Greener and whiter analytical method development and validation for determining the presence of zolpidem tartrate infused in apple juice using RP-HPLC via magnetic solid-phase extraction followed by LC-MS confirmatory analysis.

The research work entails a newly developed RP-HPLC method, aimed at analyzing the modern date rape drug, zolpidem tartrate (ZT), infused in apple juice matrix. The work relies on dispersive solid-phase extraction (DSPE) with polyethylene imine (PEI)-coated magnetic nanoparticles to preconcentrate zolpidem from the matrix, in the presence of trifluoroacetic acid (TFA) for matrix isolation, for the first time. The optimized conditions emphasize the use of an environmentally preferable mobile phase [methanol: 0.5% acetic acid (60 : 40% v/v; pH 2.50)] at a 1 ml min-1 flow rate, employed with a Platisil Octa-Decyl Silane (ODS) column (250 × 4.6 mm; 5 µm). Further, the validated results were confirmed to be within the ICH guidelines, marking the method demonstrated to be linear (R 2 = 0.9988; 0.9957), robust (% RSD below 1), sensitive (LOD = 1.8 µg ml; LOQ = 6 µg ml-1), precise and accurate (% recovery = 92-120%). Following the same conditions, a confirmatory analysis of zolpidem was accomplished using LC-MS, verifying the method's suitability notably, with good peak resolution, less matrix interference and a confirmation of the presence of zolpidem using mass spectrometry. The recycling ability of the PEI@SiO2@Fe3O4 nanoparticles was also assessed. To determine the sustainability of the proposed work, a greener and whiter assessment has been carried out in a comparative mode with previous similar works. For green tools, the recently developed AGREE software was utilized for assessing the method's greeness and it demonstrated a good green score of 0.68, supported by method assessment using ComplexGAPI software. For the assessment of the method's blue principles, the latest software utilizing the blue applicability grade index (BAGI) was applied, resulting in a decent score of 62.5. To consider sustainability, the RGB methodical software in its latest version the RGBfast model, was incorporated in the study for furnishing a balance of the three different major principles (Red-Green-Blue) and for assessing a check on sustainability of the current method compared to similar previously established proposed works.

Serum Mg, Zn and Fe levels among coronary artery disease patients in an urban south Indian region.

Nutrition plays a crucial role in CAD development, with trace elements like zinc, magnesium, copper, and iron impacting atherogenesis through their antioxidant or oxidant activity. This cross sectional study was conducted under the ICMR-STS program with IEC approval with the aim to estimate and correlate serum magnesium, zinc, and iron levels in CAD patients compared to healthy Individuals in the Urban South Indian population (50 cases, 50 controls, aged 40-70 years). Statistical analyses revealed a significant difference in serum iron levels between cases (95.10 ± 38.82 µg/dL) and controls (118.30 ± 50.54 µg/dL) with a p-value of 0.012. Serum magnesium levels showed a marginal difference between cases (1.97±0.11 mg/dL) and controls (1.92±0.15 mg/dL) with a p-value of 0.053. However, serum zinc levels did not exhibit a statistically significant difference between cases (123.47 ± 26.35 mg/dL) and controls (118.90 ± 32.77 mg/dL) with a p-value of 0.445. Thus, data shows the association between low serum iron levels and an increased risk of coronary artery disease.

Vaccine value profile for cytomegalovirus.

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformation and a leading cause of developmental disabilities such as sensorineural hearing loss (SNHL), motor and cognitive deficits. The significant disease burden from congenital CMV infection (cCMV) led the US National Institute of Medicine to rank CMV vaccine development as the highest priority. An average of 6.7/1000 live births are affected by cCMV, but the prevalence varies across and within countries. In contrast to other congenital infections such as rubella and toxoplasmosis, the prevalence of cCMV increases with CMV seroprevalence rates in the population. The true global burden of cCMV disease is likely underestimated because most infected infants (85-90 %) have asymptomatic infection and are not identified. However, about 7-11 % of those with asymptomatic infection will develop SNHL throughout early childhood. Although no licensed CMV vaccine exists, several candidate vaccines are in development, including one currently in phase 3 trials. Licensure of one or more vaccine candidates is feasible within the next five years. Various models of CMV vaccine strategies employing different target populations have shown to provide substantial benefit in reducing cCMV. Although CMV can cause end-organ disease with significant morbidity and mortality in immunocompromised individuals, the focus of this vaccine value profile (VVP) is on preventing or reducing the cCMV disease burden. This CMV VVP provides a high-level, comprehensive assessment of the currently available data to inform the potential public health, economic, and societal value of CMV vaccines. The CMV VVP was developed by a working group of subject matter experts from academia, public health groups, policy organizations, and non-profit organizations. All contributors have extensive expertise on various elements of the CMV VVP and have described the state of knowledge and identified the current gaps. The VVP was developed using only existing and publicly available information.

Multivariate associations between cognition and neighborhood geospatial characteristics in schizophrenia.

Cognitive impairment contributes to functional impairment in schizophrenia. Yet, little is known about how environmental characteristics are related to cognition in schizophrenia. By examining how cognition and the environment are intertwined, it may be possible to identify modifiable risk and protective factors that can improve cognitive outcomes in schizophrenia. We aimed to identify multivariate associations between cognition and three geospatial characteristics (built-space density, habitable green spaces, and public spaces for social interaction) within one's immediate neighborhood among individuals with schizophrenia. We recruited participants with schizophrenia from three sites - an urban metropolitan and two towns in southern India. We administered standard cognitive assessments and performed a principal axis factoring to identify episodic memory, cognitive control, and social inference-making factors for use in further analyses. We estimated geospatial characteristics of an individual's neighborhood, i.e., up to 1 km2 around the residence, by sourcing data from Google Earth. We performed unconditional and conditional (to examine the effect of clinical covariates) canonical correlation analyses to understand the multivariate relationship between cognition and geospatial characteristics. We analyzed data from 208 participants; the first canonical cognitive variate (higher social inference-making and poorer cognitive control) shared 24% of the variance (r = 0.49; P < 0.001) with the first geospatial variate (lower built density and poorer access to public spaces). Years of education, age at onset, and place of residence significantly modulated this relationship. We observe differential associations of the built environment with social and non-social cognition in schizophrenia, and highlight the clinical and demographic characteristics that shape these associations.

Virological Characteristics of Hospitalized Children With SARS-CoV-2 Infection.

BACKGROUND AND OBJECTIVES: In children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, virological characteristics and correlation with disease severity have not been extensively studied. The primary objective in this study is to determine the correlation between SARS-CoV-2 viral load (VL) in infected children with age, disease severity, and underlying comorbidities. METHODS: Children <21 years, screened for SARS-CoV-2 at the time of hospitalization, who tested positive by polymerase chain reaction were included in this study. VL at different sites was determined and compared between groups. RESULTS: Of the 102 children included in this study, 44% of the cohort had asymptomatic infection, and children with >1 comorbidity were the most at risk for severe disease. VL in children with symptomatic infection was significantly higher than in children with asymptomatic infection (3.0 × 105 vs 7.2 × 103 copies per mL; P = .001). VL in the respiratory tract was significantly higher in children <1 year, compared with older children (3.3 × 107 vs 1.3 × 104 copies per mL respectively; P < .0001), despite most infants presenting with milder illness. Besides the respiratory tract, SARS-CoV-2 RNA was also detectable in samples from the gastrointestinal tract (saliva and rectum) and blood. In 13 children for whom data on duration of polymerase chain reaction positivity was available, 12 of 13 tested positive 2 weeks after initial diagnosis, and 6 of 13 continued to test positive 4 weeks after initial diagnosis. CONCLUSIONS: In hospitalized children with SARS-CoV-2, those with >1 comorbid condition experienced severe disease. SARS-CoV-2 VL in the respiratory tract is significantly higher in children with symptomatic disease and children <1 year of age.

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents.

BACKGROUND: In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products. METHODS: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion. RESULTS: The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high-risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis. CONCLUSIONS: Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence and ensure the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.

Multicenter Interim Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion. RESULTS: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

Multicenter Initial Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. RESULTS: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated.

Clinical Diagnostic Testing for Human Cytomegalovirus Infections.

Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.

Quantitative analysis of dental age estimation by incremental line of cementum.

AIM: This study aims to examine the correlation between age and number of incremental lines in human dental cementum among single-rooted teeth (incisors and canines) and to assess the best tooth to estimate age group by studying cementum under phase-contrast microscope and to assess the use of cementum in age estimation. MATERIALS AND METHODS: The present study was carried out in the Department of Oral Pathology and Microbiology. A sample of eighty single-rooted undecalcified longitudinal ground sections is prepared from freshly collected teeth with age noted separately and observed under phase-contrast microscope, photographed and counted. Counting the number of alternating dark and light lines of the cementum and adding them to the average age at which the analyzed tooth erupts provided an estimate of the chronological age of the individual. RESULTS: The results obtained in the present study were statistically significant and positive correlation was observed between the actual age and the estimated age. The number of incremental lines was found to be gradually increased with increase in age of the individual. On an average, ±2 years of age difference were observed in our study on comparing the actual age with estimated age. CONCLUSION: Hence, the incremental lines of the cementum were found to be gradually increased with increase in age and hence can be used as one of the adjuvant tools in dental age estimation.

Neonatal herpes simplex virus infections.

Neonatal herpes simplex virus (HSV) is an uncommon but devastating infection in the newborn, associated with significant morbidity and mortality. The use of PCR for identification of infected infants and acyclovir for treatment has significantly improved the prognosis for affected infants. The subsequent use of suppressive therapy with oral acyclovir following completion of parenteral treatment of acute disease has further enhanced the long-term prognosis for these infants. This review article will discuss the epidemiology, risk factors and routes of acquisition, clinical presentation, and evaluation of an infant suspected to have the infection, and treatment of proven neonatal HSV disease.

Clinical Predictors of Sensorineural Hearing Loss and Cognitive Outcome in Infants with Symptomatic Congenital Cytomegalovirus Infection.

The objective of this study was to determine newborn clinical findings predictive of adverse clinical outcomes in infants with symptomatic congenital cytomegalovirus infection. Of 160 infants, significantly more children with central nervous system involvement had sensorineural hearing loss (P = 0.0007) and an IQ ≤70 (P < 0.0001) compared with infants with transient findings or only a petechial rash.

Validity of Moyers Mixed Dentition Analysis and a New Proposed Regression Equation as a Predictor of Width of Unerupted Canine and Premolars in Children.

INTRODUCTION: The Moyer's mixed dentition analysis forms an essential part of diagnostic procedures to determine adequacy of the space available for the erupting permanent teeth. However, its reliability among different racial groups has been questioned. OBJECTIVES: The objectives of this study were to test the reliability of Moyer's method and to produce new regression equation for Bangalore population for predicting the mesiodistal diameters of the unerupted permanent canines and premolars. MATERIALS AND METHODS: Data was collected from study models of 400 randomly selected Bangalore subjects aged 13 to 16 years with fully erupted, intact dentitions and no significant malocclusion. The mesiodistal widths of the incisors, canines and premolars of both arches were measured. This data was then utilized to predict the mesiodistal widths of canines and premolars and further compared with Moyer's table. CONCLUSION: It was found that 50% is more applicable to boys and 75% to girls. The canine premolar segment in both arches is statistically larger in men than in women (p<0.05). New regression equation was formulated, the accuracy of which needs to be evaluated further in a larger sample.

Health & nutritional status of HIV infected children in Hyderabad, India.

BACKGROUND & OBJECTIVES: Information on nutritional status of HIV infected children from India is lacking and is required before taking up nutritional supplementation trials. Thus, the aim of the present study was to assess the growth and morbidity status of HIV infected children over a period of one year in a city in southern India. METHODS: This was an observational study carried out between July 2009 and February 2011, at two orphanages in Hyderabad, India. Seventy seven HIV-positive children aged between 1 and half and 15 years, both on and not on antiretroviral therapy (ART) were included. Nutritional status was assessed longitudinally for one year by weight gain, linear growth and body composition. Serum samples were analyzed for haemoglobin, micronutrients, CD4 and CD8 counts. Dietary intakes were assessed by institutional diet survey and morbidity data were recorded every day for 12 months. RESULTS: Mean energy intakes were less than recommended dietary allowance (RDA) in all age groups. Iron and folate intakes were less than 50 per cent of RDA; 46 (59.7%) children were stunted, 36 (46.8%) were underweight and 15 (19.5%) had low BMI for age. Anaemia was observed in 35 (45.5%) children. Micronutrient deficiencies such as vitamin D (40/77; 51.9%), vitamin A (11/77; 14.3%), folate (37/77; 48.1%), iron (38/77; 49.3%) were widely prevalent. HIV viral load was higher in children not on ART and those with morbidity. Respiratory (36.6%) and dermatological illnesses (18.8%) were the commonest presentations. INTERPRETATION & CONCLUSIONS: Acute, chronic malnutrition and micronutrient deficiencies were common in HIV infected children, especially in those not on ART and having morbidity. With severe malnutrition being an alarming consequence of HIV, prophylactic nutritive care should be considered for integration into HIV care strategies besides initiation of ART to improve the nutritional status and quality of life of these children.

Comparison of saliva PCR assay versus rapid culture for detection of congenital cytomegalovirus infection.

As part of the CMV and Hearing Multicenter Screening (CHIMES) study, 72,239 newborns were screened for cytomegalovirus by rapid culture and real-time PCR of saliva samples. Of the 266 infants with congenital cytomegalovirus infection, discordance between rapid culture and PCR was observed in 14 children, and 13 were identified only by PCR, demonstrating the superiority of the PCR assay.

Oxidative enzyme changes in sorghum infested by shoot fly.

This research investigated the role of oxidative enzymes in the defense response of sorghum, Sorghum bicolor (L.) Moench (Poales: Poaceae), to the sorghum shoot fly, Atherigona soccata Rondani (Diptera: Muscidae). Changes in polyphenol oxidase and peroxidase activity and total protein content were observed in resistant and susceptible sorghum genotypes in response to A. soccata feeding. Resistant plants exhibited higher levels of peroxidase and polyphenol oxidase activities and total protein content compared with susceptible plants. Peroxidase and polyphenol oxidase activities and total protein content in the infested resistant and susceptible genotypes were higher when compared with their control plants, respectively. These findings suggest that resistant genotypes may be able to tolerate shoot fly feeding by increasing their peroxidase and polyphenol oxidase activities. Among the enzymes examined, differences in isozyme profiles for peroxidase and polyphenol oxidase were detected between control and infested IS 18551, M35-1, 296B, SSV 84, and DJ 6514 plants. Differences in protein profiles were observed between A. soccata infested and their respective uninfested controls of all the genotypes. In conclusion, this study revealed that these defense enzymes and proteins might attribute to the resistance mechanisms in sorghum plants against A. soccata infestation.

Preventing herpes simplex virus in the newborn.

Genital herpes simplex virus (HSV) infections are very common worldwide. Approximately 22% of pregnant women are infected genitally with HSV, and most of them are unaware of this. The most devastating consequence of maternal genital herpes is HSV disease in the newborn. Although neonatal HSV infections remain uncommon, due to the significant morbidity and mortality associated with the infection, HSV infection in the newborn is often considered in the differential diagnosis of ill neonates. This review summarizes the epidemiology and management of neonatal HSV infections and discusses strategies to prevent HSV infection in the newborn.

Management of neonatal herpes simplex virus infection and exposure.

Neonatal herpes simplex virus (HSV) infections are rare but are associated with significant morbidity and mortality. Advances in diagnostic modalities to identify these infants, as well as the development of safe and effective antiviral therapy, have revolutionised the management of affected infants. This review will summarise the epidemiology of neonatal HSV infections and discuss the management of infants with HSV exposure and infection.