Studies on the effect of curcumin and quercetin in the liver of male albino rats exposed to gamma irradiation.

Ionizing radiation produces deleterious effects on living organisms. The present investigation has been carried out to study the prophylactic as well as the therapeutic effects of treated rats with quercetin (Quer) and curcumin (Cur), which are two medicinal herbs known for their antioxidant activities against damages induced by whole-body fractionated gamma irradiation. Exposure of rats to whole-body gamma irradiation induced a significant decrease in erythrocyte (RBC), leukocyte (WBCs), platelet count (Plt), hemoglobin concentration (Hb), hematocrit (Hct %), mean erythrocyte hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and mean erythrocyte volume (MCV); a high increase in plasma thiobarbituric acid reactive substances (TBARS); a nonsignificant statistical decrease in the mean value of serum glutathione (GSH); a significant increase in plasma alanine transferase (ALT), aspartate transferase (AST), alkaline phosphates (ALP), serum total protein, serum total cholesterol levels, total triglycerides levels, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels; and with marked histological changes and structural changes measured by Fourier transform infrared (FTIR). Applying both quercetin and curcumin pre- and postexposure to gamma radiation revealed a remarkable improvement in all the studied parameters. The cellular damage by gamma radiation is greatly mitigated by the coadministration of curcumin and quercetin before radiation exposure.

How multidisciplinary clinics may mitigate socioeconomic barriers to care for chronic limb-threatening ischemia.

OBJECTIVE: Although multidisciplinary clinics improve outcomes in chronic limb-threatening ischemia (CLTI), their role in addressing socioeconomic disparities is unknown. Our institution treats patients with CLTI at both traditional general vascular clinics and a multidisciplinary Limb Preservation Program (LPP). The LPP is in a minority community, providing expedited care at a single facility by a consistent team. We compared outcomes within the LPP with our institution's traditional clinics and explored patients' perspectives on barriers to care to evaluate if the LPP might address them. METHODS: All patients undergoing index revascularization for CLTI from 2014 to 2023 at our institution were stratified by clinic type (LPP or traditional). We collected clinical and socioeconomic variables, including Area Deprivation Index (ADI). Patient characteristics were compared using χ2, Student t, or Mood median tests. Outcomes were compared using log-rank and multivariable Cox analysis. We also conducted semi-structured interviews to understand patient-perceived barriers. RESULTS: From 2014 to 2023, 983 limbs from 871 patients were revascularized; 19.5% of limbs were treated within the LPP. Compared with traditional clinic patients, more LPP patients were non-White (43.75% vs 27.43%; P < .0001), diabetic (82.29% vs 61.19%; P < .0001), dialysis-dependent (29.17% vs 13.40%; P < .0001), had ADI in the most deprived decile (29.38% vs 19.54%; P = .0061), resided closer to clinic (median 6.73 vs 28.84 miles; P = .0120), and had worse Wound, Ischemia, and foot Infection (WIfI) stage (P < .001). There were no differences in freedom from death, major adverse limb event (MALE), or patency loss. Within the most deprived subgroup (ADI >90), traditional clinic patients had earlier patency loss (P = .0108) compared with LPP patients. Multivariable analysis of the entire cohort demonstrated that increasing age, heart failure, dialysis, chronic obstructive pulmonary disease, and increasing WIfI stage were independently associated with earlier death, and male sex was associated with earlier MALE. Ten traditional clinic patients were interviewed via convenience sampling. Emerging themes included difficulty understanding their disease, high visit frequency, transportation barriers, distrust of the health care system, and patient-physician racial discordance. CONCLUSIONS: LPP patients had worse comorbidities and socioeconomic deprivation yet had similar outcomes to healthier, less deprived non-LPP patients. The multidisciplinary clinic's structure addresses several patient-perceived barriers. Its proximity to disadvantaged patients and ability to conduct multiple appointments at a single visit may address transportation and visit frequency barriers, and the consistent team may facilitate patient education and improve trust. Including these elements in a multidisciplinary clinic and locating it in an area of need may mitigate some negative impacts of socioeconomic deprivation on CLTI outcomes.

Patient's satisfaction towards healthcare services and its associated factors at the highest patient loads government primary care clinic in Pahang.

INTRODUCTION: Patient satisfaction is widely used to monitor the quality of health care services. A significant patient load may influence health care services and patient satisfaction. Klinik Kesihatan Bandar Kuantan, Pahang (KKBK) has the highest patient loads in Pahang state, followed by Klinik Kesihatan Beserah and Klinik Kesihatan Kurnia. There are up to 700 attendees at KKBK per day, representing a population of 209679. KKBK had receives several complaints and patient unhappiness with its health care services, despite the administration's efforts to improve the clinics healthcare delivery. Thus, this study aimed to measure patients' satisfaction towards health care services at Pahang's highest patient loads primary care clinic. MATERIALS AND METHODS: A cross-sectional study was conducted at Klinik Kesihatan Bandar Kuantan, Kuantan, Pahang. Patients were selected using stratified random sampling, and 201 participants were selected. The selected participants were asked to fill up the self-administered validated questionnaires consisting of background characteristics and Patient Satisfaction Questionnaire 18 (PSQ-18). Data collection period was from March 2022 to August 2022. Descriptive analysis was used to describe the background characteristics of respondents and the score of patient satisfaction. Multiple linear regression was used to determine the factors associated with patient satisfaction while adjusting for cofounders. RESULTS: A total of 201 eligible data points were analysed in the study. The respondent mean age was 47.1 ± 16.9. Most respondents were Malay (68.7%), having secondary education (54.2%) and predominantly from the B40 income class (88.1%). The overall mean patient satisfaction score was 3.83 ± 0.31. There were significant associations between overall satisfaction with patient education level (B = -0.144; 95% CI -0.246, -0.042; p = 0.006), waiting time (B = -0.371; 95% CI -0.534, -0.209; p = 0.001) and consultation duration (B = -0.154; 95% CI -0.253, -0.055; p = 0.0020). It was found that patients with secondary education were less satisfied compared to patients with primary education level on health care services they received. Meanwhile, those who were not happy with the waiting time and consultation duration showed less satisfaction with overall healthcare services. CONCLUSION: Despite serving the most significant number of patients in Pahang state, most of the patient were satisfied by the health care services at Klinik Kesihatan Bandar Kuantan. However, it is recommended to improve the waiting time and the consultation time in this clinic.

Matched Ligands for Small, Stable Colloidal Nanoparticles of Copper, Cuprous Oxide and Cuprous Sulfide.

This work applies organometallic routes to copper(0/I) nanoparticles and describes how to match ligand chemistries with different material compositions. The syntheses involve reacting an organo-copper precursor, mesitylcopper(I) [CuMes]z (z=4, 5), at low temperatures and in organic solvents, with hydrogen, air or hydrogen sulfide to deliver Cu, Cu2 O or Cu2 S nanoparticles. Use of sub-stoichiometric quantities of protonated ligand (pro-ligand; 0.1-0.2 equivalents vs. [CuMes]z ) allows saturation of surface coordination sites but avoids excess pro-ligand contaminating the nanoparticle solutions. The pro-ligands are nonanoic acid (HO2 CR1 ), 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (HO2 CR2 ) or di(thio)nonanoic acid, (HS2 CR1 ), and are matched to the metallic, oxide or sulfide nanoparticles. Ligand exchange reactions reveal that copper(0) nanoparticles may be coordinated by carboxylate or di(thio)carboxylate ligands, but Cu2 O is preferentially coordinated by carboxylate ligands and Cu2 S by di(thio)carboxylate ligands. This work highlights the opportunities for organometallic routes to well-defined nanoparticles and the need for appropriate ligand selection.

Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19.

BACKGROUND: Given the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility. METHODS: One hundred and eighty patients diagnosed to have COVID-19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21-29 ng/mL, deficient at <20 ng/mL. RESULTS: Ninety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96-4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95-8.55]; P < 0.001). CONCLUSIONS: Vitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. IMPACT: Vitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action. To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19. Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents. Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.

Fluorescence imaging approaches for eco-friendly determination of perampanel in human plasma and application for therapeutic drug monitoring.

Antiepileptic drugs are among the most common medications that require therapeutic drug monitoring (TDM). Indeed, TDM provides a realistic approach to adjust drug doses for epilepsy based on plasma concentrations to optimize its clinical outcome. The most common technique for TDM is high-performance liquid chromatography, which has a very low green profile among analytical techniques. Perampanel (PER) is an inherently fluorescent compound that its fluorophore readily allows sensitive and quantitative measurements. This paper describes the development and validation of a sensitive, specific, and eco-friendly spectrofluorimetric method for the determination of PER. Experimental parameters affecting fluorescence intensity of the compound, including solvent dilution, temperature, and excitation wavelength, were studied and optimized. The developed spectrofluorimetric method was established in acetonitrile at λex  = 295 nm and λem  = 431 nm over a concentration range of 5-60 ng/ml. The adopted method was applied for the determination of PER in human plasma; it was effective in the range of 15-50 ng/ml. The proposed method was found to be sensitive and specific for PER and can be applied successfully in TDM of PER and in quality control laboratories.

The transcriptome of early GGT/KRT19-positive hepatocellular carcinoma reveals a downregulated gene expression profile associated with fatty acid metabolism.

Hepatocellular carcinoma expressing hepatobiliary progenitor markers, is considered of poor prognosis. By using a hepatocarcinogenesis model, laser capture microdissection, and RNA-Sequencing analysis, we identified an expression profile in GGT/KRT19-positive experimental tumors; 438 differentially expressed genes were found in early and late nodules along with increased collagen deposition. Dysregulated genes were involved in Fatty Acid Metabolism, RXR function, and Hepatic Stellate Cells Activation. Downregulation of Slc27a5, Acsl1, and Cyp2e1, demonstrated that Retinoid X Receptor α (RXRα) function is compromised in GGT/KRT19-positive nodules. Since RXRα controls NRF2 pathway activation, we determined the expression of NRF2 targeted genes; Akr1b8, Akr7a3, Gstp1, Abcc3, Ptgr1, and Txnrd1 were upregulated, indicating NRF2 pathway activation. A comparative analysis in human HCC showed that SLC27A5, ACSL1, CYP2E1, and RXRα gene expression is mutually exclusive with KRT19 gene expression. Our results indicate that the downregulation of Slc27a5, Acsl1, Rxrα, and Cyp2e1 genes is an early event within GGT/KRT19-positive HCC.

Dosimetric Study of Heat-Treated Calcium-Aluminum-Silicon Borate Dosimeter for Diagnostic Radiology Applications.

The production of thermoluminescence (TL) dosimeters fabricated from B2O3-CaF2-Al2O3-SiO2 doped with Cu and Pr for use in diagnostic radiology is the main goal of this research. The TL samples were synthesized via the melt-quench technique processed by melting the mixture at 1200 °C for 1 h, and, after cooling, the sample thus created was divided into two samples and retreated by heating for 2 h (referred to as TLV30) and for 15 h (referred to as TLV17). SEM and EDS analyses were performed on the TL samples to confirm the preparation process and to investigate the effects of irradiation dosimetry on the TL samples. Furthermore, the TL samples were irradiated with γ-rays using a 450 Ci 137Cs irradiator and variable X-ray beams (5-70 mGy). Two important diagnostic radiology applications were considered: CT (6-24 mGy) and mammography (2.72-10.8 mGy). Important dosimetric properties, such as the glow curves, reproducibility, dose-response linearity, energy dependence, minimum dose detectability and fading, were investigated for the synthetized samples (TLV17 and TLV30), the results of which were compared with the Harshaw TLD-100. The TLV17 dosimeter showed higher sensitivity than TLV30 in all applied irradiation procedures. The dose-response linearity coefficients of determination R2 for TLV17 were higher than TLD-100 and TLV30 in some applications and were almost equal in others. The reproducibility results of TLV17, TLV30 and TLD-100 were less than 5%, which is acceptable. On the other hand, the results of the fading investigations showed that, in general, TLV17 showed less fading than TLV30. Both samples showed a significant decrease in this regard after the first day, and then the signal variation became essentially stable though with a slight decrease until the eighth day. Therefore, it is recommended to read the TL dosimeters after 24 h, as with TLD-100. The SEM images confirmed the existence of crystallization, whilst the EDS spectra confirmed the presence of the elements used for preparation. Furthermore, we noticed that TLV17 had grown dense crystals that were larger in size compared to those of TLV30, which explains the higher sensitivity in TLV17. Overall, despite the fading, TLV17 showed greater radiation sensitivity and dose-response linearity compared with TLD-100. The synthetized TL samples showed their suitability for use as dosimeters in diagnostic radiology radiation dosimetry.

Increased Demand for Pharmaceutical Drugs Containing Potassium Iodide In Connection with the Russia-Ukraine Conflict.

The current conflict between Russia and Ukraine increased concerns in the German population of a release of radioactive substances, e.g.radioactive iodine. A high dose of potassium iodide (PI) may prevent accumulation of radioactive iodine in the thyroid gland. Therefore, the German government keeps a sufficient quantity of PI in stock for public supply in case of an emergency. We investigated ambulatory drug dispensing rates of PI and found that the total dispensing of PI (statutory health insurance (SHI), private health insurance (PHI), and overthe-counter (OTC)) increased by 106% from February to March 2022. Changes in PI dispensing were mainly due to an increase in OTC sales, where PI as an antidote showed a sevenfold increase from around 930 packages (February 2022) to 6,500 packages (March 2022), while SHI and PHI dispensing remained relatively low. Furthermore, we investigated whether these changes in dispensing raised the number of suspected adverse drug reactions (ADR). We found no increase of ADR reports related to the use of PI-containing medicinal products between February and September 2022, neither in our national pharmacovigilance nor in the European EudraVigilance database. The data suggest that the mere possibility of a nuclear disaster in Ukraine raised the demand of PI in Germany. Thus, timely and proactive information and reassurance of the public of supply reliability by the Government in a case of a nuclear emergency could be helpful in preventing potential drug shortages and unfounded concern.

The Effects of Osteoarthritis on Depressive Symptomatology Among Older U.S. Military Veterans.

Osteoarthritis (OA) is a leading cause of disability among older adults. By 2050, approximately 60 million will suffer from arthritis adding up to a total societal cost of $65 billion. Chronic illnesses resulting in pain, and functional decline have been associated with depression in previous studies.A causal model was developed and tested using structural equation modeling that examined depression scores of 503 older (age 50-85), male Veterans with moderate to severe symptomatic OA of the knee\hip.The results of the structural equation modeling produced a final model of depressive symptomatology that fit the data well (Chi square = 12.23, DF = 11, p = .346; TLI = .99; CFI = 1.00; RMSEA = .02).The findings indicate the central role that OA severity (pain, stiffness, and functional difficulties) plays in the mental health of older Veterans in terms of the level of reported depressive symptoms.

Radiological and environmental hazards of granitic rocks in Wadi Faliq El Sahl and El Waar area, North Eastern Desert, Egypt.

Chronologically, the main exposures in the study area include; tonalite, granodiorite, adamellite, Hammamat Sediments, monzogranite, syenogranite, rapakivi syenogranite, alkali feldspar granite and dykes. This work aims to determine the suitability of the granitic rocks for using as ornamental stones through detecting their radiological and ecological impacts. The studied samples were measured radiometrically by using Na-I detector for determination of 226Ra, 232Th and 40K concentrations. External hazard indices (Hex) in some samples are more than unity, also, the (Raeq) are higher than the exemption limits (370 Bq.kg-1) exceeds the upper limit of exposure. The hierarchical cluster analysis (HCA) was applied to investigate the correlation between the radionuclides and the corresponding radiological hazard variables. Based on the statistical analysis, 232Th and 226Ra mainly contribute to the radioactive risk of the studied rocks. Regarding ecological indices, 42.1% of younger granite samples have Pollution load index values greater than 1, indicating deterioration, while the majority of older granite samples are lower than 1 suggesting perfection samples. Where, some sample from the older granitoids and younger granites have many radiological and ecological parameters greater than the recommended international limits, so, these samples should not be used in construction for safety reasons.

Population Pharmacokinetics of Antimalarial Naphthoquine in Combination with Artemisinin in Tanzanian Children and Adults: Dose Optimization.

The combination antimalarial therapy of artemisinin-naphthoquine (ART-NQ) was developed as a single-dose therapy, aiming to improve adherence relative to the multiday schedules of other artemisinin combination therapies. The pharmacokinetics of ART-NQ has not been well characterized, especially in children. A pharmacokinetic study was conducted in adults and children over 5 years of age (6 to 10, 11 to 17, and ≥18 years of age) with uncomplicated malaria in Tanzania. The median weights for the three age groups were 20, 37.5, and 55 kg, respectively. Twenty-nine patients received single doses of 20 mg/kg of body weight for artemisinin and 8 mg/kg for naphthoquine, and plasma drug concentrations were assessed at 13 time points over 42 days from treatment. We used nonlinear mixed-effects modeling to interpret the data, and allometric scaling was employed to adjust for the effect of body size. The pharmacokinetics of artemisinin was best described by one-compartment model and that of naphthoquine by a two-compartment disposition model. Clearance values for a typical patient (55-kg body weight and 44.3-kg fat-free mass) were estimated as 66.7 L/h (95% confidence interval [CI], 57.3 to 78.5 L/h) for artemisinin and 44.2 L/h (95% CI, 37.9 to 50.6 L/h) for naphthoquine. Nevertheless, we show via simulation that patients weighing ≥70 kg achieve on average a 30% lower day 7 concentration compared to a 48-kg reference patient at the doses tested, suggesting dose increases may be warranted to ensure adequate exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT01930331.).

Grafting enhances drought tolerance by regulating stress-responsive gene expression and antioxidant enzyme activities in cucumbers.

Water scarcity is a major limiting factor for crop yield production in arid and water-stressed areas worldwide. Cucumber plants have a high transpiration ratio and are vulnerable to drought. Grafting commercial genotypes onto selected strong rootstocks has been useful in mitigating the effects of drought. Therefore, this study aimed to evaluate the possibility of using a novel rootstock plant's tolerance to water-deficit stress in inducing drought tolerance in cucumbers by activating the stress-response gene expression and the antioxidant system, which improved the cucumber quality and yield under water-deficit conditions. This field experiment was conducted for > 2 years, 2020 and 2021, with five drought stress tolerant genotypes (i.e., rootstock) and drought-sensitive genotype Luerans (i.e., a scion). They were subjected to various deficit irrigation levels for 12 days, and their agro-physiological and molecular responses to water-deficit stress were assessed. The results of the study showed that the agronomical parameters, including the leaf area (LA), leaf water content (LWC), number of leaves, plant height, root dry matter shoot dry matter, rates of leaf appearance and stem elongation, and total yield significantly increased with grafted cucumber plants than with non-grafted cucumber plants (control) under normal and stressful conditions.Similar results were observed in the physiological measurements in terms of antioxidant enzymes, abscisic acid levels, gibberellic acid content, and lower lipid peroxidation (malondialdehyde, MDA). Grafting of Luerans (section) on five rootstocks significantly raised the activity of antioxidant enzymes (catalase and peroxidase), improved the gibberellic acid and proline accumulation, and reduced the content of lipid peroxidation and abscisic acid. Furthermore, the real-time polymerase chain reaction expression results revealed that transcript levels of the stress-response genes CsAGO1 and CsDCLs increased rapidly and continuously in five rootstock grafting. Concurrently, these findings suggest that grafting with local varieties of novel drought-tolerant rootstock genotypes could improve drought tolerance in drought-sensitive cucumber genotypes.

Racial and Neighborhood-Level Disparities in COVID-19 Incidence among Patients on Hemodialysis in New York City.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected socially disadvantaged populations. Whether disparities in COVID-19 incidence related to race/ethnicity and socioeconomic factors exist in the hemodialysis population is unknown. METHODS: Our study involved patients receiving in-center hemodialysis in New York City. We used a validated index of neighborhood social vulnerability, the Social Vulnerability Index (SVI), which comprises 15 census tract-level indicators organized into four themes: socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. We examined the association of race/ethnicity and the SVI with symptomatic COVID-19 between March 1, 2020 and August 3, 2020. COVID-19 cases were ascertained using PCR testing. We performed multivariable logistic regression to adjust for demographics, individual-level social factors, dialysis-related medical history, and dialysis facility factors. RESULTS: Of the 1378 patients on hemodialysis in the study, 247 (17.9%) developed symptomatic COVID-19. In adjusted analyses, non-Hispanic Black and Hispanic patients had significantly increased odds of COVID-19 compared with non-Hispanic White patients. Census tract-level overall SVI, modeled continuously or in quintiles, was not associated with COVID-19 in unadjusted or adjusted analyses. Among non-Hispanic White patients, the socioeconomic status SVI theme, the minority status and language SVI theme, and housing crowding were significantly associated with COVID-19 in unadjusted analyses. CONCLUSIONS: Among patients on hemodialysis in New York City, there were substantial racial/ethnic disparities in COVID-19 incidence not explained by neighborhood-level social vulnerability. Neighborhood-level socioeconomic status, minority status and language, and housing crowding were positively associated with acquiring COVID-19 among non-Hispanic Whites. Our findings suggest that socially vulnerable patients on dialysis face disparate COVID-19-related exposures, requiring targeted risk-mitigation strategies.

Wide-Bite-Angle Diphosphine Ligands in Thermally Activated Delayed Fluorescent Copper(I) Complexes: Impact on the Performance of Electroluminescence Applications.

We report a series of seven cationic heteroleptic copper(I) complexes of the form [Cu(P^P)(dmphen)]BF4, where dmphen is 2,9-dimethyl-1,10-phenanthroline and P^P is a diphosphine chelate, in which the effect of the bite angle of the diphosphine ligand on the photophysical properties of the complexes was studied. Several of the complexes exhibit moderately high photoluminescence quantum yields in the solid state, with ΦPL of up to 35%, and in solution, with ΦPL of up to 98%. We were able to correlate the powder photoluminescence quantum yields with the % Vbur of the P^P ligand. The most emissive complexes were used to fabricate both organic light-emitting diodes and light-emitting electrochemical cells (LECs), both of which showed moderate performance. Compared to the benchmark copper(I)-based LECs, [Cu(dnbp)(DPEPhos)]+ (maximum external quantum efficiency, EQEmax = 16%), complex 3 (EQEmax = 1.85%) showed a much longer device lifetime (t1/2 = 1.25 h and >16.5 h for [Cu(dnbp)(DPEPhos)]+ and complex 3, respectively). The electrochemiluminescence (ECL) properties of several complexes were also studied, which, to the best of our knowledge, constitutes the first ECL study for heteroleptic copper(I) complexes. Notably, complexes exhibiting more reversible electrochemistry were associated with higher annihilation ECL as well as better performance in a LEC.

Optimization of localized surface plasmon resonance hot spots in surface-enhanced infrared absorption spectroscopy aluminum substrate as an optical sensor coupled to chemometric tools for the purity assay of quinary mixtures.

Surface-enhanced infrared absorption spectroscopy offers an alternative to conventional IR spectroscopy and utilizes the signal enhancement exerted by the plasmon resonance of nanostructured metal thin films. Citrate-capped silver nanoparticles were prepared in a single-step method, and their morphology was identified using transmission electron microscopy, scanning electron microscopy, ultraviolet/visible spectrophotometry, and Zetasizer. The nanoparticles generated were deposited on the surface of cheap aluminum slides for different durations aiming for the selection of the best time producing a thin film, suitable to act as a lab-on-a-chip SEIRA substrate. These substrates were coupled to partial least squares regression tools for simultaneous resolving of the quinary mixture in commercial dosage forms of bisoprolol, perindopril, bisoprolol acid degradation product, bisoprolol alkali degradation product, and perindoprilat in concentration ranges of 15-75, 60-300, 15-55, 12-60, and 20-80 µg/mL with limits of detection values of 0.69, 3.43, 0.97, 1.25, and 1.09 µg/mL, respectively. Overall, we could demostrate that the localized surface plasmon resonance sensor coupled to chemometrics provides cheap, simple, selective, multiplex, rapid, and molecular specific procedures for impurity detection, which would be beneficial in many applications for quality control and quality accuracy of active pharmaceutical ingredients.

Utility of Bioluminescent Homogeneous Nucleotide Detection Assays in Measuring Activities of Nucleotide-Sugar Dependent Glycosyltransferases and Studying Their Inhibitors.

Traditional glycosyltransferase (GT) activity assays are not easily configured for rapid detection nor for high throughput screening because they rely on radioactive product isolation, the use of heterogeneous immunoassays or mass spectrometry. In a typical glycosyltransferase biochemical reaction, two products are generated, a glycosylated product and a nucleotide released from the sugar donor substrate. Therefore, an assay that detects the nucleotide could be universal to monitor the activity of diverse glycosyltransferases in vitro. Here we describe three homogeneous and bioluminescent glycosyltransferase activity assays based on UDP, GDP, CMP, and UMP detection. Each of these assays are performed in a one-step detection that relies on converting the nucleotide product to ATP, then to bioluminescence using firefly luciferase. These assays are highly sensitive, robust and resistant to chemical interference. Various applications of these assays are presented, including studies on the specificity of sugar transfer by diverse GTs and the characterization of acceptor substrate-dependent and independent nucleotide-sugar hydrolysis. Furthermore, their utility in screening for specific GT inhibitors and the study of their mode of action are described. We believe that the broad utility of these nucleotide assays will enable the investigation of a large number of GTs and may have a significant impact on diverse areas of Glycobiology research.

Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults.

BACKGROUND: A vaccine would be an ideal tool for reducing malaria's impact. PfSPZ Vaccine (radiation attenuated, aseptic, purified, cryopreserved Plasmodium falciparum [Pf] sporozoites [SPZ]) has been well tolerated and safe in >1526 malaria-naive and experienced 6-month to 65-year-olds in the United States, Europe, and Africa. When vaccine efficacy (VE) of 5 doses of 2.7 × 105 PfSPZ of PfSPZ Vaccine was assessed in adults against controlled human malaria infection (CHMI) in the United States and Tanzania and intense field transmission of heterogeneous Pf in Mali, Tanzanians had the lowest VE (20%). METHODS: To increase VE in Tanzania, we increased PfSPZ/dose (9 × 105 or 1.8 × 106) and decreased numbers of doses to 3 at 8-week intervals in a double blind, placebo-controlled trial. RESULTS: All 22 CHMIs in controls resulted in parasitemia by quantitative polymerase chain reaction. For the 9 × 105 PfSPZ group, VE was 100% (5/5) at 3 or 11 weeks (P < .000l, Barnard test, 2-tailed). For 1.8 × 106 PfSPZ, VE was 33% (2/6) at 7.5 weeks (P = .028). VE of dosage groups (100% vs 33%) was significantly different (P = .022). Volunteers underwent repeat CHMI at 37-40 weeks after last dose. 6/6 and 5/6 volunteers developed parasitemia, but time to first parasitemia was significantly longer than controls in the 9 × 105 PfSPZ group (10.89 vs 7.80 days) (P = .039), indicating a significant reduction in parasites in the liver. Antibody and T-cell responses were higher in the 1.8 × 106 PfSPZ group. CONCLUSIONS: In Tanzania, increasing the dose from 2.7 × 105 to 9 × 105 PfSPZ increased VE from 20% to 100%, but increasing to 1.8 × 106 PfSPZ significantly reduced VE. CLINICAL TRIALS REGISTRATION: NCT02613520.

Accuracy of Hospital Discharge Codes in Medicare Claims for Knee and Hip Replacement Patients.

BACKGROUND: Despite the importance of the hospital discharge destination field ("discharge code" hereafter) for research and payment reform, its accuracy is not well established. OBJECTIVES: The aim of this study was to examine the accuracy of discharge codes in Medicare claims. DATA SOURCES: 2012-2015 Medicare claims of knee and hip replacement patients. RESEARCH DESIGN: We identified patients' discharge location in claims and compared it with the discharge code. We also used a mixed-effects logistic regression to examine the association of patient and hospital characteristics with discharge code accuracy. RESULTS: Approximately 9% of discharge codes were inaccurate. Long-term care hospital discharge codes had the lowest accuracy rate (41%), followed by acute care transfers (72%), inpatient rehabilitation facility (80%), and home discharges (83%). Most misclassifications occurred within 2 broad groups of postacute care settings: home-based and institutional care. The odds of inaccurate discharge codes were higher for Medicaid-enrolled patients and safety-net and low-volume hospitals. CONCLUSIONS: Inaccurate hospital discharge coding may have introduced bias in studies relying on these codes (eg, evaluations of Medicare bundled payment models). Inaccuracy was more common among Medicaid-enrolled patients and safety-net and low-volume hospitals, suggesting more potential bias in existing study findings pertaining to these patients and hospitals.

Nematic Correlation Length in Iron-Based Superconductors Probed by Inelastic X-Ray Scattering.

Nematicity is ubiquitous in electronic phases of high-T_{c} superconductors, particularly in the Fe-based systems. We used inelastic x-ray scattering to extract the temperature-dependent nematic correlation length ξ from the anomalous softening of acoustic phonon modes in FeSe, underdoped Ba(Fe_{0.97}Co_{0.03})_{2}As_{2}, and optimally doped Ba(Fe_{0.94}Co_{0.06})_{2}As_{2}. In all cases, we find that ξ is well described by a power law (T-T_{0})^{-1/2} extending over a wide temperature range. Combined with the previously reported Curie-Weiss behavior of the nematic susceptibility, these results point to the mean-field character of the nematic transition, which we attribute to a sizable nematoelastic coupling that is likely detrimental to superconductivity.