Study of secondary organic aerosol formation and aging using ambient air in an oxidation flow reactor during high pollution events over Delhi.

Secondary aerosols constitute a significant fraction of atmospheric aerosols, yet our understanding of their formation mechanism and fate is very limited. In this work, the secondary organic aerosol (SOA) formation and aging of ambient air of Delhi are studied using a potential aerosol mass (PAM) reactor, an oxidation flow reactor (OFR), coupled with aerosol chemical speciation monitor (ACSM), proton transfer reaction time of flight mass spectrometer (PTR-ToF-MS), and scanning mobility particle sizer with counter (SMPS + C). The setup mimics atmospheric aging of up to several days with the generation of OH radicals. Variations in primary volatile organic compounds (VOCs) and oxygenated volatile organic compounds (OVOCs) as a function of photochemical age were investigated. Primary VOCs such as benzene, toluene, xylene, trimethyl benzene, etc. decrease and OVOCs like formic acid, formaldehyde, acetone, ethanol, etc. increase substantially upon oxidation in OFR. The highest organic aerosol (OA) enhancement was observed for the 4.2 equivalent photochemical days of aging i.e., 1.84 times the ambient concentration, and net OA loss was observed at very high OH exposure, typically after 8.4 days of photochemical aging due to heterogeneous oxidation followed by fragmentation/evaporation. In ambient air, OA enhancement is highest during nighttime due to the high concentrations of precursor VOCs in the atmosphere. SMPS + C results demonstrated substantial new particle formation upon aging and decrement in preexisting aerosol mass. This is the first experimental study conducting an in-situ evaluation of potential SOA mass generated from the ambient aerosols in India.

Apical Aneurysms and Mid-Left Ventricular Obstruction in Hypertrophic Cardiomyopathy.

BACKGROUND: Apical left ventricular (LV) aneurysms in hypertrophic cardiomyopathy (HCM) are associated with adverse outcomes. The reported frequency of mid-LV obstruction has varied from 36% to 90%. OBJECTIVES: The authors sought to ascertain the frequency of mid-LV obstruction in HCM apical aneurysms. METHODS: The authors analyzed echocardiographic and cardiac magnetic resonance examinations of patients with aneurysms from 3 dedicated programs and compared them with 63 normal controls and 47 controls with apical-mid HCM who did not have aneurysms (22 with increased LV systolic velocities). RESULTS: There were 108 patients with a mean age of 57.4 ± 13.5 years; 40 (37%) were women. A total of 103 aneurysm patients (95%) had mid-LV obstruction with mid-LV complete systolic emptying. Of the patients with obstruction, 84% had a midsystolic Doppler signal void, a marker of complete flow cessation, but only 19% had Doppler systolic gradients ≥30 mm Hg. Five patients (5%) had relative hypokinesia in mid-LV without obstruction. Aneurysm size is not bimodal but appears distributed by power law, with large aneurysms decidedly less common. Comparing mid-LV obstruction aneurysm patients with all control groups, the short-axis (SAX) systolic areas were smaller (P < 0.007), the percent SAX area change was greater (P < 0.005), the papillary muscle (PM) areas were larger (P < 0.003), and the diastolic PM areas/SAX diastolic areas were greater (P < 0.005). Patients with aneurysms had 22% greater SAX PM areas compared with those with elevated LV velocities but no aneurysms (median: 3.00 cm2 [IQR: 2.38-3.70 cm2] vs 2.45 [IQR: 1.81-2.95 cm2]; P = 0.004). Complete emptying occurs circumferentially around central PMs that contribute to obstruction. Late gadolinium enhancement was always brightest and the most transmural apical of, or at the level of, complete emptying. CONCLUSIONS: The great majority (95%) of patients in the continuum of apical aneurysms have associated mid-LV obstruction. Further research to investigate obstruction as a contributing cause to apical aneurysms is warranted.

Impact of COVID-19 Pandemic Lockdown in Ambient Concentrations of Aromatic Volatile Organic Compounds in a Metropolitan City of Western India.

The real-time Benzene, Toluene, Ethylbenzene, and Xylenes (BTEX) concentrations were measured in a metropolitan city of India during January to May of 2020 and 2014-2015-2018 to assess the impact of emission reduction during the COVID-19 lockdown. The total BTEX (∑BTEX) concentrations were 11.5 ± 9.0, 15.7 ± 16, 5.3 ± 5.0, 2.9 ± 2.0, and 0.93 ± 1.2 ppbv in January-May 2020, respectively. The evening rush hour peaks of BTEX during lockdown decreased by 4-5 times from the same period of years 2014-2015-2018. A significant decline in background concentrations suggests a regional-scale reduction in anthropogenic emissions. The contributions of ∑TEX compounds to ∑BTEX increased from 42% to 59% in winter to 64%-75% during the lockdown under hot summer conditions. While emission reductions dominated during the lockdown period, the meteorological and photochemical factors may also have contributed. Meteorological influence on actual observed BTEX data was removed by normalizing with ventilation coefficient (VC). The actual ambient air reductions of 85%-90% and VC-normalized reductions of 54%-88% of the BTEX concentrations during lockdown were estimated compared to those during the same period of 2014-2015-2018. The estimated changes using nighttime data, which take into account BTEX photooxidation removal, are ∼8% lower than the VC-normalized estimates using all data. These significant reductions in BTEX concentrations are consistent with the change in people's movement as inferred from mobility data during the lockdown. Although enforced, the significant decline in ambient BTEX levels during lockdown was a good change for the air quality. The study suggests a need for more effective science-based policies that consider local and regional factors.

Management of hospital beds and ventilators in the Gauteng province, South Africa, during the COVID-19 pandemic.

We conducted an observational retrospective study on patients hospitalized with COVID-19, during March 05, 2020, to October 28, 2021, and developed an agent-based model to evaluate effectiveness of recommended healthcare resources (hospital beds and ventilators) management strategies during the COVID-19 pandemic in Gauteng, South Africa. We measured the effectiveness of these strategies by calculating the number of deaths prevented by implementing them. We observed differ ences between the epidemic waves. The length of hospital stay (LOS) during the third wave was lower than the first two waves. The median of the LOS was 6.73 days, 6.63 days and 6.78 days for the first, second and third wave, respectively. A combination of public and private sector provided hospital care to COVID-19 patients requiring ward and Intensive Care Units (ICU) beds. The private sector provided 88.4% of High care (HC)/ICU beds and 49.4% of ward beds, 73.9% and 51.4%, 71.8% and 58.3% during the first, second and third wave, respectively. Our simulation results showed that with a high maximum capacity, i.e., 10,000 general and isolation ward beds, 4,000 high care and ICU beds and 1,200 ventilators, increasing the resource capacity allocated to COVID- 19 patients by 25% was enough to maintain bed availability throughout the epidemic waves. With a medium resource capacity (8,500 general and isolation ward beds, 3,000 high care and ICU beds and 1,000 ventilators) a combination of resource management strategies and their timing and criteria were very effective in maintaining bed availability and therefore preventing excess deaths. With a low number of maximum available resources (7,000 general and isolation ward beds, 2,000 high care and ICU beds and 800 ventilators) and a severe epidemic wave, these strategies were effective in maintaining the bed availability and minimizing the number of excess deaths throughout the epidemic wave.

Development of an Early Alert System for an Additional Wave of COVID-19 Cases Using a Recurrent Neural Network with Long Short-Term Memory.

The impact of the still ongoing "Coronavirus Disease 2019" (COVID-19) pandemic has been and is still vast, affecting not only global human health and stretching healthcare facilities, but also profoundly disrupting societal and economic systems worldwide. The nature of the way the virus spreads causes cases to come in further recurring waves. This is due a complex array of biological, societal and environmental factors, including the novel nature of the emerging pathogen. Other parameters explaining the epidemic trend consisting of recurring waves are logistic-organizational challenges in the implementation of the vaccine roll-out, scarcity of doses and human resources, seasonality, meteorological drivers, and community heterogeneity, as well as cycles of strengthening and easing/lifting of the mitigation interventions. Therefore, it is crucial to be able to have an early alert system to identify when another wave of cases is about to occur. The availability of a variety of newly developed indicators allows for the exploration of multi-feature prediction models for case data. Ten indicators were selected as features for our prediction model. The model chosen is a Recurrent Neural Network with Long Short-Term Memory. This paper documents the development of an early alert/detection system that functions by predicting future daily confirmed cases based on a series of features that include mobility and stringency indices, and epidemiological parameters. The model is trained on the intermittent period in between the first and the second wave, in all of the South African provinces.

Emissions of non-methane volatile organic compounds from a landfill site in a major city of India: impact on local air quality.

Emissions from landfills are a significant source of non-methane volatile organic compounds (NMVOCs) in urban environments. NMVOCs play an important role in atmospheric chemistry, and elevated concentrations of some compounds are responsible for air quality deterioration. This study is based on the measurements of a suite of 20 C2-C8 NMVOCs at 21 upwind and downwind sites of the largest landfill in western India. Ethane, ethylene and aromatics were the dominant compounds; the concentrations of BTEX in the downwind regions were up to three times higher than their concentrations at upwind sites. The emission ratios of BTEX and other NMVOCs were different from those for residential, commercial, and industrial sources characterizing the emissions from burning and decomposition of organic material. The slope of ΔToluene/ΔBenzene of 0.64 is about three times higher than that determined at the main road junctions of the city. Ranking by Prop-Equiv, the top NMVOCs were isoprene, cis-2-Butene, m + p-xylenes, propylene, ethylene and trans-2-Butene account for 72-75% of the total Prop-Equiv concentrations. Alkenes played the dominant role in ozone formation, followed by aromatic and alkane groups. In addition to landfill emissions, contributions from traffic-related emissions to ambient concentrations of aromatic VOCs were also significant at some sites. Although the experiment was not designed to characterize the emissions from a specific source, the analysis suggests the substantial contributions from both decomposition and burning of landfill materials. The main difficulty in characterizing VOC emissions from landfills is the spatial and temporal variability of emissions from a large area.

Emissions and atmospheric concentrations of α-pinene at an urban site of India: Role of changes in meteorology.

The measurements of a monoterpene (α-pinene) were performed by the PTR-TOF-MS instrument at an urban site of India from mid-January to March 2014. The daytime concentration increased from 0.15 ppb in the second-half of January to 0.40 ppb in the second-half of March. Both the nighttime and daytime ratios of α-pinene/benzene in the second-half of March were 2-3 times higher their respective values from mid-January to first-half of February. The ratios of α-pinene/benzene increased from ∼0.27 ppb ppb-1 at lower temperatures to ∼0.51 ppb ppb-1 at higher temperatures indicating the increase of biogenic emissions in March. The concentration of α-pinene exhibited exponential decline with wind speed, but the rate of decrease in February was about twice that for March. The nighttime ratios of α-pinene/isoprene were greater than those measured in the daytime, suggesting temperature-dependent biogenic emissions of α-pinene. From mid-January to March, the increase of ∼53% in the biogenic contributions of α-pinene were associated with the change in meteorological conditions. Our analysis suggests that the combined effect of the northwest wind flow and higher air temperatures in March favored the emissions of BVOCs from local vegetation. The exceptionally high concentrations of α-pinene up to 6 ppb were measured during the Holi bonfire festival. This is the first study reporting the change in α-pinene during winter-summer transition over India. In the urban regions of developing countries, high emissions of BVOCs from vegetation and of NOx from anthropogenic sources can act as a source of ozone.

In silico analysis and molecular characterization of Influenza A (H1N1) pdm09 virus circulating and causing major outbreaks in central India, 2009-2019.

BACKGROUND AND OBJECTIVES: Influenza A/H1N1pdm09 causes respiratory illness and remains a concern for public health. Since its first emergence in 2009, the virus has been continuously circulating in the form of its genetic variants. Influenza A/H1N1pdm09 surveillance is essential for uncovering emerging variants of epidemiologic and vaccine efficacy. The present study attempts in silico analysis and molecular characterization of Influenza A (H1N1) pdm09 virus circulating and causing major outbreaks in central India during 2009-2019. MATERIALS AND METHODS: We have investigated the antigenic drift analysis of 96 isolates' hemagglutinin (HA) gene sequences (59 central Indian and 37 local Indian and 28 global reference HA gene sequences) of Influenza A/H1N1pdm09 viruses from 2009 to 2019. The study includes mutational (Multiple sequence Alignment), phylogenetic (Maximum Likelihood Method), and statistical analysis (Covariance and correlation) of HA sequences submitted in NCBI, IRD and GISAID from central India. RESULTS: Phylogenetic analysis indicated maximum clustering of central Indian HA gene sequences in genogroup 6B. Analysis of amino acid sequence alignment revealed changes in receptor binding site (RBS). The frequency of S220T amino acid substitution was found to be high followed by S202T, K300E A273T, K180Q. The Karl Pearson correlation coefficient (r) and covariance between the number of mutations and the death toll was found +0.246 and +100.3 respectively. CONCLUSION: The study identifies the continuous genetic variations in the HA gene sequences of circulating Influenza A/H1N1pdm09 in central India from the year 2009 to 2019. Further suggesting importance of monitoring the gradual evolution of the virus with regards to an increase in virulence, pathogenicity and vaccine efficacy timely.

SPECT myocardial perfusion imaging in liver transplantation candidates.

BACKGROUND: The optimal cardiovascular evaluation prior to liver transplantation remains controversial and includes stress echocardiography, stress MPI, cardiac CTA, and coronary angiography. This study summarizes our experience of the past decade using SPECT MPI in patients with end-stage liver disease, including patient characteristics, stress testing protocols, test results, the need for repeat testing, and downstream testing. METHODS: All patients who underwent a clinically indicated stress SPECT MPI study as part of their pre-liver transplant evaluation from 2004 to 2014 were reviewed from the Nuclear Cardiology database. Results of perfusion imaging, repeat testing, subsequent angiography, and need for revascularization were reviewed. RESULTS: A total of 2500 patients were referred for SPECT MPI, of those 111 had known CAD and 271 underwent more than one MPI study. Compared to other patients undergoing stress MPI, pre-liver transplant patients were younger, had fewer cardiac risk factors and lower prevalence of prior cardiac history, and used pharmacologic stress more often. During the study decade, patient age increased, prevalence of hypertension increased and smoking decreased, prevalence of known CAD increased, and the number of abnormal studies decreased. Abnormal perfusion results were present in 7.8% of pre-liver transplant patients compared to 34.3% of all other patients. In a multivariate model, age and lower ejection fraction were associated with an abnormal MPI result. Of the 64 patients who underwent subsequent invasive or non-invasive coronary angiography after an abnormal MPI, obstructive CAD was diagnosed in 25 patients (1.0%), non-obstructive CAD was diagnosed in 23 patients (0.9%), and normal coronaries found in 16 patients (0.6%); a total of 18 (0.7%) of these underwent coronary revascularization. The average time to repeat testing was 27.2 ± 17.9 months. In a multivariate model, younger age and exercise stress were associated with repeat testing. In only 17 patients out of 271 with a normal initial perfusion, the repeat study became abnormal. The use of stress-first imaging was successful in 80% of patients with a reduction in Tc-99m dose from 39.1 to 18.3 mCi. CONCLUSION: Abnormal SPECT MPI results in candidates for liver transplantation are infrequent compared to non-liver transplant patients and the incidence of obstructive CAD on subsequent angiography even less. Repeat testing in those on the transplant waiting list after initial normal test results appears to be of limited value. Stress-first protocols may be considered for the majority of these patients to reduce testing time and radiation exposure.

Investigation of emission characteristics of NMVOCs over urban site of western India.

This is the first study to characterize the variation and emission of C2-C5 non-methane volatile organic compounds (NMVOCs) in a semi-urban site of western India based on measurements during February-December 2015. Anthropogenic NMVOCs show clear seasonal dependence with highest in winter and lowest in monsoon season. Biogenic NMVOCs likes isoprene show highest mixing ratios in the pre-monsoon season. The diurnal variation of NMVOC species can be described by elevated values from night till morning and lower values in the afternoon hours. The elevated levels of NMVOCs during night and early morning hours were caused mainly by weaker winds, temperature inversion and reduced chemical loss. The correlations between NMVOCs, CO and NOx indicate the dominant role of various local emission sources. Use and leakage of liquefied petroleum gas (LPG) contributed to the elevated levels of propane and butanes. Mixing ratios of ethylene, propylene, CO, NOx, etc. show predominant emissions from combustion of fuels in automobiles and industries. The Positive Matrix Factorization (PMF) source apportionments were performed for the seven major emission sectors (i.e. Vehicular exhaust, Mixed industrial emissions, Biomass/Fired brick kilns/Bio-fuel, Petrochem, LPG, Gas evaporation, Biogenic). Emissions from vehicle exhaust and industry-related sources contributed to about 19% and 40% of the NMVOCs, respectively. And the rest (41%) was attributed to the emissions from biogenic sources, LPG, gasoline evaporation and biomass burning. Diurnal and seasonal variations of NMVOCs were controlled by local emissions, meteorology, OH concentrations, long-range transport and planetary boundary layer height. This study provides a good reference for framing environmental policies to improve the air quality in western region of India.

Oral bacterial flora and oral cancer: The possible link?

Oral cancer exhibits multifactorial etiology with tobacco and alcohol long been implicated as the primary risk factors. In addition, betel nut, dietary factors and poor oral hygiene have also been found to have a role in the etiology of oral cancer. Past research has uncovered a great deal of information regarding the association of exogenous bacteria with cancer. However, our definitive knowledge of the oral commensal bacteria and oral cancer link remains inadequate. In the present article, we hypothesize a causal role for oral bacterial flora in oral cancer although an indirect one. We propose that the normal bacterial flora in conjunction with the already established risk factors such as alcohol consumption may play a role in cancer development. The continued exploration of this topic may aid in better understanding of the pathogenesis of oral cancer thereby helping in appropriate treatment and better prognosis.

Contribution of biogenic and photochemical sources to ambient VOCs during winter to summer transition at a semi-arid urban site in India.

This paper presents the sources and characteristics of ambient volatile organic compounds (VOCs) measured using PTR-TOF-MS instrument in a metropolitan city of India during winter to summer transition period. Mixing ratios of VOCs exhibited strong diurnal, day-to-day and episodic variations. Methanol was the most dominant species with monthly mean values of 18-22 pbbv. The emission ratios of VOCs relative to benzene calculated from nighttime data were used to estimate the relative contributions of vehicle exhaust and other sources. The increasing daytime ratios of oxygenated-VOCs (OVOCs)/benzene and isoprene/benzene from February to March indicates increasing contribution of photo-oxidation and biogenic sources. Daytime fractions of acetone (18%), acetaldehyde (15%) and isoprene (4.5%) to the sum of measured VOCs in March were higher than those in February. Variations of VOCs at lower temperatures (<25 °C) were predominantly controlled by anthropogenic sources. At high temperatures, particularly in the range of 32-40 °C during March, levels of OVOCs and isoprene were influenced by biogenic emissions. The emissions of OVOCs from vehicle exhaust were estimated to be smaller (20-40%) than those from other sources. The contributions of biogenic and secondary sources to OVOCs and isoprene increased by 10-15% from winter to summer. This study provides evidence that the winter-to-summer transition has an impact on sources and composition of VOCs in tropical urban areas.

Ambient particulate matter and carbon monoxide at an urban site of India: Influence of anthropogenic emissions and dust storms.

Continuous measurements of PM2.5, PM10 and CO were conducted at an urban site of Udaipur in India from April 2011 to March 2012. The annual mean concentrations of PM2.5, PM10 and CO were 42 ± 17 µg m-3, 114 ± 31 µg m-3 and 343 ± 136 ppbv, respectively. Concentrations of both particulate and CO showed high values during winter/pre-monsoon (dry) period and lowest in the monsoon season (wet). Local anthropogenic emission and long-range transport from open biomass burning sources along with favourable synoptic meteorology led to elevated levels of pollutants in the dry season. However, higher values of PM10/PM2.5 ratio during pre-monsoon season were caused by the episodes of dust storm. In the monsoon season, flow of cleaner air, rainfall and negligible emissions from biomass burning resulted in the lowest levels of pollutants. The concentrations of PM2.5, PM10 and CO showed highest values during morning and evening rush hours, while lowest in the afternoon hours. In winter season, reductions of PM2.5, CO and PM10 during weekends were highest of 15%, 13% and 9%, respectively. In each season, the highest PM2.5/PM10 ratio coincided with the highest concentrations of pollutants (CO and NOX) indicating predominant emissions from anthropogenic sources. Exceptionally high concentrations of PM10 during the episode of dust storm were due to transport from the Arabian Peninsula and Thar Desert. Up to ∼32% enhancements of PM10 were observed during strong dust storms. Relatively low levels of O3 and NOx during the storm periods indicate the role of heterogeneous removal.

Extracellular matrix in oral squamous cell carcinoma: Friend or foe?

BACKGROUND: Oral squamous cell carcinoma (OSCC) primarily spreads through direct invasion and/or lymphatic route. During the invasion, tumor cells break through the basement membrane, penetrate the connective tissue to interact with the extracellular matrix (ECM). An attempt was made to evaluate the connective tissue changes in different grades of OSCCs and their influence in predicting the biological behavior of these tumors. MATERIALS AND METHODS: A total of 30 histologically proven cases comprising 5 normal mucosa, 10 well-differentiated OSCC's, 10 moderately differentiated OSCC's, and 5 poorly differentiated OSCC's were examined for the presence of any ECM changes by using special stains. Interpretation of staining intensity was carried out and statistically analyzed. RESULTS: Van Gieson stain showed abundant thick collagen fibers, dispersed collagen fibers, thin few dispersed collagen fibers in well-, moderately- and poorly-differentiated OSCC's, respectively. Verhoeff's Van-Gieson showed negative staining for elastic fibers around tumor islands in different grades of OSCCs. PAS stain showed moderate staining for glycoprotein in well-differentiated OSCC and negative in moderately and poorly differentiated cases. Picrosirius red stain showed Type 1 collagen fibers in well and moderately differentiated OSCC cases and Type 3 collagen fibers in poorly differentiated cases. CONCLUSION: The observations of this study revealed altered staining reactions of the collagenous stroma and glycoproteins suggesting that tumor cells may release certain enzymes that play a role in the manipulation of ECM to enhance their own survival.

Spindle Cell Carcinoma of the Mandibular Gingiva - A Case Report.

Spindle cell carcinoma is a malignancy of epithelial origin often mimicking its mesenchymal counterpart thus posing a diagnostic challenge. It is a rare biphasic malignant tumour mostly encountered in the upper aerodigestive tract. The chief differential diagnoses of spindle cell carcinoma are true superficial sarcomas and they especially need to be differentiated from fibrosarcoma. This presentation reports a spindle cell carcinoma of the gingiva and highlights the difficulties encountered in the diagnosis. It also emphasizes the importance of accurate and thorough diagnosis of malignant spindle cell lesions to determine the appropriate therapeutic modality.

Prenatal exposure to a novel antipsychotic quetiapine: impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats.

Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat.

Drug labeling and exposure in neonates.

IMPORTANCE: Federal legislation has led to a notable increase in pediatric studies submitted to the Food and Drug Administration (FDA), resulting in new pediatric information in product labeling. However, approximately 50% of drug labels still have insufficient information on safety, efficacy, or dosing in children. Neonatal information in labeling is even scarcer because neonates comprise a vulnerable subpopulation for which end-point development is lagging and studies are more challenging. OBJECTIVE: To quantify progress made in neonatal studies and neonatal information in product labeling as a result of recent legislation. DESIGN, SETTING, AND PARTICIPANTS: We identified a cohort of drug studies between 1997 and 2010 that included neonates as a result of pediatric legislation using information available on the FDA website. We determined what studies were published in the medical literature, the legislation responsible for the studies, and the resulting neonatal labeling changes. We then examined the use of these drugs in a cohort of neonates admitted to 290 neonatal intensive care units (NICUs) (the Pediatrix Data Warehouse) in the United States from 2005 to 2010. EXPOSURE: Infants exposed to a drug studied in neonates as identified by the FDA website. MAIN OUTCOMES AND MEASURES: Number of drug studies with neonates and rate of exposure per 1000 admissions among infants admitted to an NICU. RESULTS: In a review of the FDA databases, we identified 28 drugs studied in neonates and 24 related labeling changes. Forty-one studies encompassed the 28 drugs, and 31 (76%) of these were published. Eleven (46%) of the 24 neonatal labeling changes established safety and effectiveness. In a review of a cohort of 446,335 hospitalized infants, we identified 399 drugs used and 1,525,739 drug exposures in the first 28 postnatal days. Thirteen (46%) of the 28 drugs studied in neonates were not used in NICUs; 8 (29%) were used in fewer than 60 neonates. Of the drugs studied, ranitidine was used most often (15,627 neonates, 35 exposures per 1000 admissions). CONCLUSIONS AND RELEVANCE: Few drug labeling changes made under pediatric legislation include neonates. Most drugs studied are either not used or rarely used in US NICUs. Strategies to increase the study of safe and effective drugs for neonates are needed.

Prenatal exposure of a novel antipsychotic aripiprazole: impact on maternal, fetal and postnatal body weight modulation in rats.

Nearly all atypical antipsychotic drugs (AAPDs) of second- generation are associated with body weight gain in adults with prolonged exposure; but reports on third-generation AAPDs like Aripiprazole (ARI) and weight gain are scanty and ambiguous. This may be attributed to some unknown mechanism of action, the study of which is essential to investigate gestational exposure of equivalent therapeutic doses of ARI on maternal and fetal weight gain and its longlasting impact on postnatal development and growth of offspring in rodent model. 30 pregnant Wistar rats were exposed to selected doses (2mg, 3mg and 5mg/kg BW) of ARI from GD3-21 orally, with control subjects. Half of the pregnant subjects of each group were sacrificed at GD22 and rest dams were allowed to deliver normally and pups were reared postnatally up to 10 weeks of age. In ARI treated groups, there was no substantial alteration of body weight gain and food intake in pregnant subjects while significant reduction was found in fetal and postnatal (pre-and post weaning) body weight gain. ARI was found neutral for substantial weight gain in pregnant rats but may induce significant weight loss in fetuses, creating long-lasting negative impact on offspring growth (in weight) till PND70. Therefore, ARI could be a good alternative of second- generation AAPDs for adult females but may not be safe for developing fetuses and offspring.

Association of single nucleotide polymorphisms in vascular endothelial growth factor gene with bladder cancer risk.

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific potent mitogen involved in a number of pathologic processes, including angiogenesis, tumor growth, and metastasis. Polymorphisms of VEGF gene have been associated with susceptibility to several cancers. VEGF gene susceptibility to bladder cancer (BC), however, still remains controversial. We analyzed association of the -2578C/A, -7C/T, -2549I/D, and -1001G/C polymorphism of the VEGF gene with bladder cancer (BC) risk and interaction of these polymorphisms with lifestyle and demographic factors. We genotyped -2578C/A, -7C/T, -2549I/D and -1001G/C by PCR-restriction fragment length polymorphism and amplification refractory mutation specific method to evaluate risk in 200 BC patients and 250 healthy controls from North Indian population. Significant association for BC risk in heterozygous CA genotype (1.69-fold) in VEGF-2578C/A and heterozygous genotype of VEGF-1001G/C (p = 0.032) was observed. Interestingly, VEGF-2549I/D genotype showed reduced risk for BC. The gene-gene combination analysis revealed DD-GG with reduced risk (p = 0.018) of VEGF-2549I/D and VEGF-1001G/C, and combination CA-GG of VEGF-2578C/A and VEGF-1001G/C demonstrated 1.75-fold risk for BC. Our findings suggested that polymorphism -2578C/A and -1001G/C in the promoter of VEGF gene may play a significant role in mediating the bladder cancer risk, whereas VEGF-2549I/D genotype appears to be protective for BC.

Treatment and prophylaxis of invasive candidiasis.

Invasive candidiasis (IC) is a leading cause of morbidity and mortality in preterm infants. Even if successfully treated, IC can cause significant neurodevelopmental impairment. Preterm infants are at increased risk for hematogenous Candida meningoencephalitis owing to increased permeability of the blood-brain barrier, so antifungal treatment should have adequate central nervous system penetration. Amphotericin B deoxycholate, lipid preparations of amphotericin B, fluconazole, and micafungin are first-line treatments of IC. Fluconazole prophylaxis reduces the incidence of IC in extremely premature infants, but its safety has not been established for this indication, and as yet, the product has not been shown to reduce mortality in neonates. Targeted prophylaxis may have a role in reducing the burden of disease in this vulnerable population.