Clinical Utility of Pro-inflammatory Oligomeric Glycoprotein Tenascin-C in the Diagnosis of Seropositive and Seronegative Rheumatoid Arthritis.

Owing to limited usefulness of Rheumatoid Factor and anti-CCP in rheumatoid arthritis, there is a need to identify a more sensitive and specific biomarker to detect rheumatoid arthritis (RA), particularly seronegative RA cases. Tenascin-C is an extracellular matrix glycoprotein, which has been implicated in the pathophysiology of RA. The objective of our study was to evaluate the diagnostic utility of serum Tenascin-C in seropositive and seronegative rheumatoid arthritis patients. We conducted a cross-sectional case control study. Sixty patients who fulfilled the ACR 2010 criteria for rheumatoid arthritis were included in the study. Thirty patients were found to be positive for RF and/or anti-CCP and 30 were negative for both RF and anti-CCP. Thirty age and gender-matched healthy subjects were taken as controls. Serum Tenascin-C was measured by quantitative sandwich enzyme immunoassay technique. The mean serum concentration of Tenascin-C in controls, seronegative and seropositive cases was 0.66 ng/ml, 20.54 ng/ml and 23.42 ng/ml, respectively. Tenascin-C levels were significantly higher in RA cases compared to controls (p < 0.0001). There was no significant difference in Tenascin-C between seropositive and seronegative cases (p = 0.603). ROC curve analysis showed a sensitivity of 96.6% and specificity of 100% with AUC of 0.98 at 2.21 ng/ml as cut-off value for diagnosing RA. Tenascin-C is elevated in both seronegative and seropositive RA, which indicates that it can be used as a sensitive marker for RA. The addition of Tenascin-C to the existing RF and anti-CCP may help in identifying a large number of patients with RA, particularly seronegative rheumatoid arthritis cases.

Molecular Evaluation of Joubert Syndrome and Hearing Impairment in a Patient with Ataxic Cerebral Palsy.

Joubert syndrome (JBTS) is a rare autosomal recessive or X-linked congenital brain malformation with strong genetic heterogeneity. Other neurological features of JBTS include hypotonia, ataxia, developmental delay, and cognitive impairment. Hearing loss with JBTS has been reported in the literature. We present the case of a 3.5-year-old boy born to a healthy consanguineous South Indian couple who was presented with ataxic cerebral palsy (CP) and hearing impairment; medical reports confirmed typical brain malformations of JBTS. Hearing impairment was screened by audiological assessment, which confirmed the presence of severe-profound hearing loss with outer hair cell dysfunction. Whole-exome sequencing (WES) was performed to know the molecular aspects of the condition and to detect any novel mutations. The homozygous mutation AHI1 c.2023G > A associated with JBTS type 3 and GJB2 c.71G > A mutation associated with hearing impairment were identified. Sanger sequencing was performed to validate the result and it identified heterozygous AHI1 c.2023G > A and GJB2 c.71G > A in the patient's parents. This study confirms the diagnosis of JBTS by WES helps identify the genetic causes of hereditary disorders that accelerate genetic evaluation and counseling for at-risk families.

PMM2 -CDG T237M Mutation in a Patient with Cerebral Palsy-Like Phenotypes Reported from South India.

Congenital disorder of glycosylation (CDG) is an autosomal recessively inherited disorder. Hypotonia, stroke-like episodes, and peripheral neuropathy are also associated with the condition that typically develops during infancy. The patient, a 12-year-old girl born to healthy consanguineous parents, was diagnosed with cerebral palsy as a child. The affected patient has hypotonia, inadequate speech, strabismus, and developmental delay with mild mental retardation, which are key symptoms of CDG. Whole-exome sequencing (WES) identified the known missense pathogenic variant PMM2 c.710 C > T, p.T237M in the patient coding for the phosphomannomutase 2 (PMM2) confirming molecular testing of CDG. The patient's parents carried heterozygous PMM2 c.710 C > T variants. This study highlights the importance of WES in patients with a developmental disability or other neurological conditions, which is also useful in screening risk factors in couples with infertility or miscarriage issues.

Prevalence of Hearing Impairment in High-Risk Neonates at Kalaburagi Region of Northern Karnataka: A Hospital-Based Cross-Sectional Study.

The study estimated the prevalence of hearing impairment in high-risk neonates and effect of high-risk factors on the hearing. A hospital-based cross sectional study was conducted on 327 neonates with high-risk factors. All the high-risk babies were screened using TEOAE and AABR followed by diagnostic ABR testing. Six (2%) of high-risk neonates were found to have bilateral severe sensorineural hearing loss. Risk factors associated with hearing impairment include multiple risk factors of Preterm delivery, hyperbilirubinemia, congenital anomalies, neonatal sepsis, viral or bacterial infection, positive family history of hearing loss and prolonged NICU stay. Further, the inclusion of AABR along with TEOAE has been shown to be a useful tool in reducing false-positive rates and identifying hearing loss.

Investigation of Different Time-Frequency Representations for Intelligibility Assessment of Dysarthric Speech.

Speech disorders linked to neurological problems affect person's ability to communicate through speech. Dysarthria is one of the speech disorders caused due to muscle weakness producing slow, slurred and less intelligible speech. Automatic intelligibility assessment of dysarthria from speech can be used as a promising clinical tool in treatment. This paper explores the use of perceptually enhanced Fourier transform spectrograms and Constant-Q transform spectrograms with CNN to assess word level and sentence level intelligibility of dysarthric speech from UA and TORGO databases. Constant-Q transform and perceptually enhanced mel warped STFT spectrograms performed better in the classification task.

Evaluation of Galectin-3 as a Novel Diagnostic Biomarker in Patients with Heart Failure with Preserved Ejection Fraction.

Background Heart failure is a complex cardiovascular disease with a variety of etiologies and heterogeneity. The N-terminal pro-B-type natriuretic peptide (NT-proBNP) value has limited usefulness in diagnosing heart failure with preserved ejection fraction (HFpEF). Aim The aim of the present study is to evaluate serum Galectin-3 as a diagnostic biomarker in patients with HFpEF and to compare Galectin-3 with NT-proBNP levels. Materials and Methods A cross-sectional case-control study including 63 cases of heart failure with ejection fraction ≥50% confirmed by echocardiography. NT-proBNP levels in serum were measured by electrochemiluminescence immunoassay and Galectin-3 levels in serum were measured by using an enzyme-linked-immunosorbent serologic assay kit. Results The median levels of serum Galectin-3 and NT-proBNP in patients were significantly higher than those of controls (26.59 vs. 5.27 and 927 vs. 49.3, p < 0.0001). A positive correlation was observed between serum levels of Galection-3 and NT-ProBNP ( r : 0.21, p = 0.048). At cut-off values of 10.1 ng/mL and 160 pg/mL, serum Galectin-3 has 77.78% sensitivity, 95% specificity with an area under the curve (AUC) of 0.93, and serum NT-proBNP has 71.43% sensitivity, 100% specificity with an AUC of 0.87, respectively, for diagnosing HFpEF. The comparison of receiver operating characteristics curves showed that Galectin-3 has better AUC compared with NT-proBNP in diagnosing HFpEF. Serum Galectin-3 showed a positive correlation with NT-proBNP and lipid parameters. Conclusion Galectin-3 with higher sensitivity and AUC can be used as a valuable biomarker for the diagnosis of HFpEF. Simultaneous testing of both Galectin-3 and NT-proBNP can further improve the detection of patients with HFpEF.

Temporal characteristics of stop consonants in pediatric cochlear implant users.

Objectives: The benefits of Cochlear Implant (CI) in improving speech production abilities in children with hearing impairment can be reflected through acoustic analysis. The primary aim of the study was to investigate the temporal characteristics of stop consonants in Malayalam speaking children using CI. Methods: Twelve children using CI and 12 age- and gender-matched typically developing children (TDC) participated in the study. Simple bisyllabic words with selected target consonants were elicited through a picture naming task and were recorded. Acoustic analysis was carried out using Praat software to derive the acoustic measures - Voice Onset Time (VOT), Burst duration and Closure duration. Results: The results of the study revealed that children using CI differed significantly from TDC for a few target consonants in burst duration and closure duration. However, VOT did not show any significant difference between children using CI and TDC. Conclusion: With early implantation and intensive speech intervention, there is a significant improvement in the speech of children using CI. Yet may have minor deficits which could impact the naturalness of speech. The study highlights the importance of acoustic analyses in identifying these speech errors at a finer level and utilizing the same to evaluate intervention efficacy.

Manner and place differences in Kannada coronal consonants: Articulatory and acoustic results.

This study investigated articulatory differences in the realization of Kannada coronal consonants of the same place but different manner of articulation. This was done by examining tongue positions and acoustic formant transitions for dentals and retroflexes of three manners of articulation: stops, nasals, and laterals. Ultrasound imaging data collected from ten speakers of the language revealed that the tongue body/root was more forward for the nasal manner of articulation compared to stop and lateral consonants of the same place of articulation. The dental nasal and lateral were also produced with a higher front part of the tongue compared to the dental stop. As a result, the place contrast was greater in magnitude for the stops (being the prototypical dental vs retroflex) than for the nasals and laterals (being apparently alveolar vs retroflex). Acoustic formant transition differences were found to reflect some of the articulatory differences, while also providing evidence for the more dynamic articulation of nasal and lateral retroflexes. Overall, the results of the study shed light on factors underlying manner requirements (aerodynamic or physiological) and how the factors interact with principles of gestural economy/symmetry, providing an empirical baseline for further cross-language investigations and articulation-to-acoustics modeling.

Whole exome sequencing identifies a novel homozygous frameshift mutation in the ASPM gene, which causes microcephaly 5, primary, autosomal recessive.

Microcephaly is a genetically heterogeneous disorder and is one of the frequently notable conditions in paediatric neuropathology which exists either as a single entity or in association with other co-morbidities. More than a single gene is implicated in true microcephaly and the list is growing with the recent advancements in sequencing technologies. Using massive parallel sequencing, we identified a novel frame shift insertion in the abnormal spindle-like microcephaly-associated protein gene in a client with true autosomal recessive primary microcephaly.  Exome sequencing in the present case helped in identifying the true cause behind the disease, which helps in the premarital counselling for the sibling to avoid future recurrence of the disorder in the family.

Antitoxin activity of aqueous extract of Cyclea peltata root against Naja naja venom.

OBJECTIVES: Snakebites are a significant and severe global health problem. Till date, anti-snake venom serum is the only beneficial remedy existing on treating the snakebite victims. As antivenom was reported to induce early or late adverse reactions to human beings, snake venom neutralizing potential for Cyclea peltata root extract was tested for the present research by ex vivo and in vivo approaches on Naja naja toxin. MATERIALS AND METHODS: Ex vivo evaluation of venom toxicity and neutralization assays was carried out. The root extracts from C. peltata were used to evaluate the Ex vivo neutralization tests such as acetylcholinesterase, protease, direct hemolysis assay, phospholipase activity, and procoagulant activity. Gas chromatography-mass spectrometry (GC-MS) analysis from root extracts of C. peltata was done to investigate the bioactive compounds. RESULTS: The in vivo calculation of venom toxicity (LD50) of N. naja venom remained to be 0.301 µg. C. peltata root extracts were efficiently deactivated the venom lethality, and effective dose (ED50) remained to be 7.24 mg/3LD50 of N. naja venom. C. peltata root extract was found effective in counteracting all the lethal effects of venom. GC-MS analysis of the plant extract revealed the presence of antivenom compounds such as tetradecanoic and octadecadienoic acid which have neutralizing properties on N. naja venom. CONCLUSION: The result from the ex vivo and in vivo analysis indicates that C. peltata plant root extract possesses significant compounds such as tetradecanoic acid hexadecanoic acid, heptadecanoic acid, and octadecadienoic acid which can counteract the toxins present in N. naja.

Articulation and acoustics of Kannada affricates: A case of geminate /ʧ/.

Affricates have been observed to be problematic in phonological acquisition and disordered speech across languages, due to their relatively complex spatial and temporal articulatory patterns. Remediation of difficulties in the production of affricates requires understanding of how these sounds are typically produced. This study presents the first systematic articulatory and acoustic investigation of voiceless geminate affricate /ʧ/ in Kannada (a Dravidian language), compared to the palatal glide and the voiceless dental stop. Ultrasound data from 10 normal speakers from Mysore, India revealed that /ʧ/ is produced with the tongue shape intermediate between the palatal glide and the dental stop, and with the laminal constriction at the alveolar ridge. The observed articulatory differences are reflected in acoustic formant patterns of vowel transitions and stop/affricate bursts. Altogether, the results show that the Kannada consonant in question is an alveolopalatal affricate, supporting some of the previous descriptive phonetic accounts of the language and raising questions for further research on normal and disordered speech. The results and our survey of literature also suggest that affricates in South Asian languages tend to be phonetically variable and historically unstable compared to other consonant articulations.

Nasalance in Cochlear Implantees.

OBJECTIVES: Speech intelligibility is severely affected in children with congenital profound hearing loss. Hypernasality is a problem commonly encountered in their speech. Auditory information received from cochlear implants is expected to be far superior to that from hearing aids. Our study aimed at comparing the percentages of nasality in the speech of the cochlear implantees with hearing aid users and also with children with normal hearing. METHODS: Three groups of subjects took part in the study. Groups I and II comprised 12 children each, in the age range of 4-10 years, with prelingual bilateral profound hearing loss, using multichannel cochlear implants and digital hearing aids respectively. Both groups had received at least one year of speech therapy intervention since cochlear implant surgery and hearing aid fitting respectively. The third group consisted of age-matched and sex-matched children with normal hearing. The subjects were asked to say a sentence which consisted of only oral sounds and no nasal sounds ("Buy baby a bib"). The nasalance score as a percentage was calculated. RESULTS: Statistical analysis revealed that the children using hearing aids showed a high percentage of nasalance in their speech. The cochlear implantees showed a lower percentage of nasalance compared to children using hearing aids, but did not match with their normal hearing peers. CONCLUSION: The quality of speech of the cochlear implantees was superior to that of the hearing aid users, but did not match with the normal controls. The study suggests that acoustic variables still exist after cochlear implantation in children, with hearing impairments at deviant levels, which needs attention. Further research needs to be carried out to explore the effect of the age at implantation as a variable in reducing nasality in the speech and attaining normative values in cochlear implantees, and also between unilateral versus bilateral implantees.

Reattachment of fractured tooth fragment with fiber post: a case series with 1-year followup.

Coronal fractures of the anterior teeth are common sequelae of dental trauma. In case of complex fractures, where the fractured segment is available and there is close approximation of the segment to the remaining tooth, root canal treatment followed by reattachment of the fractured segment with fiber post reinforcement is a feasible option. The procedure is simple and economic and needs less chair-side time as compared to many conventional methods. In addition, the procedure provides good and long-lasting esthetics, because the original morphology, color, and surface texture are maintained. This paper reports three cases of complex coronal tooth fracture successfully managed using tooth fragment reattachment.

Marine yeasts-a review.

Yeasts are ubiquitous in their distribution and populations mainly depend on the type and concentration of organic materials. The distribution of species, as well as their numbers and metabolic characteristics were found to be governed by existing environmental conditions. Marine yeasts were first discovered from the Atlantic Ocean and following this discovery, yeasts were isolated from different sources, viz. seawater, marine deposits, seaweeds, fish, marine mammals and sea birds. Near-shore environments are usually inhabited by tens to thousands of cells per litre of water, whereas low organic surface to deep-sea oceanic regions contain 10 or fewer cells/litre. Aerobic forms are found more in clean waters and fermentative forms in polluted waters. Yeasts are more abundant in silty muds than in sandy sediments. The isolation frequency of yeasts fell as the depth of the sampling site is increased. Major genera isolated in this study were Candida, Cryptococcus, Debaryomyces and Rhodotorula. For biomass estimation ergosterol method was used. Classification and identification of yeasts were performed using different criteria, i.e. morphology, sexual reproduction and physiological/biochemical characteristics. Fatty acid profiling or molecular sequencing of the IGS and ITS regions and 28S gene rDNA ensured accurate identification.

Enforcing periodic secondary structures in hybrid peptides: a novel hybrid foldamer containing periodic gamma-turn motifs.

This note describes the design, synthesis, and conformational studies of a novel hybrid foldamer that adopts a definite compact, three-dimensional structure determined by a combined effect of the special conformational properties of the foldamer constituents. The striking feature of this de novo designed foldamer is its ability to display periodic gamma-turn conformations stabilized by intramolecular hydrogen bonds. Conformational investigations by single-crystal X-ray studies, solution-state NMR, and ab initio MO theory at the HF/6-31G* level strongly support the prevalence of gamma-turn motifs in both the di- and tetrapeptide foldamers, which are presumably stabilized by bifurcated hydrogen bonds in the solid and solution states. The strategy disclosed herein for the construction of hybrid foldamers with periodic gamma-turn motifs has the potential to significantly augment the conformational space available for foldamer design with diverse backbone structures and conformations.

Management of postmolar gestational trophoblastic disease with methotrexate and folinic acid: 15 years of experience.

OBJECTIVE: To study the incidence of postmolar gestational trophoblastic disease (GTD) following hydatidiform mole and to evaluate the effectiveness of single-agent chemotherapy using methotrexate with folinic acid rescue. STUDY DESIGN: A prospective study of all cases of hydatidiform mole diagnosed and treated in the department of obstetrics and gynecology, Medical College, Calicut, India, was started in June 1990 to determine the incidence of postmolar GTD and the effectiveness of single-agent chemotherapy with methotrexate and folinic acid in postmolar nonmetastatic GTD. RESULTS: For the 15-year period from June 1990 to May 2005, 1,569 cases of hydatidiform mole were diagnosed and managed at our institution. The incidence of postmolar GTD among 1,569 cases of hydatidiform mole was 20.4%. Of the 321 cases of postmolar GTD diagnosed, 284 patients (88.5%) achieved complete remission with the methotrexate/folinic acid regimen. Fourteen multiparous patients (4.4%) underwent hysterectomy with methotrexate/folinic acid and achieved remission. Thus, 92.9% of patients with postmolar GTD had complete remission with the methotrexate/folinic acid regimen. The rest of the cases required multiagent therapy. CONCLUSION: Regular follow-up of patients after evacuation of hydatidiform mole will detect cases of postmolar GTD at an early stage. Single-agent chemotherapy with methotrexate was effective in 92.9% of our cases.

Prospective evaluation of abnormal liver function tests in pregnancy.

Abnormalities in liver function tests (LFT) during pregnancy are a commonly encountered problem often associated with serious consequences especially when it occurs in the third trimester. The spectrum of abnormal liver functions in pregnancy can be fairly wide and diagnostic work up often challenging. There is insufficient prospective data on the spectrum and outcome of liver disease in pregnant population from south India. This study was performed to assess the causes of deranged liver function in the pregnant population and also to prospectively determine the outcome of liver dysfunction in pregnancy. All abnormal LFT results observed in serum samples from pregnant patients attending the obstetric unit of our hospital from January 2003 to January 2005 were evaluated and prospectively followed throughout pregnancy. Laboratory investigations included coagulation profile, renal function tests, serology for viral markers (HBsAg, anti-HCV, IgM anti-HEV and IgM anti-HAV) and other relevant biochemical tests. In those with liver dysfunction in the third trimester the maternal and perinatal outcome was evaluated. A total of 125 patients were identified with abnormalities in LFT results during this period. The majority of causes were related to pregnancy specific conditions (57.6%). Most episodes of abnormal LFT occurred in the third trimester (59.2%). Hyperemesis gravidarum (55.8%) and viral hepatitis (47%) were the most common causes of abnormal LFT in the first and second trimesters respectively. HELLP (28.3%) and AFLP (14.8%) were the most common causes of abnormal LFT in the third trimester. There were no mAternal deaths due to liver dysfunction in the first or second trimester. Liver dysfunction in the third trimester (74 patients) was associated with serious consequences. DIC was the most common complication (20.2%). The overall and perinatal mortality was 20.2% and 24.6% respectively. AFLP and HELLP syndromes were associated with poor maternal and fetal outcome. We conclude that liver dysfunctions were directly related to pregnancy in the majority of patients especially in the third namely trimester. Incidence of the most serious conditions AFLP and HELLP syndromes is much greater than what has been reported and is often associated with a high maternal mortality and poor perinatal outcome.