Assessment of Hearing in Patients with Head Injury: A Prospective Study.

Background: Hearing impairment is a well-known outcome of head trauma. The most prevalent site of injury is the peripheral structures. Hearing loss dissipates in most cases but can continue in some cases and may improve in some. Objectives: To evaluate the incidence of hearing loss and ascertain its type and degree in patients with head injury. To estimate the progression or regression of hearing loss in head injury patients during follow-up. Material and Methods: 60 patients with head injuries with any ear symptoms were included in the study. The severity of head injury is graded according to the Glasgow Coma Scale (GCS). Patients were subjected to High Resolution Computed Tomogram (HRCT) temporal bone, and Pure Tone Audiometry (PTA) was performed within 24 h of presenting. PTA repeated after 3 months. The degree of hearing loss and its progression or regression were assessed. Results: Of the 60 patients, 56 (93.3%) had hearing loss on PTA. 50 Cases (83.3%) showed conductive hearing loss (CHL). 6 (10%) had mixed hearing loss (MHL). 4 cases with MHL had a transverse temporal bone fracture on radiological evaluation. 41 (68.3%) had mild CHL, 4 (6.7%) had moderate MHL, and 2 (3.3%) had moderately severe MHL. PTA values reduced significantly from 1st to 2nd visit in both ears. Conclusion: In our study, there was significant improvement in hearing during follow-up, after 3 months of head injury indicating improvement in hearing. The improvement in hearing was noticed in all cases except for one case with transverse temporal bone fracture and moderately severe hearing loss. Routine otological examination should be considered in all patients with head injuries. Meticulous and timely management of these cases can significantly reduce morbidity in the patient.

Design, synthesis and anticancer activity of 5-((2-(4-bromo/chloro benzoyl) benzofuran-5-yl) methyl)-2-((1-(substituted)-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde analogues.

Novel 5-((2-(4-bromo/chloro benzoyl) benzofuran-5-yl) methyl)-2-((1-(substituted)-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde analogues about twenty-one were synthesized all through standard chemical procedures. The structure of the compounds were confirmed by 1H NMR, 13C NMR and Mass spectral analysis after purification. All the compounds were screened for In Vitro lung and cervical cancer activity against A-549 and HeLa cell lines, respectively, by MTT assay protocol using various nanomolar (nM) concentrations. IC50 value were calculated from cell viability data. 2-(trifluoromethyl)benzyl substituted derivative presented outstanding activity against both the cell lines compared to standard drug doxorubicin. The methoxy, chloro, fluoro and formyl substituted analogues showed a moderate activity and whereas methyl substituted analogues activity was poor. The morphological deformation of both cell lines by best IC50 value analogues proved as potent inhibitors of cancer cells growth. Molecular docking studies were performed against extracellular signal-regulated kinase 2 and fibroblast growth factor receptor 2 these results are incredibly in agreement with the investigational data.

Algal turf structure and composition vary with particulate loads on coral reefs.

Algal turfs trap and retain particulates, however, little is known about the relationship between particulate accumulation and taxonomic composition of algal turfs. We investigated how particulate mass related to algal turf structure (length and density) and community composition (taxonomic and functional) on two disparate reefs. Particulate mass was positively related to algal turf length. By contrast, the relationship between particulate mass and turf density was more complex and followed a negative parabolic shape; density increased with particulate mass before stabilising and then declining. Community analyses showed taxonomic, but not functional group compositions differed significantly between reefs and with increasing particulate mass. Our results suggest high loads of particulates accumulated in algal turfs are related to a longer, lower density turf structure, typified by filamentous forms such as Cladophora. Changes in algal turf structure and composition could have a variety of bottom-up influences on coral reef ecosystems.

Prebiological Membranes and Their Role in the Emergence of Early Cellular Life.

Membrane compartmentalization is a fundamental feature of contemporary cellular life. Given this, it is rational to assume that at some stage in the early origins of life, membrane compartments would have potentially emerged to form a dynamic semipermeable barrier in primitive cells (protocells), protecting them from their surrounding environment. It is thought that such prebiological membranes would likely have played a crucial role in the emergence and evolution of life on the early Earth. Extant biological membranes are highly organized and complex, which is a consequence of a protracted evolutionary history. On the other hand, prebiotic membrane assemblies, which are thought to have preceded sophisticated contemporary membranes, are hypothesized to have been relatively simple and composed of single chain amphiphiles. Recent studies indicate that the evolution of prebiotic membranes potentially resulted from interactions between the membrane and its physicochemical environment. These studies have also speculated on the origin, composition, function and influence of environmental conditions on protocellular membranes as the niche parameters would have directly influenced their composition and biophysical properties. Nonetheless, the evolutionary pathways involved in the transition from prebiological membranes to contemporary membranes are largely unknown. This review critically evaluates existing research on prebiotic membranes in terms of their probable origin, composition, energetics, function and evolution. Notably, we outline new approaches that can further our understanding about how prebiotic membranes might have evolved in response to relevant physicochemical parameters that would have acted as pertinent selection pressures on the early Earth.

Formation of Abasic Oligomers in Nonenzymatic Polymerization of Canonical Nucleotides.

Polymerization of nucleotides under prebiotically plausible conditions has been a focus of several origins of life studies. Non-activated nucleotides have been shown to undergo polymerization under geothermal conditions when subjected to dry-wet cycles. They do so by a mechanism similar to acid-catalyzed ester-bond formation. However, one study showed that the low pH of these reactions resulted in predominantly depurination, thereby resulting in the formation of abasic sites in the oligomers. In this study, we aimed to systematically characterize the nature of the oligomers that resulted in reactions that involved one or more of the canonical ribonucleotides. All the reactions analyzed showed the presence of abasic oligomers, with purine nucleotides being affected the most due to deglycosylation. Even in the reactions that contained nucleotide mixtures, the presence of abasic oligomers was detected, which suggested that information transfer would be severely hampered due to losing the capacity to base pair via H-bonds. Importantly, the stability of the N-glycosidic linkage, under conditions used for dry-wet cycling, was also determined. Results from this study further strengthen the hypothesis that chemical evolution in a pre-RNA World would have been vital for the evolution of informational molecules of an RNA World. This is evident in the high degree of instability displayed by N-glycosidic bonds of canonical purine ribonucleotides under the same geothermal conditions that otherwise readily favors polymerization. Significantly, the resultant product characterization in the reactions concerned underscores the difficulty associated with analyzing complex prebiotically relevant reactions due to inherent limitation of current analytical methods.

Efficacy of Tinnitus Retraining Therapy, A Modish Management of Tinnitus: Our Experience.

Tinnitus retraining therapy involves masking of tinnitus at sound perception level in combination with structured counselling sessions. To assess efficacy of Tinnitus retraining therapy (TRT) in Patients of Tinnitus with Sensori Neural Hearing loss. Prospective study was carried out on patients who presented with Tinnitus in ENT OPD from December 2015 to December 2016. Severity of tinnitus was documented using Tinnitus handicap inventory scale. Response to tinnitus is evaluated at the end of 3 months. In our study 57 patients in age group 21-78 years were selected and Tinnitus retraining therapy was administered. Most of patients had moderate (75.43%) perception of tinnitus before initiation of therapy. After completion of therapy tinnitus completely disappeared in 34 (59.65%) patients. Improvement in Tinnitus perception was observed in total of 49 (85.96%) patients. There was no improvement in Tinnitus perception in 8 (14.03%) patients. TRT aims in reducing the tinnitus perception by inducing habituation of tinnitus-induced reactions allowing patients to achieve control over their tinnitus, live a normal life, and participate in everyday activities.

Osteopontin, Cardiovascular Risk Factors and Carotid Intima-Media Thickness in Chronic Kidney Disease.

The pleiotropic cytokine osteopontin (OPN) is found to be involved in the pathogenesis of both kidney and cardiovascular disease (CVD). We evaluated the relationship between OPN, other cardiovascular risk factors and carotid intima-media thickness (CIMT) in chronic kidney disease (CKD) (predialysis) patients. This is a 2-year cross-sectional prospective study involving 75 patients with CKD from stage 1 to stage 5 attending the nephrology outpatient department and 25 healthy controls. Routine biochemical parameters were analyzed on clinical chemistry Autoanalyzer Beckman Coulter DXC 600 Synchron, USA. OPN was estimated by ELISA method. Carotid intima-media wall thickness was estimated by Doppler of carotid vessels. Serum OPN and other nontraditional cardiovascular risk factors such as CIMT, lipoprotein (a) Lp(a), fibrinogen, and homocysteine were significantly increased in patients of CKD compared to controls. OPN, Lp(a), fibrinogen, CIMT, parathyroid hormone, and homocysteine progressively increased from early stages of CKD and increased further with progression of the disease, but nitric oxide (NO) level progressively decreased with progression of CKD. OPN showed a positive correlation with CIMT, Lp(a), fibrinogen, and homocysteine and negative correlation with estimated glomerular filtration rate and NO. There was a close direct association between circulating levels of OPN and the presence of atherosclerotic plaques in carotid arteries of patients with CKD. Osteopontin and nontraditional CVD risk factors are altered in early stages of CKD and might predict adverse outcomes in these patients.

Correction: Synthesis of barbituric acid containing nucleotides and their implications for the origin of primitive informational polymers.

Correction for 'Synthesis of barbituric acid containing nucleotides and their implications for the origin of primitive informational polymers' by Chaitanya V. Mungi et al., Phys. Chem. Chem. Phys., 2016, 18, 20144-20152.

Mechanistic insight in potential dual role of sinigrin against Helicoverpa armigera.

The adverse effect of glucosinolates on diverse phytophagous insects is well documented, but its impact on insect physiology has remained enigmatic. Here we report insights into detrimental effects of plant glucosinolate molecule, sinigrin, on Helicoverpa armigera growth and development. In-silico screening of multiple glucosinolates predicted sinigrin as one of the potential inhibitor of H. armigera cathepsin B and L. Insects fed on sinigrin containing diet showed significantly reduced growth (20-30%), delayed pupation (10-15%), decreased fecundity (50-80%) and developmental abnormalities. Further, sinigrin showed 50-60% inhibition of ex-vivo cathepsin like activity which might be a reason for growth and development related abnormalities. In-vitro and mass spectrometry studies highlighted the cytotoxicity caused due to the hydrolysis of sinigrin, into toxic isothiocyanates, in presence of H. armigera whole body extract. In conclusion, insect cathepsin inhibition and isothiocyanate mediated cytotoxicity lead to the dual adverse effect of sinigrin on H. armigera.

Employment Status of Patients Receiving Maintenance Dialysis - Peritoneal and Hemodialysis: A Cross-sectional Study.

The long-term dialysis therapy for end-stage renal disease takes a heavy toll of quality of life of the patient. Several factors such as fatigue and decreased physical capability, impaired social and mental functioning, contribute to this forlorn state. To meld maintenance dialysis treatment with a regular employment can be a serious test. A cross-sectional study of employment of patients on hemodialysis and peritoneal dialysis in a state government tertiary institute in South India was performed between June 2015 and December 2015. Patients who completed 3 months of regular dialysis were only included in the study. The number of patients on hemodialysis was 157 and on peritoneal dialysis was 69. The employment status before the initiation of dialysis was 60% (93 out of 155) and 63.7% (44 out of 69) in hemodialysis and peritoneal dialysis, respectively. After initiation, the loss of employment was observed in 44% (41 out of 93) in hemodialysis and 51.2% (26 out of 44) in peritoneal dialysis (P = 0.2604). Even though there was fall of absolute number of job holders in both the blue and white collar jobs, the proportion of jobholders in the white collar job holders improved. On univariate analysis, the factors which influenced the loss of employment were males, age between 50 and 60 years, number of comorbidities >2, illiteracy and blue collar versus white collar job before the initiation of dialysis. The majority of patients had the scores above 80 on Karnofsky performance scale and the majority belonged upper and middle classes than lower classes on modified Kuppuswamy's socioeconomic status scale; however, the loss of employment was also disproportionately high. There appeared a substantial difference in the attitude of the patients toward the employment. There was no difference between hemodialysis and peritoneal dialysis in the loss of employment of our patients.

Validation of olfactory deficit as a biomarker of Alzheimer disease.

BACKGROUND: We evaluated smell identification as a biomarker for Alzheimer disease (AD) by assessing its utility in differentiating normal aging from an amnestic disorder and determining its predictive value for conversion from amnestic mild cognitive impairment (aMCI) to AD. METHODS: Cross-sectional study (AD = 262, aMCI = 110, controls = 194) measuring smell identification (University of Pennsylvania Smell Identification Test [UPSIT]) and cognitive status was performed, as well as longitudinal analysis of aMCI participants (n = 96) with at least 1 year follow-up (mean 477.6 ± 223.3 days), to determine conversion by National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. RESULTS: Odor identification and disease status were highly correlated after correcting for age, sex, and APOE (p < 0.001). Receiver operating characteristic (ROC)/area under the curve (AUC) was similar for the 40-item UPSIT, the top 10 smells in our study, and the 10-item subset previously proposed. Smeller/nonsmeller based on the 10-item subset with a cutoff of 7 (≤7, nonsmeller; >7, smeller) had a sensitivity and specificity of 88% and 71% for identifying AD and 74% sensitivity and 71% specificity for identifying an amnestic disorder. A total of 36.4% of participants with impaired olfaction and 17.3% with intact olfaction converted to AD (p = 0.03). The ROC/AUC for prediction of conversion to AD was 0.62. CONCLUSIONS: Olfactory identification deficit is a useful screening tool for AD-related amnestic disorder, with sensitivity and specificity comparable to other established biomarkers, with benefits such as ease of administration and low cost. Olfactory identification deficit can be utilized to stratify risk of conversion from aMCI to AD and enrich clinical trials of disease-modifying therapy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that smell identification (10-item UPSIT subset) accurately identifies patients with amnestic disorders.

Analysis of a novel multiplex polymerase chain reaction assay as a sensitive tool for the diagnosis of indeterminate and tuberculoid forms of leprosy.

OBJECTIVE/BACKGROUND: Clinical diagnosis of indeterminate and tuberculoid leprosy is often difficult due to limited and confounding signs and symptoms. In the current study, we evaluated the utility of new multiplex polymerase chain reaction (PCR) using Mycobacterium leprae-specific DNA sequences in the pseudogene regions of ML1545, ML2180, and ML2179 for PCR-based diagnosis of indeterminate leprosy (IND) and leprosy cases across the immunological spectrum. The sensitivity was compared with that of RLEP PCR. METHODS: DNA was extracted from paraffin-embedded skin biopsy specimens of 220 leprosy cases, which were divided into IND (41), tuberculoid form (3), borderline tuberculoid (42), midborderline (3), borderline lepromatous (n=59), and lepromatous leprosy (72) cases. PCR positivity of both multiplex and RLEP PCR were compared in all the samples. A decision tree was constructed using the classification and regression trees algorithm to predict the probability of PCR positivity with the new multiplex PCR scheme in various clinical groups of leprosy. Sensitivity of each pseudogene target was determined using real-time PCR assays, and specificity was confirmed by PCR amplification of DNA extracted from three other mycobacterial species and skin biopsies of 44 non-leprosy cases. RESULTS: A multiplex PCR positivity of 75.61% was noted in IND cases when compared to that of 58.54% using RLEP PCR (P < 0.05). Enhanced multiplex PCR positivity was noted across various clinical groups in comparison to RLEP PCR. The decision tree classifier has predicted statistically significant probability for multiplex PCR positivity among RLEP-PCR negative group and clinical groups with a low bacillary load. CONCLUSION: This new multiplex PCR scheme can support the diagnosis of indeterminate and tuberculoid forms of leprosy with limited clinical manifestations and can be implemented in basic clinical/diagnostic setting that possess conventional PCR facilities.

Genomic diversity in Mycobacterium leprae isolates from leprosy cases in South India.

OBJECTIVE: The Objective of this study was to identify the strain diversity of Mycobacterium leprae in terms of SNP types and subtypes stratified as per genomic single nucleotide polymorphisms, in clinical isolates of leprosy patients from a tertiary care leprosy center in South India. Further, the associations of SNP types with clinical outcomes in leprosy were also investigated. METHODS: DNA was extracted from excisional skin biopsies of a total of 172 newly diagnosed untreated leprosy patients from a clinic in Tamil Nadu, in south India, that also serves patients from neighboring states. All the leprosy patients were those who voluntarily reported at the clinic during the study period of one year i.e., 2015. Clinical and histopathological details were collected at diagnosis and leprosy was confirmed through bacteriological smear examination and PCR for M. leprae specific RLEP region. SNP types and subtypes were determined by PCR amplification and Sanger sequencing of PCR products. RESULTS: M. leprae specific RLEP gene amplification was achieved in 160 out of 172 patients. Among 160 specimens 118(73.75%) were type 1 and 42 (26.25%) were type 2 and on subtyping it was noted that 88/160 (55.00%) were 1D, 25/160 (15.62%) 1C, 5/160 (3.12%) 1A, 33/160 (20.62%) 2G and 9/160 (5.62%) were 2H. CONCLUSION: Our results indicated that subtype 1D is predominant in the south Indian population. We also noted 2G, 1C and 1A in the patient sample tested. Additionally we identified subtype 2H for the first time in India.

Odor identification deficit in mild cognitive impairment and Alzheimer's disease is associated with hippocampal and deep gray matter atrophy.

Even in early stages, Alzheimer's disease (AD) is associated with olfactory deficit. We assess the association of volumetric differences in subcortical deep gray matter (DGM) structures and odor identification deficit (OID) in subjects with amnestic mild cognitive impairment (aMCI), AD and normal controls (NCs), and relate findings to the current gold standard right sided memory measure, visual reproduction. Eighty subjects (19 aMCI; 42 CE; 19 NC) were included in this study. We obtained olfactory testing and normalized structural brain volumes from 3T T1 MRI scans. Associations between MRI, olfactory- and memory impairment were studied using Pearson- and partial-correlation adjusted for age. AD patients had significantly higher olfactory deficits, lower visual reproduction scores, and reduced brain volumes (p<0.05). Within aMCI, OID was associated with lower right hippocampal- and left amygdala volume (p<0.05). In AD, OID was associated with bilaterally lower hippocampus and left amygdala volumes. In contrast, visual reproduction was associated with bilateral volume loss regardless of study group. OID is a more specific marker of early pathological right mesial-temporal involvement than the currently regarded gold standard of right sided-memory (visual reproduction). OID may be valuable in the longitudinal evaluation of disease modifying treatments in early disease course.

Mycobacterium leprae specific genomic target in the promoter region of probable 4-alpha-glucanotransferase (ML1545) gene with potential sensitivity for polymerase chain reaction based diagnosis of leprosy.

With the absence of an effective diagnostic tool for leprosy, cases with negative bacteriological index and limited clinical manifestations often pose diagnostic challenges. In this study, we investigated the utility of a novel Mycobacterium leprae specific 112-bp DNA sequence in the promoter region of probable 4-alpha-glucanotransferase (pseudogene, ML1545) for polymerase chain reaction (PCR) based diagnosis of leprosy in comparison to that of the RLEP gene. DNA was extracted from slit skin scrapings of 180 newly diagnosed untreated leprosy cases that were classified as per Ridley Jopling classifications and bacteriological index (BI). Primers were designed using Primer Blast 3.0 and PCR was performed with annealing temperatures of 61°C for ML1545 and 58°C for the RLEP gene using conventional gradient PCR. The results indicated a significant increase in PCR positivity of ML1545 when compared to RLEP across the study groups (164/180 [91.11%] were positive for ML1545 whereas 114/180 (63.33%) were positive for RLEP [p<.0001, z=6.3]). Among 58 leprosy cases with negative BI, 28 (48.28%) were positive for RLEP and 48 (82.76%) were positive for ML1545 (p=.0001, z=3.8). Of the 42 borderline tuberculoid leprosy cases, 23 (54.76%) were positive for RLEP whereas 37 (88.09%) were positive for ML1545 (p<.0001, z=3.9). Increase in PCR positivity for ML1545 was also noted in lepromatous leprosy and BI-positive groups. ML1545 can be a potential gene target for PCR-based diagnosis of leprosy especially in cases where clinical manifestations were minimal.

Synthesis of barbituric acid containing nucleotides and their implications for the origin of primitive informational polymers.

Given that all processes in modern biology are encoded and orchestrated by polymers, the origin of informational molecules had to be a crucial and significant step in the origin of life on Earth. An important molecule in this context is RNA that is thought to have allowed the transition from chemistry to biology. However, the RNA molecule is comprised of intramolecular bonds which are prone to hydrolysis, especially so under the harsh conditions of the early Earth. Furthermore, the formation of nucleotides with extant bases and their subsequent polymerization have both been problematic, to say the least. Alternate heterocycles, in contrast, have resulted in nucleosides in higher yields, suggesting a viable and prebiotically relevant solution to the longstanding "nucleoside problem". In the present study, we have synthesized a nucleotide using ribose 5'-monophosphate (rMP) and barbituric acid (BA), as the base analog, using dry-heating conditions that are thought to be prevalent in several regimes of the early Earth. Polymerization of the resultant monomers, i.e. BA-nucleotides, was also observed when dehydration-rehydration cycles were carried out at low pH and high temperature. The resulting RNA-like oligomers have intact bases unlike in reactions that were carried out with canonical nucleotides, which resulted in abasic sites under acidic conditions due to cleavage of the N-glycosidic linkages. Furthermore, the incorporation of BA directly into preformed sugar-phosphate backbones was also observed when rMP oligomers were subjected to heating with BA. The results from our aforementioned experiments provide preliminary evidence that BA could have been a putative precursor of modern nucleobases, which could have been incorporated into primitive informational polymers that predated the molecules of an RNA world. Moreover, they also highlight that the prebiotic soup, which would have been replete with alternate heterocycles, could have allowed the sampling of other such heterocycles, which would have had a selective advantage under pertinent selection pressures. Importantly, these kinds of processes have implications for shaping the prebiotic landscape that allowed for the emergence of primitive informational polymers of the pre-RNA world(s), prior to the emergence of a putative RNA world.