Conformational changes in the IgG molecule of lepromatous sera using laser Raman spectroscopy

In the present work we report our studies on IgG separated from the serum of lepromatous patients and non-lepromatous leprosy cases using Laser Raman Spectroscopy. Striking spectral changes in LL cases have been observed in the following special regions: (a) the amide I and III, (b) the S-S and C-S stretching (c) the skeletal bending and (d) skeletal stretching regions. These changes indicate a decrease in the amount of beta-structure and a transition towards alpha-helical conformation.     

Preliminary observations on the role of the mesonephros in the development of the adrenal cortex

The interrelationship between mesonephros, adrenal cortex, and gonads was studied in 28- and 31-day old sheep fetuses by means of light microscopy on plastic sections. At these stages, the adrenal cortex is just beginning to develop and the mesonephros is undergoing involution; its regression is accompanied by mobilization of cells from the glomerulus of a peculiar nephron situated in the proximal third of the organ, and referred to as “giant” because of its large size. The mobilized cells egress from this glomerulus organized in trabeculae, some of which reach the cranial extremity of the adrenal cortex while others coalesce into a prominent cellular formation which extends uninterrupted toward and into the developing gonads. In previous studies we have shown that the mesonephric cells which colonize the gonads differentiate into sustentacular and interstitial steroidogenic cells; the presence of an analogous cellular migration from the mesonephros to the adrenal cortex now suggests that also the adrenal cortical cells may be of mesonephric origin.     

Variable Genomic Landscapes of Advanced Melanomas with Heavy Pigmentation

BackgroundIn the current study, we examined the real-world prevalence of highly pigmented advanced melanomas (HPMel) and the clinicopathologic, genomic, and ICPI biomarker signatures of this class of tumors.Materials and MethodsOur case archive of clinical melanoma samples for which the ordering physician requested testing for both PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP) was screened for HPMel cases, as well as for non-pigmented or lightly pigmented advanced melanoma cases (LPMel).ResultsOf the 1268 consecutive melanoma biopsies in our archive that had been submitted for PD-L1 IHC, 13.0% (165/1268) were HPMel and 87.0% (1103/1268) were LPMel. In the HPMel cohort, we saw a significantly lower tumor mutational burden (TMB, median 8.8 mutations/Mb) than in the LPMel group (11.4 mut/Mb), although there was substantial overlap. In examining characteristic secondary genomic alterations (GA), we found that the frequencies of GA in TERTp, CDKN2A, TP53, and PTEN were significantly lower in the HPMel cases than in LPMel. A higher rate of GA in CTNNB1, APC, PRKAR1A, and KIT was identified in the HPMel cohort compared with LPMel.ConclusionsIn this study, we quantified the failure rates of melanoma samples for PD-L1 testing due to high melanin pigmentation and showed that CGP can be used in these patients to identify biomarkers that can guide treatment decisions for HPMel patients. Using this practical clinical definition for tumor pigmentation, our results indicate that HPMel are frequent at 13% of melanoma samples, and in general appear molecularly less developed, with a lower TMB and less frequent secondary GA of melanoma progression.     

Latent autoimmune diabetes in adults: A distinct but heterogeneous clinical entity

Latent autoimmune diabetes in adults (LADA) accounts for 2%-12% of all cases of diabetes. Patients are typically diagnosed after 35 years of age and are often misdiagnosed as type II Diabetes Mellitus (DM). Glycemic control is initially achieved with sulfonylureas but patients eventually become insulin dependent more rapidly than with type II DM patients. Although they have a type II DM phenotype, patients have circulating beta (β) cell autoantibodies, a hallmark of type I DM. Alternative terms that have been used to describe this condition include type 1.5 diabetes, latent type I diabetes, slowly progressive Insulin Dependent Diabetes Mellitus, or youth onset diabetes of maturity. With regards to its autoimmune basis and rapid requirement for insulin, it has been suggested that LADA is a slowly progressive form of type I DM. However, recent work has revealed genetic and immunological differences between LADA and type I DM. The heterogeneity of LADA has also led to the proposal of criteria for its diagnosis by the Immunology of Diabetes Society. Although many workers have advocated a clinically oriented approach for screening of LADA, there are no universally accepted criteria for autoantibody testing in adult onset diabetes. Following recent advances in immunomodulatory therapies in type I DM, the same strategy is being explored in LADA. This review deals with the contribution of the genetic, immunological and metabolic components involved in the pathophysiology of LADA and recent approaches in screening of this distinct but heterogeneous clinical entity.     

Inner retinal abnormalities in X-linked retinitis pigmentosa with RPGR mutations

PURPOSE: To investigate in vivo the retinal microstructure in X-linked retinitis pigmentosa (XLRP) caused by RPGR mutations as a prelude to treatment initiatives for this common form of RP. METHODS: Patients with RPGR-XLRP (n = 12; age range, 10-56 years) were studied by optical coherence tomography (OCT) in a wide region of central retina. Overall retinal thickness and outer nuclear layer (ONL) and inner retinal parameters across horizontal and vertical meridians were analyzed and compared. RESULTS: Retinal architecture of all patients with RPGR mutations was abnormal. At the fovea in younger patients, the ONL could be normal; but, at increasing eccentricities, there was a loss of photoreceptor laminar structure, even at the youngest ages studied. At later ages and advanced disease stages, the ONL was thin and reduced in extent. Inner retinal thickness, in contrast, was normal or hyperthick. Inner retinal thickening was detectable at all ages studied and was strongly associated with ONL loss. CONCLUSIONS: Inner retinal laminar abnormalities in RPGR-XLRP are likely to reflect a neuronal-glial retinal remodeling response to photoreceptor loss and are detectable relatively early in the disease course. These results should be factored into emerging therapeutic strategies for this form of RP.     

Evaluation of Factors in Relation with the Non-Compliance to Curative Intent Radiotherapy among Patients of Head and Neck Carcinoma: A Study from the Kumaon Region of India

Introduction:

Radiotherapy (RT)-based curative regimens for head and neck squamous cell carcinomas (HNSCC) deliver a dose of 66–70 Gray (Gy) over a period of 6–7 weeks, and incomplete treatments are unlikely to result in cure. Non-compliance to RT is major contributory factor to treatment failure.

Aims:

To assess the proportion of patients who do not complete planned treatment after initiation of curative RT. This study also aims to explore a possible relationship of non-compliance due to socio-economic, disease-related and treatment-related factors.

Materials and Methods:

The records of HNSCC patients treated from January 2012–December 2013 were audited. Data from the treatment records were to collect patient-related, disease-related, and social demographic parameters. Of the patients who had not completed treatment, the reasons behind the same were investigated.

Results:

Of the 324 patients of HNSCC who were initiated on radical RT, a total of 76 patients were found to have discontinued treatment without authorization of the treating clinician. There was no significant predilection for treatment non-compliance with regards to patient age, educational status, religion, site of the disease, use of neoadjuvant chemotherapy, or use of concurrent chemotherapy. There tended to be a higher association of treatment non-compliance among patients residing >100 km away from the treatment center, patients hailing from hilly regions, patients without the below poverty line (BPL) card, unemployed patients, and patients with stage IV-A/B disease. Of the 76 patients who did not complete treatment, telephonic questionnaire could be obtained from 54 patients. Causes for non-compliance included preference for traditional healers (22.2%), fear of toxicity (7.4%), logistic reasons (18.5%), financial reasons (24.1%), and lack of interest/faith in RT (5.6%).

Conclusion:

There is a high incidence of treatment default among patients of HNSCC during RT in this region. The revelation of the higher propensity for treatment default among patients from distant, hilly regions, unemployed, patients without BPL cards, and stages-IVA/IVB highlights the need for specific interventions for these special populations.     

Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of activation

Microglia, the resident immune cells of the central nervous system (CNS), are thought to contribute to the pathogenesis of age-related neurodegenerative disorders. It has been hypothesized that microglia undergo age-related changes in gene expression patterns that give rise to pathogenic phenotypes. We compared the gene expression profiles in microglia isolated ex vivo from the retinas of mice ranging from early adulthood to late senescence. We discovered that microglial gene expression demonstrated progressive change with increasing age, and involved genes that regulate microglial supportive functions and immune activation. Molecular pathways involving immune function and regulation, angiogenesis, and neurotrophin signaling demonstrated age-related change. In particular, expression levels of complement genes, C3 and CFB, previously associated with age-related macular degeneration (AMD), increased with aging, suggesting that senescent microglia may contribute to complement dysregulation during disease pathogenesis. Taken together, senescent microglia demonstrate age-related gene expression changes capable of altering their constitutive support functions and regulation of their activation status in ways relating to neuroinflammation and neurodegeneration in the CNS.     

Invasive pulmonary aspergillosis in an immunocompetent patient with severe dengue fever

We report a case of a 65-year-old female diagnosed with sever dengue fever. She started showing recovery from dengue fever with medical management. On day 6 of admission, she had leukocytosis, altered mental sensorium, and hemoptysis. Chest tomography showed air space consolidation with multiple nodules in the left upper and middle lobe sputum and bronchoalveolar lavage cultures were positive for Aspergillus flavus. The patient showed improvement with voriconazole and therapy was continued for 6 weeks.