Optimizing the White Light Emission of Pr3+ Activated SrCeO3 Perovskite by Controlling the Excitation Wavelength for High CRI wLED Applications.

The current research illustrates excitation energy-triggered photoluminescent characteristics of Pr3+ions in SrCeO3 providing a practical approach for developing high CRI wLED and its applications. SrCeO3: xPr3+ (x = 0, 0.005, 0.01, 0.02, 0.03 wt) perovskites synthesized by fuel excess gel combustion method generate high CRI (~98) for wLED applications. Crystalline phosphors with orthorhombic structures having space group Pnma were confirmed by XRD. The unit cell volume expansion occurred with an increase in Pr3+ concentration was verified through the Rietveld refinement technique. Surface morphology, particle distribution, and size were observed via FE-SEM imaging, and detected a well-defined regular distorted spherical structure with average grain size 0.826 µm for Pr3+ doped SrCeO3. Elemental mapping and EDS analysis identified the uniform distribution and elemental purity of SrCeO3: 0.01 Pr3+. Further, the molecular vibrations and modes were analyzed from the Raman spectrum. Moreover, the average particle size assessed via TEM analysis was found to be ~83.2 nm, consistent with XRD analysis. UV-visible absorption spectra for optical energy-band gap analysis showed a decrease in band gap energy with an increase in Pr3+ concentration, realizing an effective energy transfer from Ce4+ to Pr3+. PL measurements showed a huge variety of emission transitions, corresponding to excitations 290 nm, 321 nm, 373 nm, and 449 nm. The critical dopant concentration instigated by concentration quenching was 1 wt% Pr3+, ascribed to dipole-dipole interaction. The fluorescence lifetime of the optimal sample was 4.835 µs. Commission International de I'Eclairage (CIE) diagram exposes the white light emanation of SrCeO3: Pr3+. Among which white light with high CRI (~98) and comparably low CCT (~6311 K) was obtained for SrCeO3: 0.01 Pr3+ at 373 nm excitation. The obtained results recommend that SrCeO3: Pr3+ perovskite as an efficient white phosphor for fabricating high-performance wLEDs.

Evaluation of the AV7909 Anthrax Vaccine Toxicity in Sprague Dawley Rats Following Three Intramuscular Administrations.

AV7909 is a next-generation anthrax vaccine under development for post-exposure prophylaxis following suspected or confirmed Bacillus anthracis exposure, when administered in conjunction with the recommended antibacterial regimen. AV7909 consists of the FDA-approved BioThrax® vaccine (anthrax vaccine adsorbed) and an immunostimulatory Toll-like receptor 9 agonist oligodeoxynucleotide adjuvant, CPG 7909. The purpose of this study was to evaluate the potential systemic and local toxicity of AV7909 when administered via repeat intramuscular injection to the right thigh muscle (biceps femoris) to male and female Sprague Dawley rats. The vaccine was administered on Days 1, 15, and 29 and the animals were assessed for treatment-related effects followed by a 2-week recovery period to evaluate the persistence or reversibility of any toxic effects. The AV7909 vaccine produced no apparent systemic toxicity based on evaluation of clinical observations, body weights, body temperature, clinical pathology, and anatomic pathology. Necrosis and inflammation were observed at the injection sites as well as in regional lymph nodes and adjacent tissues and were consistent with immune stimulation. Antibodies against B. anthracis protective antigen (PA) were detected in rats treated with the AV7909 vaccine, confirming relevance of this animal model for the assessment of systemic toxicity of AV7909. In contrast, sera of rats that received saline or soluble CPG 7909 alone were negative for anti-PA antibodies. Overall, 3 intramuscular immunizations of Sprague Dawley rats with AV7909 were well tolerated, did not induce mortality or any systemic adverse effects, and did not result in any delayed toxicity.

Distribution of water in the pores of periodic mesoporous organosilicates - a proton solid state MAS NMR study.

Solid state proton (1H) magic angle spinning (MAS) NMR has been employed to study the distribution of confined water in ethane substituted periodic mesoporous organosilicate (PMOE) materials. Proton spectra acquired at different hydration levels are analysed and interpreted in terms of water clusters of various sizes and distributions of water layers on the pore surface. For comparison, we also performed similar experiments on SBA-15. The formation of larger clusters at lower hydration suggests that the pores of PMOE are getting filled with water at lower hydration levels than those in SBA-15. For PMOE, the simultaneous presence of two major resonances in the ranges 3.6-4.1 ppm and 4.4-5.2 ppm and their behaviour upon hydration imply a water layer distribution that is the sum of two contributions, corresponding to fully filled and partially filled pores or pore segments. Furthermore, the behaviour mentioned above suggests that both radial and axial filling mechanisms play a significant role in the hydration process. For SBA-15, as a function of hydration, we observed a smooth variation in the proton chemical shift of the main dynamic resonance. In accordance with previous studies, this is attributed to the gradual increase in the average thickness of water layers with an increase in hydration, and to a pore filling mechanism that is predominantly radial.

Integration of Single-Center Data-Driven Vital Sign Parameters into a Modified Pediatric Early Warning System.

OBJECTIVES: Pediatric early warning systems using expert-derived vital sign parameters demonstrate limited sensitivity and specificity in identifying deterioration. We hypothesized that modified tools using data-driven vital sign parameters would improve the performance of a validated tool. DESIGN: Retrospective case control. SETTING: Quaternary-care children's hospital. PATIENTS: Hospitalized, noncritically ill patients less than 18 years old. Cases were defined as patients who experienced an emergent transfer to an ICU or out-of-ICU cardiac arrest. Controls were patients who never required intensive care. Cases and controls were split into training and testing groups. INTERVENTIONS: The Bedside Pediatric Early Warning System was modified by integrating data-driven heart rate and respiratory rate parameters (modified Bedside Pediatric Early Warning System 1 and 2). Modified Bedside Pediatric Early Warning System 1 used the 10th and 90th percentiles as normal parameters, whereas modified Bedside Pediatric Early Warning System 2 used fifth and 95th percentiles. MEASUREMENTS AND MAIN RESULTS: The training set consisted of 358 case events and 1,830 controls; the testing set had 331 case events and 1,215 controls. In the sensitivity analysis, 207 of the 331 testing set cases (62.5%) were predicted by the original tool versus 206 (62.2%; p = 0.54) with modified Bedside Pediatric Early Warning System 1 and 191 (57.7%; p < 0.001) with modified Bedside Pediatric Early Warning System 2. For specificity, 1,005 of the 1,215 testing set control patients (82.7%) were identified by original Bedside Pediatric Early Warning System versus 1,013 (83.1%; p = 0.54) with modified Bedside Pediatric Early Warning System 1 and 1,055 (86.8%; p < 0.001) with modified Bedside Pediatric Early Warning System 2. There was no net gain in sensitivity and specificity using either of the modified Bedside Pediatric Early Warning System tools. CONCLUSIONS: Integration of data-driven vital sign parameters into a validated pediatric early warning system did not significantly impact sensitivity or specificity, and all the tools showed lower than desired sensitivity and specificity at a single cutoff point. Future work is needed to develop an objective tool that can more accurately predict pediatric decompensation.

Changing Management of the Patent Ductus Arteriosus: Effect on Neonatal Outcomes and Resource Utilization.

Objective This historical cohort study investigated how a shift toward a more conservative approach of awaiting spontaneous closure of the patent ductus arteriosus (PDA) in preterm infants has affected neonatal outcomes and resource utilization. Methods We retrospectively studied very low birth weight infants diagnosed with a PDA by echocardiogram (ECHO) in 2006-2008 (era 1), when medical or surgical PDA management was emphasized, to those born in 2010-2012 (era 2) when conservative PDA management was encouraged. Multiple regression analyses adjusted for gestational age were performed to assess differences in clinical outcomes and resource utilization between eras. Results More infants in era 2 (35/89, 39%) compared with era 1 (22/120, 18%) had conservative PDA management (p < 0.01). Despite no difference in surgical ligation rate, infants in era 2 had ligation later (median 24 vs. 8 days, p < 0.0001). There was no difference in clinical outcomes between eras, while number of ECHOs per patient was the only resource measure that increased in era 2 (median 3 vs. 2 ECHOs, p = 0.003). Conclusion In an era of more conservative PDA management, no increase in adverse clinical outcomes or significant change in resource utilization was found. Conservative PDA management may be a safe alternative for preterm infants.

Anticancer potential of pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2-methyl propyl) (PPDHMP) extracted from a new marine bacterium, Staphylococcus sp. strain MB30.

Marine bacterium, strain MB30 isolated from the deep sea sediment of Bay of Bengal, India, exhibited antimicrobial activity against human pathogenic bacteria. Based on the 16S rRNA sequence homology and subsequent phylogenetic tree analysis, the strain MB30 was identified as Staphylococcus sp. The bioactive metabolite produced by the strain MB30 was purified through silica gel column chromatography and preparative HPLC. Purified metabolite was further characterized by FT-IR, LC-MS and NMR analyses. On the basis of spectroscopic data, the metabolite was identified as pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2-methyl propyl) (PPDHMP). The PPDHMP exhibited in vitro anticancer potential against lung (A549) and cervical (HeLa) cancer cells in a dose-dependent manner with the IC50 concentration of 19.94 ± 1.23 and 16.73 ± 1.78 µg ml(-1) respectively. The acridine orange (AO)/ethidium bromide (EB) and 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining of the IC50 concentration of PPDHMP-treated cancer cells exhibited an array of morphological changes such as nuclear condensation, cell shrinkage and formation of apoptotic bodies. The PPDHMP-treated cancer cells induced the progressive accumulation of fragmented DNA in a time-dependent manner. Based on the flow cytometric analysis, it has become evident that the compound was also effective in arresting the cell cycle at G1 phase. Further, the Western blotting analysis confirmed the down-regulation of cyclin-D1, cyclin dependent kinase (CDK-2), anti-apoptotic Bcl-2 family proteins (Bcl-2 and Bcl-xL), activation of caspase-9 and 3 with the cleavage of PARP. The PPDHMP-treated cancer cells also showed the inhibition of migration and invasive capacity of cancer cells. In the present investigation, for the first time, we have reported the extraction, purification and characterization of an anticancer metabolite, PPDHMP from a new marine bacterium, Staphylococcus sp. strain MB30.

Expanding the phenotype of hawkinsinuria: new insights from response to N-acetyl-L-cysteine.

Hawkinsinuria is a rare disorder of tyrosine metabolism that can manifest with metabolic acidosis and growth arrest around the time of weaning off breast milk, typically followed by spontaneous resolution of symptoms around 1 year of age. The urinary metabolites hawkinsin, quinolacetic acid, and pyroglutamic acid can aid in identifying this condition, although their relationship to the clinical manifestations is not known. Herein we describe clinical and laboratory findings in two fraternal twins with hawkinsinuria who presented with failure to thrive and metabolic acidosis. Close clinical follow-up and laboratory testing revealed previously unrecognized hypoglycemia, hypophosphatemia, combined hyperlipidemia, and anemia, along with the characteristic urinary metabolites, including massive pyroglutamic aciduria. Treatment with N-acetyl-L-cysteine (NAC) restored normal growth and normalized or improved most biochemical parameters. The dramatic response to NAC therapy supports the idea that glutathione depletion plays a key role in the pathogenesis of hawkinsinuria.

Phenazine-1-carboxamide (PCN) from Pseudomonas sp. strain PUP6 selectively induced apoptosis in lung (A549) and breast (MDA MB-231) cancer cells by inhibition of antiapoptotic Bcl-2 family proteins.

Phenazine-1-carboxamide (PCN), a naturally occurring simple phenazine derivative isolated from Pseudomonas sp. strain PUP6, exhibited selective cytotoxic activity against lung (A549) and breast (MDA-MB-231) cancer cell lines in differential and dose-dependent manner compared to normal peripheral blood mononuclear cells. PCN-treated cancer cells showed the induction of apoptosis as evidenced by the release of low level of LDH, morphological characteristics, production of reactive oxygen species, loss of mitochondrial membrane potential (ΔΨm) and induction of caspase-3. At molecular level, PCN instigates apoptosis by mitochondrial intrinsic apoptotic pathway via the overexpression of p53, Bax, cytochrome C release and activation of caspase-3 with the inhibition of oncogenic anti-apoptotic proteins such as PARP and Bcl-2 family proteins (Bcl-2, Bcl-w and Bcl-xL). The in silico docking studies of PCN targeted against the anti-apoptotic members of Bcl-2 family proteins revealed the interaction of PCN with the BH3 domain, which might lead to the induction of apoptosis due to the inhibition of antiapoptotic proteins. Due to its innate inhibition potential of antiapoptotic Bcl-2 family proteins, PCN may be used as potent anticancer agent against both lung and breast cancer.

Enzymatic Pre-treatment of Wastewater to Minimize Recovery by Reverse Transcriptase PCR of RNA from Inactive Bacteriophages.

Quantitative viral risk assessments for wastewaters are notoriously difficult. The often considered quantitative reverse transcriptase PCR reflects poorly on virus infectivity rates leading to inaccurate risk interpretations. Various techniques focused on the degradation of the nucleic acids of non-infective viruses were previously employed. We comparatively assessed the effectiveness of such enzymatic treatments for MS2 bacteriophage in treated wastewaters. The single use of RNase A at an appropriate concentration may be as effective as the combination of RNase followed by Proteinase K and more rapid. While all tested enzymatic treatments minimized recovery of RNA (>95 %) in the absence of infective MS2, none completely eliminated the signal recovery. Selection of any enzymatic protocol for minimizing recovery of RNA from degraded, non-infective viruses should balance the methods efficacy with its expediency.

Development and standardization of tinnitus handicap inventory in malayalam.

INTRODUCTION: Tinnitus is defined as the perception of sound mainly due to the activity within the central nervous system without any mechanical, vibratory activity within the cochlea. Administration of tinnitus related questionnaires along with the audiological test battery is recommended in routine clinical practice. Tinnitus Handicap Inventory (THI) is one of the useful and widely recognized tools for quantifying the impact of tinnitus on daily life. India, being a multilingual country with a multicultural background, there is no such inventories available in many of the local Indian languages except in Tamil and Kannada. MATERIALS & METHODS: The English THI was translated to Malayalam by a faculty who is qualified and proficient in Malayalam language. Then the translated THI was given to 40 native Malayalam speakers for content validity. The final THI-M was administered on 50 tinnitus patient. Obtained data was then subjected for statistical analysis using SPSS Statistics 17.0. RESULTS: Reliability statistics revealed an alpha score of 0.855 for the overall inventory. Across the three subscales, i.e. emotional, functional and catastrophic, a global alpha score of 0.766, 0.693 and 0.630, respectively. The alpha score remained the same even after deleting any single item. CONCLUSION: The results of the current study conclude that, THI-M has a good reliability/internal consistency as per the Cronbach's alpha score. THI-M can be considered as a reliable tool that can be used across the State by Hearing Professionals in assessment and management.

Influence of chitosan and Cissus quandrangularis coating on osseointegration in titanium implants in rabbits: A preclinical in vivo study.

BACKGROUND: Titanium (Ti) implants has been criticized for the tiring wait for osseointegration, often making the patient reconsider implant treatment. Surface treated Ti implants are emerging as a promising solution with superior osseointegration, early loading protocols and shortened period of edentulousness. The aim of this study is to assess the osseointegration of Ti surface coated with novel Cissus quandrangularis Chitosan Hydrogel (CqChH) compared to Commercially pure (Cp) implants. METHODS: 24 Cp Ti implants were divided into 2 subgroups (n = 12). The test group consisted of Ti implants surface treated with the novel hydrogel and control group consisted of Cp Ti implants. 3 % CqChH was prepared and was coated on the Ti implants prior to placement in the femur and tibial heads of rabbits. Implant Stability Quotient (ISQ) was recorded at the 6th and 12th week. Animals were sacrificed and subjected to Removal Torque Quotient (RTQ). The samples were retrieved en bloc and stained for histopathologic analysis. The collected data was subjected to statistical analysis using Unpaired student t-Test. RESULTS: At the end of 6th week CqChH coated implants did not show any statistically significant difference in both ISQ and RTQ values compared to Cp ones. However, at the end of the 12th week CqChH coated implants demonstrated significantly higher ISQ (73.91 ± 4.39) and RTQ (75.96 ± 14.10) compared to Cp ones. CONCLUSIONS: This study demonstrated that the novel hydrogel coating applied to the implant's surface exhibited not only enhanced bone regeneration but also elicited a new bone formation.

Remineralising potential of Ocimum basilicum varnish and fluoride varnish on initial enamel caries: An in vitro microscopic study.

Background: The focus of caries research has switched to early identification and non-invasive treatment of carious lesions. Aim: This study aimed to evaluate and compare the remineralising potential of Ocimum (O.) basilicum varnish and fluoride varnish on initial enamel caries. Method: The authenticated O. basilicum seeds were procured from a repository, and the extract was prepared using the Soxhlet method, which was vortexed with Indian Pharmaceutical (IP)-graded chemicals to obtain varnish. Extracted premolar tooth samples were divided into three groups of 33 each after demineralisation with a pH of 4.5 for 48 hours at 37°C. Each group was subjected to remineralisation twice daily with respective agents for 4 minutes for 30 consecutive days. Each sample was ground-sectioned through an enamel window. The lesion depth was measured using a light microscope (Leica™ DM2500) and ImageJ software. The data were evaluated using analysis of variance (ANOVA) and post hoc analysis. Results: The mean (± SD) pre-treatment lesion depth across the groups ranged from 242.11 ± 26.144 µm to 352.66 ± 34.531 µm. The highest lesion depth recovery rate of 45.938% was recorded for the fluoride varnish group, followed by 36.015% in the O. basilicum varnish group, which was statistically significant by Tukey's post hoc analysis (p < 0.001). The gingival fibroblast cells were viable by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Conclusion: The O. basilicum varnish demonstrated a homogenous layer of mineral deposition. However, the remineralising efficacy was slightly lesser than that of the fluoride varnish. Hence, the novel O. basilicum-based remineralisation agent appears to have potential as a non-invasive alternative to topical fluorides in the therapy of early caries lesions.

Predictive medicinal metabolites from Momordica dioica against comorbidity related proteins of SARS-CoV-2 infections.

Momordica dioica have proven medicinal potential of antidiabetic, antiviral and immune stimulating properties. Flavonoids and triterpenoids from M. dioica were more extensively investigated for antiviral, antidiabetic and immunomodulatory activities. In this present study, we have predicted the reported bioactive flavonoids and triterpenoids of the plant against the SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), spike protein, angiotensin converting enzyme (ACE-2) receptor and dipeptidyl peptidase (DPP4) receptor through molecular docking and in silico ADME predictions methods. According to the binding affinities, the two triterpenoids, hederagenin and oleanolic acid exhibited the best docking scores with these proteins than the catechin and quercetin with compared to standard remdesivir, favipiravir and hydroxychloroquine. The in vitro protein-drug studies have also showed significant interaction of catechin and quercetin compounds than standard drugs. The in silico binding studies correlated with the in silico binding studies. Further, M. dioica being used as antidiabetic and its metabolite had significant interaction with DDP4, a comorbidity protein involved in aiding the viral entry. Out of all the natural ligands, quercetin was reported relatively good and safe for humans with high gastrointestinal tract permeability and poor blood brain barrier crossing abilities. Hence, M. dioica phytocompounds reflects promising therapeutic properties against SARS-CoV-2 infections under comorbid conditions such as diabetes, cardiovascular disease and kidney disorders.Communicated by Ramaswamy H. Sarma.

Design of New Improved Curcumin Derivatives to Multi-targets of Cancer and Inflammation.

BACKGROUND: Curcumin is a major active principle of Curcuma longa. There are more than 1700 citations in the Medline, reflecting various biological effects of curcumin. Most of these biological activities are associated with the antioxidant, anti-inflammatory and antitumor activity of the molecule. Several reports suggest various targets of natural curcumin that include growth factors, growth factor receptor, cytokines, enzymes and gene regulators of apoptosis. This review focuses on the improved curcumin derivatives that target the cancer and inflammation. METHODOLOGY: In this present review, we explored the anticancer drugs with curcumin-based drugs under pre-clinical and clinical studies with critical examination. Based on the strong scientific reports of patentable and non-patented literature survey, we have investigated the mode of the interactions of curcumin-based molecules with the target molecules. RESULTS: Advanced studies have added new dimensions of the molecular response of cancer cells to curcumin at the genomic level. However, poor bioavailability of the molecule seems to be the major limitation of the curcumin. Several researchers have been involved to improve the curcumin derivatives to overcome this limitation. Sufficient data of clinical trials to various cancers that include multiple myeloma, pancreatic cancer and colon cancer, have also been discussed. CONCLUSION: The detailed analysis of the structure-activity relationship (SAR) and common synthesis of curcumin-based derivatives have been discussed in the review. Utilising the predictions of in silico coupled with validation reports of in vitro and in vivo studies have concluded many targets for curcumin. Among them, cancer-related inflammation genes regulating curcumin-based molecules are a very promising target to overcome hurdles in the multimodality therapy of cancer.

Immunoexpression of TTF1 and p63 Differentiates Lung Adenocarcinomas in Sputum Samples.

CONTEXT: Differentiating NSCLC as either adeno or squamous type and identification of Epidermal Growth Factor Receptor (EGFR) mutations is clinically relevant for lung cancer patients for selecting treatment. Thyroid transcription factor-1 (TTF-1) and p63 were demonstrated as useful markers for histologic typing of lung cancer. Mutation and overexpression of EGFR has been reported in a subset of non-small cell lung cancers. If these markers can be validated for the differential diagnosis of adenocarcinoma in a sputum sample itself, it will be highly beneficial for lung cancer patients. AIMS: To evaluate whether immunocytochemical expression of TTF-1, p63, and EGFR proteins in sputum samples can be used for differential diagnosis of lung adenocarcinoma by comparing with that of the corresponding tissue samples. SETTINGS AND DESIGN: Ninety sputum samples and matched tissue samples were used for the study. SUBJECTS AND METHODS: Monolayered smears and cell blocks of sputum and the corresponding tissue samples were immunostained with the standard ABC method. The expression patterns of these markers were analyzed statistically and compared with clinic-pathological parameters. STATISTICAL ANALYSIS USED: Chi-square test and paired t-test. RESULTS: The p63 protein had a positive expression in 73.9% of SCC whereas TTF1 had positive expression in 75.8% of ADC. The EGFR expression was positive in 27 cases of adenocarcinoma, 21 cases of SCC and 19 cases of NSCLC. CONCLUSIONS: Immunocytochemistry of the aforementioned antibodies in sputum samples can be used as supplementary evidence for the subtyping of NSCLC.

Atranorin, an antimicrobial metabolite from lichen Parmotrema rampoddense exhibited in vitro anti-breast cancer activity through interaction with Akt activity.

Atranorin (ATR), lichenized secondary metabolite and depside molecule with several biological potentials such as antimicrobial, anticancer, anti-inflammatory, antinociceptive, wound healing and photoprotective activities. Cytotoxic reports of ATR are documented in several cancer cells and in vivo models but its molecular interaction studies are poorly understood. Therefore, in this present investigation, we have used the in silico studies with biological validation of the molecular targets for the anti-breast cancer mechanism of ATR. The molecular docking studies with the breast cancer oncoproteins such as Bcl-2, Bax, Akt, Bcl-w and Bcl-xL revealed the highest interaction was observed with the Akt followed by Bax, Bcl-xL and Bcl-2 & least with the Bcl-w proteins. The cytotoxicity studies showed ATR selectively inhibited MDA MB-231 and MCF-7 breast cancer cells in differential and dose-dependent manner with the IC50 concentration of 5.36 ± 0.85 µM and 7.55 ± 1.2 µM respectively. Further mechanistic investigations revealed that ATR significantly inhibited ROS production and significantly down-regulated the anti apoptotic Akt than Bcl-2, Bcl-xL and Bcl-w proteins with a significant increase in the Bax level and caspases-3 activity in the breast cancer cells when comparison with Akt inhibitor, ipatasertib. In vitro biological activities well correlated with the molecular interaction data suggesting that atranorin had higher interaction with Akt than Bax and Bcl-2 but weak interaction with Bcl-w and Bcl-xL. In this present study, the first time we report the interactions of atranorin with molecular targets for anti-breast cancer potential. Hence, ATR represents the nature-inspired molecule for pharmacophore moiety for design in targeted therapy.Communicated by Ramaswamy H. Sarma.

Cost of Tuberculosis Care in Programmatic Settings from Karnataka, India: Is It Catastrophic for the Patients?

BACKGROUND: TB diagnostic and treatment services in India are provided free of cost in the programmatic context across the country. There are different costs incurred during health care utilization, and this study was conducted to estimate such costs. Methodology. A longitudinal study was conducted among patients of three urban tuberculosis units (TUs) of Davangere, Belagavi, and Bengaluru, Karnataka. Trained data collectors administered a validated questionnaire and recorded monthly costs incurred by the patients which are expressed in median Indian National Rupees (INR). The analysis was done using SPSS version 23.0. A p value of <0.05 was taken as statistically significant. RESULTS: Among 214 patients, about 37%, 42%, and 21% belonged to Davangere, Belagavi, and Bengaluru, respectively. Median total pre- and postdiagnostic costs incurred across the three TUs were 3800 and 4000 INR, respectively. The direct nonmedical cost was higher for accommodation (median cost of 800 INR) and direct medical cost for non-TB drugs (median cost of 2000 INR). However, maximum direct medical and nonmedical costs were attributed to hospital admissions (1200 INR) and accommodation costs (700 INR) in the postdiagnostic period, respectively. The median indirect cost incurred was 300 INR overall, and the maximum total indirect cost was 40000 INR in the postdiagnostic period. About one-third of patients faced loss of income and 19.6% faced coping costs. Patients spent about 6.7% (0.97%-52.3%) of their income on TB treatment. About 12.3% patients faced catastrophic expenditure. Median cost was significantly higher among those seeking private health care facilities (12100 INR in private vs. 6800 INR in public; p < 0.05) during the prediagnostic period. Prediagnostic and diagnostic out-of-pocket expenditures (OPE) were significantly higher across all the three centres (p < 0.05). CONCLUSION: The TB patients experienced untoward expenditure under programmatic settings. The costs encountered by one in eight patients were catastrophic by nature.

Baseline Results: The Association Between Cardiovascular Risk and Preclinical Alzheimer's Disease Pathology (ASCEND) Study.

BACKGROUND: The rate of AD for African Americans (AAs) is 64% higher than for non-Hispanic White Americans (Whites). It is hypothesized that poor peripheral vascular function, in combination with genetics, stress, and inflammation may directly contribute to the accumulation of AD pathologic biomarkers. These risk factors may disproportionately affect AAs. OBJECTIVE: Our objective was to determine if in a healthy middle-aged cohort at risk for AD (1) AD biomarkers in CSF differ by race, (2) peripheral vascular dysfunction and cognition are related to a higher burden of CSF AD biomarkers, and (3) these relationships differ by race. METHODS: We enrolled 82 cognitively normal, middle-aged (45 and older) adults including AAs and Whites at high risk for AD due to parental history. Study procedures included lumbar puncture, vascular ultrasound, and cognitive testing. RESULTS: While participants were in overall good health, AAs exhibited poorer indices of preclinical vascular health, including higher central SBP, central MAP, and EndoPAT AI, a marker of arterial stiffness. AAs also had significantly less cerebrospinal fluid tau burden than Whites. After polynomial regression analysis, adjusted for age, gender, education, and ApoE4 status, race significantly modified the relationship between total tau, phospho-tau, and Trails B, a marker of executive function. Small differences in tau correlated with poorer cognition in AAs. CONCLUSION: In a healthy middle-aged cohort at risk for AD, AAs had worse peripheral vascular health and worse cognition than Whites. Despite lower tau burden overall, race modified the relationship between tau and cognition, such that small differences in tau between AAs was related to worse cognition when compared to Whites.

Immunocytochemistry on Sputum Samples Predicts Prognosis of Lung Cancer.

CONTEXT: Despite sputum cytology being accepted as a simple and noninvasive diagnostic method for lung cancer, the clinical usefulness of sputum for evaluation of prognosis is yet to be explored. Validation of some of the markers in sputum for prognosis prediction will be highly useful for selective therapy. AIMS: This study was aimed to evaluate a reliable panel of immunocytochemical markers for their significance to predict survival. MATERIALS AND METHODS: We have analyzed the expression of p53, p16, galectin-3, and epidermal growth factor receptor (EGFR) proteins in sputum samples processed in a mucolytic agent/cellblock and compared the same with that of the corresponding tissue samples. RESULTS: Overexpression of p16 and EGFR was found to have a better survival benefit, whereas positive p53 and galectin-3 expressions had shorter period of survival. Expression patterns of all these four proteins were more or less similar in smears, cellblocks of sputum, and tissue samples except for slight changes in staining intensity which was not found to be statistically significant. No significant difference was found in the association of these proteins with survival pattern between sputum and tissue samples. CONCLUSION: This is the first report of immunocytochemistry of a panel of markers on cells exfoliated in sputum samples which suggests that analysis of immunocytochemical markers in sputum samples can be attempted as a cost-effective and reliable predictor of prognosis and survival. Accumulation of mutated p53, overexpression of galectin-3, and lower expression of p16 and EGFR proteins were found to predict poor prognosis for lung cancer.

Histochemical and Immunohistochemical Analysis of Collagen Fibers and Microvascular Density in Various Grades of Oral Submucous Fibrosis.

BACKGROUND AND OBJECTIVE: This study was aimed to evaluate the collagen fibers qualitatively and its correlation with microvascular density in various grades of oral submucous fibrosis (OSMF). MATERIAL AND METHODS: The present study comprised of total 40 cases of oral submucous fibrosis. Picrosirius red staining was done on all the specimens' sections. They were analyzed for the colour and orientation of collagen fibers. Morphometric measurements were done using image analysis on immunohistochemical stained sections for Factor VIII-related antigen and analyzed for microvascular density. RESULTS: Picrosirius red polarizing microscopy results revealed that there was a shift in the colour of collagen fibers from greenish yellow to orange red and red colour as the severity of the oral submucous fibrosis increased. The collagen fibers showed mixed orientation in early oral submucous fibrosis and parallel orientation in advanced oral submucous fibrosis. There was a significant decrease in microvascular density from early to advanced oral submucous fibrosis. CONCLUSION: The change in the colours and orientation of collagen fibers in early and advanced oral submucous fibrosis could be attributed to the fibre thickness, type of collagen, alignment and packing, cross-linking of the fibers and the section thickness. However, in advanced cases the vascularity is reduced which may predispose to epithelial atrophy and subsequent malignant changes.