Treatment of Tinnitus with Intratympanic Injection of Dexamethasone Versus Oral Drugs.

Tinnitus is a symptom of cochlear dysfunction, which can disturb the patient emotionally and physically. As anxiety and tinnitus persist concurrently, certain benzodiazepines have been administered as possible tinnitus treatment options. In addition to pharmacological medications, certain studies have looked at the use of vitamins to treat tinnitus. Intratympanic steroids have been successfully used in various studies as well, for the treatment of tinnitus. A clinical based interventional study was taken up among the patients visiting the ENT OPD of a State Medical College and Hospital. 160 subjects were included in the study by convenient sampling method, taking the inclusion and the exclusion criteria into consideration. Out of them, 80 subjects were given an intratympanic injection of dexamethasone and rest 80 were given oral drugs like alprazolam and vitamin B complex. Among the patients who were treated with intratympanic dexamethasone, significant improvement was seen in 36 of them, with a p value of 0.00 as compared to those who were given oral drugs, in which only 10 showed improvement, with a p value of 0.32. The improvement of the symptoms is significantly related with the duration of the symptoms in our study. Patients presenting with severe SNHL was the commonest presentation but had the least improvement (29.6%). Patients presenting within one year of occurrence of the symptoms had maximum improvement. Intratympanic dexamethasone can be considered as a good alternative for improvement of symptoms of tinnitus.

Toll-interacting protein in the freshwater fish Labeo rohita exhibits conserved structural motifs of higher eukaryotes and is distinctly expressed in pathogen-associated molecular pattern stimulations and bacterial infections.

Toll-interacting protein (Tollip) is a critical regulator of TOLL- like receptor (TLR)-signaling pathway. It is predominantly associated with TLR2 and TLR4 during acute inflammatory conditions and inhibits the TLR-mediated nuclear factor-kappa activation by suppressing the autophosphorylation of interleukin-1 receptor-associated kinase and its kinase activity. This article describes the Tollip of Labeo rohita (LrTollip), a highly valuable freshwater fish from the Indian subcontinent. The full-length LrTollip complementary DNA (1412 nucleotides) encodes a 276-amino acid (aa) protein, depicting a highly conserved target of the Myb1 (Tom1)-binding domain (TBD; 1-53 aa), conserved core domain 2 (C2; 54-151 aa), and coupling of ubiquitin to endoplasmic reticulum degradation (CUE; 231-273 aa) domains of mouse and human counterparts. The key amino acids exerting the critical functions of Tollip, such as phospholipids recognition and ubiquitination, are present in the C2 and CUE domains of LrTollip, respectively. LrTollip is widely expressed in the kidneys, gills, spleen, liver, and blood, and among these tested tissues, the highest expression is observed in blood. In response to TLR ligands and NOD-like receptor (NLR) ligands stimulations and Aeromonas hydrophila, Edwardsiella tarda, and Bacillus subtilis infections, LrTollip gene expression is induced in various organs/tissues with remarkable difference in their kinetics. These data together suggest the important role of LrTollip in TLR- and NLR-signal transduction pathways and immune-related diseases in fish.

Molecular characterization and expressional quantification of lgp2, a modulatory co-receptor of RLR-signalling pathway in the Indian major carp Labeo rohita following pathogenic challenges and PAMP stimulations.

Lgp2 (laboratory of genetics and physiology 2) is a cytosolic viral sensor of the RLR (retinoic acid-inducible gene 1 like receptor) family member without the caspase recruitment domain, having both inhibitory and stimulatory roles in RLR-signalling pathway. In India, Labeo rohita (rohu) is one of the leading and economically favoured freshwater fish species. Several immunological sentry proteins have been reported in this fish species, but no information is available on the RLR members. This study was aimed at cloning and characterization of full-length lgp2-cDNA (complementary DNA) in rohu and investigation of its expressional modulations following various pathogen-associated molecular pattern stimulations and bacterial infections. The full-length lgp2-cDNA sequence obtained through rapid amplification of cDNA ends-PCR consisted of 2299 nucleotides with an open reading frame of 2034 bp encoding 677 amino acids. In rohu-Lgp2, four conserved domains - a DEAD/DEAH box helicase domain, Pfam type-III restriction enzyme domain, helicase superfamily c-terminal domain and RIG-I C-terminal regulatory domain - have been detected. Within these domains, several important functional motifs, such as ATP-binding site, ATPase motif, RNA unwinding motif and RNA-binding sites, have also been identified. In healthy rohu, lgp2 gene was abundantly expressed in gill, liver, kidney, spleen and blood. In response to both in vitro and in vivo treatments using double-stranded RNA (poly I:C), lgp2 gene expression was significantly (P < 0.05) upregulated in all tested tissues and also in the LRG (Labeo rohita gill) cells. lgp2 gene expression significantly (P < 0.05) increased on stimulation of LRG cells using γ-d-glutamyl-meso-diaminopimelic acid and muramyl dipeptide. In vivo treatment using lipopolysaccharide and Aeromonas hydrophila-derived RNA resulted in both up- and down-regulation of lgp2 gene expression. Upon gram-positive and gram-negative bacterial infections, the expression of the lgp2 gene increased at different times in almost all the tested tissues. These integrated observations in rohu suggest that Lgp2 is an antiviral and antibacterial cytosolic receptor. SIGNIFICANCE STATEMENT: Lgp2, a cytosolic viral sensor of retinoic acid-inducible gene 1 like receptor family member, has been cloned in Labeo rohita. The complete sequence of rohu lgp2-complementary DNA consisted of 2299 nucleotides with an open reading frame of 2034 bp encoding 677 amino acids. It consisted of a DExDc, RES-III, HELICc, Pfam RIG-I_C-RD, ATP-binding site, ATPase motif, RNA unwinding motif and RNA-binding site. Upon bacterial infection, double-stranded RNA and various pathogen-associated molecular pattern stimulations, lgp2 gene expression significantly increased, indicating its role as an antiviral and antibacterial cytosolic receptor.

Molecular characterization and expressional modulation of IRAK1 as downstream signaling adaptor molecule of TLR-signaling pathways in Labeo rohita following PAMPs stimulation and bacterial infections.

Interleukin-1 receptor associated kinase (IRAK1) is one of the crucial signal transduction mediators in TLR/IL-1R signaling pathways in host immune system. To investigate about it in rohu (Labeo rohita), one of the economically important freshwater fish species in the Indian subcontinent, we cloned, characterized and analyzed its expression following bacterial infection and pathogens associated molecular patterns (PAMPs) stimulation. The full-length cDNA of rohu IRAK1 (LrIRAK1) consisted of 2765 nucleotide (nt) having an ORF of 2115 nt encoding a polypeptide of 704 amino acids (aa) with a molecular mass of 70.4 kDa. Structurally, LrIRAK1 consisted of twenty-nine helix, twelve strands and forty one coils making one N-terminal death domain (19-94 aa) and a central serine threonine kinase catalytic domain (or kinase domain) (188-489aa). In addition to these two prominent domains, LrIRAK1 also contained highly conserved amino acids viz., lysine 215 and aspartic acid 314 and threonine 185, 361 which were reported to be important for kinase and phosphorylation activity respectively in other animals. Similar to higher vertebrates, LrIRAK1 also consisted of CDK1 (cyclin-dependent kinase1) at 338-352 aa; NEK2 (NIMA-related kinase 2) at 47-61 aa; NEK6 (NIMA-related kinase 6) at 581-595 aa and AMPK (AMP- activated protein kinase) motif at 518-538 aa. Phylogenetically, LrIRAK1 is closely related to cave fish, common carp exhibiting high similarity (~95%) and identity (~90%). In the uninfected fish, the LrIRAK1 expression was highest in liver (~11.5 fold) and lowest in blood. In response to Aeromonas hydrophila, Edwardsiella tarda and Bacillus subtilis infection and various TLR and NLR-ligands stimulation, the expression of LrIRAK1 was markedly enhanced at various time points in almost all the tested tissues. These results together suggest the key role of LrIRAK1 in pattern recognition receptors (PRRs)-mediated host defense against pathogenic insults.

Molecular characterization and expression analysis of two crucial MAPKs- jnk1 and erk1 as cellular signal transducers in Labeo rohita in response to PAMPs stimulation and pathogenic invasion.

Mitogen-activated protein kinases (MAPKs) are crucial Ser/Thr protein kinases that play important roles in innate immunity by converting extracellular stimuli into a wide range of cellular responses, including the production of cytokines. In this study, two MAPK genes, jnk1 and erk1, were cloned and characterized in rohu (Labeo rohita), a commercially important freshwater fish species in the Indian subcontinent. In healthy rohu, both jnk1 and erk1 gene expressions were highest in the spleen as compared to gill, liver, blood and kidney tissues. In vitro stimulation of the L. rohita gill (LRG) cell line with γ-D-glutamyl-meso-diaminopimelic acid, muramyl dipeptide and polyinosinic: polycytidylic acid (poly I:C) resulted in significantly enhanced expressions of jnk1 and erk1 genes. In the in vivo experiments, jnk1 and erk1 gene expressions were also enhanced in lipopolysaccharides and poly I:C-treatment. Infection of rohu fingerlings with Aeromonas hydrophila and Bacillus subtilis revealed significantly enhanced expressions of the jnk1 and erk1 genes in all of the tested organs/tissues. Together these results imply the important role of jnk1 and erk1 genes in fish during pathogenic invasion and diseases.

Early and middle childhood developmental, cognitive, and psychiatric outcomes of Malawian children affected by retinopathy positive cerebral malaria.

The objective is to determine the short -and long-term developmental, cognitive, and psychiatric effects of retinopathy positive cerebral malaria (CM-R) among young children in a prospective study assessing them around the onset of disease and again 2 years at preschool and again at school age. In total, 109 children were recruited from the Queen Elizabeth Central Hospital in Blantyre, Malawi, (N = 49) with CM-R and non-malaria controls  (N = 60). Children were assessed for overall motor, language, and social skills using the Malawi Developmental Assessment Tool (MDAT) at preschool age. At school age, the same children were then given the Kaufman Assessment Battery for Children, second edition (KABC-II), which assessed global cognitive performancememory, and learning; as well as the Test of Variables of Attention (TOVA), which assessed attention. The Achenbach Child Development Checklist (CBCL) was administered at both time points to assess emotional and behavioral patterns. Controls scored significantly better on all KABC-II global domains as well as on the mental processing index than their CM-R group counterparts, but showed no performance differences in the TOVA and CBCL assessments at school age, or in the MDAT and CBCL assessments at preschool age. The MDAT total score was significantly correlated with the KABC-II sequential processing, learning, and mental processing index among CM-R survivors but not among controls. Persisting neurocognitive effects of CM can be captured with the KABC-II at school age. The MDAT at preschool age is correlated with the KABC-II among CM-R survivors and can be used to capture early emerging developmental deficits due to CM-R.

Heightened activity in social reward networks is associated with adolescents' risky sexual behaviors.

Adolescent sexual risk behavior can lead to serious health consequences, yet few investigations have addressed its neurodevelopmental mechanisms. Social neurocircuitry is postulated to underlie the development of risky sexual behavior, and response to social reward may be especially relevant. Typically developing adolescents (N=47; 18M, 29F; 16.3±1.4years; 42.5% sexual intercourse experience) completed a social reward fMRI task and reported their sexual risk behaviors (e.g., lifetime sexual partners) on the Youth Risk Behavior Survey (YRBS). Neural response and functional connectivity to social reward were compared for adolescents with higher- and lower-risk sexual behavior. Adolescents with higher-risk sexual behaviors demonstrated increased activation in the right precuneus and the right temporoparietal junction during receipt of social reward. Adolescents with higher-risk sexual behaviors also demonstrated greater functional connectivity between the precuneus and the temporoparietal junction bilaterally, dorsal medial prefrontal cortex, and left anterior insula/ventrolateral prefrontal cortex. The greater activation and functional connectivity in self-referential, social reward, and affective processing regions among higher sexual risk adolescents underscores the importance of social influence underlying sexual risk behaviors. Furthermore, results suggest an orientation towards and sensitivity to social rewards among youth engaging in higher-risk sexual behavior, perhaps as a consequence of or vulnerability to such behavior.

Concordance between maternal recall of birth complications and data from obstetrical records.

BACKGROUND: Prenatal complications are associated with poor outcomes in the offspring. Access to medical records is limited in the United States and investigators often rely on maternal report of prenatal complications. STUDY DESIGN AND AIMS: We tested concordance between maternal recall and birth records in a community-based sample of mothers participating in a longitudinal study in order to determine the accuracy of maternal recall of perinatal complications. SUBJECTS: Participants were 151 biological mothers, who were interviewed about gestational age at birth, birthweight, and the most commonly occurring birth complications: nuchal cord and meconium aspiration when the female child was on average 6years old, and for whom birth records were obtained. OUTCOME MEASURES: Concordance between reports was assessed using one-way random intra-class coefficients for continuous measures and kappa coefficients for dichotomous outcomes. Associations between maternal demographic and psychological factors and discrepancies also were tested. RESULTS: Concordance was excellent for continuously measured birthweight (ICC=0.85, p<0.001) and good for gestational age (ICC=0.68, p<0.001). Agreement was good for low birthweight (<2500g) (kappa=0.67, p<0.001), fair for preterm delivery (<37weeks gestation) (kappa=0.44, p<0.001), and poor for nuchal cord or meconium aspiration. Most discrepancies were characterized by presence according to birth record and absence according to maternal recall. Receipt of public assistance was associated with a decrease in discrepancy in report of nuchal cord. CONCLUSIONS: Concordance between maternal retrospective report and medical birth records varies across different types of perinatal events. There was little evidence that demographic or psychological factors increased the risk of discrepancies. Maternal recall based on continuous measures of perinatal factors may yield more valid data than dichotomous outcomes.

The effect of prenatal docosahexaenoic acid supplementation on infant outcomes in African American women living in low-income environments: A randomized, controlled trial.

IMPORTANCE: African American women living in urban, low-income environments are at high risk for poor nutrition during pregnancy and birth complications. OBJECTIVE: To test the effectiveness of prenatal docosahexaenoic acid (DHA) supplementation on birth outcomes and infant development in a sample of African American women with Medicaid insurance and living in the city of Pittsburgh. DESIGN: The Nutrition and Pregnancy Study (NAPS) is a double-blind, randomized controlled trial of prenatal DHA supplementation conducted between 2012 and 2014. SETTING: Participants were recruited from obstetric clinics at the University of Pittsburgh Medical Center. PARTICIPANTS: Sixty-four pregnant, African American women were enrolled at 16-21 weeks of gestation and randomized to either 450mg/day of DHA (22:6n-3)(n=43) or a soybean placebo (n=21). Four women (6.3%) withdrew from the study: two participants from each study arm; complete data were obtained for 49 infants (76.5%) at the 3-month assessment. INTERVENTIONS: Supplementation with DHA or placebo continued from the beginning of enrollment through delivery. MAIN OUTCOME AND MEASURES: Data on birth outcomes were collected from medical records. At approximately 3 months post-partum, mothers brought their infants to the laboratory where the Bayley Scales of Infant Development (BSID-III) were administered and cortisol response to the Face-to-Face Still-Face (FFSF) paradigm was assessed. RESULTS: Infants of mothers who received DHA supplementation had higher birth weight (3.174g versus 2.890g) than infants of mothers receiving placebo (F [2.40]=6.09, p=0.018, eta=0.36), and were more likely to have a 1-min Apgar score greater than 8 (OR=5.99 [95% CI=1.25-28.75], p=0.025). Infants of mothers who received DHA compared with infants of mothers receiving placebo had lower levels of cortisol in response to the FFSF paradigm (F [1.32]=5.36, p=0.018, eta=0.36). None of the scores on the BSID-III differed as a function of active supplement versus placebo. CONCLUSIONS: Infants of women living in urban, low-income environments who received DHA supplementation had more optimal birth outcomes and more modulated cortisol response to a stressor. DHA supplementation may be effective in attenuating the negative effects of prenatal stress on offspring development.