Quality by design-steered development and validation of analytical and bioanalytical methods for raloxifene: Application of Monte Carlo simulations and variance inflation factor.

A sensitive, rapid, reproducible, and economical HPLC method is reported for the quantification of raloxifene hydrochloride employing Quality by Design (QbD) principles. Factor screening studies, employing Taguchi design, indicated buffer volume percentage and isocratic flow rate as the critical method parameters (CMPs), which significantly influence the chosen critical analytical attributes, that is, tailing factor and theoretical plate number. Method conditions were subsequently optimized using face-centered cubic design with magnitude of variance inflation factor for assessing multicollinearity among CMPs. Method operable design region (MODR) was earmarked and liquid chromatographic separation optimized using 0.05 M citrate buffer, acetonitrile, and methanol (57:40:3 v/v/v) as ggmobile phase at 0.9 mL min-1 flow rate, λmax of 280 nm, and column temperature of 40°C. Validation of the developed analytical method was accomplished as per International Council on Harmonization (ICH) guidelines confirming high levels of linearity, precision, accuracy, robustness, and sensitivity. Application of Monte Carlo simulations enabled the attainment of best plausible chromatographic resolution and corroboration of the demarcated MODR. Establishment and validation of the bioanalytical method using rat plasma samples, along with forced degradation and stability studies, corroborated the aptness of developed HPLC methods for drug quantification in the biological fluids, as well as in bulk and marketed dosage forms.

A glass matrices-assisted quantum dots-based biosensor for selective capturing and detection of Escherichia coli.

Bacterial contamination of water and food is a grave health concern rendering humans quite vulnerable to disease(s), and proving, at times, fatal too. Exploration of the novel diagnostic tools is, accordingly, highly called for to ensure rapid detection of the pathogenic bacteria, particularly Escherichia coli. The current manuscript, accordingly, reports the use of silane-functionalized glass matrices and antibody-conjugated cadmium telluride (CdTe) quantum dots (QDs) for efficient detection of E. coli. Synthesis of QDs (size: 5.4-6.8 nm) using mercaptopropionic acid (MPA) stabilizer yielded stable photoluminescence (∼62%), corroborating superior fluorescent characteristics. A test sample, when added to antibody-conjugated matrices, followed by antibody-conjugated CdTe-MPA QDs, formed a pathogen-antibody QDs complex. The latter, during confocal microscopy, demonstrated rapid detection of the selectively captured pathogenic bacteria (10 microorganism cells/10 µL) with enhanced sensitivity and specificity. The work, overall, encompasses establishment and design of an innovative detection platform in microbial diagnostics for rapid capturing of pathogens in water and food samples.

COVID-19 Disrupted Provision and Utilization of Health and Nutrition Services in Uttar Pradesh, India: Insights from Service Providers, Household Phone Surveys, and Administrative Data.

BACKGROUND: The coronavirus (COVID-19) pandemic may substantially affect health systems, but little primary evidence is available on disruption of health and nutrition services. OBJECTIVES: This study aimed to 1) determine the extent of disruption in provision and utilization of health and nutrition services induced by the pandemic in Uttar Pradesh, India; and 2) identify how adaptations were made to restore service provision in response to the pandemic. METHODS: We conducted longitudinal surveys with frontline workers (FLWs, n = 313) and mothers of children <2 y old (n = 659) in December 2019 (in-person) and July 2020 (by phone). We also interviewed block-level managers and obtained administrative data. We examined changes in service provision and utilization using Wilcoxon matched-pairs signed-rank tests. RESULTS: Compared with prepandemic, service provision reduced substantially during lockdown (83-98 percentage points, pp), except for home visits and take-home rations (∼30%). Most FLWs (68%-90%) restored service provision in July 2020, except for immunization and hot cooked meals (<10%). Administrative data showed similar patterns of disruption and restoration. FLW fears, increased workload, inadequate personal protective equipment (PPE), and manpower shortages challenged service provision. Key adaptations made to provide services were delivering services to beneficiary homes (∼40%-90%), social distancing (80%), and using PPE (40%-50%) and telephones for communication (∼20%). On the demand side, service utilization reduced substantially (40-80 pp) during the lockdown, but about half of mothers received home visits and food supplementation. Utilization for most services did not improve after the lockdown, bearing the challenges of limited travel (30%), nonavailability of services (26%), and fear of catching the virus when leaving the house (22%) or meeting service providers (14%). CONCLUSIONS: COVID-19 disrupted the provision and use of health and nutrition services in Uttar Pradesh, India, despite adaptations to restore services. Strengthening logistical support, capacity enhancement, performance management, and demand creation are needed to improve service provision and utilization during and post-COVID-19.

Provision and utilisation of health and nutrition services during COVID-19 pandemic in urban Bangladesh.

The COVID-19 pandemic is expected to have profound effects on healthcare systems, but little evidence exists on service provision, utilisation, or adaptations. This study aimed to (1) examine the changes to health and nutrition service delivery and utilisation in urban Bangladesh during and after enforcement of COVID-19 restrictions and (2) identify adaptations and potential solutions to strengthen delivery and uptake. We conducted longitudinal surveys with health care providers (n = 45), pregnant women (n = 40), and mothers of children <2 years (n = 387) in February 2020 (in-person) and September 2020 (by phone). We used Wilcoxon matched-pairs signed-rank tests to compare the changes before and during the pandemic. Services delivery for women and children which require proximity were severely affected; weight and height measurements fell by 20-29 percentage points (pp) for pregnant women and 37-57 pp for children, and child immunisations fell by 38 pp. Declines in service utilisation were large, including drops in facility visitations (35 pp among pregnant women and 67 pp among mothers), health and nutrition counselling (up to 73 pp), child weight measurements (50 pp), and immunisations (61 pp). The primary method of adaptation was provision of services over phone (37% for antenatal care services, 44%-49% for counselling). Despite adaptations to service provision, continued availability of routine maternal and child health services did not translate into service utilisation. Further investments are needed to provide timely and accurate information on COVID-19 to the general public, improve COVID-19 training and provide incentives for health care providers and ensure availability of personal protective equipment for providers and beneficiaries.

QbD-driven development and characterization of superparamagnetic iron oxide nanoparticles (SPIONS) of a bone-targeting peptide for early detection of osteoporosis.

Osteoporosis is a metabolic disorder that leads to deterioration of bones. The major challenges confronting osteoporosis therapy include early-stage detection and regular disease monitoring. The present studies employed D-aspartic acid octapeptide (-D-Asp-)8 as bone-targeting peptide for evaluating osteoporosis manifestation, and superparamagnetic iron oxide nanoparticles (SPIONs) as nanocarriers for MRI-aided diagnosis. Thermal decomposition technique was employed to synthesize SPIONs, followed by surface-functionalization with hydrophilic ligands. Failure mode effect analysis and factor screening studies were performed to identify concentrations of SPIONs and ligand as critical material attributes, and systematic optimization was subsequently conducted employing face-centered cubic design. The optimum formulation was delineated using desirability function, and design space demarcated with 178.70 nm as hydrodynamic particle size, -24.40 mV as zeta potential, and 99.89 % as hydrophilic iron content as critical quality attributes. XRD patterns ratified lattice structure and SQUID studies corroborated superparamagnetic properties of hydrophilic SPIONs. Bioconjugation of (-D-Asp-)8 with SPIONs (1:1) was confirmed using UV spectroscopy, FTIR and NMR studies. Cell line studies indicated successful targeting of SPIONs to MG-63 human osteoblasts, ratifying enormous bone-targeting and safety potential of peptide-tethered SPIONs as MRI probes. In vivo MRI imaging studies in rats showcased promising contrast ability and safety of peptide-conjugated SPIONs.

QbD-driven development of phospholipid-embedded lipidic nanocarriers of raloxifene: extensive in vitro and in vivo evaluation studies.

Raloxifene (RLX) is popularly indicated in treatment of osteoporosis and prevention of breast cancer. Owing to its poor aqueous solubility, high pre-systemic metabolism, intestinal glucuronidation, and P-glycoprotein (P-gp) efflux, however, it demonstrates low (< 2%) and inconsistent oral bioavailability. The current work, Quality by Design (QbD)-driven development of phospholipid-embedded nanostructured lipidic carriers (NLCs) of RLX, accordingly, was undertaken to potentiate its lymphatic uptake, augment oral bioavailability, and possibly reduce drug dosage. Factor screening and failure mode effect analysis (FMEA) studies were performed to delineate high-risk factors using solid lipid (glyceryl monostearate), liquid lipid (vitamin E), and surfactant (Tween 80). Response surface optimization studies were performed employing the Box-Behnken design. Mathematical and graphical methods were adopted to embark upon the selection of optimized NLCs with various critical quality attributes (CQAs) of mean particle size as 186 nm, zeta potential of - 23.6 mV, entrapment efficiency of 80.09%, and cumulative drug release at 12 h of 83.87%. The DSC and FTIR studies, conducted on optimized NLCs, indicated successful entrapment of drug into the lipid matrix. In vitro drug release studies demonstrated Fickian diffusion mechanism. In vivo pharmacokinetic studies in rats construed significant improvement in AUC0-72 h (4.48-folds) and in Cmax (5.11-folds), unequivocally indicating markedly superior (p < 0.001) oral bioavailability of RLX-NLCs vis-à-vis marketed tablet formulation. Subsequently, level "A" in vitro/in vivo correlation (IVIVC) was also successfully attempted between the percentages of in vitro drug dissolved and of in vivo drug absorbed at the matching time points. In vitro cytotoxicity and cellular uptake studies also corroborated higher efficacy and successful localization of coumarin-6-loaded NLCs into MG-63 cells through microfluidic channels.

Theranostic Approach for the Management of Osteoporosis.

Osteoporosis (OP) is a bone-metabolic disorder, causing micro-architecture degeneration and a decrease in bone density. Nutritional deficiency, i.e., calcium, vitamin D, and hormonal imbalances are the primary cause for the occurrence of OP. Although conventional diagnostic techniques and therapies are available and found to be effective only at a later stage, though still lack prevention strategies. Thus, the patients tend to suffer incidence of fractures and many difficulties to manage their day-to-day activities at an elderly stage. Numerous nanomaterial(s) possessing unique physicochemical, optical, and electrical properties are reported nowadays to be employed for both early-stage detections of disease and its treatment. Amongst these nanomaterials, superparamagnetic iron oxide nanoparticles (SPIONs) possessing strong magnetic susceptibility, less in vivo toxicity, and surface functionalities are extensively employed for MRI contrast imaging agents in the area of disease diagnosis, and drug delivery tools for various therapies. Therefore, this review highlights the pathophysiology of OP, conventional techniques of diagnosis, and the application of SPIONs for diagnostic and treatment purposes of osteoporosis.

Concurrent Undernutrition and Overnutrition within Indian Families between 2006 and 2021.

Background: The double burden of malnutrition (DBM), characterized by concurrent undernutrition and overnutrition, is a growing global concern. Families share resources and eating behaviors and programs often target households, yet evidence of the DBM at the family level is scarce. Objectives: This study examined trends and inequality in the intrahousehold DBM in India between 2006 and 2021. Methods: Data were from 3 waves of India's National Family Health Survey (NFHS 2006, 2016, and 2021). We examined 3 types of household member (with children aged <5 y) combinations: mother-child (N = 328,039 across 3 waves), father-child, and parent (mother and father)-child (N = 47,139 for each pair). The DBM was defined as one or more individuals with undernutrition (either wasting or stunting in children or underweight in adults) and one or more overweight individuals within the same household. DBM was examined over time, at national and subnational levels, and by residence and wealth. Results: Nearly all DBM was in the form of an overweight parent and an undernourished weight or stunted child. The prevalence of parent-child DBM increased from 15% in 2006 to 26% in 2021. Father-child pairs experienced the most rapid DBM increase, from 12% in 2006 to 22% in 2021, an 83% increase, driven by increasing overweight among men. In 2021, the DBM was highest in North-Eastern and Southern states, and among relatively rich households from urban areas. The increase in the DBM was faster in rural areas and among poor households compared with that in urban areas and rich households. Urban-rural and rich-poor inequalities in the DBM have decreased over time. Conclusions: The intrahousehold DBM has increased over time, affecting 1 in 4 households in India in 2021. Family-based interventions that can simultaneously address child underweight and parent overweight are required to address India's increasing intrahousehold DBM.

Changes in anemia and anthropometry during adolescence predict learning outcomes: findings from a 3-year longitudinal study in India.

BACKGROUND: Anemia and poor physical growth during adolescence have far-ranging consequences, but limited longitudinal evidence exists on how changes in these factors relate to changes in learning skills as adolescents mature. OBJECTIVES: We examined the association between changes in anemia and physical growth during adolescence and learning outcomes. METHODS: We used longitudinal data from the Understanding the Lives of Adolescents and Young Adults (UDAYA) project, which surveyed adolescents aged 10-19 y in northern India in 2015-2016 and 2018-2019 (n = 5963). We used multilevel mixed-effects logistic regression models to examine associations between changes in anemia/thinness/stunting status (4 groups: never, improved, new, and persistent) and reading (ability to read a story) and math proficiency (ability to solve division problems) at follow-up. RESULTS: Persistent anemia and stunting were higher among girls than among boys (46% compared with 8% and 37% compared with 14%, respectively), but persistent thinness was lower (7% compared with 16%). Improvement in anemia, thinness, and stunting was 1.4-1.7 times higher among boys than among girls. Boys who were anemic in both waves were 74% [adjusted odds ratio (AOR): 0.26; 95% CI: 0.12, 0.59] and 65% (AOR: 0.35; 95% CI: 0.16, 0.76) less likely to be able to read a story and solve division problems, respectively, than boys who were nonanemic in both waves. Persistent thinness in boys was negatively associated with both reading (AOR: 0.37; 95% CI: 0.21, 0.66) and math proficiency (AOR: 0.27; 95% CI: 0.16, 0.46). Persistent stunting contributed to lower reading and math proficiency in boys and girls (AORs: 0.29-0.46). Boys whose anemia or thinness status improved and girls whose stunting status improved had similar learning skills at follow-up as those who were never anemic/thin/stunted. CONCLUSIONS: Persistent anemia, thinness, and short stature during adolescence were associated with poor learning. Programs targeted at adolescents should contribute to nurturing environments that foster healthy growth and learning.

Cyclodextrin Derivative Enhances the Ophthalmic Delivery of Poorly Soluble Azithromycin.

Azithromycin (AZM), a macrolide antibiotic used for the treatment of chlamydial conjunctivitis, is less effective for the treatment of this disease due to its poor bioavailability (38%). Various alternatives have been developed for improving the physicochemical properties (i.e., solubility) of the AZM without much success. To overcome the problems associated with AZM, an inclusion complex employing a modified cyclodextrin, i.e., sulfobutylether-ß-cyclodextrin (SBE-ß-CD), was prepared and characterized by phase solubility studies and PXRD techniques. The results portrayed the formation of an inclusion complex of AZM with SBE-ß-CD in 1:2 molar stoichiometric ratios. This inclusion complex was later incorporated into a polymer matrix to prepare an in situ gel. Various combinations of Carbopol 934P and hydroxypropyl methylcellulose (HPMC K4M) polymers were used and evaluated by rheological and in vitro drug release studies. The optimized formulation (F4) containing Carbopol 934P (0.2% w/v) and HPMC K4M (0.2% w/v) was evaluated for clarity, pH, gelling capacity, drug content, rheological properties, in vitro drug release pattern, ocular irritation test, and antimicrobial efficacy. Finally, owing to the improved antimicrobial efficacy and increased residence time, the AZM:SBE-ß-CD in situ gel was found to be a promising formulation for the efficient treatment of bacterial ocular disease.

Disruptions, restorations and adaptations to health and nutrition service delivery in multiple states across India over the course of the COVID-19 pandemic in 2020: An observational study.

BACKGROUND: Modeling studies estimated severe impacts of potential service delivery disruptions due to COVID-19 pandemic on maternal and child nutrition outcomes. Although anecdotal evidence exists on disruptions, little is known about the actual state of service delivery at scale. We studied disruptions and restorations, challenges and adaptations in health and nutrition service delivery by frontline workers (FLWs) in India during COVID-19 in 2020. METHODS: We conducted phone surveys with 5500 FLWs (among them 3118 Anganwadi Workers) in seven states between August-October 2020, asking about service delivery during April 2020 (T1) and in August-October (T2), and analyzed changes between T1 and T2. We also analyzed health systems administrative data from 704 districts on disruptions and restoration of services between pre-pandemic (December 2019, T0), T1 and T2. RESULTS: In April 2020 (T1), village centers, fixed day events, child growth monitoring, and immunization were provided by <50% of FLWs in several states. Food supplementation was least disrupted. In T2, center-based services were restored by over a third in most states. Administrative data highlights geographic variability in both disruptions and restorations. Most districts had restored service delivery for pregnant women and children by T2 but had not yet reached T0 levels. Adaptations included home delivery (60 to 96%), coordinating with other FLWs (7 to 49%), and use of phones for counseling (~2 to 65%). Personal fears, long distances, limited personal protective equipment, and antagonistic behavior of beneficiaries were reported challenges. CONCLUSIONS: Services to mothers and children were disrupted during stringent lockdown but restored thereafter, albeit not to pre-pandemic levels. Rapid policy guidance and adaptations by FLWs enabled restoration but little remains known about uptake by client populations. As COVID-19 continues to surge in India, focused attention to ensuring essential services is critical to mitigate these major indirect impacts of the pandemic.

Impact of COVID-19 on household food insecurity and interlinkages with child feeding practices and coping strategies in Uttar Pradesh, India: a longitudinal community-based study.

OBJECTIVES: The COVID-19 pandemic has profound negative impacts on people's lives, but little is known on its effect on household food insecurity (HFI) in poor setting resources. This study assessed changes in HFI during the pandemic and examined the interlinkages between HFI with child feeding practices and coping strategies. DESIGN: A longitudinal survey in December 2019 (in-person) and August 2020 (by phone). SETTING: Community-based individuals from 26 blocks in 2 districts in Uttar Pradesh, India. PARTICIPANTS: Mothers with children <2 years (n=569). MAIN OUTCOMES AND ANALYSES: We measured HFI by using the HFI Access Scale and examined the changes in HFI during the pandemic using the Wilcoxon matched-pairs signed-rank tests. We then assessed child feeding practices and coping strategies by HFI status using multivariable regression models. RESULTS: HFI increased sharply from 21% in December 2019 to 80% in August 2020, with 62% households changing the status from food secure to insecure over this period. Children in newly or consistently food-insecure households were less likely to consume a diverse diet (adjusted OR, AOR 0.57, 95% CI 0.34 to 0.95 and AOR 0.51, 95% CI 0.23 to 1.12, respectively) compared with those in food-secure households. Households with consistent food insecurity were more likely to engage in coping strategies such as reducing other essential non-food expenditures (AOR 2.2, 95% CI 1.09 to 4.24), borrowing money to buy food (AOR 4.3, 95% CI 2.31 to 7.95) or selling jewellery (AOR 5.0, 95% CI 1.74 to 14.27) to obtain foods. Similar findings were observed for newly food-insecure households. CONCLUSIONS: The COVID-19 pandemic and its lockdown measures posed a significant risk to HFI which in turn had implications for child feeding practices and coping strategies. Our findings highlight the need for further investment in targeted social protection strategies and safety nets as part of multisectoral solutions to improve HFI during and after COVID-19.

Demographic, nutritional, social and environmental predictors of learning skills and depression in 20,000 Indian adolescents: Findings from the UDAYA survey.

OBJECTIVES: Adolescent wellbeing is critical to breaking the intergenerational cycle of poverty and one in five of the world's adolescents live in India. We explored predictors of learning skills and depression in Indian adolescents. METHODS: Data on adolescents aged 10-19y (three groups: 5,840 unmarried males, 8,953 unmarried females, 4,933 married females) were available from the state-representative Understanding the Lives of Adolescents and Young Adults survey in Uttar Pradesh and Bihar. Multivariable logistic regression models adjusted for cluster sampling design and state fixed effects were used to examine factors (demographic, health/nutrition, social, and environmental) associated with three outcomes: reading proficiency, math proficiency, and depressive symptoms. FINDINGS: Learning skills were poor (28-61% lacked basic reading and math skills depending on adolescent group and outcome) and depression was common (8-26%). Better learning skills were predicted by greater household wealth (AOR 1.72-2.55 depending on group) and household head education (AOR 1.03-1.07 per year), being in school (AOR 4.19-18.65), parental support (AOR 1.11-1.39), having gender equal attitudes (AOR 1.56-2.67), number of food groups consumed at least weekly (unmarried females: AOR 1.11), and having an improved latrine (AOR 1.33-1.51). Poorer learning skills were predicted by family substance use (AOR 0.68-0.74), underweight (males: AOR 0.74), witnessing parental violence (AOR 0.66-0.78). Depressive symptoms were predicted by witnessing parental violence (AOR 1.51-1.92) and experiencing sexual abuse (AOR 2.30-6.16). CONCLUSION: Factors across multiple life dimensions are associated with learning skills and depression in Indian adolescents. Adolescent-focused policies and programs should consider health/nutrition, social, and environmental aspects of life in vulnerable individuals.

Faith-based organizations and sustainable sheltering operations in Mississippi after Hurricane Katrina: implications for informal network utilization.

INTRODUCTION: In the aftermath of Hurricane Katrina, a significant number of faith-based organizations (FBOs) that were not a part of the formal National Response Plan (NRP) initiated and sustained sheltering operations. OBJECTIVE: The objective of this study was to examine the sheltering operations of FBOs, understand the decision-making process of FBO shelters, and identify the advantages and disadvantages of FBO shelters. METHODS: Verbal interviews were conducted with FBO shelter leaders. Inclusion criteria were: (1) opening in response to the Katrina disaster; (2) operating for more than three weeks; and (3) being a FBO. Enrolled shelters were examined using descriptive data methods. RESULTS: The majority of shelters operating in Mississippi up to three weeks post-Katrina were FBO-managed. All of the operating FBO shelters in Mississippi that met the inclusion criteria were contacted with a response rate of 94%. Decisions were made by individuals or small groups in most shelters regarding opening, operating procedures, and closing. Most FBOs provided at least one enabling service to evacuees, and all utilized informal networks for sheltering operations. Only 25% of FBOs had disaster plans in place prior to Hurricane Katrina. CONCLUSIONS: Faith-based organization shelters played a significant role in the acute phase of the Katrina disaster. Formal disaster training should be initiated for these organizations. Services provided by FBOs should be standardized. Informal networks should be incorporated into national disaster planning.

Novel controlled ionic gelation strategy for chitosan nanoparticles preparation using TPP-ß-CD inclusion complex.

The aim of this study was to develop a novel controlled ionic gelation strategy for chitosan nanoparticle preparation to avoid particle aggregation tendency associated with conventional ionic gelation process. In this study inclusion complexation behaviour of sodium tripolyphosphate (TPP) with beta cyclodextrin (ß-CD) has been investigated. The TPP-ß-CD inclusion complex was characterized by FT-IR, XRD and DSC techniques. The complexation behaviour was also investigated by molecular docking study. The results showed that the TPP molecule formed inclusion complex with ß-CD. Further, TPP-ß-CD inclusion complex was used to prepare chitosan nanoparticles. The chitosan nanoparticles based on TPP-ß-CD inclusion complex had smaller size of 104.2nm±0.608, good PDI value of 0.346±0.016 and acceptable zeta potential of +27.33mV±0.416. The surface characteristics of chitosan nanoparticles were also observed with transmission electron microscopy. Results indicates that TPP-ß-CD inclusion complex can be used for the formation of chitosan nanoparticles with smaller and more uniform particle size in comparison to conventional TPP based chitosan nanoparticles.