Cut-insert-stitch editing reaction (CIStER) sequence for surgical chemical glycan editing.

Post-synthetic surgical editing enables synthesizing diverse molecules from a common scaffold. Editing carbohydrates by inserting a foreign glycan is still a far-reaching goal for synthetic chemists. In this study, a one-pot-three-step chemical approach was employed to edit glycoconjugates. It is comprised of three steps: the first is a 'cut' step, cleaving one of the interglycosidic bonds and producing an intermediate that could be intercepted with 4-mercaptotoluene; second step activates the thiotolyl glycoside in the presence of an aglycon containing an orthogonally activatable ethynylcycloxyl carbonate moiety; and the third step involves 'stitching' by activating the carbonate donor. The cut-insert stitch-editing reaction (CIStER) is demonstrated by inserting branched and linear arabinans reminiscent of M. tuberculosis cell wall from the same designer trimannoside. Glycosylating an activated hydroxyacid (serinyl, steroidal, and lipid) after cutting the interglycosidic bond and stitching in the presence of base extendes the CIStER approach to the synthesis of glycohybrids.

Dolutegravir-induced hand-foot skin reaction in a seropositive male: A rare presentation.

Hand-foot skin reaction (HFSR) is a specific but uncommon cutaneous side effect mainly following chemotherapeutic drugs such as multitargeted kinase inhibitors. HFSR is reversible and non-life-threatening. HFSR, also known as palmoplantar erythrodysesthesia, presents with various degrees of erythema, edema, hyperkeratosis, blister, and sometimes with a fine white scale. Dolutegravir, a first next-generation integrase inhibitor, is used with other antiretroviral therapy (ART) to treat mainly HIV infections. HFSR is diagnosed depending on the suggestive association of drug intake and characteristic palmoplantar eruption. ART can cause several cutaneous adverse drug reactions though no case report of dolutegravir-induced HFSR has been reported till date in literature. Here, we present a case of HFSR in a seropositive male on ART.

Hydrometeorological field instrumentation in Lesser Himalaya to advance research for future water and food security.

Hydrometeorological monitoring and continuous data collection in ungauged mountainous regions are exciting and challenging for water resource planners compared to the measurement in plain areas. Lesser Himalayas in the mountainous areas face the insufficiency of continuous hydrometeorological data, hindering our understanding of hydrological processes and hampering integrated water resources management. This present study focuses on the setup of the field instruments for collecting hydrometeorological data and analyzing continuously collected data at Aglar watershed to assess hydrometeorological parameters' spatial and temporal distribution. The instrumentation includes monitoring one sub-surface flow, five stream flows, four rain gauges, and one automatic weather station. The relationship between the stage and the discharge was established based on the collected data for three streams. The analyzed seasonal rainfall revealed 726.7 mm of rain occurred during the monsoon with an intensity of less than 16 mm/day. The Paligaad sub-watershed displayed a flashy response towards the rainfall events, whereas the Upper Aglar exhibited a wide range of dampening runoff responses for different rainfall events. The monitored sub-surface flow varies annually, and during the monsoon season, interflow and baseflow hydrograph decayed more rapidly at the rate of 0.04 day-1 and 0.78 day-1, respectively. The installed AWS has been used to measure crop water requirements and plan for better strategies to cope with future food and water security. The high-frequency generated data will help answer the queries related to hydrological responses of different watershed characteristics.

Could It be Wolf Isotopic Response?: Occurrence of Dermatophytoses on Vitiliginous Skin-Case Series of Five Cases from a Tertiary Care Centre in India.

Wolf isotopic response is the occurrence of new dermatoses on areas of the skin with previous but still active dermatoses. Vitiligo is an acquired disorder characterized by the loss of functional melanocytes which manifests as circumscribed depigmented macules and patches. Dermatophytoses are superficial fungal infections caused by three genera of fungi (Microsporum, Trichophyton, and Epidermophyton) that have the unique ability to invade and multiply within keratinized tissue (skin, hair, and nail). The appearance of dermatophyte infection on previously present vitiligo lesion is an uncommon example of Wolf response. We describe a case series of five vitiligo patients that presented to our OPD over 1 year period.

Coordinated activities of Myosin Vb isoforms and mTOR signaling regulate epithelial cell morphology during development.

The maintenance of epithelial architecture necessitates tight regulation of cell size and shape. However, mechanisms underlying epithelial cell size regulation remain poorly understood. We show that the interaction of Myosin Vb with Rab11 prevents the accumulation of apically derived endosomes to maintain cell-size, whereas that with Rab10 regulates vesicular transport from the trans-Golgi. These interactions are required for the fine-tuning of the epithelial cell morphology during zebrafish development. Furthermore, the compensatory cell growth upon cell-proliferation inhibition involves a preferential expansion of the apical domain, leading to flatter epithelial cells, an efficient strategy to cover the surface with fewer cells. This apical domain growth requires post-trans-Golgi transport mediated by the Rab10-interacting Myosin Vb isoform, downstream of the mTOR-Fatty Acid Synthase (FASN) axis. Changes in trans-Golgi morphology indicate that the Golgi synchronizes mTOR-FASN-regulated biosynthetic input and Myosin Vb-Rab10 dependent output. Our study unravels the mechanism of polarized growth in epithelial cells and delineates functions of Myosin Vb isoforms in cell size regulation during development.

Climate change water vulnerability and adaptation mechanism in a Himalayan City, Nainital, India.

Urban water management is a growing concern in India's rapidly urbanizing cities. Population growth and climatic variability are exuberating the impact on surface and underground water supply. Understanding the causes and the extent of water vulnerability is required for developing effective strategies for water insecurities. This study attempts to assess the water vulnerability across different wards of a touristic city of Himalaya-Nainital using IPCC approach considering the three dimensions: exposure, sensitivity, and adaptive capacity. Seven indicators, mostly spatial, i.e. edaphic (aspect, elevation) and climatic (land surface temperature) besides some water infrastructural (distance to water distribution) and population, were considered for development of vulnerability index using Analytical Hierarchy Process for assigning weights. These indicators were simple to extract and easy to obtain and mostly available from secondary sources and were capable to account the variability at micro-level. Moreover, the current adaptation mechanisms for water security were also derived through conducting surveys by randomly selecting households across the wards. Staff House and Harinagar wards were the most vulnerable. The survey results that the adaptation mechanism should be managed at individual and organization level. Policy measures such as optimum use of water, grey water recycling, spring rejuvenation, rain water harvesting, and leakage proof infrastructure with intervention of new technologies, may be adopted and implemented for reducing the water vulnerability in the city along with the public participation. The appropriate measures for water vulnerability would further provide support for improving the facilities to the tourists in the city thereby improved economic opportunities to the locals.

Extracorporeal Therapy in Dermatology.

Extracorporeal therapy is a treatment modality where human blood undergoes favorable technical modifications and is reintroduced into the same patient. Since the last four decades this technique has been deployed in the management of difficult and refractory disorders in dermatology. Over a period of time newer techniques like immunoadsorption has emerged and opened new vistas in management of morbid dermatoses. In extracorporeal photopheresis a patient's leukocytes are separated and treated outside with Ultra Violet A in presence of 8-methoxypsoralen. Double filtration plasmapheresis and Immunoadsorption are techniques to remove offending immune complexes. They are safe and reduce the need of toxic medications that are conventionally used in recalcitrant skin diseases. In recent years immunoadsorption is emerging as first-line therapy in condition like immunobullous diseases. High cost is one of the important factors limiting their wider use in developing countries like India. Our review discusses different extracorporeal therapies, their applications, recommendations and guidelines based on various clinical trials.

Disseminated violaceous plaques in a HIV-1-positive patient from eastern India: A manifestation of Kaposi's sarcoma.

Kaposi's sarcoma (KS) is an angioproliferative disorder primarily of viral etiology, though multiple cofactors are also responsible. Human herpes virus-8, a gamma herpes virus, is considered to be the causative agent. Acquired immunodeficiency syndrome-associated KS has different clinical pictures than those seen in other types of KS. As it progresses rapidly, early institution of highly active antiretroviral therapy (HAART) after proper diagnosis is expected. Though HAART has reduced the prevalence of KS in HIV disease, HAART has not eliminated the disease. Here, we report a case who is HIV 1 and hepatitis B surface antigen positive with numerous violaceous plaques over the face, upper extremities, and trunk along with oral mucosal involvement. He had received ten sessions of electron beam radiotherapy on the face, and the facial lesions have healed with residual hyperpigmentation.

Disseminated Cutaneous Rhinosporidiosis: Revisited.

A vegetative growth in the nasal mucosa and nasopharynx present for a considerable period of time raises the possibility of rhinosporidiosis. Such presentation in the Indian subcontinent is not rare but erythematous cauliflower-like or tumor-like growths often reaching large size present on various areas of the skin without necessarily involving the nasal apparatus are often confusing to the attending clinician. A dermatologist may suspect the disseminated form of cutaneous rhinosporidiosis and perform a diagnostic histopathology. Early institution of treatment may give significant relief to the patient.

Randomized controlled trial of topical mupirocin versus mupirocin with sucralfate combination in chronic skin ulcers.

OBJECTIVES: The objective of this study was to carry out a head-to-head comparison of topical sucralfate combined with mupirocin versus mupirocin alone in the treatment of chronic skin ulcers with respect to both effectiveness and safety. MATERIALS AND METHODS: A parallel-group, open-label, randomized, controlled trial (CTRI/2015/12/006443) was carried out with patients suffering from skin ulcers of Wagner grading 1 or 2 persisting for over 4 weeks. Ninety-six patients were recruited in total, and the modified intention-to-treat analysis dataset included 44 participants treated with mupirocin 2% and 46 treated with combined mupirocin 2% and sucralfate 7% ointment. Both medications were applied topically thrice daily for 6 weeks. Ulcer area assessed using millimeter graph paper and wound infection score assessed on a three-point scale were effectiveness measures. Treatment-emergent adverse reactions that were reported by patients or observed by the investigators were recorded. RESULTS: The median ulcer area was significantly reduced in the combined treatment group at the end of treatment. Clinically, 41.3% of the participants in the combined group showed complete ulcer healing at 6 weeks compared to 18.18% in the mupirocin alone group (P = 0.022). The wound infection score declined significantly from baseline by the end of 3 weeks of treatment in both the groups. The frequency of qualitative wound attributes, namely pain, discharge, and erythema, remained comparable between the groups except for discharge which disappeared completely from all remaining ulcers in the combined group but was still present in 11.36% of the participants treated with mupirocin alone (P = 0.025) at 6 weeks. Adverse events were few, all local, mild, and tolerable. CONCLUSIONS: The wound healing effect of topical sucralfate adds to the antimicrobial effect of mupirocin toward the overall improvement of chronic skin ulcers. The effect of combined topical treatment needs comparison with other topical medications and wound healing strategies.

MORFAN Syndrome: A Rarity but a Reality!

Acanthosis nigricans (AN) describes clinically hyperpigmented skin, which most commonly affects the flexural areas such as axilla, groin and neck. It is usually a benign condition associated with obesity, insulin resistance, and hyperinsulinemia; endocrinopathy; or malignancy, in particular, gastrointestinal adenocarcinoma. It can also occur in association with various genetic syndromes involving various organ systems. Few such known syndromes are Berardinelli-Seip syndrome, Alström syndrome, Leprechaunism, and Bardet-Biedl syndrome. MORFAN syndrome, which associates mild mental retardation, pre- and post-natal overgrowth, remarkable facies and diffuse and widespread AN, is a rare entity.

Clinicopathological Study of Primary Cutaneous Amyloidosis in a Tertiary Care Center of Eastern India Reveals Insignificant Association with Friction, Scrubbing, and Photo-Exposure: How valid is the "Keratinocyte Hypothesis"?

INTRODUCTION: Primary cutaneous amyloidosis (PCA) can be classified into four principal categories: macular amyloidosis, lichen amyloidosis, biphasic, and nodular amyloidosis. Some unusual variants such as widespread diffuse hyperpigmentation without papules, poikiloderma like involvement, lesions following Blaschko's line, etc., have also been reported. However, not much data are available regarding the demography, epidemiology, clinical patterns, and distribution and histopathological findings, especially from the eastern part of India. AIMS: We conducted a cross-sectional, institution-based study to evaluate clinicopathological pattern and factors of PCA in eastern India. MATERIALS AND METHODS: We recorded clinical and histopathological findings of 100 consecutive patients of PCA presenting to a tertiary care institution of Kolkata in eastern India. RESULTS: We found female patients of PCA outnumber male (M:F =1:1.9) with majority of patients being young adults (56%) between 20 and 40 years of age. More than half (54%) of the patients were pruritic. The severity of pruritus is significantly more associated with lichenoid and biphasic variants over macular amyloidosis. Positive family history was recorded in 17% of cases. Macular variant was the most common variant constituting 48% of the total PCA. We also found that the association with history of friction and scrubbing and photo-exposure were statistically insignificant. However, duration of the disease has statistically significant association with the disease morphology. Congo red stain showed these deposits as reddish orange substance in 28 patients out of 64 patients' samples on which Congo red could be performed. CONCLUSION: Our study revealed that many concepts of pathogenesis of PCA including friction and photoexposure might have lesser importance. However, morphological types were significantly associated with the duration of the disease and symptom severity.

LED virtual windows are valuable in windowless consultation rooms.

INTRODUCTION: Due to the design of Hvidovre Hospital, the outpatient clinic of the Department of Paediatrics has windowless consultation rooms. Work environment surveys revealed that nurses and doctors working in these windowless rooms considered the lack of natural light a considerable health problem. This study evaluated the effects of installing light-emitting diode (LED) virtual windows in these rooms. METHODS: Four similar windowless consultations rooms located next to each other were used in the study. All had older T-5 fluorescent luminaires installed. In two of these rooms, Servodan LED virtual windows depicting various natural scenes were installed. The illuminance and correlated colour temperature (CCT) of each room's lighting was measured, and a work environment questionnaire was filled out by nurses and doctors working in each room. RESULTS: A total of 113 questionnaires were collected and evaluated. LED virtual windows produced an improved perception of lighting conditions, both at the desk (p < 0.001) and in the rooms in general (p < 0.001) and improved the overall positive experience of the rooms (p = 0.02). A tendency towards concentration difficulties was reported less often in the rooms with LED virtual windows, (p = 0.11). Retinal illuminance (p = 0.02) as well as CCT at the desk (p < 0.005) and at the retina (p < 0.01) alike were increased in rooms with LED virtual windows. CONCLUSIONS: LED virtual windows improved the lighting experience, the impression of the space, the retinal illuminance and the CCT at the desk and at the retina in the windowless rooms. FUNDING: none. TRIAL REGISTRATION: not relevant.

Use of Fine Needle Aspirate from Peripheral Nerves of Pure-neural Leprosy for Cytology and Polymerase Chain Reaction to Confirm the Diagnosis: A Follow-up Study of 4 Years.

BACKGROUND: Pure neural leprosy (PNL) still remains a diagnostic challenge because of the absence of sine qua non skin lesions of leprosy and a confirmatory diagnostic method. The authors had earlier described a simple yet objective technique of combining fine needle aspiration cytology (FNAC) coupled with a multiplex polymerase chain reaction (PCR) in a pilot study, wherein the technique showed promise of a reliable diagnostic tool. In the pursuit of further evidence, the authors carried out a 4-year study with PNL cases to find the efficacy and reliability of the said method in a larger sample size. AIM: This study was conducted to find the efficacy, reliability, and reproducibility of FNAC coupled with multiplex PCR and Ziehl-Neelsen (ZN) staining in identifying the cases of PNL. MATERIALS AND METHODS: All cases that were suspected to be suffering from PNL, following evaluation by two independent observers were included in the study and were subjected to FNAC from the affected nerve, and the aspirates were evaluated for cytology, ZN staining, and multiplex PCR for Mycobacterium leprae genome. In addition, serum anti-PGL1 levels were also performed in all the study subjects. Fifteen non-PNL cases were also included in the control arm. RESULTS: A total of 47 cases were included in the test arm and subjected to FNAC. Conventional ZN staining could demonstrate acid-fast bacilli (AFB) in only 15 out of 47 cases (31.91%) while M. leprae DNA could be elicited in 37 (78.72%) cases by the multiplex PCR. Only 13 (27.65%) out of 47 cases showed anti-PGLI-1 antibody positivity. On cytological examination of the nerve aspirates, only 11 (23.40%) cases showed epithelioid cells whereas nonspecific inflammation was seen in 26 (75.60%) cases. CONCLUSION: The results of this study conducted over a larger sample size corroborate with the findings of our pilot study. In a resource poor set up, FNAC in combination with ZN staining and multiplex PCR is a rapid, simple, and easily performed test, which can give a reproducible and objective diagnosis in cases of PNL.