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BACKGROUND: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels. METHODS: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%). RESULTS: Live birth at 32 weeks' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks' gestation or later and one fetus before fetal loss at 22 weeks and 5 days' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity. CONCLUSIONS: Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.).
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Anticorpos Monoclonais Humanizados , Transfusão de Sangue Intrauterina , Eritroblastose Fetal , Imunoglobulina G , Humanos , Feminino , Gravidez , Recém-Nascido , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Adulto , Imunoglobulina G/sangue , Transfusão de Sangue Intrauterina/efeitos adversos , Nascido Vivo , Isoanticorpos/sangue , Receptores Fc , Idade Gestacional , Antígenos de Histocompatibilidade Classe IRESUMO
OBJECTIVE: This study investigated sex differences in all-cause mortality and life span between women undergoing premature menopause and men using propensity score matching analysis. METHODS: Data were from the National Health and Nutrition Examination Survey (1999-2018) and the National Health and Nutrition Examination Survey III (1988-1994). We included 3,214 women experiencing premature menopause and 23,067 men. The participants were all older than 40 years. Propensity score matching analysis created matched cohorts of women and men using a 1:1 ratio. We employed Cox proportional hazard models to estimate unadjusted and adjusted hazard ratios (HR) (95% confidence interval [CI]) for the association between sex and both all-cause mortality and survival up to the 75th percentile of life span. A subgroup analysis examined the effects of hormone therapy on mortality and life span. RESULTS: Compared with men in the matched cohorts, the adjusted HR values (95% CI) for all-cause mortality in women with age at menopause at <35, 35 to 39, and <40 years were 0.65 (0.54-0.78), 0.72 (0.59-0.87), and 0.67 (0.60-0.76), respectively. However, the adjusted HR values (95% CI) for women and men to survive to the 75th percentile of life span were not statistically significant. Besides, there was no significant difference in the mean life span between deceased women and men in the matched cohorts. In the subgroup analysis, the mean life span did not differ significantly between deceased women taking hormone therapy and men. However, the average life span of women never using hormone therapy was significantly longer than that of men (78.3 ± 11.6 vs 76.6 ± 11.9 years, P = 0.0154). CONCLUSIONS: Women experiencing premature menopause had lower risks of all-cause mortality than men, but the advantage that women had in terms of life span was insignificant.
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Few details are known about the fate of the Franklin Expedition after it departed England in 1845. What we do know is derived from the archaeological record, Inuit testimony and brief communications written in 1847 and 1848 from the Expedition. During the 1860s, Charles Francis Hall went to the Arctic in search of survivors, papers, and relics. During Hall's second expedition, two Inuit testimonies emerged which reported unusual site(s) on the Westcoast of King William Island which were reputedly build by the Expedition. Hall believed these sites were either a burial site or a cemented document vault(s). The first testimony, recorded by Hall himself, was obtained from a Pelly Bay Inuk, Su-pung-er, in 1866. The second, was collected from Pelly Bay Inuit by members of Hall's support team, including Peter Bayne, in Hall's absence in 1868. Eventually, the second testimony was sold to the Canadian Government in the form of a report written by George Jamme after Bayne's death in 1928. Until now, only extracts of the Jamme Report have been available. This paper describes the background to the Jamme report and presents it in its entirety along with critiques so that scholars in the future may have this tool.
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Previous research has demonstrated that complex carbohydrates (maltodextrins) can be perceived in the oral cavity. However, little research has been conducted to thoroughly investigate complex carbohydrate taste perception and contributing factors. This study explored the effects of the degree of polymerization and the concentration of complex carbohydrates on taste perception. Additionally, the impact of lactisole and acarbose on carbohydrate taste perception was investigated. Using a blinded, Latin Square design, participants (n = 40) received samples (control) or samples with acarbose (5 mM) or lactisole (1.4 mM). Per visit, participants received solutions: (1) short chain maltodextrin (average DP 6) (SCM), (2) long chain maltodextrin (average DP 24) (LCM), (3) maltose, and (4) glucose. Samples were evaluated in duplicate, both at low concentration and high concentration. Participants tasted the samples and rated sweetness, starchiness, and viscosity (mouthfeel) perceived on a 10 cm continuous line scale and perceived intensity on a Labelled Magnitude Scale. There was a significant effect of degree of polymerisation on sweetness (p = 0.001) and intensity (p = 0.001). For low concentration samples, no significant differences were found between LCM and acarbose LCM or SCM and acarbose SCM for sweetness, starchiness, or mouthfeel (all p > 0.05). Significant differences were observed between LCM and lactisole LCM for sweetness (1.1 ± 0.1 vs. 2.5 ± 0.3, p = 0.001), starchiness (1.4 ± 0.2 vs. 2.3 ± 0.3, p = 0.005), and mouthfeel (1.4 ± 0.2 vs. 2.3 ± 0.3, p = 0.013). In conclusion, the taste perception of maltodextrins is influenced by the degree of polymerisation. Furthermore, for this study, the sweet taste receptor was not involved in maltodextrin taste perception. While salivary α-amylase did not appear to influence taste perception with low concentration maltodextrins, further investigation is necessary.
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BACKGROUND: Surgeons routinely apply papaverine, lidocaine, or verapamil to produce acute vasodilation and prevent vasospasms during microvascular surgeries. There is evidence that topical vasodilators may induce postoperative endothelial and smooth muscle dysfunction, which would present after the acute vasodilatory effects of the topical drugs wear off. Therefore, the purpose of the current study was to evaluate the lasting effects of papaverine, lidocaine, and verapamil on human deep inferior epigastric perforator artery vasodilatory function after the acute effects of the topical drugs had worn off. METHODS: Deep inferior epigastric arterial samples were obtained from 12 patients during surgery. Each artery was dissected into four rings which where incubated for 1 minute in either physiological saline solution (control), papaverine (30 mg/mL), lidocaine (20 mg/mL), or verapamil (2.5 mg/mL), followed by a 2-hour washout. Endothelial-dependent and -independent vasorelaxation were then assessed by the isometric tension responses to acetylcholine or sodium nitroprusside, respectively. RESULTS: Peak acetylcholine-evoked vasorelaxation (mean ± standard deviation) was not different between control (62 ± 23%) and lidocaine (57 ± 18%, p = 0.881), but was reduced (all p < 0.002) in papaverine (22 ± 27%) and verapamil (22 ± 20%). Peak sodium nitroprusside-evoked vasorelaxation was not different (all p > 0.692) among control (132 ± 35%), lidocaine (121 ± 22%), and verapamil (127 ± 22%), but was less in papaverine (104 ± 41%; p = 0.045) than control. CONCLUSION: Surgically used doses of papaverine and verapamil, but not lidocaine, have lasting negative effects on arterial vasodilatory function despite the acute effects of the drugs having worn off. These findings, in conjunction with the spasmolytic properties of each drug, may help guide the selection of an optimal topical vasodilator for use during microvascular surgeries.
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The purpose of this study is to examine the association between autism spectrum disorder (ASD) severity and having a special education or early intervention plan and the impact of adverse childhood experiences (ACEs) on this association. This study used the 2020-2021 National Survey of Children's Health (NSCH) and included 2,537 children aged 3-17 years old who currently have ASD. Multivariable logistic regression, controlling for demographic and family characteristics and health status, was used to explore the association between autism severity and having an early intervention plan. The analysis was stratified by the number of ACEs to explore their role in the association. Children with moderate or severe ASD were more likely to have a special education or early intervention plan than those with mild ASD in the crude and adjusted models. This association continued to be true for children who experienced 1 ACE (aOR: 2.28, 95%CI: 1.09-4.77) but not true for those who experienced no ACEs (aOR: 1.16, 95%CI: 0.70-1.94) and 2 or more ACEs (aOR: 1.84, 95%CI: 0.92-3.69). Results demonstrate that children with moderate or severe autism were more likely to receive early intervention or special education. This association changed depending on the number of ACEs experiences.
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BACKGROUND: The appropriate surgical approach for pancreatic ductal adenocarcinoma (PDAC) is determined by the tumor's relation to the porto-mesenteric axis. Although the extent and location of lymphadenectomy is dependent on the type of resection, a pancreatoduodenectomy (PD), distal pancreatectomy (DP), or total pancreatectomy (TP) are considered equivalent oncologic operations for pancreatic neck tumors. Therefore, we aimed to assess differences in histopathological and oncological outcomes for surgical approaches in the treatment of pancreatic neck tumors. METHODS: Patients with resected PDAC located in the pancreatic neck were identified from the National Cancer Database (2004-2020). Patients with metastatic disease were excluded. Furthermore, patients with 90-day mortality and R2-resections were excluded from the multivariable Cox-regression analysis. RESULTS: Among 846 patients, 58% underwent PD, 25% DP, and 17% TP with similar R0-resection rates (p = 0.722). Significant differences were observed in nodal positivity (PD:44%, DP:34%, TP:57%, p < 0.001) and mean-number of examined lymph nodes (PD:17.2 ± 10.4, DP:14.7 ± 10.5, TP:21.2 ± 11.0, p < 0.001). Furthermore, inadequate lymphadenectomy (< 12 nodes) was observed in 30%, 44%, and 19% of patients undergoing PD, DP, and TP, respectively (p < 0.001). Multivariable analysis yielded similar overall survival after DP (HR:0.83, 95%CI:0.63-1.11), while TP was associated with worse survival (HR:1.43, 95%CI:1.08-1.89) compared to PD. CONCLUSION: While R0-rates are similar amongst all approaches, DP is associated with inadequate lymphadenectomy which may result in understaging disease. However, this had no negative influence on survival. In the premise that an oncological resection of the pancreatic neck tumor is feasible with a partial pancreatectomy, no benefit is observed by performing a TP.
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Carcinoma Ductal Pancreático , Pancreatectomia , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Humanos , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Masculino , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Feminino , Estudos Retrospectivos , Pancreatectomia/métodos , Idoso , Pessoa de Meia-Idade , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/mortalidade , Excisão de Linfonodo , Estudos de CoortesRESUMO
30% of spontaneously occurring twins are monozygotic, of which two-thirds are monochorionic, possessing a single placenta. A common placental mass with shared inter-twin placental circulation is key to the development and management of complications unique to monochorionic gestations. In this Consult, we review general considerations and a contemporary approach to twin-twin transfusion syndrome and twin anemia polycythemia sequence, providing management recommendations based on the available evidence. The following are Society for Maternal-Fetal Medicine recommendations: (1) we recommend routine first trimester sonographic determination of chorionicity and amnionicity (GRADE 1B); (2) we recommend that ultrasound surveillance for twin-twin transfusion syndrome begin at 16 weeks of gestation for all monochorionic-diamniotic twin pregnancies and continue at least every 2 weeks until delivery, with more frequent monitoring indicated with clinical concern (GRADE 1C); (3) we recommend that routine sonographic surveillance for twin-twin transfusion syndrome minimally include assessment of amniotic fluid volumes on both sides of the inter-twin membrane and evaluation for the presence or absence of urine-filled fetal bladders, and ideally incorporate Doppler study of the umbilical arteries (GRADE 1C); (4) we recommend fetoscopic laser surgery as the standard treatment for stage II through stage IV twin-twin transfusion syndrome presenting between 16 and 26 weeks of gestation (GRADE 1A); (5) we recommend expectant management with at least weekly fetal surveillance for asymptomatic patients continuing pregnancies complicated by stage I twin-twin transfusion syndrome, and consideration for fetoscopic laser surgery for stage I twin-twin transfusion syndrome presentations between 16 and 26 weeks of gestation complicated by additional factors such as maternal polyhydramnios-associated symptomatology (GRADE 1B); (6) we recommend an individualized approach to laser surgery for early- and late-presenting twin-twin transfusion syndrome (GRADE 1C); (7) we recommend that all patients with twin-twin transfusion syndrome qualifying for laser therapy be referred to a fetal intervention center for further evaluation, consultation, and care (Best Practice); (8) after laser therapy, we suggest weekly surveillance for 6 weeks followed by resumption of every-other-week surveillance thereafter, unless concern exists for post-laser twin-twin transfusion syndrome, post-laser twin anemia polycythemia sequence, or fetal growth restriction (GRADE 2C); (9) following the resolution of twin-twin transfusion syndrome after fetoscopic laser surgery, and without other indications for earlier delivery, we recommend delivery of dual-surviving monochorionic-diamniotic twins at 34 to 36 weeks of gestation (GRADE 1C); (10) in twin-twin transfusion syndrome pregnancies complicated by post-treatment single fetal demise, we recommend full-term delivery (39 weeks) of the surviving co-twin to avoid complications of prematurity unless indications for earlier delivery exist (GRADE 1C); (11) we recommend that fetoscopic laser surgery should not influence the mode of delivery (Best Practice); (12) we recommend that prenatal diagnosis of twin anemia polycythemia sequence minimally requires either middle cerebral artery Doppler peak systolic velocity values >1.5 multiples of the median and <1.0 multiples of the median in donor and recipient twins, respectively, or an inter-twin Δ middle cerebral artery peak systolic velocity >0.5 multiples of the median (GRADE 1C); (13) we recommend that providers consider incorporating middle cerebral artery Doppler peak systolic velocity determinations into all monochorionic twin ultrasound surveillance beginning at 16 weeks of gestation (GRADE 1C); (14) consultation with a specialized fetal care center is recommended when twin anemia polycythemia sequence progresses to a more advanced disease stage (≥ stage II) prior to 32 weeks of gestation or when concern arises for co-existing complications such as twin-twin transfusion syndrome (Best Practice).
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In this paper, we describe the Project Extension for Community Healthcare Outcomes+ (ECHO+) model and evaluation plan for incorporating changes to primary care delivery, improving patient and clinician outcomes, and making long-term system improvements.
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Atenção Primária à Saúde , Melhoria de Qualidade , Serviços de Saúde Rural , Atenção Primária à Saúde/organização & administração , Humanos , Melhoria de Qualidade/organização & administração , Serviços de Saúde Rural/organização & administração , Arkansas , Oklahoma , West Virginia , Avaliação de Programas e Projetos de SaúdeRESUMO
Client-provider communication about family planning (FP) remains an important strategy for preventing unintended pregnancy. Yet, the literature lacks empirical studies examining whether and how women's intendedness of a recent pregnancy may impact subsequent receipt of FP counseling. We investigated whether the intendedness of a recent pregnancy is associated with subsequent missed opportunities (MOs) for FP counseling, taking into account compositional and contextual factors. We performed a secondary analysis using pooled data from the 2016, 2017 and 2018 Performance Monitoring and Accountability 2020 cross-sectional surveys conducted in Nigeria, adjusting for complex design effects. Weighted multilevel logistic regression modeling was used to examine the relationships between pregnancy intention and MOs, overall and at the health facility, using two-level random intercept models. In the analytic sample of women within 24 months postpartum (N = 6479), nearly 60% experienced MOs for FP counseling overall and even 45% of those who visited a health facility visit in the past 12 months (N = 4194) experienced MOs. In the multivariable models adjusted for individual-/household- and community-level factors, women whose recent birth was either mistimed or unwanted were just as likely to have MOs for FP counseling as their counterparts whose pregnancy was intended (p > 0.05). Factors independently associated with a MOs include individual/household level factors such as level of education, exposure to FP media, household wealth index and contextual-level variables (geographic region). While evidence that pregnancy intendedness is associated with MOs for FP counseling remains inconclusive, efforts to mitigate these MOs requires prioritizing women's prior pregnancy intentions as well as equipping healthcare providers with the capacity need to provide high-quality client-centered FP counseling, particularly for women whose recent birth was unintended.
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Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) has not been adequately addressed. This study sought to test the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 year). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) of maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after the cessation of exercise and central and peripheral hemodynamics were assessed. MSNA was directly recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+ 15 ± 5 burst/100 bpm) and ExPECO 40% (+ 22 ± 4 burst/100 bpm) and returned to pre-HG levels during ExCON trials. Vasodilation, assessed by the change in leg vascular conductance during PLM, was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate that elevated MSNA attenuates the vasodilatory response to PLM and that the magnitude of reduction in vasodilation during PLM is graded in relation to the degree of sympathoexcitation.
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We present results from a covariance ion imaging study, which employs extensive filtering, on the relationship between fragment momenta to gain deeper insight into photofragmentation dynamics. A new data analysis approach is introduced that considers the momentum partitioning between the fragments of the breakup of a molecular polycation to disentangle concurrent fragmentation channels, which yield the same ion species. We exploit this approach to examine the momentum exchange relationship between the products, which provides direct insight into the dynamics of molecular fragmentation. We apply these techniques to extensively characterize the dissociation of 1-iodopropane and 2-iodopropane dications prepared by site-selective ionization of the iodine atom using extreme ultraviolet intense femtosecond laser pulses with a photon energy of 95 eV. Our assignments are supported by classical simulations, using parameters largely obtained directly from the experimental data.
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OBJECTIVE: Laser interstitial thermal therapy (LITT) is an alternative to anterior temporal lobectomy (ATL) for the treatment of temporal lobe epilepsy that has been found by some to have a lower procedure cost but is generally regarded as less effective and sometimes results in a subsequent procedure. The goal of this study is to incorporate subsequent procedures into the cost and outcome comparison between ATL and LITT. METHODS: This single-center, retrospective cohort study includes 85 patients undergoing ATL or LITT for temporal lobe epilepsy during the period September 2015 to December 2022. Of the 40 patients undergoing LITT, 35 % (N = 14) underwent a subsequent ATL. An economic cost model is derived, and difference in means tests are used to compare the costs, outcomes, and other hospitalization measures. RESULTS: Our model predicts that whenever the percentage of LITT patients undergoing subsequent ATL (35% in our sample) exceeds the percentage by which the LITT procedure alone is less costly than ATL (7.2% using total patient charges), LITT will have higher average patient cost than ATL, and this is indeed the case in our sample. After accounting for subsequent surgeries, the average patient charge in the LITT sample ($103,700) was significantly higher than for the ATL sample ($88,548). A second statistical comparison derived from our model adjusts for the difference in effectiveness by calculating the cost per seizure-free patient outcome, which is $108,226 for ATL, $304,052 for LITT only, and $196,484 for LITT after accounting for the subsequent ATL surgeries. SIGNIFICANCE: After accounting for the costs of subsequent procedures, we found in our cohort that LITT is not only less effective but also results in higher average costs per patient than ATL as a first course of treatment. While cost and effectiveness rates will vary across centers, we also provide a model for calculating cost effectiveness based on individual center data.
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Lobectomia Temporal Anterior , Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Terapia a Laser , Humanos , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/economia , Feminino , Masculino , Lobectomia Temporal Anterior/economia , Lobectomia Temporal Anterior/métodos , Adulto , Terapia a Laser/economia , Terapia a Laser/métodos , Estudos Retrospectivos , Epilepsia Resistente a Medicamentos/economia , Epilepsia Resistente a Medicamentos/cirurgia , Pessoa de Meia-Idade , Adulto Jovem , Resultado do TratamentoRESUMO
When The Principles of Humane Experimental Technique was published in 1959, authors William Russell and Rex Burch had a modest goal: to make researchers think about what they were doing in the laboratory and to do it more humanely. Sixty years later, their groundbreaking book was celebrated for inspiring a revolution in science and launching a new field: The 3Rs of alternatives to animal experimentation. On November 22, 2019, some pioneering and leading scientists and researchers in the field gathered at the Johns Hopkins Bloomberg School of Public Health in Baltimore for the 60 Years of the 3Rs Symposium: Lessons Learned and the Road Ahead. The event was sponsored by the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), the Foundation for Chemistry Research and Initiatives, the Alternative Research & Development Foundation (ARDF), the American Cleaning Institute (ACI), the International Fragrance Association (IFRA), the Institute for In Vitro Sciences (IIVS), John "Jack" R. Fowle III, and the Society of Toxicology (SoT). Fourteen presentations shared the history behind the groundbreaking publication, international efforts to achieve its aims, stumbling blocks to progress, as well as remarkable achievements. The day was a tribute to Russell and Burch, and a testament to what is possible when people from many walks of life science, government, and industry work toward a common goal.
William Russell and Rex Burch published their book The Principles of Humane Experimental Technique in 1959. The book encouraged researchers to replace animal experiments where it was possible, to refine experiments with animals in order to reduce their suffering, and to reduce the number of animals that had to be used for experiments to the minimum. Sixty years later, a group of pioneering and leading scientists and researchers in the field gathered to share how the publication came about and how the vision inspired international collaborations and successes on many different levels including new laws. The paper includes an overview of important milestones in the history of alternatives to animal experimentation.
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Experimentação Animal , Alternativas aos Testes com Animais , Animais , Alternativas aos Testes com Animais/métodos , Bem-Estar do Animal , Projetos de PesquisaRESUMO
The Drosophila melanogaster male accessory gland (AG) is a functional analog of the mammalian prostate and seminal vesicles containing two secretory epithelial cell types, termed main and secondary cells. This tissue is responsible for making and secreting seminal fluid proteins and other molecules that contribute to successful reproduction. The cells of this tissue are binucleate and polyploid, due to variant cell cycles that include endomitosis and endocycling during metamorphosis. Here, we provide evidence of additional cell cycle variants in this tissue. We show that main cells of the gland are connected by ring canals that form after the penultimate mitosis, and we describe an additional post-eclosion endocycle required for gland maturation that is dependent on juvenile hormone signaling. We present evidence that the main cells of the D. melanogaster AG undergo a unique cell cycle reprogramming throughout organ development that results in step-wise cell cycle truncations culminating in cells containing two octoploid nuclei with under-replicated heterochromatin in the mature gland. We propose this tissue as a model to study developmental and hormonal temporal control of cell cycle variants in terminally differentiating tissues.
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Ciclo Celular , Drosophila melanogaster , Animais , Masculino , Drosophila melanogaster/crescimento & desenvolvimento , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Hormônios Juvenis/metabolismoRESUMO
This study uses survey data to compare rates of political participation between US physicians and nonphysicians from 2017 to 2021.
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Médicos , Política , Feminino , Humanos , Masculino , Médicos/psicologia , Médicos/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Chemical reactions are often characterized by their transition state, which defines the critical geometry the molecule must pass through to move from reactants to products. Roaming provides an alternative picture, where in a dissociation reaction, the bond breaking is frustrated and a loosely bound intermediate is formed. Following bond breaking, the two partners are seen to roam around each other at distances of several Ångstroms, forming a loosely bound, and structurally ill-defined, intermediate that can subsequently lead to reactive or unreactive collisions. Here, we present a direct and time-resolved experimental measurement of roaming. By measuring the photoelectron spectrum of UV-excited acetaldehyde with a femtosecond extreme ultraviolet pulse, we captured spectral signatures of all of the key reactive structures, including that of the roaming intermediate. This provided a direct experimental measurement of the roaming process and allowed us to identify the time scales by which the roaming intermediate is formed and removed and the electronic potential surfaces upon which roaming proceeds.
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OBJECTIVE: To examine changes in prenatal opioid prescription exposure following new guidelines and policies. STUDY DESIGN: Cohort study of all (262,284) Wisconsin Medicaid-insured live births 2010-2019. Prenatal exposures were classified as analgesic, short term, and chronic (90+ days), and medications used to treat opioid use disorder (MOUD). We describe overall and stratified temporal trends and used linear probability models with interaction terms to test their significance. RESULT: We found 42,437 (16.2%) infants with prenatal exposure; most (90.5%) reflected analgesic opioids. From 2010 to 2019, overall exposure declined 12.8 percentage points (95% CI = 12.1-13.1). Reductions were observed across maternal demographic groups and in both rural and urban settings, though the extent varied. There was a small reduction in chronic analgesic exposure and a concurrent increase in MOUD. CONCLUSION: Broad and sustained declines in prenatal prescription opioid exposure occurred over the decade, with little change in the percentage of infants chronically exposed.
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Analgésicos Opioides , Medicaid , Transtornos Relacionados ao Uso de Opioides , Humanos , Feminino , Wisconsin , Medicaid/estatística & dados numéricos , Gravidez , Analgésicos Opioides/uso terapêutico , Estados Unidos , Adulto , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Estudos de Coortes , Recém-Nascido , Adulto Jovem , Masculino , Cuidado Pré-Natal/estatística & dados numéricos , Complicações na Gravidez/tratamento farmacológicoRESUMO
Per- and polyfluoroalkyl substances (PFAS) are widely used, and their fluorinated state contributes to unique uses and stability but also long half-lives in the environment and humans. PFAS have been shown to be toxic, leading to immunosuppression, cancer, and other adverse health outcomes. Only a small fraction of the PFAS in commerce have been evaluated for toxicity using in vivo tests, which leads to a need to prioritize which compounds to examine further. Here, we demonstrate a prioritization approach that combines human biomonitoring data (blood concentrations) with bioactivity data (concentrations at which bioactivity is observed in vitro) for 31 PFAS. The in vitro data are taken from a battery of cell-based assays, mostly run on human cells. The result is a Bioactive Concentration to Blood Concentration Ratio (BCBCR), similar to a margin of exposure (MoE). Chemicals with low BCBCR values could then be prioritized for further risk assessment. Using this method, two of the PFAS, PFOA (Perfluorooctanoic Acid) and PFOS (Perfluorooctane Sulfonic Acid), have BCBCR values < 1 for some populations. An additional 9 PFAS have BCBCR values < 100 for some populations. This study shows a promising approach to screening level risk assessments of compounds such as PFAS that are long-lived in humans and other species.