exposure Child Exposure to Parental Violence and Psychological Distress Associated With Delayed Milestones By pediatrics.aappublications.org Published On :: 2013-11-04T00:07:14-08:00 It has previously been shown that exposure to intimate partner violence and/or parental depression or anxiety may increase a child’s risk for specific adverse health outcomes.By using a large pediatric primary care sample, this study examined associations of child exposure to intimate partner violence and parental psychological distress with developmental milestone attainment by analyzing their combined and separate effects while adjusting for other family factors. (Read the full article) Full Article
exposure Reducing Children's Exposure to Secondhand Smoke at Home: A Randomized Trial By pediatrics.aappublications.org Published On :: 2013-11-04T00:07:11-08:00 The World Health Organization estimates that ~700 million children breathe tobacco smoke polluted air, particularly at home. Educational strategies either directly or indirectly targeting household decision-makers through other family members are effective in reducing children's exposure in private homes.Intensive intervention was effective in decreasing children’s personal exposure to secondhand smoke (SHS), educating mothers about SHS, and promoting smoking restrictions at home. However, superiority over minimal intervention to decrease children’s personal exposure to SHS was not statistically significant. (Read the full article) Full Article
exposure Health Care Worker Exposures to Pertussis: Missed Opportunities for Prevention By pediatrics.aappublications.org Published On :: 2013-12-16T00:07:03-08:00 The incidence of pertussis has significantly increased, and infection can result in severe disease among young children. This highly contagious disease may frequently be transmitted in pediatric health care settings, necessitating effective infection control practices to reduce exposure risk.Despite institutional guidelines, pediatric health care workers (HCWs) are frequently exposed to pertussis because of delayed or incomplete adherence to infection control practices. Inconsistent reporting may also result in missed HCW exposures, increasing the risk of subsequent transmission to patients. (Read the full article) Full Article
exposure Infant Self-Regulation and Early Childhood Media Exposure By pediatrics.aappublications.org Published On :: 2014-04-14T00:07:31-07:00 Several studies suggest that excessive media use in early childhood predicts poorer developmental outcomes. It has not been studied whether infants with self-regulation problems, who may be at higher developmental risk, develop excessive media use habits.This study shows that infants and toddlers with self-regulation difficulties (ie, problems with self-soothing, sleep, emotional regulation, and attention) view more media at 2 years of age, independent of other important confounders. (Read the full article) Full Article
exposure Parental Smoking Exposure and Adolescent Smoking Trajectories By pediatrics.aappublications.org Published On :: 2014-05-12T00:06:53-07:00 It is well-established that parental smoking is associated with adolescent smoking initiation and regular tobacco use. However, we know less about how exposure to specific types of parental smoking affect adolescent smoking and progression to regular smoking in young adulthood.Among adolescents with parents who are nicotine dependent, each previous year of parental smoking increases the likelihood they will be in a heavy smoking trajectory. Parental smoking cessation early in their children’s life is critical to prevent smoking in families. (Read the full article) Full Article
exposure Prenatal Tobacco Exposure and Cotinine in Newborn Dried Blood Spots By pediatrics.aappublications.org Published On :: 2014-05-12T00:06:52-07:00 Cotinine assays for dried blood spots have been developed but not deployed in a large sample of newborn specimens.Cotinine levels consistent with active maternal smoking were detectable in 12% of newborn blood spots, although 41% of the mothers reportedly did not smoke. Data confirm that reported smoking during pregnancy is an imperfect measure of prenatal tobacco smoke exposure. (Read the full article) Full Article
exposure Exposure to Electronic Cigarette Television Advertisements Among Youth and Young Adults By pediatrics.aappublications.org Published On :: 2014-06-02T00:06:37-07:00 Electronic cigarettes have unknown health risks and youth and young adults increasingly use them. E-cigarette companies are marketing e-cigarettes using television ads. The content of these ads may appeal to young people because they emphasize themes of independence and maturity.E-cigarette companies advertise to a broad television audience that includes 24 million youth. The reach and frequency of these ads increased dramatically between 2011 and 2013. If current trends continue, youth awareness and use of e-cigarettes are likely to increase. (Read the full article) Full Article
exposure Disparities in Early Exposure to Book Sharing Within Immigrant Families By pediatrics.aappublications.org Published On :: 2014-06-02T00:06:37-07:00 Parents in disadvantaged households are less likely to book share with their children during early childhood. These children are more likely to enter school with delays in emergent literacy and language skills, apparent as early as the age of 3.This study examines the effect of parental immigrant status as a predictor of reading and sharing books with children. This research disentangles immigrant status from other variables thought to explain disparities in familial practices related to emergent literacy. (Read the full article) Full Article
exposure Pre- and Postnatal Exposure to Parental Smoking and Allergic Disease Through Adolescence By pediatrics.aappublications.org Published On :: 2014-08-18T00:07:03-07:00 Exposure to second-hand tobacco smoke during pregnancy and infancy has been linked to development of asthma, rhinitis, and eczema in young children. It is unclear whether these risks persist into adolescence.Exposure to second-hand smoke in utero or during infancy influences the development of allergic disease up to adolescence. Excess risks for asthma and rhinitis were seen primarily in early childhood, whereas those for eczema occurred at later ages. (Read the full article) Full Article
exposure Pediatric Exposure to Laundry Detergent Pods By pediatrics.aappublications.org Published On :: 2014-11-10T00:06:18-08:00 Case studies, abstracts, and small-sample research studies have shown that laundry detergent pods pose important poisoning risks to young children.From 2012 through 2013, 17 230 children exposed to laundry detergent pods were reported to US poison control centers. Among children exposed, 4.4% were hospitalized and 7.5% experienced a moderate or major medical outcome, including 1 confirmed death. (Read the full article) Full Article
exposure Postnatal Growth Following Prenatal Lead Exposure and Calcium Intake By pediatrics.aappublications.org Published On :: 2014-11-24T00:06:59-08:00 Lead is an ubiquitous environmental pollutant, and no safe threshold for blood lead level in children has been discovered yet. Prenatal lead exposure affects growth of children.Low level of prenatal lead exposure of <5.0 μg/dL affects postnatal children’s growth, which was further intensified by low calcium intake. (Read the full article) Full Article
exposure Misdiagnosis and Missed Diagnoses in Foster and Adopted Children With Prenatal Alcohol Exposure By pediatrics.aappublications.org Published On :: 2015-01-12T00:05:25-08:00 Researchers speculate that children with fetal alcohol spectrum disorders often are not recognized or diagnosed correctly.This is the first study to assess the rate of missed diagnoses and misdiagnosis in foster and adopted children with fetal alcohol spectrum disorders. (Read the full article) Full Article
exposure Antibiotic Exposure in Infancy and Risk of Being Overweight in the First 24 Months of Life By pediatrics.aappublications.org Published On :: 2015-03-30T00:05:22-07:00 Subtherapeutic doses of antibiotics have been used as growth promoters in animal farming since the 1950s. Antibiotic exposure during infancy is associated with increased body mass in humans.The weight-promoting effect of antibiotics is most pronounced when the exposure occurs at <6 months of age or repeatedly during infancy. Increased body mass is distinctly associated with exposure to cephalosporins and macrolides, especially in boys. (Read the full article) Full Article
exposure Early Psychosocial Exposures, Hair Cortisol Levels, and Disease Risk By pediatrics.aappublications.org Published On :: 2015-05-04T00:05:18-07:00 Early psychosocial exposures are increasingly recognized as crucial to health throughout life. A possible mechanism is physiologic dysregulation due to stress. Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal axis activity.Added early psychosocial exposures seem to increase infant long-term hypothalamic-pituitary-adrenal axis activity and risk of common childhood diseases in a cumulative manner, supporting the model of physiologic dysregulation as a plausible mechanism through which early detrimental exposures determine health outcomes. (Read the full article) Full Article
exposure Antibiotic Exposure and Juvenile Idiopathic Arthritis: A Case-Control Study By pediatrics.aappublications.org Published On :: 2015-07-20T00:07:28-07:00 The etiology of juvenile idiopathic arthritis (JIA) is poorly understood. A recent study suggested a link between antibiotics and JIA but did not examine the potential for confounding from infections or the role of antibiotic timing.Antibiotics were associated with newly diagnosed JIA in a dose- and time-dependent manner after adjusting for infection and other confounders. Antibiotics may play a role in the pathogenesis of JIA. (Read the full article) Full Article
exposure Trends in Emergency Department Visits for Unsupervised Pediatric Medication Exposures, 2004-2013 By pediatrics.aappublications.org Published On :: 2015-09-07T00:07:56-07:00 Unsupervised medication exposures increased during the previous decade, despite child-resistant packaging and caregiver education. To achieve the Healthy People 2020 objective of reducing emergency department visits for unintentional pediatric medication overdoses, targeted interventions including improved safety packaging may be needed.Since 2010, emergency department visits for unsupervised medication exposures started to decrease. Most visits involved solid dose medications, typically for adult use. Most liquid medication exposure visits involved 4 over-the-counter pediatric products and may be more readily amenable for interventions. (Read the full article) Full Article
exposure Exposure and Use of Mobile Media Devices by Young Children By pediatrics.aappublications.org Published On :: 2015-11-02T00:06:44-08:00 Interactive mobile media devices have revolutionized children’s access to and experience of media, but research is lagging behind its adoption. A critical first step is to understand when and how young children adopt mobile media devices.Our study found almost universal exposure, early adoption, and use of mobile media devices among young children in an urban, low-income, minority community. Studies are needed to update guidelines on the use of mobile media by young children. (Read the full article) Full Article
exposure Population Pharmacokinetics and Exposure-Response Relationships of Baloxavir Marboxil in Patients Infected with Influenza at High Risk of Influenza Complications [Clinical Therapeutics] By aac.asm.org Published On :: 2020-04-20T08:36:47-07:00 Baloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor, baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11846 plasma concentration data items from 1827 subjects including 2341 plasma concentration data items from 664 patients at high risk of influenza complications. A three-compartment model with first-order elimination and first-order absorption with lag time well described the plasma concentration data. Body weight and race were found to be the most important factors influencing clearance and volume of distribution. The exposures in high-risk patients were similar to those in otherwise healthy patients, and no pharmacokinetic difference was identified regarding any risk factors for influenza complications.Exposure-response analyses were performed regarding the time to improvement of symptoms and the reduction in the influenza virus titer in high-risk patients. The analyses suggested that body weight-based dosage, 40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg, can shorten the time to improvement of influenza symptoms and reduce virus titer for both type A and B influenza virus regardless of the exposure levels of the high-risk patients as well as for the otherwise healthy influenza patients.The results of our population pharmacokinetic and exposure-response analyses in patients with risk factors of influenza complications should provide useful information on the pharmacokinetic and pharmacodynamic characteristics of baloxavir marboxil and also for the optimization of dose regimens. Full Article
exposure Optimal dose or optimal exposure? Consideration for linezolid in tuberculosis treatment [Letters] By aac.asm.org Published On :: 2020-05-04T08:49:24-07:00 Exploring different ways of minimising linezolid toxicity without compromising efficacy is a major quest in the treatment of drug resistant tuberculosis (TB).... Full Article
exposure Reply to Kim et al., "Optimal Dose or Optimal Exposure? Consideration for Linezolid in Tuberculosis Treatment" [Author Reply] By aac.asm.org Published On :: 2020-05-04T08:49:24-07:00 We thank Kim and colleagues for their interest in our study.... Full Article
exposure DPH Announces Potential Hepatitis A Exposure at Food Establishment in Middletown By news.delaware.gov Published On :: Thu, 11 Apr 2019 21:18:37 +0000 Updated Information: DPH Announces Potential Exposure at Two Additional Food Establishments and Updated Timeline DOVER – The Division of Public Health (DPH) announced today that employees and patrons of Buffalo Wild Wings located at 540 W. Main St., Middletown, may have been exposed to the hepatitis A virus between March 31 and April 10, 2019. When […] Full Article Delaware Health and Social Services Division of Public Health News Delaware public health Hepatitis A infectious disease
exposure Hepatitis A Exposure Update: DPH Announces Potential Exposure at Two Additional Food Establishments, Updated Timeline By news.delaware.gov Published On :: Sat, 13 Apr 2019 03:06:32 +0000 he Division of Public Health (DPH) is providing updated information regarding a potential Hepatitis A exposure at a Buffalo Wild Wings food establishment in Middletown, which was announced on Thursday, April 11, 2019. Full Article Delaware Health and Social Services Division of Public Health News food safety Hepatitis A public health
exposure Milford Woman Charged with Animal Cruelty After Dog Dies From Excessive Heat Exposure, Tethering By news.delaware.gov Published On :: Wed, 24 Jul 2019 20:31:31 +0000 fficers from the Delaware Division of Public Health (DPH) Office of Animal Welfare (OAW) arrested a Milford woman on Tuesday July 23, 2019, following the death of a dog that was tethered outside of a home during dangerously hot temperatures. Full Article Delaware Health and Social Services Division of Public Health News animal control animal cruelty Delaware Animal Services heat safety Office of Animal Welfare pet safety
exposure Vizag gas leak explained: What exactly is styrene gas and how does exposure to it affect human body? By www.financialexpress.com Published On :: 2020-05-07T18:09:00+05:30 Vizag gas leak shocks the nation! India, yet again, has had to face another gas tragedy at a time when people are already grappling with Coronavirus pandemic. Full Article Health Lifestyle
exposure Visakhapatnam gas leak: AIIMS director says long-term health effects due to styrene vapour exposure small By www.financialexpress.com Published On :: 2020-05-07T19:21:00+05:30 Guleria said inhalation and ingestion of styrene can cause effect the skin and the eyes. Full Article Health Lifestyle
exposure ICICI Bank confirms $100-m exposure to troubled Singapore oil firm Hin Leong Trading By www.financialexpress.com Published On :: 2020-04-22T04:15:00+05:30 The regulatory norms with respect to provisioning and asset recognition are uniform for Indian banks’ domestic and foreign exposures. Full Article Banking & Finance Industry
exposure Banks set to declare Cox and Kings exposure as ‘fraud’ account By www.financialexpress.com Published On :: 2020-04-30T00:50:00+05:30 This classification will require banks to make provisions of 100% of the total amount due to them as per Reserve Bank of India (RBI) guidelines. Full Article Banking & Finance Industry
exposure Small Businesses Tapping COVID-19 Loans Hit With Data Exposure By packetstormsecurity.com Published On :: Wed, 22 Apr 2020 15:05:07 GMT Full Article headline government privacy usa virus data loss
exposure Prosecuted for COVID-19 exposure of employees REALLY? By www.eversheds.com Published On :: 2020-03-19 Amidst the attention grabbing hysteria of Coronavirus headlines, some commentators have speculated that employers may be about to face prosecution if they don’t take all precautions possible to protect staff and third parties from infection. I... Full Article
exposure Foreign-Currency Exposures and the Financial Channel of Exchange Rates: Eroding Monetary Policy Autonomy in the Asia and Pacific Region? By feedproxy.google.com Published On :: 2020-04-13 00:00:00 Foreign-currency exposures on an economy’s external balance sheet may jeopardize financial stability when the exchange rate depreciates. Full Article
exposure Foreign-Currency Exposures and the Financial Channel of Exchange Rates: Eroding Monetary Policy Autonomy in the Asia and Pacific Region? By www.adb.org Published On :: 2020-04-13 00:00:00 Foreign-currency exposures on an economy’s external balance sheet may jeopardize financial stability when the exchange rate depreciates. Full Article
exposure FDA commissioner in self-quarantine after exposure to person with COVID-19 By feeds.reuters.com Published On :: Sat, 09 May 2020 00:38:14 -0400 U.S. Food and Drug Administration Commissioner Stephen Hahn is in self-quarantine for a couple of weeks after coming into contact with someone who tested positive for COVID-19, an FDA spokesman told Reuters late on Friday. Full Article topNews
exposure Health Tip: Prevent Exposure to Poison Ivy By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Health Tip: Prevent Exposure to Poison IvyCategory: Health NewsCreated: 4/27/2010 8:10:00 AMLast Editorial Review: 4/27/2010 12:00:00 AM Full Article
exposure Selenium Helped Cells 'Reboot' After Exposure to Cancer-Causing Chemicals By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Selenium Helped Cells 'Reboot' After Exposure to Cancer-Causing ChemicalsCategory: Health NewsCreated: 4/27/2010 2:10:00 PMLast Editorial Review: 4/28/2010 12:00:00 AM Full Article
exposure Prenatal Pesticide Exposure May Harm Kids' Brains By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Prenatal Pesticide Exposure May Harm Kids' BrainsCategory: Health NewsCreated: 5/1/2012 11:01:00 AMLast Editorial Review: 5/1/2012 12:00:00 AM Full Article
exposure Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine [Neuroscience] By www.pnas.org Published On :: 2020-05-05T10:31:24-07:00 The initial response to an addictive substance can facilitate repeated use: That is, individuals experiencing more positive effects are more likely to use that drug again. Increasing evidence suggests that psychoactive cannabinoid use in adolescence enhances the behavioral effects of cocaine. However, despite the behavioral data, there is no neurobiological... Full Article
exposure Habituation of the cardiovascular response to restraint stress is inhibited by exposure to other stressor stimuli and exercise training [RESEARCH ARTICLE] By jeb.biologists.org Published On :: 2020-04-23T22:21:31-07:00 Ricardo Benini, Leandro A. Oliveira, Lucas Gomes-de-Souza, Bruno Rodrigues, and Carlos C. Crestani This study evaluated the effect of exposure to either a chronic variable stress (CVS) protocol or social isolation, as well as treadmill exercise training, in the habituation of the cardiovascular response upon repeated exposure to restraint stress in rats. The habituation of the corticosterone response to repeated restraint stress was also evaluated. For this, animals were subjected to either acute or 10 daily sessions of 60 min of restraint stress. CVS and social isolation protocols lasted for 10 consecutive days, whereas treadmill training was performed for 1 h per day, 5 days per week for 8 weeks. We observed that the increase in serum corticosterone was reduced during both the stress and the recovery period of the 10th session of restraint. Habituation of the cardiovascular response was identified in terms of a faster return of heart rate to baseline values during the recovery period of the 10th session of restraint. The increase in blood pressure and the decrease in tail skin temperature were similar at the 1st and 10th session of restraint. Exposure to CVS, social isolation or treadmill exercise training inhibited the habituation of the restraint-evoked tachycardia. Additionally, CVS increased the blood pressure response at the 10th session of restraint, whereas social isolation enhanced both the tachycardia during the first session and the drop in skin temperature at the 10th session of restraint. Taken together, these findings provide new evidence that pathologies evoked by stress might be related to impairment in the habituation process to homotypic stressors. Full Article
exposure Skeletal muscle thermogenesis induction by exposure to predator odor [RESEARCH ARTICLE] By jeb.biologists.org Published On :: 2020-04-16T05:19:55-07:00 Erin Gorrell, Ashley Shemery, Jesse Kowalski, Miranda Bodziony, Nhlalala Mavundza, Amber R. Titus, Mark Yoder, Sarah Mull, Lydia A. Heemstra, Jacob G. Wagner, Megan Gibson, Olivia Carey, Diamond Daniel, Nicholas Harvey, Meredith Zendlo, Megan Rich, Scott Everett, Chaitanya K. Gavini, Tariq I. Almundarij, Diane Lorton, and Colleen M. Novak Non-shivering thermogenesis can promote negative energy balance and weight loss. In this study, we identified a contextual stimulus that induces rapid and robust thermogenesis in skeletal muscle. Rats exposed to the odor of a natural predator (ferret) showed elevated skeletal muscle temperatures detectable as quickly as 2 min after exposure, reaching maximum thermogenesis of >1.5°C at 10–15 min. Mice exhibited a similar thermogenic response to the same odor. Ferret odor induced a significantly larger and qualitatively different response from that of novel or aversive odors, fox odor or moderate restraint stress. Exposure to predator odor increased energy expenditure, and both the thermogenic and energetic effects persisted when physical activity levels were controlled. Predator odor-induced muscle thermogenesis is subject to associative learning as exposure to a conditioned stimulus provoked a rise in muscle temperature in the absence of the odor. The ability of predator odor to induce thermogenesis is predominantly controlled by sympathetic nervous system activation of β-adrenergic receptors, as unilateral sympathetic lumbar denervation and a peripherally acting β-adrenergic antagonist significantly inhibited predator odor-induced muscle thermogenesis. The potential survival value of predator odor-induced changes in muscle physiology is reflected in an enhanced resistance to running fatigue. Lastly, predator odor-induced muscle thermogenesis imparts a meaningful impact on energy expenditure as daily predator odor exposure significantly enhanced weight loss with mild calorie restriction. This evidence signifies contextually provoked, centrally mediated muscle thermogenesis that meaningfully impacts energy balance. Full Article
exposure Alkaline guts contribute to immunity during exposure to acidified seawater in the sea urchin larva [RESEARCH ARTICLE] By jeb.biologists.org Published On :: 2020-04-06T07:24:08-07:00 Meike Stumpp, Inga Petersen, Femke Thoben, Jia-Jiun Yan, Matthias Leippe, and Marian Y. HuLarval stages of the abulacraria superphylum including echinoderms and hemichordates have highly alkaline midguts. To date the reason for the evolution of such extreme pH conditions in the gut of these organisms remains unknown. Here, we test the hypothesis that analogous to the acidic stomachs of vertebrates, these alkaline conditions may represent a first defensive barrier to protect from environmental pathogens.pH-optimum curves for five different species of marine bacteria demonstrated a rapid decrease in proliferation rates by 50-60% between pH 8.5 and 9.5. Using the marine bacterium Vibrio diazotrophicus which elicits a coordinated immune response in the sea urchin larva of Strongylocentrotus purpuratus, we studied the physiological responses of the midgut pH regulatory machinery to this pathogen. Gastroscopic microelectrode measurements demonstrate a stimulation of midgut alkalization upon infection with V. diazotrophicus accompanied by an upregulation of acid-base transporter transcripts of the midgut. Pharmacological inhibition of midgut alkalization resulted in an increased mortality rate of larvae during Vibrio infection. Reductions in seawater pH resembling ocean acidification (OA) conditions lead to moderate reductions in midgut alkalization. However, these reductions in midgut pH do not affect the immune response and resilience of sea urchin larvae to a Vibrio infection under OA conditions.Our study addressed the evolutionary benefits of the alkaline midgut of ambulacraria larval stages. The data indicate that alkaline conditions in the gut may serve as a first defensive barrier against environmental pathogens and that this mechanism can compensate for changes in seawater pH. Full Article
exposure Thermo-TRPs and gut microbiota are involved in thermogenesis and energy metabolism during low temperature exposure of obese mice [RESEARCH ARTICLE] By jeb.biologists.org Published On :: 2020-04-27T01:37:03-07:00 Jing Wen, Tingbei Bo, Xueying Zhang, Zuoxin Wang, and Dehua WangAmbient temperature and food composition can affect energy metabolism of the host. Thermal transient receptor potential (thermo-TRPs) ion channels can detect temperature signals and are involved in the regulation of thermogenesis and energy homeostasis. Further, the gut microbiota has also been implicated in thermogenesis and obesity. In the present study, we tested the hypothesis that thermo-TRPs and gut microbiota are involved in reducing diet-induced obesity (DIO) during low temperature exposure. C57BL/6J mice in obese (body mass gain >45%), lean (body mass gain <15%), and control (body mass gain<1%) groups were exposed to high (23±1°C) or low (4±1°C) ambient temperature for 28 days. Our data showed that low temperature exposure attenuated DIO, but enhanced brown adipose tissue (BAT) thermogenesis. Low temperature exposure also resulted in increased norepinephrine (NE) concentrations in the hypothalamus, decreased TRP melastatin 8 (TRPM8) expression in the small intestine, and altered composition and diversity of gut microbiota. In DIO mice, there was a decrease in overall energy intake along with a reduction in TRP ankyrin 1 (TRPA1) expression and an increase in NE concentration in the small intestine. DIO mice also showed increases in Oscillospira, [Ruminococcus], Lactococcus, and Christensenella and decreases in Prevotella, Odoribacter, and Lactobacillus at the genus level in fecal samples. Together, our data suggest that thermos-TRPs and gut microbiota are involved in thermogenesis and energy metabolism during low temperature exposure in DIO mice. Full Article
exposure Evaluation of Quantitative Relationship Between Target Expression and Antibody-Drug Conjugate Exposure Inside Cancer Cells [Articles] By dmd.aspetjournals.org Published On :: 2020-04-09T08:02:00-07:00 Antibody-drug conjugates (ADCs) employ overexpressed cell surface antigens to deliver cytotoxic payloads inside cancer cells. However, the relationship between target expression and ADC efficacy remains ambiguous. In this manuscript, we have addressed a part of this ambiguity by quantitatively investigating the effect of antigen expression levels on ADC exposure within cancer cells. Trastuzumab-valine-citrulline-monomethyl auristatin E was used as a model ADC, and four different cell lines with diverse levels of human epidermal growth factor receptor 2 (HER2) expression were used as model cells. The pharmacokinetics (PK) of total trastuzumab, released monomethyl auristatin E (MMAE), and total MMAE were measured inside the cells and in the cell culture media following incubation with two different concentrations of ADC. In addition, target expression levels, target internalization rate, and cathepsin B and MDR1 protein concentrations were determined for each cell line. All the PK data were mathematically characterized using a cell-level systems PK model for ADC. It was found that SKBR-3, MDA-MB-453, MCF-7, and MDA-MB-468 cells had ~800,000, ~250,000, ~50,000, and ~10,000 HER2 receptors per cell, respectively. A strong linear relationship (R2 > 0.9) was observed between HER2 receptor count and released MMAE exposure inside the cancer cells. There was an inverse relationship found between HER2 expression level and internalization rate, and cathepsin B and multidrug resistance protein 1 (MDR1) expression level varied slightly among the cell lines. The PK model was able to simultaneously capture all the PK profiles reasonably well while estimating only two parameters. Our results demonstrate a strong quantitative relationship between antigen expression level and intracellular exposure of ADCs in cancer cells. SIGNIFICANCE STATEMENT In this manuscript, we have demonstrated a strong linear relationship between target expression level and antibody-drug conjugate (ADC) exposure inside cancer cells. We have also shown that this relationship can be accurately captured using the cell-level systems pharmacokinetics model developed for ADCs. Our results indirectly suggest that the lack of relationship between target expression and efficacy of ADC may stem from differences in the pharmacodynamic properties of cancer cells. Full Article
exposure Evidence from a mouse model on the dangers of thirdhand electronic cigarette exposure during early life By openres.ersjournals.com Published On :: 2020-04-19T07:30:11-07:00 Electronic cigarettes (e-cigarettes) have been used in many countries for >10 years and in this time, there has been a division of opinions amongst both the general public and health professionals regarding the benefit or harms of e-cigarettes. Prior to the reporting of a new phenomenon known as vaping-associated pulmonary injury (VAPI), public opinion about the relative harm of e-cigarettes were increasing but they were perceived as less harmful than cigarettes by one third of people [1]. The recent cases of severe illness and death attributable to VAPI were first described in September 2019 [2]. VAPI appears to be related to either the addition of cannabis/cannabis derivates or vitamin E acetate [3], and as such has not caused radical swing away from the use of e-cigarettes without cannabis or cannabis derivates. Full Article
exposure Two-Way Short Message Service (SMS) Communication May Increase Pre-Exposure Prophylaxis Continuation and Adherence Among Pregnant and Postpartum Women in Kenya By ghspjournal.org Published On :: 2020-03-31T15:28:55-07:00 ABSTRACTIntroduction:We evaluated a 2-way short message service (SMS) communication platform to improve continuation of pre-exposure prophylaxis (PrEP) for HIV prevention among Kenyan women who initiated PrEP within routine maternal child health (MCH) and family planning clinics.Methods:We adapted an existing SMS platform (Mobile WACh [mWACh]) to send PrEP-tailored, theory-based SMS and allow clients to communicate with a remote nurse. Women who did not have HIV and who were initiating PrEP at 2 MCH/family planning clinics in Kisumu County, Kenya, from February to October 2018, were offered enrollment into the mWACh-PrEP program; SMS communication was free. We evaluated acceptability, satisfaction, and implementation metrics. In a pre/postevaluation, we compared PrEP continuation at 1-month postinitiation among women who initiated PrEP in the period before (n=166) versus after mWACh-PrEP implementation, adjusting for baseline differences.Results:Of the 334 women who were screened for enrollment into the mWACh-PrEP program; 193 (58%) were eligible and of those, 190 (98%) accepted enrollment. Reasons for ineligibility (n=141) included no phone access (29%) and shared SIM cards (25%). Median age was 25 years (interquartile range=22–30), and 91% were MCH clients. Compared to women who initiated PrEP in the month before mWACh-PrEP implementation, women who enrolled in mWACh-PrEP were more likely to return for their first PrEP follow-up visit (40% vs. 53%; adjusted risk ratio [aRR]=1.26; 95% confidence interval [CI]= 1.06, 1.50; P=.008) and more likely to continue PrEP (22% vs. 43%; aRR=1.75; 95% CI=1.21, 2.55; P=.003). Among those who returned, 99% reported successful receipt of SMS through the mWACh-PrEP system and 94% reported that mWACh-PrEP helped them understand PrEP better. Concerns about PrEP use, how it works, and side effects accounted for the majority (80%) of issues raised by participants using SMS.Conclusions:Two-way SMS expanded support for PrEP and opportunities for dialogue beyond the clinic and enabled women to ask and receive answers in real time regarding PrEP, which facilitated its continued use. Full Article
exposure Impact of Daptomycin Dose Exposure Alone or in Combination with {beta}-Lactams or Rifampin against Vancomycin-Resistant Enterococci in an In Vitro Biofilm Model [Susceptibility] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 Enterococcus faecium strains are commonly resistant to vancomycin and β-lactams. In addition, E. faecium often causes biofilm-associated infections and these infections are difficult to treat. In this context, we investigated the activity of dosing regimens using daptomycin (DAP) (8, 10, 12, and 14 mg/kg of body weight/day) alone and in combination with ceftaroline (CPT), ampicillin (AMP), ertapenem (ERT), and rifampin (RIF) against 2 clinical strains of biofilm-producing vancomycin-resistant Enterococcus faecium (VREfm), namely, strains S447 and HOU503, in an in vitro biofilm model. HOU503 harbors common LiaS and LiaR substitutions, whereas S447 lacks mutations associated with the LiaFSR pathway. MIC results demonstrated that both strains were susceptible to DAP and resistant to CPT, AMP, ERT, and RIF. The 168-h pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor models (simulating human antibiotic exposures) were used with titanium and polyurethane coupons to evaluate the efficacy of antibiotic combinations. DAP 12 and 14 achieved bactericidal activity against S447 but lacked such effect against HOU503. Addition of ERT and RIF enhanced DAP activity, allowing DAP 8 and 10 plus ERT or RIF to produce bactericidal activity against both strains at 168 h. While DAP 8 and 10 plus CPT improved killing, they did not reach bactericidal reduction against S447. Combination of AMP, CPT, ERT, or RIF resulted in enhanced and bactericidal activity for DAP against HOU503 at 168 h. Our data provide further support for the use of combinations of DAP with AMP, ERT, CPT, and RIF in infections caused by biofilm producing VREfm. Further research involving DAP combinations against biofilm-producing enterococci is warranted. Full Article
exposure Novel Insights into Plasmodium vivax Therapeutic Failure: CYP2D6 Activity and Time of Exposure to Malaria Modulate the Risk of Recurrence [Epidemiology and Surveillance] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 Plasmodium vivax relapse is one of the major causes of sustained global malaria transmission. Primaquine (PQ) is the only commercial drug available to prevent relapses, and its efficacy is dependent on metabolic activation by cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 function, caused by allelic polymorphisms, leads to the therapeutic failure of PQ as a radical cure for P. vivax malaria. Here, we hypothesized that the host immune response to malaria parasites modulates susceptibility to P. vivax recurrences in association with CYP2D6 activity. We performed a 10-year retrospective study by genotyping CYP2D6 polymorphisms in 261 malaria-exposed individuals from the Brazilian Amazon. The immune responses against a panel of P. vivax blood-stage antigens were evaluated by serological assays. We confirmed our previous findings, which indicated an association between impaired CYP2D6 activity and a higher risk of multiple episodes of P. vivax recurrence (risk ratio, 1.75; 95% confidence interval [CI], 1.2 to 2.6; P = 0.0035). An important finding was a reduction of 3% in the risk of recurrence (risk ratio, 0.97; 95% CI, 0.96 to 0.98; P < 0.0001) per year of malaria exposure, which was observed for individuals with both reduced and normal CYP2D6 activity. Accordingly, subjects with long-term malaria exposure and persistent antibody responses to various antigens showed fewer episodes of malaria recurrence. Our findings have direct implications for malaria control, since it was shown that nonimmune individuals who do not respond adequately to treatment due to reduced CYP2D6 activity may present a significant challenge for sustainable progress toward P. vivax malaria elimination. Full Article
exposure Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir [Pharmacology] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopinavir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interactions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing <15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of antituberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treatment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with first-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identified: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treatment with rifampin and LPV/r-4:4 but remained within the median adult recommended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure significantly decreased during concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identifier NCT02348177.) Full Article
exposure FDA commissioner in self-quarantine after exposure to person with COVID-19 By feeds.reuters.com Published On :: Sat, 09 May 2020 00:38:14 -0400 U.S. Food and Drug Administration Commissioner Stephen Hahn is in self-quarantine for a couple of weeks after coming into contact with someone who tested positive for COVID-19, an FDA spokesman told Reuters late on Friday. Full Article domesticNews
exposure ICICI Bank tags $100 mn Singapore Hin Leong exposure as NPA, makes provisions - Moneycontrol.com By news.google.com Published On :: Sat, 09 May 2020 13:28:00 GMT ICICI Bank tags $100 mn Singapore Hin Leong exposure as NPA, makes provisions Moneycontrol.comICICI Bank Q4 net up 26% at ₹1,221 cr but misses estimates on virus provisions LivemintICICI Bank Q4 Results: Profit Rises 26% Even As Provisions Nearly Triple BloombergQuintICICI Bank Q4 profit grows by 26%, misses estimates on COVID-19 provisions; NPAs dip Moneycontrol.comICICI Bank Q4 net profit likely to jump to ₹3,510 crore LivemintView Full coverage on Google News Full Article
exposure FDA chief self-quarantines after exposure to Pence aide By www.politico.com Published On :: Sat, 09 May 2020 00:57:24 GMT FDA Commissioner Stephen Hahn is asymptomatic and tested negative for the virus on Friday, one senior administration official said. Full Article
exposure FDA commissioner in self-quarantine after exposure to person with COVID-19 By feeds.reuters.com Published On :: Sat, 09 May 2020 00:38:14 -0400 U.S. Food and Drug Administration Commissioner Stephen Hahn is in self-quarantine for a couple of weeks after coming into contact with someone who tested positive for COVID-19, an FDA spokesman told Reuters late on Friday. Full Article healthNews