Pregnant Women's Oral Health-Related Quality of Life and Lifestyle Factors.

Introduction: Pregnancy is often associated with a number of oral manifestations. There is a change in lifestyle factors and dental care during pregnancy. Aim: We conducted this cross-sectional study to determine how lifestyle factors affect oral health-related quality of life (OHRQOL) in pregnant women residing in Bero block, Jharkhand. Methods: The study included a total of 400 pregnant women aged 18-45. The assessment of lifestyle factors and OHRQOL was done using Health Practice Index (HPI) Index and Oral Health Impact Profile-14 (OHIP-14), respectively. Data was collected through face-to-face interviews. Results: Forty percent of the pregnant women showed low OHRQOL. The majority of them were not using mouthwash and were brushing their teeth using faulty techniques. The results of logistic regression analysis showed that women with poor lifestyle scores (Odds Ratio [OR] =3.8, P-value <0.0001*), and systemic diseases (OR = 2.6, P-value < 0.001*) were more likely to have poor OHRQOL. Conclusion: Pregnancy is associated with poor OHRQOL and poor lifestyle scores. Effective policies for oral health need to be drafted for this group.

Direct observation of chemo-mechanical coupling in DnaK by single-molecule force experiments.

Protein allostery requires a communication channel for functional regulation between distal sites within a protein. In the molecular chaperone Hsp70, a two-domain enzyme, the ATP/ADP status of an N-terminal nucleotide-binding domain regulates the substrate affinity of a C-terminal substrate-binding domain. Recently available three-dimensional structures of Hsp70 in ATP/ADP states have provided deep insights into molecular pathways of allosteric signals. However, direct mechanical probing of long-range allosteric coupling between the ATP hydrolysis step and domain states is missing. Using laser optical tweezers, we examined the mechanical properties of a truncated two-domain DnaK(1-552ye) in apo/ADP/ATP- and peptide-bound states. We find that in the apo and ADP states, DnaK domains are mechanically stable and rigid. However, in the ATP state, substrate-binding domain (SBD)∗ye is mechanically destabilized as the result of interdomain docking followed by the unfolding of the α-helical lid. By observing the folding state of the SBD, we could observe the continuous ATP/ADP cycling of the enzyme in real time with a single molecule. The SBD lid closure is strictly coupled to the chemical steps of the ATP hydrolysis cycle even in the presence of peptide substrate.

Top-Up Clozapine for Risperidone LAI-Related Acute Dystonia and TR Bipolar in an Adolescent with ID-Putting the Cart before the Horse?

Objectives: Young patients with intellectual disability (ID) have both diagnostic and therapeutic challenges. These include, inter alia, diagnostic overshadowing, diagnostic slippage and heightened vulnerability to adverse drug reactions. These would portent a generally poor prognostication. Methods: This is a case-study of an adolescent with intellectual disability long-hospitalized for co-morbid treatment-resistant bipolar mood disorder that failed to respond to ECT. Patient partially responded to LAI risperidone with repeated ADRs. Top-up with low-dose clozapine (100 mg/d) was pursued. Results: Low-dose clozapine top-up complemented therapeutic response (mood lability and paranoia) and strikingly safeguarded effectively against risperidone-related extrapyramidal side effects. Conclusions: Add-on clozapine remains a viable option, albeit off-label, in young patients with ID and treatment-resistant affective/schizophreniform psychoses. Clozapine has an edge over other agents in the setting of dyskinesias.

Probable Methylphenidate-Related Reversible "Visual Snow" in a Child With ADHD.

OBJECTIVES: Visual snow syndrome is relatively a recently recognized neurological entity presenting primarily with positive visual disturbance. Etiology is largely speculative. METHODS: Authors report here on a child case of ADHD that developed a probable visual snow syndrome related to methylphenidate. RESULTS AND CONCLUSIONS: Although remaining rare, prescribers ought to be cognizant of such unusual methylphenidate-related perceptual alterations.

Successful Add-on Viloxazine to Clozapine-Responsive Schizophrenia Mitigated Cognitive, Negative and Metabolic Domains.

Early-onset schizophrenia is notorious for poor prognostication and treatment-refractoriness. Clozapine remains a viable option, albeit off-label, but is clearly underutilized in this population. Use is typically fraught with panoply of drastic side effects. Here, authors report on an adolescent case with schizophrenia that responded ultimately to clozapine. Add-on viloxazine was advantageous spanning different symptom domains, mitigating metabolic parameters and addressing clozapine-sialorrhea. This might open new venues for such complicated, yet commonplace, clinical scenarios.

Low-Dose Risperidone for an Autistic Child with Comorbid ARFID and Misophonia.

Avoidant/Restrictive Food Intake Disorder and misophonia seem to be overrepresented in autism spectrum disorder. Literature is mute on psychopharmacotherapy in these complex presentations. Here, authors report on a challenging case of low-functioning ASD child with comorbid ARFID and misophonia that responded favorably to a low-dose risperidone. This is followed by a brief discussion of purported pharmacodynamic mechanisms and relevant literature.

Prevalence and Distribution of Selected Dental Anomalies in the Patients Reporting to Dental Institute, RIMS, Ranchi.

AIM: The purpose of this study was to determine the prevalence of developmental dental anomalies in the East Indian subpopulation. MATERIALS AND METHODS: The study was based on clinical examination, evaluation of dental casts, and radiographs of 2385 Indian patients (1169 males and 1216 females), who visited Dental Institute, Rajendra Institute of Medical Sciences, Ranchi. These patients were examined for shape anomalies, number anomalies, structural anomalies, and positional anomalies. RESULTS: It was observed that 5.83% of patients reported with a dental anomaly. Males reported with higher incidence with a male-to-female ratio of 1: 0.96. Microdontia was the most common anomaly. Unilateral microdontia was more common than bilateral and was more prominent in males (9.05%). It was observed that peg laterals were frequently encountered developmental anomaly at 1.34%, while the incidence of amelogenesis imperfecta and dentinogenesis imperfecta was 0.29% and 0.33%, respectively. The present demography reported a very low incidence of dens, fusion, hyperdontia, hypodontia, and macrodontia at <0.01%, whereas anomalies such as transportation, transmigration, and hypodontia of the maxillary molar reported no prevalence. CONCLUSION: The percentage of dental anomalies although low should be treated as soon as possible to avoid further complications. The results of our study can serve as an indicator to ascertain the pattern of dental anomalies in Jharkhand. This might help to plan the dental treatment of the community.

Discerning Dynamic Signatures of Membrane-Bound α-Synuclein Using Site-Specific Fluorescence Depolarization Kinetics.

α-Synuclein is an intrinsically disordered protein that adopts an α-helical structure upon binding to the negatively charged lipid membrane. Binding-induced conformational change of α-synuclein plays a crucial role in the regulation of synaptic plasticity. In this work, we utilized the fluorescence depolarization kinetics methodology to gain the site-specific dynamical insights into the membrane-bound α-synuclein. We took advantage of the nonoccurrence of Cys in α-synuclein and created single-Cys variants at different sites for us to be able to label it with a thiol-active fluorophore. Our fluorescence depolarization results reveal the presence of three dynamically distinct types of motions of α-synuclein on POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol)) small unilamellar vesicles (SUVs): (i) the (local) wobbling-in-cone motion of the fluorophore on the subnanosecond timescale, (ii) the backbone segmental mobility on the nanosecond timescale, and (iii) a slow depolarization component with a characteristic long rotational correlation time (∼60 ns) that is independent of the residue position. This characteristic timescale could potentially arise due to global tumbling of the protein-membrane complex, the global reorientation of only the protein within the membrane, and/or the translation diffusion of the protein on the curved membrane surface that could result in fluorescence depolarization due to the angular displacement of the transition dipole. In order to discern the molecular origin of the characteristic long rotational correlation time, we then carried our depolarization experiments varying the curvature of the membrane and varying the binding affinity by changing the lipid headgroup. These experiments revealed that the long rotational correlation time primarily arises due to the translational diffusion of α-synuclein on the curved membrane surface with a diffusion coefficient of ∼8.7 × 10-10 m2/s. The site-specific fluorescence depolarization methodology will find broad application in quantifying diffusion of a wide range of membrane-associated proteins involved in functions and diseases.

Hyperthyroidism due to involvement of thyroid gland in disseminated tuberculosis: A rare entity.

Involvement of the thyroid gland with tuberculosis (TB) is unusual and is commonly associated with hypothyroidism. Involvement of the thyroid as a part of disseminated TB is even rarer. Dissemination is an indication of immunosuppression. We present a 16-year-old immunocompetent girl with disseminated TB involving the thyroid gland and the right radius bone with features of hyperthyroidism. The patient responded well to anti-TB treatment.

Orbital tuberculosis with involvement of the eyelid: An unusual presentation.

Although cases of ocular tuberculosis (TB) are increasing, involvement of the eyelid and orbit are unusual. These cases occur secondary to the presence of TB elsewhere in the body, usually pulmonary TB. The primary infection of orbit or eyelid is a rare occurrence. We report a 4-year-old child with primary orbital TB and involvement of the eyelid. The diagnosis of TB should not be missed in patients with ocular symptoms (especially in India) as it is a treatable condition and delays in diagnosis or incorrect diagnosis can lead to serious sequelae.

A rare presentation of disseminated tuberculosis: Prostatic abscess.

Involvement of the prostate by tuberculosis (TB) occurs rarely and tuberculosis prostate abscess is an even rarer occurrence. It has been reported in immunocompromised patients, mainly human immunodeficiency virus seropositive individuals. We are reporting a case of tuberculosis prostatic abscess in an immunocompetent patient with relapse of TB.

Stepwise unfolding of human ß2-microglobulin into a disordered amyloidogenic precursor at low pH.

Amyloid fibril formation by human ß2-microglobulin (ß2m) is associated with dialysis-related amyloidosis. In order to understand the mechanism of protein misfolding, it is important to characterize the nature and properties of various intermediates formed during protein unfolding. In this work, we studied the effect of pH change on the unfolding of ß2m using a range of spectroscopic readouts. In order to investigate the local structural changes, we created single tryptophan (W60 and W95) mutants of ß2m. The equilibrium results suggested that in the acid-unfolded state of ß2m at pH 2.5, the W60 residue attains non-native local structure whereas the W95 residue becomes more exposed. Our stopped-flow kinetic data revealed that ß2m undergoes unfolding in a stepwise manner. Initial unfolding of ß2m involves non-uniform protein expansion with the unpacking of tertiary structure and significant core solvation while maintaining a native-like structure around residue W95. The resolved-phase of unfolding exhibits a timescale of ~500 ms that describes the transition from the native-like swollen intermediate to an acid-induced disordered state. Taken together, our results demonstrate that ß2m has a complex pH-induced unfolding mechanism yielding a disordered amyloidogenic precursor comprising both exposed and buried segments.

Renal tuberculosis presenting as acute pyelonephritis - A rarity.

One of the major health problems faced particularly by the developing world since ages is that of tuberculosis (TB). Genito-urinary tuberculosis (GUTB) is the second most common extrapulmonary TB, with kidney being the most frequent site of infection. Due to the diverse and atypical clinical manifestations of urinary TB, the disease is easy to misdiagnose. The diagnosis of renal TB should be suspected in a nonspecific bacterial cystitis associated with a therapeutic failure or a sterile pyuria and a past history of pulmonary TB with important radiologic findings, particularly with the help of CT scan. Here, we describe a case of renal TB where no clinical or radiological features suggestive of renal TB were present. The diagnosis was only evident after the histopathological examination of the excised kidney. This case highlights the importance of suspecting renal TB as an important cause of kidney disease, which can lead to irreversible renal function loss particularly in an endemic area, and also the diversity that this disease may acquire in its presentation leading to misdiagnosis. In such a case, particularly in a high endemic area for TB, therapeutic trial of ATT may also be considered to avoid unnecessary surgical intervention and end-stage renal disease.

Characterization of Salt-Induced Oligomerization of Human ß2-Microglobulin at Low pH.

Misfolding and amyloid aggregation of human ß2-microglobulin (ß2m) have been linked to dialysis-related amyloidosis. Previous studies have shown that in the presence of different salt concentrations and at pH 2.5, ß2m assembles into aggregates with distinct morphologies. However, the structural and mechanistic details of the aggregation of ß2m, giving rise to different morphologies, are poorly understood. In this work, we have extensively characterized the salt-induced oligomers of the acid-unfolded state of ß2m using an array of biophysical tools including steady-state and time-resolved fluorescence, circular dichroism, dynamic light scattering, and atomic force microscopy imaging. Fluorescence studies using the oligomer-sensitive molecular rotor, 4-(dicyanovinyl)-julolidine, in conjunction with the light scattering and cross-linking assay indicated that at low salt (NaCl) concentrations ß2m exists as a disordered monomer, capable of transforming into ordered amyloid. In the presence of higher concentrations of salt, ß2m aggregates into a larger oligomeric species that does not appear to transform into amyloid fibrils. Site-specific fluorescence experiments using single Trp variants of ß2m revealed that the middle region of the protein is incorporated into these oligomers, whereas the C-terminal segment is highly exposed to bulk water. Additionally, stopped-flow kinetic experiments indicated that the formation of hydrophobic core and oligomerization occur concomitantly. Our results revealed the distinct pathways by which ß2m assembles into oligomers and fibrils.

Correlation between clinical characteristics, spirometric indices and high resolution computed tomography findings in patients of chronic obstructive pulmonary disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease affecting the airways, leading to significant morbidity and mortality throughout the world. There is a need to have a holistic evaluation of COPD patients, other than just measuring the level of obstruction as performed by spirometry. High resolution computed tomography (HRCT) scan of thorax partly fulfills this requirement. MATERIALS AND METHODS: Fifty patients of COPD (confirmed on spirometry as per the GOLD guidelines 2014 guidelines) were enrolled, out of which 35 patients got a HRCT done. Complete clinical evaluation was done. The Philips computer program for lung densitometry was used with these limits (-800/-1, 024 Hounsfield unit [HU]) to calculate densities, after validating densitometry values with phantoms. We established the area with a free hand drawing of the region of interest, then we established limits (in HUs) and the computer program calculated the attenuation as mean lung density (MLD) of the lower and upper lobes. RESULTS: There was a significant correlation between smoking index and anteroposterior tracheal diameter (P = 0.036). Tracheal index was found to be decreasing with increasing disease severity which was statistically significant (P = 0.037). Mean upper lobe MLD was -839.27 HU, mean lower lobe MLD was -834.91 HU and the mean MLD was -837.08 HU. The lower lobes MLD were found to be decreasing with increasing disease severity. A mild linear correlation of pre forced expiratory volume in the first second (FEV1) was observed with lower lobe and total average MLD while a mild linear correlation of Post-FEV1 was observed with both coronal (P = 0.042) and sagittal (P = 0.001) lower lobes MLD. In addition, there was a linear correlation between both pre (P = 0.050) and post (P = 0.024) FEV1/forced vital capacity with sagittal lower lobe MLD. A predictive model can be derived to quantify obstruction severity (FEV1). CONCLUSION: HRCT may be an important additional tool in the holistic evaluation of COPD. HRCT can well be correlated with the spirometric and clinical features and the level of obstruction can be indirectly derived from it by measuring the MLD.