Awareness of issues related to sleep disordered breathing amongst practicing physicians

BACKGROUND: Most of the sleep related breathing disorders currently in India are both under diagnosed and under treated. The exact prevalence of sleep disordered breathing (SDB) in our country is not clearly known and this is partly due to lack of awareness amongst physicians and lack of formal epidemiological data from Indian subcontinent. Several international agencies have emphasised the urgent need for medical training at all levels in sleep medicine, so as to include an exposure to the broader aspects of sleep medicine. OBJECTIVE: To assess the knowledge of practicing chest physicians on the issues related to sleep disordered breathing in the local set-up. METHODS: A standardised questionnaire with strong face validity was utilised for this purpose to interview 65 physicians at their work place. RESULTS: The overall awareness about sleep disordered breathing amongst the practicing physicians in Hyderabad, Secunderabad and the neighbouring district of Warangal was poor. There was no association between professsional qualifications and level of awareness. Furthermore, the awareness was found to be similarly low both amongst young and middle aged physicians and this was statistically significant (p<0.001). CONCLUSION: The overall awareness about sleep disordered breathing amongst practicing physicians in and around Hyderabad is rather poor.     

Mast cell renin and a local renin-angiotensin system in the airway: role in bronchoconstriction

We previously reported that mast cells express renin, the rate-limiting enzyme in the renin-angiotensin cascade. We have now assessed whether mast cell renin release triggers angiotensin formation in the airway. In isolated rat bronchial rings, mast cell degranulation released enzyme with angiotensin I-forming activity blocked by the selective renin inhibitor BILA2157. Local generation of angiotensin (ANG II) from mast cell renin elicited bronchial smooth muscle contraction mediated by ANG II type 1 receptors (AT(1)R). In a guinea pig model of immediate type hypersensitivity, anaphylactic mast cell degranulation in bronchial rings resulted in ANG II-mediated constriction. As in rat bronchial rings, bronchoconstriction (BC) was inhibited by a renin inhibitor, an AT(1)R blocker, and a mast cell stabilizer. Anaphylactic release of renin, histamine, and beta-hexosaminidase from mast cells was confirmed in the effluent from isolated, perfused guinea pig lung. To relate the significance of this finding to humans, mast cells were isolated from macroscopically normal human lung waste tissue specimens. Sequence analysis of human lung mast cell RNA showed 100% homology between human lung mast cell renin and kidney renin between exons 1 and 10. Furthermore, the renin protein expressed in lung mast cells was enzymatically active. Our results demonstrate the existence of an airway renin-angiotensin system triggered by release of mast-cell renin. The data show that locally produced ANG II is a critical factor governing BC, opening the possibility for novel therapeutic targets in the management of airway disease.     

Destabilization of amyloid fibrils on interaction with MoS2-based nanomaterials

The present work is motivated by the established concept that the structure and energetics of biomacromolecules can be modulated by confining their dimensions in the nanoscale. In particular, here we use force-field methods to understand the stability of amyloid fibrils at nanostructured interfaces, which can be useful for the development of new therapeutics for Alzheimer''s disease. We explore the binding modes and structural properties of fibrils at the interface of molybdenum disulphide nanotubes and the nanosurface using classical molecular dynamics simulations. We find that in general the MoS₂ materials induces disruptions in the structure of the amyloid fibrils where the beta sheet conformation of the fibrils changes to a turned conformation, and it is large in the case of nanotubes in comparison to the nanosurfaces. The intermolecular hydrogen bonds, hydrophilic and hydrophobic contacts between the monomer peptides in the fibril are reduced due to their adsorption onto the MoS₂ materials, which results in a destabilization of the fibril. The destabilization of fibril is to some extent compensated for by the van der Waals interactions between the fibril and MoS₂. Overall the results indicate that MoS₂-based materials can be useful in inhibiting the aggregation of smaller protofibrils to matured fibrils and to bust the already formed fibrils. Therapeutic materials should not exhibit any cross interaction with other off-targets compounds. In order to test whether the MoS₂ nanomaterial has any such effect we have studied its interaction with two additional biomacromolecules, the human serum albumin and p53 protein, and we report no significant changes in the secondary structure of these biomolecules. Through molecular docking studies we also established that the drug binding ability of HSA is not altered by its surface binding to MoS₂ nanosurface.

The present work computationally establishes that the structure and energetics of fibril-like biomacromolecules can be modulated by confining them on the MoS₂ based nanomaterials.     

Clinical and epidemiological predictors of transmission in Severe Acute Respiratory Syndrome (SARS)

Background  

Only a minority of probable SARS cases caused transmission. We assess if any epidemiological or clinical factors in SARS index patients were associated with increased probability of transmission.     

Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that most commonly evolves from preexisting prostate adenocarcinoma (PCA). Using Next Generation RNA-sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, and 5 benign prostate tissue (BEN), and validated findings on tumors from a large cohort of patients (37 NEPC, 169 PCA, 22 BEN) using IHC and FISH. We discovered significant overexpression and gene amplification of AURKA and MYCN in 40% of NEPC and 5% of PCA, respectively, and evidence that that they cooperate to induce a neuroendocrine phenotype in prostate cells. There was dramatic and enhanced sensitivity of NEPC (and MYCN overexpressing PCA) to Aurora kinase inhibitor therapy both in vitro and in vivo, with complete suppression of neuroendocrine marker expression following treatment. We propose that alterations in Aurora kinase A and N-myc are involved in the development of NEPC, and future clinical trials will help determine from the efficacy of Aurora kinase inhibitor therapy. SIGNIFICANCE: We report on the largest in-depth molecular analysis of NEPC and provide new insight into molecular events involved in the progression of prostate cancer.     

Transoral Incisionless Fundoplication 2.0 Procedure Using EsophyX™ for Gastroesophageal Reflux Disease

Background  

Transoral incisionless fundoplication (TIF) using the EsophyX™ system has been introduced as a possible alternative for the treatment of gastroesophageal reflux disease (GERD). The efficacy of this procedure in our centers was evaluated.     

Early intervention with phosphodiesterase‐5 inhibitors after prostate brachytherapy improves subsequent erectile function

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To examine the early use of phosphodiesterase‐5 inhibitor (PDE‐5i; sildenafil citrate) in preventing subsequent erectile dysfunction (ED) after (monotherapy) prostate brachytherapy (PB, an accepted option for Gleason 6 or low‐volume Gleason 7 prostate cancer), as PB is currently being offered more frequently in younger patients, and ED can be a side‐effect often within the first 12 months after treatment.

PATIENTS AND METHODS

We examined a single‐surgeon series of 69 patients who had been treated with PB from 2002 to 2005. All patients had a follow‐up of ≥1 year; prospectively, and patients had baseline, 6‐ and 12‐month assessments using the Sexual Health Inventory for Men (SHIM) and International Index of Erectile Function (IIEF)‐6 scores. The 69 patients were divided into early treatment with PDE‐5i (31) and not treated with PDE‐5i (38), and their SHIM and IIEF‐6 scores were compared at baseline, 6 and 12 months. Daily sildenafil (25–50 mg) was given immediately after PB for 12 months. Overall, for the entire group, the mean prostate‐specific antigen (PSA) level was 6.8 ng/mL; 78% had Gleason 6 cancer and 20% had Gleason 7 (3 + 4) cancer. The mean age in the early PDE‐5i group was 64.8 years, and was 66.0 years in the no‐PDE‐5i group. The mean radiation dose in the early PDE‐5i group was 50.2 Gy, and 43.9 Gy in the other group (P= 0.08).

RESULTS

In the no‐PDE‐5i group, the mean baseline SHIM score of 17.1 decreased rapidly to 9.1 at 6 months (P= 0.01) and stayed at 9.3 at 12 months (P= 0.01). In the early PDE‐5i group, the mean baseline SHIM score of 21.8 decreased slightly to 17.6 at 6 months (P= 0.2), and was maintained at 17.9 at 12 months (P= 0.2). Using the Wilcoxon rank‐sum test, the 6‐ and 12‐month SHIM scores in the two groups (P < 0.001). The IIEF‐6 questionnaire confirmed the SHIM analysis.

CONCLUSIONS

After PB patients had a significant decline in SHIM/IIEF‐6 scores at 6 and 12 months. Our results indicate a 50% decrease in the quality of their erections. This provides an opportunity to initiate early intervention with PDE‐5i or perhaps vacuum constriction devices or intraurethral alprostadil. In this study, the early use of PDE‐5i after PB maintained erectile function at both 6 and 12 months.