Atypical presentation of scrub typhus encephalitis with cerebral hemorrhage

Scrub typhus, an arthropod borne infection caused by the rickettsial organism Orientia tsutsugamushi, is a fairly common disease in north-eastern sub-Himalayan India, particularly the forest areas, and is known to manifest with varied presentations ranging from non-specific fever to severe multi-organ complications. Hemorrhagic manifestations described in the literature are mostly gastrointestinal and genitourinary, secondary to vasculitis and/or thrombocytopenia, but reports of cerebral hemorrhage have been extremely rare. We report a case from sub-Himalayan eastern India where a 23 years old male tea plantation worker presented with recurrent convulsions with magnetic resonance imaging (MRI) brain showing multiple parenchymal hemorrhages with encephalitis involving both the cerebral hemispheres. Although patient developed fever and acute kidney injury later in the course, these were not the presenting complaints despite fever being the most consistent sign of a scrub typhus infection. We suggest consideration of scrub typhus as a differential diagnosis of a cerebral hemorrhage in endemic regions

Neutron Star Physics in the Square Kilometre Array Era: An Indian Perspective

It is an exceptionally opportune time for astrophysics when a number of next-generation mega-instruments are poised to observe the Universe across the entire electromagnetic spectrum with unprecedented data quality. The Square Kilometre Array (SKA) is undoubtedly one of the major components of this scenario. In particular, the SKA is expected to discover tens of thousands of new neutron stars giving a major fillip to a wide range of scientific investigations. India has a sizeable community of scientists working on different aspects of neutron star physics with immediate access to both the uGMRT (an SKA pathfinder) and the recently launched X-ray observatory Astrosat. The current interests of the community largely centre around studies of (a) the generation of neutron stars and the SNe connection, (b) the neutron star population and evolutionary pathways, (c) the evolution of neutron stars in binaries and the magnetic fields, (d) the neutron star equation of state, (e) the radio pulsar emission mechanism, and (f) the radio pulsars as probes of gravitational physics. Most of these studies are the main goals of the SKA first phase, which is likely to be operational in the next four years. This article summarizes the science goals of the Indian neutron star community in the SKA era, with significant focus on coordinated efforts among the SKA and other existing/upcoming instruments

Etiological Study of Fever of Unknown Origin in Patients Admitted to Medicine Ward of a Teaching Hospital of Eastern India

Background: In a developing country, infectious disease remains the most important cause of fever, but the noncommunicable diseases, like malignancy, are fast becoming important differential diagnoses. An important clinical problem is the cases labeled as fever of unknown origin (FUO), which often evade diagnosis. Objective: The present study was undertaken to find the cause of FUO in a tertiary care hospital of eastern India. Materials and Methods: This is a prospective study of inpatients, with regard to both clinical signs and investigations. Results: The main diagnosis in the end was tuberculosis, closely followed by hematological malignancy. A substantial number of cases remained undiagnosed despite all investigations. The provisional diagnosis matched with the final in around two thirds of the cases. While for younger patients leukemia was a significant diagnosis, for older ones, extra-pulmonary tuberculosis was a main concern. Interpretation: In India, infectious disease still remains the most important cause of fever. Thus the initial investigations should always include tests for that purpose in a case of FUO. Conclusion: Geographic variations and local infection profiles should always be considered when investigating a case of FUO. However, some of the cases always elude diagnosis, although the patients may respond to empirical therapy

Atypical presentation of scrub typhus encephalitis with cerebral hemorrhage

International audienceScrub typhus, an arthropod borne infection caused by the rickettsial organism Orientia tsutsugamushi, is a fairly common disease in north-eastern sub-Himalayan India, particularly the forest areas, and is known to manifest with varied presentations ranging from non-specific fever to severe multi-organ complications. Hemorrhagic manifestations described in the literature are mostly gastrointestinal and genitourinary, secondary to vasculitis and/or thrombocytopenia, but reports of cerebral hemorrhage have been extremely rare. We report a case from sub-Himalayan eastern India where a 23 years old male tea plantation worker presented with recurrent convulsions with magnetic resonance imaging (MRI) brain showing multiple parenchymal hemorrhages with encephalitis involving both the cerebral hemispheres. Although patient developed fever and acute kidney injury later in the course, these were not the presenting complaints despite fever being the most consistent sign of a scrub typhus infection. We suggest consideration of scrub typhus as a differential diagnosis of a cerebral hemorrhage in endemic regions

Interaction of KSHV with Host Cell Surface Receptors and Cell Entry

Virus entry is a complex process characterized by a sequence of events. Since the discovery of KSHV in 1994, tremendous progress has been made in our understanding of KSHV entry into its in vitro target cells. KSHV entry is a complex multistep process involving viral envelope glycoproteins and several cell surface molecules that is utilized by KSHV for its attachment and entry. KSHV has a broad cell tropism and the attachment and receptor engagement on target cells have an important role in determining the cell type-specific mode of entry. KSHV utilizes heparan sulfate, integrins and EphrinA2 molecules as receptors which results in the activation of host cell pre-existing signal pathways that facilitate the subsequent cascade of events resulting in the rapid entry of virus particles, trafficking towards the nucleus followed by viral and host gene expression. KSHV enters human fibroblast cells by dynamin dependant clathrin mediated endocytosis and by dynamin independent macropinocytosis in dermal endothelial cells. Once internalized into endosomes, fusion of the viral envelope with the endosomal membranes in an acidification dependent manner results in the release of capsids which subsequently reaches the nuclear pore vicinity leading to the delivery of viral DNA into the nucleus. In this review, we discuss the principal mechanisms that enable KSHV to interact with the host cell surface receptors as well as the mechanisms that are required to modulate cell signaling machinery for a successful entry

CIB1 synergizes with EphrinA2 to regulate Kaposi's sarcoma-associated herpesvirus macropinocytic entry in human microvascular dermal endothelial cells.

KSHV envelope glycoproteins interact with cell surface heparan sulfate and integrins, and activate FAK, Src, PI3-K, c-Cbl, and Rho-GTPase signal molecules in human microvascular dermal endothelial (HMVEC-d) cells. c-Cbl mediates the translocation of virus bound α3β1 and αVβ3 integrins into lipid rafts (LRs), where KSHV interacts and activates EphrinA2 (EphA2). EphA2 associates with c-Cbl-myosin IIA and augmented KSHV-induced Src and PI3-K signals in LRs, leading to bleb formation and macropinocytosis of KSHV. To identify the factor(s) coordinating the EphA2-signal complex, the role of CIB1 (calcium and integrin binding protein-1) associated with integrin signaling was analyzed. CIB1 knockdown did not affect KSHV binding to HMVEC-d cells but significantly reduced its entry and gene expression. In contrast, CIB1 overexpression increased KSHV entry in 293 cells. Single virus particle infection and trafficking during HMVEC-d cell entry was examined by utilizing DiI (envelope) and BrdU (viral DNA) labeled virus. CIB1 was associated with KSHV in membrane blebs and in Rab5 positive macropinocytic vesicles. CIB1 knockdown abrogated virus induced blebs, macropinocytosis and virus association with the Rab5 macropinosome. Infection increased the association of CIB1 with LRs, and CIB1 was associated with EphA2 and KSHV entry associated signal molecules such as Src, PI3-K, and c-Cbl. CIB1 knockdown significantly reduced the infection induced EphA2, Src and Erk1/2 activation. Mass spectrometry revealed the simultaneous association of CIB1 and EphA2 with the actin cytoskeleton modulating myosin IIA and alpha-actinin 4 molecules, and CIB1 knockdown reduced EphA2's association with myosin IIA and alpha-actinin 4. Collectively, these studies revealed for the first time that CIB1 plays a role in virus entry and macropinocytosis, and suggested that KSHV utilizes CIB1 as one of the key molecule(s) to coordinate and sustain the EphA2 mediated signaling involved in its entry, and CIB1 is an attractive therapeutic target to block KSHV infection

Involvement of novel PKC isoforms in FFA induced defects in insulin signaling

Involvement of novel PKCs (nPKCs) in the negative regulation of insulin-signaling pathway is a current interest of many workers investigating the cause for insulin resistance and type 2 diabetes. Free fatty acids (FFAs) are recently shown to be the major players in inducing insulin resistance in insulin target cells. They are also found to be involved in activating nPKCs associated with the impairment of insulin sensitivity. In this overview, we describe PKC δ, θ and ε linked to the FFA induced damage of insulin-signaling molecules