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Waterproofing is an essential component in building construction to maintain the integrity of buildings with reduced maintenance cost. A comprehensive waterproofing system is an integrated combination of factors, and includes product selection, membrane detail, substrate preparation, design, installation and maintenance. It is designed to work under different environmental conditions, substrates and applications. Proper understanding of the issues related to waterproofing membrane systems is important to minimise the waterproofing failures in both commercial and residential buildings. This paper aims to discuss Standards and Codes; membrane systems and performance, waterproofing practices, design and installation techniques, inspection and testing and quality assurance adopted by the waterproofing industry in Australia.

Objectives: To describe patterns of medication for opioid use disorder (MOUD) during pregnancies in the opioid use disorder (OUD) cohort of MAT-LINK, a sentinel surveillance network of pregnancies at US clinical sites., Methods: Seven clinical sites providing care for pregnant people with OUD collected electronic health record data. Pregnancies were included in this analysis if (1) the pregnancy outcome occurred between January 2014 and August 2021, (2) the person had OUD, and (3) there was any electronic health record-documented MOUD during pregnancy. Analyses describing MOUD type, demographic characteristics, and timing during pregnancy were performed., Results: Among 3911 pregnancies with any documented MOUD, more than 90% of pregnancies with methadone were to publicly insured people, which was greater than percentages for pregnancies with other MOUD. Buprenorphine with naloxone and naltrexone were two MOUD types that were increasingly common among pregnant people in recent years. In most pregnancies, prenatal care and MOUD were first documented in the same trimester. During the first, second, and third trimesters, there were 37%, 61%, and 91% of pregnancies with MOUD, respectively. Approximately 87% (n = 3412) had only 1 documented MOUD type, versus 2 or 3 types. However, discontinuity in MOUD across trimesters was still observed., Conclusions: In MAT-LINK's OUD cohort, the overall frequency of MOUD improved over the course of pregnancy. Contextual factors, such as insurance status and year of pregnancy outcome, might influence MOUD type. Prenatal care and MOUD might be facilitators for one another; however, there are still opportunities to improve early linkage and continuous access to both prenatal care and MOUD during pregnancy., Competing Interests: KM reports complementary meeting registration when presenting at the Infectious Diseases Society for Obstetrics and Gynecology, American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine. PMS reports funding as a principal investigator from the National Institute on Alcohol Abuse and Alcoholism for Project REACT (neural underpinnings of emotional regulation and drinking to cope); the National Institute on Drug Abuse for Project Vida (prenatal opioid use disorder and posttraumatic stress disorder); and the National Institute of Mental Health for Project Raptor (Attention and Posttraumatic Stress Disorder) and as a coinvestigator from the National Institute on Alcohol Abuse and Alcoholism on Project AsCENd (Neuroimaging of Child Attention Development); the National Institute on Drug Abuse Helping to End Addiction Long-term initiative for Integrative Management of chronic Pain and OUD for Whole Recovery (pain and prenatal opioid use) and for the HEALthy Brain and Child Development study; and relationships with New Mexico Postpartum Support International as a board chair and the New Mexico Perinatal Collaborative as a board member. NSS reports funding from PreTel Inc and Mae Stone Goode for work not related to this report; Natera for consulting fees; UpToDate for writing; and various legal reviews. TW reports funding from Duke University for a National Institutes of Health–funded project on Eating, Sleeping, Consoling for Neonatal Opioid Withdrawal Syndrome (ESC-NOW): a function-based assessment and management approach; the National Institute on Drug Abuse for CADENCE (Continuous and Data-Driven Care); the American Academy of Pediatrics for work as a subject matter expert on maternal-infant health and opioid use; and the National Advanced Practice and Low Risk Neonatal Nurses Conferences for presentations on neonatal opioid withdrawal syndrome. JML reports funding from TD Bank for an institutional grant; Wolters Kluwer for an UpToDate piece on sleep apnea during pregnancy; Hologic for a 1-time fee; Elsevier for serving as a textbook editor; Goldasich, Vick & Fulk for a fee; Sleep Disorder Research Advisory Board for being a member; the National Institutes of Health for work on a personalized integrated chronotherapy for perinatal depression; March of Dimes for travel expenses related to being a board member; Society for Maternal-Fetal Medicine for travel expenses related to being a board member; American Board of Obstetrics and Gynecology for travel expenses related to being a board member; and Preeclampsia Foundation for blood pressure cuffs for her institution. No other potential conflicts of interest were disclosed., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Introduction: As perinatal drug overdoses continue to rise, reliable approaches are needed to monitor overdose trends during pregnancy and postpartum. This analysis aimed to determine the sensitivity, specificity, positive predictive value, and negative predictive value of ICD-9/10-CM codes for drug overdose events among people in the MATernaL and Infant clinical NetworK (MAT-LINK) with medication for opioid use disorder during pregnancy., Methods: People included in this analysis had electronic health record documentation of medication for opioid use disorder and a known pregnancy outcome from January 1, 2014, through August 31, 2021. Data were analyzed during pregnancy through 1 year postpartum. The Centers for Disease Control and Prevention's drug overdose case definitions were used to categorize overdose based on ICD-9/10-CM codes. These codes were compared to abstracted electronic health record data of any drug overdose. Analyses were conducted between May 2023 and May 2024., Results: Among 3,911 pregnancies with electronic health record-documented medication for opioid use disorder, the sensitivity of ICD-9/10-CM codes for capturing drug overdose during pregnancy was 32.7%, while specificity was 98.5%, positive predictive value was 23.4%, and negative predictive value was 99.0%. The sensitivity of ICD-9/10-CM codes for capturing drug overdose postpartum was 30.9%, while specificity was 98.4%, positive predictive value was 25.9%, and negative predictive value was 98.8%., Conclusions: The sensitivity and positive predictive value of ICD-9/10-CM codes for capturing drug overdose compared with abstracted electronic health record data during the perinatal period was low in this cohort of people with medication for opioid use disorder during pregnancy, though the specificity and negative predictive value were high. Incorporating other data from electronic health records and outside the healthcare system might provide more comprehensive insights on nonfatal drug overdose in this population., (Published by Elsevier Inc.)

Mechanosensitive neurons are important sensors of bladder distention, but their role in urologic disease remains unclear. Our current knowledge about how disease alters bladder sensation comes from studies that focus primarily on peptidergic nociceptors, leaving our understanding of neuropeptide-negative mechanoreceptors incomplete. In this study, we found that a substantial proportion of neurofilament heavy (NFH)-positive A fibers innervating the bladder were calcitonin gene-related peptide (CGRP)-negative, potentially representing uncharacterized mechanoreceptors. We then identified two genetic strategies that label mechanoreceptors in mouse skin and confirmed that they likewise label bladder afferents. Cre-mediated tdTomato reporter expression driven by tyrosine kinase B (TrkB), which labels A-delta mechanoreceptors in skin, successfully labeled bladder nerve terminals. The majority of TrkB bladder afferents were CGRP-negative and NFH-positive, with more characteristic staining patterns seen at the level of the cell body. The Ret proto-oncogene also produced robust labeling of bladder afferents, where colocalization with CGRP and NFH was consistent with multiple afferent subtypes. Because TrkB labeling was more specific for putative mechanoreceptors, we directly tested the role of TrkB neurons in bladder mechanosensation in vivo. Using an intersectional genetic strategy, we selectively ablated TrkB afferents and measured bladder responses to mechanical distention using anesthetized cystometry. Compared to controls, mice with ablated TrkB afferents required higher distention pressure to elicit voids. Interestingly, after ablation, distention also increased the frequency of non-voiding contractions, a poorly understood phenotype of several urologic diseases. These genetic strategies comprise critical new tools to advance the study of mechanoreceptors in bladder function and urologic disease pathophysiology.

Internationally, it has been agreed that geologic repositories for spent fuel and radioactive waste are considered the internationally agreed upon solution for intermediate and long-term disposal. In countries where traditional nuclear waste repository host rocks (e.g., clay, salt, granite) are not available, other low permeability lithologies must be studied. Here, chalk is considered to determine its viability for disposal. Despite chalk's low bulk permeability, it may contain fracture networks that can facilitate radionuclide transport. In arid areas, groundwater salinity may change seasonally due to the mixing between brackish groundwater and fresh meteoric water. Such salinity changes may impact the radionuclides' mobility. In this study, radioactive U(VI) and radionuclide simulant tracers (Sr, Ce and Re) were injected into a naturally fractured chalk core. The mobility of tracers was investigated under abrupt salinity variations. Two solutions were used: a low ionic strength (IS) artificial rainwater (ARW; IS ∼0.002) and a high IS artificial groundwater (AGW; IS ∼0.2). During the experiments, the tracers were added to ARW, then the carrier was changed to AGW, and vice versa. Ce was mobile only in colloidal form, while Re was transported as a conservative tracer. Both Re and Ce demonstrated no change in mobility due to salinity changes. In contrast, U and Sr showed increased mobility when AGW was introduced and decreased mobility when ARW was introduced into the core. These experimental results, supported by reactive transport modeling, suggest that saline groundwater solutions promote U and Sr release via ion-exchange and enhance their migration in fractured chalk. The study emphasizes the impact of salinity variations near spent fuel repositories and their possible impact on radionuclide mobility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Cyclobenzaprine is a muscle relaxant indicated for acute pain. Little is known about cyclobenzaprine's safety during pregnancy. We explored the association between maternal cyclobenzaprine exposure and risk of birth defects among offspring., Methods: We combined data from two large, multi-site, population-based case-control studies in the United States. Cases were identified from birth defects registries across 10 states; controls were liveborn infants without birth defects randomly selected from the same catchment areas. Participants reported cyclobenzaprine use during the month before conception through the third month of pregnancy ("periconception") via computer-assisted telephone interview. We used logistic regression to assess associations between periconceptional cyclobenzaprine exposure and selected structural birth defects. We calculated crude odds ratios (OR) with corresponding 95% confidence intervals (CI)., Results: Our study included 33 615 cases and 13 110 controls. Overall, 51 case (0.15%) and 9 control (0.07%) participants reported periconceptional cyclobenzaprine use. We observed increased risk for all seven defects with ≥3 exposed cases: cleft palate (OR = 4.79, 95% CI 1.71-13.44), cleft lip (OR = 2.50, 95% CI 0.89-7.02), anorectal atresia/stenosis (OR = 6.91, 95% CI 1.67, 28.65), d-transposition of the great arteries (OR = 6.97, 95% CI 2.17-22.36), coarctation of the aorta (OR = 5.58, 95% CI 1.88-16.58), pulmonary valve stenosis (OR = 4.55, 95% CI 1.10-18.87), and secundum atrial septal defect (OR = 3.08, 95% CI 0.83-11.45)., Conclusions: Even in our large sample, cyclobenzaprine use was rare. Our estimates are unadjusted and imprecise so should be interpreted cautiously. These hypothesis-generating results warrant confirmation and further research to explore possible mechanisms., (© 2023 John Wiley & Sons Ltd.)

Problem: Medication for opioid use disorder (MOUD) is recommended for persons with opioid use disorder (OUD) during pregnancy. However, knowledge gaps exist about best practices for management of OUD during pregnancy and these data are needed to guide clinical care., Period Covered: 2014-2021., Description of the System: Established in 2019, the Maternal and Infant Network to Understand Outcomes Associated with Medication for Opioid Use Disorder During Pregnancy (MAT-LINK) is a surveillance network of seven clinical sites in the United States. Boston Medical Center, Kaiser Permanente Northwest, The Ohio State University, and the University of Utah were the initial clinical sites in 2019. In 2021, three clinical sites were added to the network (the University of New Mexico, the University of Rochester, and the University of South Florida). Persons receiving care at the seven clinical sites are diverse in terms of geography, urbanicity, race and ethnicity, insurance coverage, and type of MOUD received. The goal of MAT-LINK is to capture demographic and clinical information about persons with OUD during pregnancy to better understand the effect of MOUD on outcomes and, ultimately, provide information for clinical care and public health interventions for this population. MAT-LINK maintains strict confidentiality through robust information technology architecture. MAT-LINK surveillance methods, population characteristics, and evaluation findings are described in this inaugural surveillance report. This report is the first to describe the system, presenting detailed information on funding, structure, data elements, and methods as well as findings from a surveillance evaluation. The findings presented in this report are limited to selected demographic characteristics of pregnant persons overall and by MOUD treatment status. Clinical and outcome data are not included because data collection and cleaning have not been completed; initial analyses of clinical and outcome data will begin in 2023., Results: The MAT-LINK surveillance network gathered data on 5,541 reported pregnancies with a known pregnancy outcome during 2014-2021 among persons with OUD from seven clinical sites. The mean maternal age was 29.7 (SD = ±5.1) years. By race and ethnicity, 86.3% of pregnant persons were identified as White, 25.4% as Hispanic or Latino, and 5.8% as Black or African American. Among pregnant persons, 81.6% had public insurance, and 84.4% lived in urban areas. Compared with persons not receiving MOUD during pregnancy, those receiving MOUD during pregnancy were more likely to be older and White and to have public insurance. The evaluation of the surveillance system found that the initial four clinical sites were not representative of demographics of the South or Southwest regions of the United States and had low representation from certain racial and ethnic groups compared with the overall U.S. population; however, the addition of three clinical sites in 2021 made the surveillance network more representative. Automated extraction and processing improved the speed of data collection and analysis. The ability to add new clinical sites and variables demonstrated the flexibility of MAT-LINK., Interpretation: MAT-LINK is the first surveillance system to collect comprehensive, longitudinal data on pregnant person-infant dyads with perinatal outcomes associated with MOUD during pregnancy from multiple clinical sites. Analyses of clinical site data demonstrated different sociodemographic characteristics between the MOUD and non-MOUD treatment groups., Public Health Actions: MAT-LINK is a timely and flexible surveillance system with data on approximately 5,500 pregnancies. Ongoing data collection and analyses of these data will provide information to support clinical and public health guidance to improve health outcomes among pregnant persons with OUD and their children., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. The Maternal and Infant Network to Understand Outcomes Associated with Medication for Opioid Use Disorder During Pregnancy (MAT-LINK) is funded by the Assistant Secretary for Planning and Evaluation’s Office of the Secretary Patient-Centered Outcomes Research Trust Fund. All clinical site coauthors report funding for MAT-LINK. Katherine A. Sward reports funding from the National Institutes of Health for work with the Helping to End Addiction Long-Term (HEAL) Pain Management Effectiveness Research Network as a Data Coordinating Center. Vikrant G. Deshmukh reports a National Cancer Institute/University of Wisconsin subaward for investigating COVID-19 complications among smokers. Pilar M. Sanjuan reports funding as a principal investigator from the National Institute on Alcohol Abuse and Alcoholism for Project REACT (neural underpinnings of emotional regulation and drinking to cope); the National Institute on Drug Abuse for Project Vida (prenatal opioid use disorder and posttraumatic stress disorder); and the National Institute of Mental Health for Project Raptor (attention and post-traumatic stress disorder) and as a coinvestigator from the National Institute on Alcohol Abuse and Alcoholism on Project AsCENd (neuroimaging of child attention development); the National Institute on Drug Abuse Helping to End Addiction Long-Term initiative for Integrative Management of chronic Pain and OUD for Whole Recovery (pain and prenatal opioid use) and for the HEALthy Brain and Child Development study; and relationships with New Mexico Postpartum Support International as a board chair and the New Mexico Perinatal Collaborative as a board member. Jessie R. Maxwell reports funding from the National Institute on Drug Abuse for work as a coinvestigator on the HEALthy Brain and Childhood Development studies; the National Institutes of Health for work as a Helping to End Addiction Long-Term initiative alternate principal investigator; the National Institute on Alcohol Abuse and Alcoholism for work as a principal investigator on a project; the National Institute on Alcohol Abuse and Alcoholism for work as a coinvestigator on a local project; and the IDeA States Pediatric Clinical Trials Network for work as site principal investigator, work as a junior investigator, and meeting attendance as a member of the leadership committee. Neil S. Seligman reports funding from PreTel Inc. and Mae Stone Goode for work not related to this report; Natera for consulting fees; UpToDate for writing; and various legal reviews. Judette Louis reports funding from TD Bank for an institutional grant; Wolters Kluwer for an UpToDate piece on sleep apnea during pregnancy; Hologic for a one-time fee; Elsevier for serving as a textbook editor; Goldasich, Vick & Fulk for a fee; Sleep Disorder Research Advisory Board for being a member; the National Institutes of Health for work on a personalized integrated chronotherapy for perinatal depression; March of Dimes for travel expenses related to being a board member; Society for Maternal-Fetal Medicine for travel expenses related to being a board member; American Board of Obstetrics and Gynecology for travel expenses related to being a board member; and Preeclampsia Foundation for blood pressure cuffs for her institution. Tanner Wright reports funding from Duke University for a National Institutes of Health–funded project on Eating, Sleeping, Consoling for Neonatal Opioid Withdrawal Syndrome (ESC-NOW): a Function-Based Assessment and Management Approach; the National Institute on Drug Abuse for CADENCE (Continuous and Data-driven Care); the American Academy of Pediatrics for work as a subject matter expert on maternal–infant health and opioid use; and the National Advanced Practice and Low Risk Neonatal Nurses Conferences for presentations on neonatal opioid withdrawal syndrome. No other potential conflicts of interest were disclosed.

Introduction: The objective of this systematic review is to describe polysubstance studies and their prevalence estimates among pregnant people in the US., Methods: This review was not subject to protocol preparation or registration with the International Prospective Register of Systematic Reviews (PROSPERO) because outcome data were not reported. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist was followed. Four scientific literature databases were used to identify articles published from January 1, 2009 to June 3, 2020 reporting prenatal exposure to two or more substances in the US. A standardized process of title and abstract screening followed by a two-phase full-text review was used to assess study eligibility., Results: A total of 119 studies were included: 7 case-control studies, 7 clinical trials, 76 cohort studies, and 29 cross-sectional studies. Studies varied with respect to study design, time period, region, sampling and participant selection, substances assessed, and method of exposure ascertainment. Commonly reported polysubstance prevalence estimates among studies of pregnant people included combinations with alcohol, marijuana, and/or tobacco/nicotine. The range of prevalence estimates was wide (alcohol 1-99%; marijuana 3-95%; tobacco/nicotine 2-95%)., Discussion: Polysubstance use during pregnancy is common, especially with alcohol, marijuana, and/or tobacco/nicotine. Future research to assess polysubstance use during pregnancy could help better describe patterns and ultimately help mitigate its effects on maternal and infant health outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Opioid use disorder (OUD) poses a significant public health concern impacting maternal and infant outcomes. In 2018, the Centers for Disease Control and Prevention (CDC) partnered with the Association of State and Territorial Health Officials (ASTHO) to develop the Opioid use disorder, Maternal outcomes, and Neonatal abstinence syndrome Initiative Learning Community (OMNI LC) to identify and disseminate best practices and strategies for implementing systems-level changes in state health departments to address OUD affecting pregnant and postpartum persons and infants prenatally exposed to opioids. In 2019, the OMNI LC incorporated a field placement approach that assigned temporary field placement staff in five select OMNI LC states to provide important linkages, facilitate information sharing, and strengthen capacity among state and local health departments and other partners supporting maternal and child health communities affected by the opioid crisis. Using an implementation science framework, the field placement approach was assessed using five implementation outcome measures: appropriateness, acceptability, implementation cost, sustainability, and feasibility. Written responses from the participating OMNI LC states on these implementation outcome measures were analyzed to (1) highlight key strategies used by field placement staff, (2) assess the implementation of the OMNI LC field placement approach within the context of implementation science, and (3) identify implementation barriers. This report describes the implementation of a temporary field placement approach and suggests that this approach could be replicated to enhance state and local capacity to respond to the opioid crisis or other high-consequence events.

Manganese superoxide dismutase (MnSOD) acetylation (Ac) has been shown to be a key post-translational modification important in the regulation of detoxification activity in various disease models. We have previously demonstrated that MnSOD lysine-68 (K68) acetylation (K68-Ac) leads to a change in function from a superoxide-scavenging homotetramer to a peroxidase-directed monomer. Here, we found that estrogen receptor positive (ER+) breast cancer cell lines (MCF7 and T47D), selected for continuous growth in cisplatin (CDDP) and doxorubicin (DXR), exhibited an increase in MnSOD-K68-Ac. In addition, MnSOD-K68-Ac, as modeled by the expression of a validated acetylation mimic mutant gene ( MnSOD K68Q ), also led to therapy resistance to CDDP and DXR, altered mitochondrial structure and morphology, and aberrant cellular metabolism. MnSOD K68Q expression in mouse embryo fibroblasts (MEFs) induced an in vitro transformation permissive phenotype. Computerized molecular protein dynamics analysis of both MnSOD-K68-Ac and MnSOD-K68Q exhibited a significant change in charge distribution along the α1 and α2 helices, directly adjacent to the Mn 2+ binding site, implying that this decrease in surface charge destabilizes tetrameric MnSOD, leading to an enrichment of the monomer. Finally, monomeric MnSOD, as modeled by amber codon substitution to generate MnSOD-K68-Ac or MnSOD-K68Q expression in mammalian cells, appeared to incorporate Fe to maximally induce its peroxidase activity. In summary, these findings may explain the mechanism behind the observed structural and functional change of MnSOD-K68-Ac., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To estimate the annual percentage of women of reproductive age with private insurance or Medicaid who had opioid prescription claims during 2013-2017 and describe trends over time., Design: A secondary analysis of insurance claims data from IBM MarketScan® Commercial and Multi-State Medicaid Databases to assess outpatient pharmacy claims for prescription opioids among women aged 15-44 years during 2013-2017., Participants: Annual cohorts of 3.5-3.8 million women aged 15-44 years with private insurance and 0.9-2.1 million women enrolled in Medicaid., Main Outcome Measure: The percentage of women aged 15-44 years with outpatient pharmacy claims for opioid prescriptions., Results: During 2013-2017, the proportion of women aged 15-44 years with private insurance who had claims for opioid prescriptions decreased by 22.1 percent, and among women enrolled in Medicaid, the proportion decreased by 31.5 -percent., Conclusions: Opioid prescription claims decreased from 2013 to 2017 among insured women of reproductive age. However, opioid prescription claims remained common and were more common among women enrolled in Medicaid than those with private insurance; additional strategies to improve awareness of the risks associated with opioid prescribing may be needed.

Despite the widespread study of how injured nerves contribute to chronic pain, there are still major gaps in our understanding of pain mechanisms. This is particularly true of pain resulting from nerve injury, or neuropathic pain, wherein tactile or thermal stimuli cause painful responses that are particularly difficult to treat with existing therapies. Curiously, this stimulus-driven pain relies upon intact, uninjured sensory neurons that transmit the signals that are ultimately sensed as painful. Studies that interrogate uninjured neurons in search of cell-specific mechanisms have shown that nerve injury alters intact, uninjured neurons resulting in an activity that drives stimulus-evoked pain. This review of neuropathic pain mechanisms summarizes cell-type-specific pathology of uninjured sensory neurons and the sensory ganglia that house their cell bodies. Uninjured neurons have demonstrated a wide range of molecular and neurophysiologic changes, many of which are distinct from those detected in injured neurons. These intriguing findings include expression of pain-associated molecules, neurophysiological changes that underlie increased excitability, and evidence that intercellular signaling within sensory ganglia alters uninjured neurons. In addition to well-supported findings, this review also discusses potential mechanisms that remain poorly understood in the context of nerve injury. This review highlights key questions that will advance our understanding of the plasticity of sensory neuron subpopulations and clarify the role of uninjured neurons in developing anti-pain therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Tran and Crawford.)

Pregnant women with opioid use disorder (OUD) are at risk of overdose, infectious diseases, and inadequate prenatal care. Additional risks include adverse pregnancy and infant outcomes, such as preterm birth and neonatal abstinence syndrome. Management and treatment of OUD during pregnancy are associated with improved maternal and infant outcomes. Professional organizations, including the American College of Obstetricians and Gynecologists, recommend offering opioid agonist pharmacotherapy ( i.e. , methadone or buprenorphine) combined with behavioral therapy as standard treatment for pregnant women with OUD. Other medications and herbal supplements have also been used by pregnant women for OUD. Determining which OUD treatments optimize maternal and infant outcomes is challenging given the host of potential factors that affect these outcomes. The Centers for Disease Control and Prevention initiated the MATernaL and Infant NetworK to Understand Outcomes Associated with Treatment of Opioid Use Disorder during Pregnancy (MAT-LINK) to monitor more than 2000 mothers and their infants, using data collected from geographically diverse clinical sites. Information learned from MAT-LINK will inform the future management and treatment of pregnant women with OUD.

Current research on radionuclide disposal is mostly conducted in granite, clay, saltstone, or volcanic tuff formations. These rock types are not always available to host a geological repository in every nuclear waste-generating country, but carbonate rocks may serve as a potential alternative. To assess their feasibility, a forced gradient cross-borehole tracer experiment was conducted in a saturated fractured chalk formation. The mobility of stable Sr and Cs (as analogs for their radioactive counterparts), Ce (an actinide analog), Re (a Tc analog), bentonite particles, and fluorescent dye tracers through the flow path was analyzed. The migration of each of these radionuclide analogs (RAs) was shown to be dependent upon their chemical speciation in solution, their interactions with bentonite, and their sorption potential to the chalk rock matrix. The brackish groundwater resulted in flocculation and immobilization of most particulate RAs. Nevertheless, the high permeability of the fracture system allowed for fast overall transport times of all aqueous RAs investigated. This study suggests that the geochemical properties of carbonate rocks may provide suitable conditions for certain types of radionuclide storage (in particular, brackish, high-porosity, and low-permeability chalks). Nevertheless, careful consideration should be given to high-permeability fracture networks that may result in high radionuclide mobility.

Drinking alcohol during pregnancy can cause fetal alcohol spectrum disorders, including birth defects, behavioral disorders, and impaired cognitive development (1). Little is known about the co-use of other substances by females who drink during pregnancy. CDC used 2015-2018 data from the National Survey on Drug Use and Health (NSDUH) to estimate the overall and trimester-specific prevalence of self-reported drinking in the past 12 months, current drinking, and binge drinking, overall and by trimester, and the co-use of other substances among pregnant females aged 12-44 years. Past drinking (12 months) was reported by 64.7% of pregnant respondents. Current drinking (at least one drink in the past 30 days) was reported by 19.6% of respondents who were in their first trimester of pregnancy and 4.7% of respondents who were in their second or third trimester. Binge drinking (consuming four or more drinks on at least one occasion in the past 30 days) was reported by 10.5% of first trimester respondents and 1.4% of second or third trimester respondents. Overall, 38.2% of pregnant respondents who reported current drinking also reported current use of one or more other substances. The substances used most with alcohol were tobacco and marijuana. Self-reported drinking prevalence was substantially lower among second or third trimester respondents than among first trimester respondents. The American College of Obstetricians and Gynecologists (ACOG) recommends alcohol use and substance use disorders screening for all females seeking obstetric-gynecologic care and counseling patients that there is no known safe level of alcohol use during pregnancy (2)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy., Methods: We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes., Results: Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported., Conclusions: For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Mobility of radionuclides originating from geological repositories in the subsurface has been shown to be facilitated by clay colloids. In brackish water, however, colloids may flocculate and act to immobilize radionuclides associated with them. Furthermore, little research has been conducted on radionuclide interactions with carbonate rocks. Here, the impact of bentonite colloid presence on the transport of a cocktail of U(VI), Cs, Ce and Re through fractured chalk was investigated. Flow-through experiments were conducted with and without bentonite colloids, present as a mixture of bentonite and Ni-altered montmorillonite colloids. Ce was used as an analogue for reactive actinides in the (III) and (VI) redox states, and Re was considered an analogue for Tc. Filtered brackish groundwater (ionic strength = 170 mM) pumped from a fractured chalk aquitard in the northern Negev Desert of Israel, was used as a solution matrix. Rhenium transport was identical to that of the conservative tracer, uranine. The sorption coefficient (K d ) of U(VI), Cs and Re, calculated from batch experiments with crushed chalk, proved to be a good predictor of mass recovery in transport experiments conducted without bentonite colloids. A meaningful K d value for Ce could not be calculated due to its precipitation as a Ce-carbonate colloids. Transport of both U(VI) and Cs was indifferent to the presence of bentonite colloids. However, the addition of bentonite in the injection solution effectively immobilized Ce, decreasing its recovery from 17-41% to 0.8-1.4%. This indicates that radionuclides which interact with clay colloids that undergo flocculation and deposition may effectively be immobilized in brackish aquifers. The results of this study have implications for the prediction of potential mobility of radionuclides in safety assessments for future geological repositories to be located in fractured carbonate rocks in general and in brackish groundwater in particular., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background Our objective was to estimate receipt of preconception health care among women with congenital heart defects (CHD), according to 2017 American Heart Association recommendations, as a baseline for evaluating recommendation implementation. Methods and Results Using 2007 to 2013 IBM MarketScan Commercial Databases, we identified women with CHD diagnosis codes ages 15 to 44 years who became pregnant and were enrolled in health insurance for ≥11 months in the year before estimated conception. We assessed documentation of complete blood count, electrolytes, thyroid-stimulating hormone, liver function, ECG, comprehensive echocardiogram, and exercise stress test, using procedural codes, and outpatient prescription claims for US Food and Drug Administration category D and X cardiac-related medications. Differences were examined according to CHD severity, age, region of residence, year of conception, and documented encounters at obstetric and cardiology practices. We found 2524 pregnancies among 2003 women with CHD (14.4% severe CHD). In the 98.3% of women with a healthcare encounter in the year before conception, <1% received all and 22.6% received no American Heart Association-recommended tests or assessments (range: 54.4% for complete blood count to 3.1% for exercise stress test). Women with the highest prevalence of receipt of recommended care were 35 to 44 years old, pregnant in 2012 to 2013, or had a documented obstetric or cardiology encounter in the year before conception ( P <0.05 for all). In 9.0% of pregnancies, ≥1 prescriptions for US Food and Drug Administration category D or X cardiac-related medications were filled in the year before conception. Conclusions A low percentage of women with CHD received American Heart Association-recommended preconception health care in the year before conception.

Manganese superoxide dismutase (MnSOD) functions as a tumor suppressor; however, once tumorigenesis occurs, clinical data suggest MnSOD levels correlate with more aggressive human tumors, implying a potential dual function of MnSOD in the regulation of metabolism. Here we show, using in vitro transformation and xenograft growth assays that the MnSOD-K68 acetylation (Ac) mimic mutant (MnSOD K68Q ) functions as a tumor promoter. Interestingly, in various breast cancer and primary cell types the expression of MnSOD K68Q is accompanied with a change of MnSOD's stoichiometry from a known homotetramer complex to a monomeric form. Biochemical experiments using the MnSOD-K68Q Ac-mimic, or physically K68-Ac (MnSOD-K68-Ac), suggest that these monomers function as a peroxidase, distinct from the established MnSOD superoxide dismutase activity. MnSOD K68Q expressing cells exhibit resistance to tamoxifen (Tam) and cells selected for Tam resistance exhibited increased K68-Ac and monomeric MnSOD. These results suggest a MnSOD-K68-Ac metabolic pathway for Tam resistance, carcinogenesis and tumor progression.

Background: Benzodiazepine medications can be used to treat anxiety, a condition affecting 15% of women of childbearing age in the United States. Studies have shown conflicting results for the association between benzodiazepine use during pregnancy and birth defects., Methods: We analyzed 1997-2011 data from the National Birth Defects Prevention Study, a multisite, population-based case-control study. We assessed the prevalence of and factors associated with benzodiazepine use in pregnancy among mothers of live-born infants without a birth defect (control mothers). We used logistic regression to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between specific birth defects and benzodiazepine use; we estimated crude odds ratios (cORs) for defect categories with 3-4 exposed cases., Results: Exposure to benzodiazepines during pregnancy was rare (N = 93/11,614; 0.8%). Benzodiazepine use was more common among control mothers who were ≥30 years, non-Hispanic white, had more education, smoked, and took antidepressant medication. We observed significantly elevated ORs for any benzodiazepine and Dandy-Walker malformation (cOR: 3.1; 95% CI: 1.1, 8.6); for alprazolam and anophthalmia or microphthalmia (cOR: 4.0; 95% CI: 1.2, 13.1) and esophageal atresia or stenosis (aOR: 2.7; 95% CI: 1.2, 5.9); and lorazepam and pulmonary valve stenosis (cOR: 4.1; 95% CI: 1.2, 14.2), but sample sizes were limited and therefore CIs were wide., Conclusions: Our findings suggest that benzodiazepines use is rare and may be associated with risk for certain birth defects. However, these results need replication and should be interpreted with caution., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

In the context of geological disposal of radioactive waste, one of the controlling mechanisms for radionuclide migration through subsurface strata is sorption to mobile colloidal bentonite particles. Such particles may erode from the repository backfill or bentonite buffer and yield measurable (0.01-0.1 g/L) concentrations in natural groundwater. The extent of sorption is influenced by colloid concentration, ionic strength, radionuclide concentration, and the presence of competing metals. Uranium (VI) and cesium sorption to bentonite colloids was investigated both separately and together in low ionic strength (2.20 mM) artificial rainwater (ARW) and high ionic strength (169 mM) artificial groundwater (AGW; representative of a fractured carbonate rock aquitard). Sorption experiments were conducted as a factor of colloid concentration, initial metal concentration and opposing metal presence. It was shown that both U(VI) and Cs sorption were significantly reduced in AGW in comparison to ARW. Additionally, the sorption coefficient K d of both metals was found to decrease with increasing colloid concentration. Competitive sorption experiments indicated that at high colloid concentration (1-2 g/L), Cs sorption was reduced in the presence of U(VI), and at low colloid concentration (0.01-0.5 g/L), both Cs and U(VI) K d s were reduced when they were present together due to competition for similar sorption sites. The results from this study imply that in brackish carbonate rock aquifers, typical of the Israeli northern Negev Desert, both U(VI) and Cs are more likely to be mobile as dissolved species rather than as colloid-associated solids., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Urinary tract infections (UTIs) occur in about 8% of pregnant women, and untreated UTIs can have serious consequences, including pyelonephritis, preterm labor, low birth weight, and sepsis (1). Pregnant women are typically screened for UTIs during early pregnancy, and those with bacteriuria are treated with antibiotics (1,2). Antibiotic stewardship is critical to improving patient safety and to combating antibiotic resistance. Because of the potential risk for birth defects, including anencephaly, heart defects, and orofacial clefts, associated with use of sulfonamides and nitrofurantoin during pregnancy (3), a 2011 committee opinion from the American College of Obstetricians and Gynecologists (ACOG) recommended that sulfonamides and nitrofurantoin may be prescribed in the first trimester of pregnancy only when other antimicrobial therapies are deemed clinically inappropriate (4). To assess the effects of these recommendations, CDC analyzed the Truven Health MarketScan Commercial Database* to examine antibiotic prescriptions filled by pregnant women with UTIs. Among 482,917 pregnancies in 2014, 7.2% of women had an outpatient UTI diagnosis during the 90 days before the date of last menstrual period (LMP) or during pregnancy. Among pregnant women with UTIs, the most frequently prescribed antibiotics during the first trimester were nitrofurantoin, ciprofloxacin, cephalexin, and trimethoprim-sulfamethoxazole. Given the potential risks associated with use of some of these antibiotics in early pregnancy and the potential for unrecognized pregnancy, women's health care providers should be familiar with the ACOG recommendations and consider the possibility of early pregnancy when treating women of reproductive age., Competing Interests: No conflicts of interest were reported.

Long-term treatment in the setting of metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma (UC) has shown that current first-line chemotherapeutic agents are losing effectiveness and that there are limited treatment options available outside of radiation therapy and surgical interventions. The use of immunotherapeutic agents such as monoclonal antibodies has been considered a promising alternative for cancers that progress despite treatment with radiation therapy, surgery, and/or chemotherapeutic agents. Cancer cells escape immune surveillance by interrupting immune checkpoint pathways, resulting in dysregulation of T-cell function and so preventing its antitumor effects. In early 2017, avelumab (BAVENCIO®), a PD-L1-blocking monoclonal antibody agent, was approved for the treatment of metastatic MCC and UC. Trials that evaluated avelumab for the treatment of metastatic MCC and UC were the JAVELIN Merkel 200 Trial and the JAVELIN Solid Tumor trial, respectively. Efficacy results for both trials showed positive overall response rate (ORR) and progression-free survival rate (PFS). A strong safety profile was also established for avelumab. This review provides a brief introduction to checkpoint inhibitors and focuses on the recently approved PD-L1 inhibitor, avelumab.

Migration of colloids may facilitate the transport of radionuclides leaked from near surface waste sites and geological repositories. Intrinsic colloids are favorably formed by precipitation with carbonates in bicarbonate-rich environments, and their migration may be enhanced through fractured bedrock. The mobility of Ce(III) as an intrinsic colloid was studied in an artificial rainwater solution through a natural discrete chalk fracture. The results indicate that at variable injection concentrations (between 1 and 30 mg/L), nearly all of the recovered Ce takes the form of an intrinsic colloid of >0.45 μm diameter, including in those experiments in which the inlet solution was first filtered via 0.45 μm. In all experiments, these intrinsic colloids reached their maximum relative concentrations prior to that of the Br conservative tracer. Total Ce recovery from experiments using 0.45 μm filtered inlet solutions was only about 0.1%, and colloids of >0.45 μm constituted the majority of recovered Ce. About 1% of Ce was recovered when colloids of >0.45 μm were injected, indicating the enhanced mobility and recovery of Ce in the presence of bicarbonate.

Halo orthoses present a paradox. On the one hand, the nominally rigid immobilization they provide to the head aims to remove loads on the cervical spine following injury or surgery, and the devices are retightened routinely to maintain this. On the other hand, bone growth and remodeling are well known to require mechanical stressing. How are these competing needs balanced? To understand this trade-off in an effective, commercial halo orthosis, the authors quantified the response of a commercial halo orthosis to physiological loading levels, applied symmetrically about the sagittal plane. They showed for the first time that after a few cycles of loading analogous to a few steps taken by a patient, the support presented by a standard commercial halo orthosis becomes nonlinear. When analyzed through straightforward structural modeling, these data revealed that the nonlinearity permits mild head motion while severely restricting larger motion. These observations are useful because they open the possibility that halo orthosis installation could be optimized to transfer mild spinal loads that support healing while blocking pathological loads.