasis vulgaris is a chronic inflammatory disorder that affects the skin and joints. Mild disease is treated with topical corticosteroids (CS) which forms the first line of treatment for localized disease. While it is well established that prolonged use of oral or parenteral corticosteroids can lead to iatrogenic Cushing's syndrome and suppression of hypothalamic pituitary axis; development of these complications secondary to use of topical CS is rarely described. Since steroids have anti-inflammatory properties, their prolonged use can lead to increased susceptibility to develop bacterial and fungal infections. We hereby report a 11-year-old female with psoriasis who presented with septicaemia and features of iatrogenic Cushing's syndrome due to treatment with topical corticosteroids for 2 years. Presentation of ICS as septicemia due to topical steroid use in this age group or in a psoriatic patient has not been described in the literature so far. Patient also developed hypertension and osteopenia, which are known adverse effects of corticosteroids; but occur rarely due to topical corticosteroids.

Lichenoid drug reaction due to anti-tubercular therapy presenting as erythroderma.

First-line anti-tubercular therapy (ATT) is very effective in management of tuberculosis and is usually well tolerated. Varied spectrum of cutaneous adverse drug reactions is associated with ATT, of which lichenoid drug eruption (LDR) constitutes approximately 10% of the cases. However, LDR presenting as erythroderma is very rare. Here, we report a case of exfoliative dermatitis secondary to LDR which developed after 5 months of ATT.

A prospective study of anti-mullerian hormone and other ovarian and adrenal hormones in adult female acne.

Polycystic ovarian syndrome (PCOS) diagnosis in adult female acne (AFA) is tough owing to unreliable ultrasonography in virgins or obese females and inconsistent hyperandrogenemia. We analyzed hormones in AFA and established a diagnostic cut-off value of anti-mullerian hormone (AMH) for PCOS. Female acne patients aged ≥25 years were assessed with total testosterone (TT), sex hormone binding globulin (SHBG), free androgen index (FAI), AMH, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Rotterdam's criteria defined PCOS. AMH was measured (Access AMH assay) to calculate the diagnostic cut off value using receiver operating characteristic (ROC) curve. Of 120 cases, 25.83% had PCOS. This group had significant clinical hyperandrogenism, truncal and adolescent acne, polycystic ovarian morphology (PCOM), and raised hormones (AMH, TT, FAI, LH, and LH/FSH). AMH levels were significantly higher in the PCOS group (6.91 ± 3.85 ng/mL) and positively correlated with TT, FAI, 17OHP, LH, and LH/FSH ratio. AMH at >5.1 ng/mL (sensitivity-70.97% and specificity-82.02%) predicted PCOS and correlated with PCOM. AMH (>5.1 ng/mL) is useful for diagnosing PCOS and surrogate for hyperandrogenemia and PCOM. Its correlation with hormones in non PCOS AFA highlights its sensitivity to diagnose endocrinological derangements.

Scabies: A comprehensive review and current perspectives.

Human scabies is a contagious skin infestation caused by the parasitic mite Sarcoptes scabiei var. hominis. It is a common skin disease worldwide that occurs not only in the underprivileged sections of society but also in developed countries. In 2009, World Health Organization (WHO) recognized scabies as "neglected tropical disease (NTD)" or NTD thus emphasizing the need for community awareness and proper treatment strategies. This review attempts to summarize the varied clinical presentation of the disease and describes the advances in diagnosis and management including the ongoing search for novel agents to overcome the problems associated with conventional treatments. The literature research includes peer-reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) till February 2020 and reference lists of respective articles. Only articles published in English language were included.

Relevant diagnostic implications of the therapeutic challenge with antitubercular therapy in an unusual case of sarcoidosis mimicking lupus vulgaris.

Cutaneous manifestations in sarcoidosis are seen in 25-35% of patients with systemic disease and may be the sole manifestation in few patients. It is known that isolated cutaneous sarcoidosis is a great mimicker and can be easily misdiagnosed as other granulomatous conditions especially lupus vulgaris in regions with high burden of tuberculosis (TB). Here we present a case with cutaneous sarcoidosis who was initially misdiagnosed and treated as bifocal lupus vulgaris with antitubercular therapy (ATT) for 6 months. This nonresponsiveness to therapy prompted us to investigate the patient further for other differentials, failing which a diagnosis of cutaneous sarcoidosis was made and the patient was treated with oral steroids and methotrexate with complete clearance of lesions after 14 weeks of therapy. Our case reemphasizes the value of therapeutic trial of ATT in diagnosis of cutaneous TB and highlights the remarkable clinical mimic of sarcoidosis with lupus vulgaris.

Microcystic lymphatic malformation in a child and his mother.

A 3-year-old boy presented to us with swelling of the right upper lip and the surrounding perioral area with the multiple clear fluid-filled grouped vesicles on the mucosal surface. The patient's mother had a similar swelling located at the same anatomic location extending to the cheek and the ala of nose on the same side. Magnetic resonance imaging and histopathological examination were suggestive of microcystic lymphatic malformation (LM) in both mother and child. Although an autosomal recessive inheritance pattern has been reported for isolated cystic hygromas, no familial case of microcystic LM has been reported previously.

Late onset nevus comedonicus of scalp: a rare site for an uncommon condition.

Nevus comedonicus is an uncommon hamartoma of the pilosebaceous unit characterized by keratin filled pits simulating open comedones. It may present at birth but is more commonly seen during childhood or adolescence. The most commonly affected sites are the face, neck, trunk, and arms with a few reported cases on palms, genitalia, and scalp. We report a case of a 19-year old woman with nevus comedonicus of the scalp that appeared in adolescence. This case has been presented for its sheer rarity, atypical site, and classic appearance.

Kinetics and cellular site of glycolipid loading control the outcome of natural killer T cell activation.

CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating alpha galactosylceramide (alphaGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for alphaGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokine-biasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing alphaGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can control the balance of proinflammatory and anti-inflammatory activities of NKT cells.

Pheniramine maleate: an apparently safe drug causing bullous fixed drug eruption.

Fixed drug eruption is a delayed type hypersensitivity reaction to a drug seen most frequently with antibiotics such as tetracyclines, sulfonamides, and NSAIDs such as naproxen and ibuprofen. Although H1-antihistamines rarely elicit cutaneous adverse effects, there have been a few reports in the literature implicating them in causing fixed drug eruption, particularly the piperazine derivatives (hydroxyzine, cetirizine, levocetirizine), and loratadine. However, cutaneous drug reactions with the alkylamine derivatives like pheniramine maleate are extremely uncommon and fixed drug eruptions have not been reported with any of the alkylamine antihistamines to date. We herein report a case of multifocal bullous fixed drug eruption following ingestion of pheniramine maleate.

Robotic Resistance Treadmill Training Improves Locomotor Function in Children With Cerebral Palsy: A Randomized Controlled Pilot Study.

OBJECTIVE: To determine whether applying controlled resistance forces to the legs during the swing phase of gait may improve the efficacy of treadmill training as compared with applying controlled assistance forces in children with cerebral palsy (CP). DESIGN: Randomized controlled study. SETTING: Research unit of a rehabilitation hospital. PARTICIPANTS: Children with spastic CP (N=23; mean age, 10.6y; range, 6-14y; Gross Motor Function Classification System levels, I-IV). INTERVENTIONS: Participants were randomly assigned to receive controlled assistance (n=11) or resistance (n=12) loads applied to the legs at the ankle. Participants underwent robotic treadmill training 3 times a week for 6 weeks (18 sessions). A controlled swing assistance/resistance load was applied to both legs starting from the toe-off to mid-swing phase of gait during training. MAIN OUTCOME MEASURES: Outcome measures consisted of overground walking speed, 6-minute walk distance, and Gross Motor Function Measure scores and were assessed pre and post 6 weeks of training and 8 weeks after the end of training. RESULTS: After 6 weeks of treadmill training in participants from the resistance training group, fast walking speed and 6-minute walk distance significantly improved (18% and 30% increases, respectively), and 6-minute walk distance was still significantly greater than that at baseline (35% increase) 8 weeks after the end of training. In contrast, overground gait speed and 6-minute walk distance had no significant changes after robotic assistance training. CONCLUSIONS: The results of the present study indicated that robotic resistance treadmill training is more effective than assistance training in improving locomotor function in children with CP.

Comparison of Q-switched Nd:YAG laser alone versus its combination with ultrapulse CO2 laser for the treatment of black tattoo.

BACKGROUND: Q-switched lasers are conventionally used for the treatment of black tattoo. However, they require multiple sittings, and the response may be slow due to competing epidermal pigment in dark skin. OBJECTIVE: To compare the efficacy of Q-switched Nd:YAG laser alone with its combination with ultrapulse CO2 for the removal of black tattoo. MATERIALS AND METHODS: Sixty patients with black tattoo were randomized into two groups viz., group A and group B. Group A was treated with QS Nd:YAG laser (1064 nm) alone, and group B received combination of ablative ultrapulse CO2 followed by fixed-dose QS Nd:YAG laser (1064 nm), at 6-week interval for a maximum of 6 sittings. After each sitting, 3 independent physicians noted percentage of improvement that was evaluated using visual analogue scale (VAS) and grading system for tattoo ink lightening (TIL). RESULTS: Combination laser (group B) showed statistically significant improvement in mean VAS score in the last 2 noted visits as compared to 1st session (p < 0.007, p < 0.001) and TIL mean score in last three noted visits as compared to 1st session (p < 0.008, p < 0.020, and p < 0.004). There was no statistically significant difference in the side effect profile of both the groups. CONCLUSION: For refractory professional tattoos, combination of ultrapulse CO2 laser and QS Nd:YAG laser is superior to QS Nd:YAG laser alone.

Glycolipid activators of invariant NKT cells as vaccine adjuvants.

Natural Killer T cells (NKT cells) are a subpopulation of T lymphocytes with unique phenotypic properties and a remarkably broad range of immune effector and regulatory functions. One subset of these cells, known as invariant NKT cells (iNKT cells), has become a significant focus in the search for new and better ways to enhance immunotherapies and vaccination. These unconventional T cells are characterized by their ability to be specifically activated by a range of foreign and self-derived glycolipid antigens presented by CD1d, an MHC class I-related antigen presenting molecule that has evolved to bind and present lipid antigens. The development of synthetic α-galactosylceramides as a family of powerful glycolipid agonists for iNKT cells has led to approaches for augmenting a wide variety of immune responses, including those involved in vaccination against infections and cancers. Here we review the basic background biology of iNKT cells that is relevant to their potential for improving immune responses, and summarize recent work supporting the further development of glycolipid activators of iNKT cells as a new class of vaccine adjuvants.

Translation, Adaptation, and Validation of Hindi Version of the Pain Catastrophizing Scale in Patients with Chronic Low Back Pain for Use in India.

OBJECTIVES : This study translates the Pain Catastrophizing Scale (PCS) into Hindi and examines the psychometric properties of the translated version (Hindi PCS [Hi-PCS]) in patients with chronic low back pain (CLBP). METHODS : Forward and backward translations were performed from English to Hindi according to standard methodology. A final version was evaluated by a committee of clinical experts and Hi-PCS was then pilot-tested in 10 patients with CLBP. Cross-cultural validation of the resulting adapted Hi-PCS was done by administering Hi-PCS at baseline to 100 patients with CLBP (≥ 12 weeks pain) who were able to read and write in Hindi, and re-administering Hi-PCS after 3 days. Construct validity was assessed using factor analysis. Psychometric properties including internal consistency; test-retest reliability; and convergent validity with pain severity, functional disability, and health-related quality of life (HRQoL) were also assessed. RESULTS : Principal component analysis observed a three-factor structure, which explained 58% of the variance. Confirmatory factor analysis elicited the best fit as judged by the model fit indices. Hi-PCS as a whole was deemed to be internally consistent (Cronbach's α = 0.76). Intraclass correlation coefficient for the Hi-PCS is 0.923 (95% CI: 0.875-0.953). Hi-PCS was moderately correlated with pain intensity (r = 0.651) and functional disability (r = 0.352), and negatively correlated with QoL (r = -0.380). CONCLUSIONS : PCS translation and cross-cultural adaptation to Hindi demonstrated good factor structure along adequate psychometric properties and could be recommended for use in CLBP research in India.

Kinematic and EMG Responses to Pelvis and Leg Assistance Force during Treadmill Walking in Children with Cerebral Palsy.

Treadmill training has been used for improving locomotor function in children with cerebral palsy (CP), but the functional gains are relatively small, suggesting a need to improve current paradigms. The understanding of the kinematic and EMG responses to forces applied to the body of subjects during treadmill walking is crucial for improving current paradigms. The objective of this study was to determine the kinematics and EMG responses to the pelvis and/or leg assistance force. Ten children with spastic CP were recruited to participate in this study. A controlled assistance force was applied to the pelvis and/or legs during stance and swing phase of gait through a custom designed robotic system during walking. Muscle activities and spatial-temporal gait parameters were measured at different loading conditions during walking. In addition, the spatial-temporal gait parameters during overground walking before and after treadmill training were also collected. Applying pelvis assistance improved step height and applying leg assistance improved step length during walking, but applying leg assistance also reduced muscle activation of ankle flexor during the swing phase of gait. In addition, step length and self-selected walking speed significantly improved after one session of treadmill training with combined pelvis and leg assistance.