Leveraging hallmark Alzheimer's molecular targets using phytoconstituents: Current perspective and emerging trends.

Alzheimer's disease (AD), a type of dementia, severely distresses different brain regions. Characterized by various neuropathologies, it interferes with cognitive functions and neuropsychiatrical controls. This progressive deterioration has negative impacts not only on an individual's daily activity but also on social and occupational life. The pharmacological approach has always remained in the limelight for the treatment of AD. However, this approach is condemned with several side effects. Henceforth, a change in treatment approach has become crucial. Plant-based natural products are garnering special attention due to lesser side effects associated with their use. The current review emphasizes the anti-AD properties of phytoconstituents, throws light on those under clinical trials, and compiles information on their specific mode of actions against AD-related different neuropathologies. The phytoconstituents alone or in combinations will surely help discover new potent drugs for the effective treatment of AD with lesser side effects than the currently available pharmacological treatment.

CuO assisted borate 1393B3 glass scaffold with enhanced mechanical performance and cytocompatibility: An In vitro study.

Herein, three dimensional porous 1393B3 borate-based glass (BBG) scaffold along with their CuO derivatives (C1BBG, C2BBG, and C3BBG) tailored with trabecular bones' architecture were prepared by melt-quench route followed by foam replica technique. The properties of 'CuO incorporated' scaffolds, as compared to 'as prepared' scaffold were analyzed by a series of In vitro investigations for enhancement in biological compatibility, bioactivity, and physicomechanical performances. The in vitro study demonstrates superior mechanochemical stability of CBBGs (CuO derived 1393B3) than the pure BBG, while causing no or minimal effect on bioactivity and cytocompatibility post CuO incorporation to the BBG. In fact, the biological compatibility examined through MTT, Live/Dead, and cell adhesion study using the L929 cell lines was enhanced in the CBBGs up to 1% CuO incorporated scaffolds (C1BBG and C2BBG) in most cases. However, the enhanced biological compatibility was observed in C1BBG in comparison to other BBGs. Thus, the CuO incorporation into BBG enhanced mechanochemical and biological performance without affecting the bioactivity of the scaffold; henceforth, CBBGs could be considered neo bone tissue regenerative biomaterials.

Application of ERT, Saline Tracer and Numerical Studies to Delineate Preferential Paths in Fractured Granites.

Accurate quantification of in situ heterogeneity and flow processes through fractured geologic media remains elusive for hydrogeologists due to the complexity in fracture characterization and its multiscale behavior. In this research, we demonstrated the efficacy of tracer-electrical resistivity tomography (ERT) experiments combined with numerical simulations to characterize heterogeneity and delineate preferential flow paths in a fractured granite aquifer. A series of natural gradient saline tracer experiments were conducted from a depth window of 18 to 22 m in an injection well (IW) located inside the Indian Institute of Technology Hyderabad campus. Tracer migration was monitored in a time-lapse mode using two cross-sectional surface ERT profiles placed in the direction of flow gradient. ERT data quality was improved by considering stacking, reciprocal measurements, resolution indicators, and geophysical logs. Dynamic changes in subsurface electrical properties inferred via resistivity anomalies were used to highlight preferential flow paths of the study area. Temporal changes in electrical resistivity and tracer concentration were monitored along the vertical in an observation well located at 48 m to the east of the IW. ERT-derived tracer breakthrough curves were in agreement with geochemical sample measurements. Fracture geometry and hydraulic properties derived from ERT and pumping tests were further used to evaluate two mathematical conceptualizations that are relevant to fractured aquifers. Results of numerical analysis conclude that dual continuum model that combines matrix and fracture systems through a flow exchange term has outperformed equivalent continuum model in reproducing tracer concentrations at the monitoring wells (evident by a decrease in RMSE from 199 to 65 mg/L). A sensitivity analysis on model simulations conclude that spatial variability in hydraulic conductivity, local-scale dispersion, and flow exchange at fracture-matrix interface have a profound effect on model simulations.

Assessment of hypoxia, sedation level, and adverse events occurring during inhalation sedation using preadjusted mix of 30% nitrous oxide + 70%oxygen.

PURPOSE: To assess the efficacy of nitrous oxide (N2O)-oxygen (O2) inhalation sedation by rapid induction technique using preadjusted mix of 30% N2O and 70% O2 in children. MATERIALS AND METHODS: Sixty children with a treatment plan which included pulp therapy were recruited for the study. Children categorized 3 and 4 of Frankl behavior rating scale and American Society of Anesthesiologists health status I and II were included for the study. Children were distributed into study group (Group-I) and control group (Group-II) by fishbowl randomization. Children in Group-I were induced inhalation sedation using a preadjusted mix of 30% N2O and 70% O2 through rapid induction technique, and children in Group-II were exposed to inhalation sedation by conventional slow induction technique. Parameters such as least oxygen saturation, sedation levels by Richmond Agitation-Sedation Scale, time taken to achieve ideal sedation, maximum N2O concentrations used, and adverse events were recorded and evaluated for each procedure. Data were analyzed using independent sample t-test and Chi-square tests. RESULTS: Analysis of data showed statistically significant difference between both groups in time taken to achieve ideal sedation (P < 0.001). No significant difference was seen in incidence of hypoxia (P < 0.512), maximum N2O concentrations used (P < 0.118), and occurrence of any adverse events. CONCLUSION: None of the children from both groups exhibited hypoxia. Sense of detachment was seen in one child each from both groups. Rapid induction by preadjusted mix resulted in ideal sedation in 57% children of the Group-I; rest had achieved these levels at 40% N2O. There was a significant difference in the time taken to achieve ideal sedation by rapid induction which was almost half the time taken with slow induction.

A Nonsurgical Approach to Adolescent Breast Asymmetry Using External Prostheses.

PURPOSE: Currently, there are few nonsurgical treatment options for pediatric patients with developmental breast asymmetry. Our group established a partnership with a prosthetic unit within a local oncology center to provide custom-fit breast prostheses for young women with breast asymmetry. The purpose of this study was to describe the effect of this experience on patients' self-esteem and body image. METHODS: Patients were administered an anonymous satisfaction survey at least 1 month after their first fitting at the prosthetic unit. The survey was designed to evaluate body image, self-esteem, as well as social and emotional well-being before and after treatment. Thematic analysis was used to assess their experiences. RESULTS: Seventeen patients, aged 12-19 years, visited the prosthetic unit and subsequently completed the retrospective survey. After using the breast prostheses, 14 (82.4%) patients reported an improvement in body image and 12 (70.6%) patients reported an improvement in self-esteem. Benefits pertaining to three emergent themes were revealed: "body wholeness/symmetry," "body image and psychological well-being," and "esthetic outcome." CONCLUSIONS: Results from the survey demonstrate the ease and efficacy of a form of nonsurgical treatment for adolescent breast asymmetry. Our partnership with an adult oncology center can serve as a national model to support the development of similar treatment programs. Existing resources that have been previously used only for adult breast cancer survivors can be effectively applied to the adolescent population to ameliorate the negative psychological effects of breast asymmetry.

Central Field Index Versus Visual Field Index for Central Visual Function in Stable Glaucoma.

OBJECTIVE: To compare the variability of central field index (CFI) versus visual field index (VFI) in stable glaucoma with central fixation involvement. MATERIALS AND METHODS: For this retrospective study, we identified multiple visual fields (VFs) of patients with repeatable central fixation involvement on Humphrey VFs (24-2 and 10-2 program) which were stable (clinically and on VFs) over a very short period of 2 to 3 months. The VFI and CFI were calculated as described in earlier reports. We graded the fields as early [mean deviation (MD)>-6 dB], moderate (-6.1 to -12 dB), and severe glaucoma (<-12 dB) based on MD on 24-2 program. The variability of CFI and VFI between visits and across different severity of glaucoma was compared. Relation of the divergence to field indices and clinical parameters were assessed. RESULTS: The intervisit difference for VFI was greater than CFI ranging from -4% to 9% versus -1% to 8% in early (P=0.9), -13% to 18% versus -6% to 17% (P=0.056) in moderate, and -21% to 19% versus -9% to 9% (P<0.001) in severe glaucoma. The CFI within each group had narrower range than VFI with maximum range in severe glaucoma (33% to 95%). The divergence of CFI from VFI started at MD 24-2 beyond (worse) -10 dB. This difference between CFI and VFI was associated significantly with number of points with P<1% on 24-2 (R=80.3%). CONCLUSIONS: CFI is less variable than VFI in stable eyes with fixation involvement especially in severe glaucoma indicating need for incorporating CFI calculation for monitoring advanced disease in eyes with central defects.

Genipin-Crosslinked Gelatin-Based Emulgels: an Insight into the Thermal, Mechanical, and Electrical Studies.

The present study discusses about the preparation and characterization (thermal, mechanical, and electrical) of the genipin-crosslinked gelatin emulgels. Emulgels have gained importance in recent years due to their improved stability than emulsions and ability to control the drug release. Mustard oil was used as the representative oil. A decrease in the enthalpy and entropy of the formulations was observed with the increase in the oil fraction. The mechanical studies suggested formation of softer emulgels as the oil fraction was increased. As the proportion of the oil fraction was increased in the emulgels, there was a corresponding increase in the impedance. The drug release properties from the emulgels were also studied. Ciprofloxacin was used as the model antimicrobial drug. The drug release was higher from the emulgels whose electrical conductivity was higher.

Hypothalamic PGC-1α protects against high-fat diet exposure by regulating ERα.

High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens and estrogen receptor α (ERα) protect premenopausal females from the metabolic complications of inflammation and obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα and inflammation in vivo. HFD significantly increased palmitic acid (PA) and sphingolipids in the CNS of male mice when compared to female mice. PA, in vitro, and HFD, in vivo, reduced PGC-1α and ERα in hypothalamic neurons and astrocytes of male mice and promoted inflammation. PGC-1α depletion with ERα overexpression significantly inhibited PA-induced inflammation, confirming that ERα is a critical determinant of the anti-inflammatory response. Physiologic relevance of ERα-regulated inflammation was demonstrated by reduced myocardial function in male, but not female, mice following chronic HFD exposure. Our findings show that HFD/PA reduces PGC-1α and ERα, promoting inflammation and decrements in myocardial function in a sex-specific way.

A substitution mutation in OsCCD7 cosegregates with dwarf and increased tillering phenotype in rice.

Dwarf plant height and tillering ability are two of the most important agronomic traits that determine the plant architecture, and have profound influence on grain yield in rice. To understand the molecular mechanism controlling these two traits, an EMS-induced recessive dwarf and increased tillering1 (dit1) mutant was characterized. The mutant showed proportionate reduction in each internode as compared to wild type revealing that it belonged to the category of dn-type of dwarf mutants. Besides, exogenous application of GA3 and 24-epibrassinolide, did not have any effect on the phenotype of the mutant. The gene was mapped on the long arm of chromosome 4, identified through positional candidate approach and verified by cosegregation analysis. It was found to encode carotenoid cleavage dioxygenase7 (CCD7) and identified as an allele of htd1. The mutant carried substitution of two nucleotides CC to AA in the sixth exon of the gene that resulted in substitution of serine by a stop codon in the mutant, and thus formation of a truncated protein, unlike amino acid substitution event in htd1. The new allele will facilitate further functional characterization of this gene, which may lead to unfolding of newer signalling pathways involving plant development and architecture.

Plasma torch toothbrush a new insight in fear free dentisry.

Dental treatment is considered painful either because of fear or anxiety. Even though fear and anxiety could be managed; the needle pricks and the heat generated with drills are both painful and destructive to the tissues of the tooth. A new technology which can reduce the pain and destruction of the dental tissues will be of huge value. Plasma torch toothbrush fits into such criteria and when developed fully, will be able to apply for many of the dental procedures for increasing the efficiency.

Solitary nodular lesion of tongue- a rare entity.

The solitary, nodular lesions of the oral mucosa present a diagnostic dilemma to the dentist with their analogous presentation. The lesions that appear on the tongue, a soft muscular organ are distinct and even rarer with varied manifestations. Oral mucosa presents lesions of the tongue in all age groups that may range from a small nodular swelling and ulcer formation in an infant of a few days old to an ulcer or a lesion in a 70-year-old. The reason for the appearance of an ulcer may be trauma to the soft tissues in an infant may be due to the presence of natal teeth to the presence of a sharp tooth in the older individuals. These lesions have to be clinically and histologically correlated for the final outcome of the diagnosis, so that there is no chance of any recurrence. We present a unique case of a solitary nodular lesion on the ventral surface of tongue On a 6 year female, where there was a recurrence after surgical excision and after an unusual therapy of non surgical resolution, no recurrence was observed.

Dermatitis artefacta.

A 27-year old lady presented to our department with multiple erosive lesions over extremities, which had a very bizarre pattern and was only over accessible parts of body. A thorough history was taken and a diagnosis of dermatitis artefacta was made. We present this interesting case for its rarity and future reference.

A study on patient satisfaction with psychiatric services.

CONTEXT: Patient satisfaction with psychiatric services is an important construct, which influences multiple areas including treatment adherance and outcome. There is paucity of studies from India in this area. AIMS: To measure satisfaction of psychiatric outpatients of Mental Health Institute, Cuttack, and to assess the relationship between demographic and clinical variables with different domains of patient satisfaction. SETTINGS AND DESIGN: In a cross-sectional study, patients of age 18-60 years receiving treatment for at least six months from outpatient department of Mental Health Institute, SCB Medical College, Cuttack, were assessed. MATERIALS AND METHODS: Participants (n=60) were selected randomly. Satisfaction was assessed by Patient Satisfaction Questionnaire-18 (PSQ-18) and the diagnoses were based on the Diagnostic and Statistical Manual-IV-TR. Severity of psychiatric disorder was measured using Clinical Global Impression-severity scale. The functioning level was assessed by Global Assessment of Functioning. STATISTICAL ANALYSIS: Continuous variables compared using independent t-test or analysis of variance. RESULTS: Diagnostic break-up of the patients included anxiety disorder (36.6%), major depressive disorder (30.0%), bipolar disorder (16.6%), and schizophrenia (16.6%). Greatest level of satisfaction was noted in interpersonal aspects (71.4%) and time spent with doctors (62.4%). General satisfaction level was a little over 50% (57%). Differences between composite scores of PSQ-18 in the diagnostic categories were statistically significant; patients with depression had the highest score followed by those with anxiety disorder, bipolar, and the least was with schizophrenia patients. There was variability among the demographic and clinical groups regarding the various subscale score of PSQ-18. CONCLUSIONS: Satisfaction of psychiatric outpatients was observed to be different in various clinical and demographic groups and across many domains of satisfaction.

Synthesis, characterization and anticonvulsant activity evaluation of some 1,4-dihydropyridines and 3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-N-[2-(4-sulfamoylphenylamino)-acetyl]-4-(substituted)pyridines.

A series of 3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-4-(substituted)pyridines (1a-j) were synthesized by Hantzsch method for pyridine synthesis. Treatment with chloroacetyl chloride produced N-(2-chloroacetyl)-3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-4-(substituted)pyridines (2a-e), which on further treatment with sulfanilamide resulted in 3,5-(substituted)oxycarbonyl-1,4-dihydro-2,6-dimethyl-N-[2-(4-sulfamoylphenylamino)-acetyl]-4-(substituted)pyridines (3a-e). The structures has been established on the basis of spectral (IR, 1H-NMR, mass) and elemental analysis. Compounds 1a-j and 3a-e (5 mg/kg and 10 mg/kg) were evaluated for their anticonvulsant effect against pentylenetetrazole-induced convulsions with diazepam (4 mg/kg) as the reference. Compounds 3a-e exhibited significant (p<0.01) anticonvulsant activity compared to the control.

Effect of tumor bulk on local control and survival of patients with T1 glottic cancer: a 30-year experience.

PURPOSE: To evaluate the effect of tumor bulk on local control and survival of patients with T1 glottic cancer. METHODS AND MATERIALS: Effects of tumor bulk, T-stage, anterior-commissure involvement, treatment duration, and fraction size were analyzed in 208 patients; 136 had small tumors and 72 had bulky tumors. Anterior-commissure was involved in 54 patients. Treatment duration ranged from 39 to 64 days and fraction size ranged from 1.8 to 2.0 Gy. Median follow-up was 5.1 years. RESULTS: Five-year actuarial local control rates were 86.1% and 91.4% after radiotherapy and salvage laryngectomy. On univariate analysis, local control rates were 92.6% and 73.6% for small and bulky tumors (p = 0.03), 89.6% and 75.9% for patients without and with anterior-commissure involvement (p = 0.01), 92.6% and 75.6% when treatment duration was 50 days (p = 0.04), and 90.2% and 76.4% with 2 Gy and 1.8 Gy (p = 0.02) per fraction. On multivariate analysis, tumor bulk was the only significant factor that affected local control (p = 0.007). Ultimate local control rates after salvage were 97.1% and 80.5% for patients with small and bulky tumors. Disease-free survival rates at 5 years for small and bulky tumors were 96.3% and 84.7% (p = 0.001). Median duration to recurrence for small tumors was 30 months as compared with 11 months for bulky tumors. CONCLUSION: Tumor bulk is a highly significant prognostic factor for radiation control of T1 glottic cancer. Patients with bulky tumors had lower local control and disease-free survival rates and shorter duration to recurrence than those with small tumors.

Post-traumatic stress disorder in children and adolescents one year after a super-cyclone in Orissa, India: exploring cross-cultural validity and vulnerability factors.

BACKGROUND: It has been asserted that psychological responses to disasters in children and adolescents vary widely across cultures, but this has rarely been investigated. The objectives of the study were to clinically evaluate the construct of traumatic stress symptoms and disorder in children and adolescents after a super-cyclone in Orissa, India; to find out the prevalence at one year; compare the effect in high and low exposure areas and study the factors associated with it. METHODS: Clinical examination of children and adolescents (n = 447) was done, supplemented by a symptoms checklist based on International Classification of Mental and Behavioural Disorders, Diagnostic Criteria for Research and a semi-structured questionnaire for disaster related experiences. RESULTS: A majority of children had post-traumatic symptoms. Post-traumatic stress disorder (PTSD) was present in 30.6% (95% confidence interval: 26.4 to 34.9), and an additional 13.6% had sub-syndromal PTSD. Parents or teachers reported mental health concerns in 7.2% subjects, who were a minor proportion (12.8%) of subjects with any syndromal diagnosis (n = 196). Significantly more (43.7%) children in high exposure areas had PTSD than that (11.2%) in low exposure areas (p < 0.001). Depression was significantly associated with PTSD. Binary logistic regression analysis indicated that high exposure, lower educational level and middle socioeconomic status significantly predicted the outcome of PTSD. Extreme fear and perceived threat to life during the disaster, death in family, damage to home, or staying in shelters were not significantly associated with PTSD. CONCLUSION: Following natural disaster PTSD is a valid clinical construct in children and adolescents in Indian set up; and though highly prevalent it may be missed without clinical screening. Its manifestation and associated factors resembled those in other cultures.

Knowledge and attitude on infant oral health among graduating medical students in Kerala.

Providing dental and oral health care to all children in Kerala remains a thorny challenge. Lack of community water fluoridation, dental workforce shortages and geographical barriers all aggravate oral health and access problems. Children from low-income and minority families and children with special needs are at particular risk. Family centered disease prevention strategies are needed to reduce oral health disparities in children. Oral health promotion can take place in a primary care practitioner's office, but medical providers often lack relevant training. Present study was conducted to evaluate knowledge and attitude of graduating medical students towards infant oral health qualitative methods were used to evaluate the program.

Synthesis and crystal structure of 2,3,12,13-tetraalkoxy-21, 23-dithiaporphyrins.

21,23-Dithiaporphyrins with methoxy, butoxy, octyloxy and dodecyloxy substituents at beta-thiophene carbons were synthesised for the first time and the crystal structure of the butoxy derivative indicated that the substituents at the beta-thiophene carbons induce more planarity in the porphyrin ring.