Corpectomy for multi-level cervical spondylosis and ossification of the posterior longitudinal ligament

The choice of a surgical approach for multi-level cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) is still a controversial issue. While most of the surgeons are still performing decompression by laminectomy some are doing multi-level anterior decompression. Few neurosurgeons are performing decompression by corpectomy. We have treated 26 patients by median cervical corpectomy during the last 4 years. These patients were followed up for a mean period of 25 months. Twenty one (80%) patients had a good outcome, 2 patients remained unchanged and 3 expired. Review of the literature and our experience indicates that patients with CSM and OPLL should be operated by median cervical corpectomy (anterior approach).     

Enhanced molecular volume of conservatively pegylated Hb: (SP-PEG5K)6-HbA is non-hypertensive

Recent studies have suggested that the "pressor effect" of acellular Hb is a consequence of perturbation of the macro-and microcirculatory system in multiple ways, and that PEGylation is an effective approach for controlling the same. In an attempt to confirm this concept, a new and simple thiolation mediated, maleimide chemistry-based conservative PEGylation protocol has been developed to conjugate multiple copies of PEG-chains to Hb. This approach combines the high reactivity of maleimides towards thiols with the propensity of iminothiolane to derivatize the epsilon-amino groups of proteins into reactive thiol groups, with conservation of their positive charge. One of the PEGylated products, namely (SP-PEG5K)6-HbA, that carries on an average six copies of PEG5000 chains per Hb, is non-hypertensive in hamster top load and in rat 50% exchange transfusion models. This hexa-PEGylated-Hb has (i) a hydrodynamic volume corresponding to that of an oligomerized Hb of 256kDa, (ii) a molecular radius of approximately 6.8 nm, (iii) high oxygen affinity, (iv) lowered Bohr effect, and (v) increased viscosity and colloidal osmotic pressure. These properties of (SP-PEG5K)6-HbA are consistent with the emerging new paradigms for the design of Hb based oxygen carriers and confirm the concept that the "pressor effect" of Hb is a multifactorial event. The thiolation mediated maleimide chemistry-based PEGylation protocol described here for the generation of (SP-PEG5K)6-Hb is simple, highly efficient, and is carried out under oxy conditions. The results demonstrate that a non-hypertensive PEG-Hb can be generated by conjugation of a lower number of PEG chains than previously reported.     

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

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Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases

The expansion of trinucleotide repeat sequences is associated with several neurodegenerative diseases. The mechanism of this expansion is unknown but may involve slipped-strand structures where adjacent rather than perfect complementary sequences of a trinucleotide repeat become paired. Here, we have studied the interaction of the human mismatch repair protein MSH2 with slipped-strand structures formed from a triplet repeat sequence in order to address the possible role of MSH2 in trinucleotide expansion. Genomic clones of the myotonic dystrophy locus containing disease-relevant lengths of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two types of slipped-strand structures by annealing complementary strands of DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex slipped structures or S-DNA) or (ii) different numbers of repeats (heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of either CTG or CAG repeats were structurally distinct and could be separated electrophoretically and studied individually. Using a band-shift assay, the MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific manner. The affinity of MSH2 increased with the length of the repeat sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat sequences, implicating a strand asymmetry in MSH2 recognition. Our results are consistent with the idea that MSH2 may participate in trinucleotide repeat expansion via its role in repair and/or recombination.      

Development of a composite indicator to prioritize districts for implementation of human immunodeficiency virus programmes in Maharashtra,India

A key recommendation of the National AIDS Control Programme‐IV of India was to develop new strategies for geo‐prioritization of the human immunodeficiency virus (HIV) epidemic. We conducted this study to categorize the districts in Maharashtra (India) based on a multidimensional framework for geo‐prioritization of services. Programmatic data on trends of HIV prevalence, coverage of marginalized populations and vulnerability factors were included. A composite indicator based on these was developed, and the cumulative score was calculated for each district. HIV prevalence among general population has declined steadily from 0.60% in 2007 to 0.33% in 2017. The programme coverage was stable but inadequate for men who have sex with men (MSM). The coverage for female sex workers (FSWs) was inadequate and reduced over time. Nine districts were categorized as high priority, 13 as moderate priority and 11 were classified as low‐priority districts based on burden and vulnerability for HIV. The high‐priority districts were Pune, Solapur and Yavatmal for FSW interventions and Pune, Thane and Latur for MSM interventions. This multidimensional indicator is based on existing programmatic data, dynamic and can be made state‐specific. It is useful to categorize and prioritize districts for allocation of resources and geo‐prioritization of services in resource limited settings.     

Respiratory syncytial virus infection: Clinical presentation and management

Summary RSV infection continues to be a major cause of morbidity and mortality throughout the world. Despite advances in the understanding of its pathogenesis, limited progress has been made in prevention and treatment of RSV infection. Based on the experiences thus far it seems that control of RSV infection will be a difficult and complex task.     

A ten year serological survey of hepatitis A, B and C viruses infections in Nepal

BACKGROUND: In 1987, we reported that the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Nepal was low, as compared to hepatitis A virus (HAV) infection, and that no human T-lymphotropic type-1 (HTLV-1) infection was found in Nepal. OBJECTIVES: To determine changes in the prevalence of HAV, HBV, and HCV infections between 1987 and 1996 in inhabitants of Bhadrakali (suburban) and Kotyang (rural) villages in Nepal. STUDY DESIGN: We did a cross-sectional survey of 458 inhabitants of two Nepalese villages, to assess the prevalence of antibody to HAV (anti-HAV), antibody to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg), antibody to HCV (anti-HCV), and antibody to HTLV-I (anti-HTLV-I). RESULTS: Anti-HAV was detected in 454 (99.1%), HBsAg in 5 (1.1%), anti-HBc in 33 (7.2%) and anti-HCV in 8 (1.7%) of serum samples tested in 1996. Statistically significant differences by gender or age group were nil. The prevalence of HCV infection was significantly higher in 1996 than in 1987 after adjusting for age of subjects living in the two villages (p < 0.01). The prevalence of HBsAg was significantly higher in 1996 than 1987 in Bhadrakali after adjusting for the factor of age (p < 0.05). Between 1987 and 1996, evidence for HTLV-1 positive residents was nil. CONCLUSION: These results suggest that HAV has been endemic in Nepal for long time while not of HBV, and that HCV infection tends to be increased recently.     

A to Z: Vitamin A and zinc,the miracle duo

Dietary micronutrients such as vitamins and trace minerals are known modulators of host immune responses against common pathogens. In this respect, vitamin A and zinc have recently received increased attention. Severalin vivo andin vitro studies suggest that vitamin A may be a critical player in the mucosal immune responses in the respiratory and gastrointestinal tracts, particularly in undernourished children. The effect may be mediated primarily by stabilization of the membrane of mucosal epithelial cells, as well as enhanced leukocyte functions. The beneficial effect of vitamin A therapy in reducing measles-associated morbidity and mortality suggests its crucial role in defenses against viral pathogens. Zinc is also known affect leukocyte functions such as phagocytosis and T-lymphocyte-mediated immune responses. However, unlike vitamin A, zinc has been investigated primarily for its effects on bacterial infections. Dietary supplementation or therapeutic treatment with vitamin A and zinc may be a cheap yet effective means of preventing or treating infections in highly susceptible populations. Additional studies, however, are required to better define the types of pathogens and the specific human populations that may benefit from such therapy.