Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity

Sulfatide derived from the myelin stimulates a distinct population of CD1d-restricted natural killer T (NKT) cells. Cis-tetracosenoyl sulfatide is one of the immunodominant species in myelin as identified by proliferation, cytokine secretion, and CD1d tetramer staining. The crystal structure of mouse CD1d in complex with cis-tetracosenoyl sulfatide at 1.9 Å resolution reveals that the longer cis-tetracosenoyl fatty acid chain fully occupies the A′ pocket of the CD1d binding groove, whereas the sphingosine chain fills up the F′ pocket. A precise hydrogen bond network in the center of the binding groove orients and positions the ceramide backbone for insertion of the lipid tails in their respective pockets. The 3′-sulfated galactose headgroup is highly exposed for presentation to the T cell receptor and projects up and away from the binding pocket due to its β linkage, compared with the more intimate binding of the α-glactosyl ceramide headgroup to CD1d. These structure and binding data on sulfatide presentation by CD1d have important implications for the design of therapeutics that target T cells reactive for myelin glycolipids in autoimmune diseases of the central nervous system

Acute effects of hydroxychloroquine prophylaxis for COVID-19 in health care professionals – An online survey

707-712Hydroxychloroquine, an antimalarial, is being used worldwide for prophylaxis and treatment of Corona virus disease-19 (COVID-19). Though the drug is commonly used in many chronic inflammatory diseases for protracted periods, its safety in the new indication is still under scrutiny. Therefore, this institute based study sought to assess the acute adverse effects of hydroxychloroquine among in-house health care professionals who were taking the drug for COVID-19 prophylaxis. A questionnaire seeking information on the use of the drug was prepared and disseminated electronically to the target population. The responses were also received electronically and analysed. The participants (n=54) had taken prophylaxis for 1-7 weeks. The most common adverse effects in the cohort were nausea (02) and skin rash (02). The total number of adverse effects reported by the participants was 08. One incidence each of gastric upset (01), dizziness (01), pain abdomen (01), and chest tightness (01) was reported. None of the adverse effects were serious. Our study indicates that the prophylactic weekly single dose of hydroxychloroquine is not associated with any serious adverse effects within 1-7 weeks of initiation. Elucidation of the long term and chronic adverse effects, if any, requires further studies

Acute effects of hydroxychloroquine prophylaxis for COVID-19 in health care professionals – An online survey

Hydroxychloroquine, an antimalarial, is being used worldwide for prophylaxis and treatment of Corona virus disease-19 (COVID-19). Though the drug is commonly used in many chronic inflammatory diseases for protracted periods, its safety in the new indication is still under scrutiny. Therefore, this institute based study sought to assess the acute adverse effects of hydroxychloroquine among in-house health care professionals who were taking the drug for COVID-19 prophylaxis. A questionnaire seeking information on the use of the drug was prepared and disseminated electronically to the target population. The responses were also received electronically and analysed. The participants (n=54) had taken prophylaxis for 1-7 weeks. The most common adverse effects in the cohort were nausea (02) and skin rash (02). The total number of adverse effects reported by the participants was 08. One incidence each of gastric upset (01), dizziness (01), pain abdomen (01), and chest tightness (01) was reported. None of the adverse effects were serious. Our study indicates that the prophylactic weekly single dose of hydroxychloroquine is not associated with any serious adverse effects within 1-7 weeks of initiation. Elucidation of the long term and chronic adverse effects, if any, requires further studies

Human immunodeficiency virus endocrinopathy

Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients

IL-4 Alone without the Involvement of GM-CSF Transforms Human Peripheral Blood Monocytes to a CD1adim, CD83+ Myeloid Dendritic Cell Subset

Myeloid dendritic cells (DCs) are conventionally generated by culturing human peripheral blood monocytes in the presence of GM-CSF and IL-4. Here we report that IL-4 alone, in the absence of detectable endogenous GM-CSF, transforms human peripheral blood monocytes to a CD1adim DC subset that could be matured to CD83+ DCs. Absence of endogenous GM-CSF in IL-4-DC was demonstrated by RT-PCR and flow cytometry. With the exception of CD1a expression, surface marker, morphology and phagocytic activity of these DCs (IL-4-DC) were similar to myeloid DCs (GM-IL-4-DC) conventionally generated in the presence of GM-CSF and IL-4. Conventional GM-IL-4-DC produced less IL-12 compared with IL-4-DC after stimulation with anti-CD40 monoclonal antibody, or LPS plus IFN-g, although the difference was more prominent when LPS plus IFN-g was used as the stimulus. The GM-IL-4-DC also induced less frequent IFN- g+ T cells in a mixed leukocyte reaction (MLR) than that of IL-4-DC. Yields of IL-4-DCs were marginally lower than that of GM-IL-4-DCs. Our data indicate that peripheral blood monocytes can be transformed to CD1a-deficient myeloid DCs solely by IL-4, and these IL-4-DCs are likely to induce a stronger Th1 response than conventional GMIL- 4-DC

Privacy Preserving Multi-Party Key Exchange Protocol for Wireless Mesh Networks

Presently, lightweight devices such as mobile phones, notepads, and laptops are widely used to access the Internet throughout the world; however, a problem of privacy preservation and authentication delay occurs during handover operation when these devices change their position from a home mesh access point (HMAP) to a foreign mesh access point (FMAP). Authentication during handover is mostly performed through ticket-based techniques, which permit the user to authenticate itself to the foreign mesh access point; therefore, a secure communication method should be formed between the mesh entities to exchange the tickets. In two existing protocols, this ticket was not secured at all and exchanged in a plaintext format. We propose a protocol for handover authentication with privacy preservation of the transfer ticket via the Diffie–Hellman method. Through experimental results, our proposed protocol achieves privacy preservation with minimum authentication delay during handover operation