Outcomes After Induction of Labor Compared With Dilation and Evacuation for the Management of Rupture of Membranes in the Second Trimester.

Previable and periviable rupture of membranes is associated with significant morbidity for the pregnant patient. For those who have a choice of options and undergo active management, it is not known how the risks of induction of labor compare with those for dilation and evacuation (D&E). We performed a retrospective cohort study of patients with rupture of membranes between 14 0/7 and 23 6/7 weeks of gestation who opted for active management. Adverse events (52.2% vs 16.9%, P <.01) and time to uterine evacuation greater than 24 hours (26.7% vs 9.6%, P =.01) were more common among patients undergoing induction of labor. In a multivariable regression, induction of labor was an independent risk factor for complications (odds ratio 5.70, 95% CI, 2.35-13.82) compared with D&E. Severe complications were rare across both groups (4.4% for patients undergoing induction vs 2.6% for D&E, P =.63). Given the differing risks by termination method, access to D&E is an important treatment option for this patient population.

Perceptions of HIV risk screening strategies among patients seeking abortion, contraception, and pregnancy loss management in the United States.

OBJECTIVES: Women make up nearly a fifth of new human immunodeficiency virus (HIV) infections yearly in the United States, more than half of which could have been prevented with broader use of HIV pre-exposure prophylaxis (PrEP). We aimed to qualitatively assess (1) acceptability of an HIV risk screening strategy and PrEP provision in a family planning setting, and (2) the influence of family planning visit type (abortion, pregnancy loss management, or contraception) on HIV risk screening acceptability. STUDY DESIGN: Guided by the P3 (practice-, provider-, and patient-level) model for preventive care interventions, we conducted three focus group discussions including patients who had experienced induced abortion, early pregnancy loss (EPL), or contraception care. We developed a codebook of a priori and inductive concepts, and categorized themes by practice, provider, and patient considerations. RESULTS: We included 24 participants. Practice-level considerations included overall positive feelings about being screened for PrEP eligibility during family planning visits, though some expressed reservations about screening during EPL visits. Provider-level themes included the concept of screening tools as entry points into conversation and education, and the importance of nonjudgment in discussing sexually transmitted infection (STI) prevention. Participants often had to initiate STI prevention discussions and felt that contraception was overemphasized by their providers compared with STI prevention and PrEP care. Patient-level themes included the stigma of STIs and oral PrEP, and the dynamic nature of STI risk. CONCLUSIONS: Participants in our research had genuine interest in learning about PrEP during family planning visits. Findings from our research support the consistent inclusion of STI prevention education into family planning clinical practice using patient-centered STI screening methods. IMPLICATIONS: Family planning encounters, including visits for contraception and abortion, are generally appropriate times to discuss HIV PrEP. Patient-centered conversations are an important adjunct to HIV risk screening tools.

Near real time monitoring and forecasting for COVID-19 situational awareness.

In the opening months of the pandemic, the need for situational awareness was urgent. Forecasting models such as the Susceptible-Infectious-Recovered (SIR) model were hampered by limited testing data and key information on mobility, contact tracing, and local policy variations would not be consistently available for months. New case counts from sources like John Hopkins University and the NY Times were systematically reliable. Using these data, we developed the novel COVID County Situational Awareness Tool (CCSAT) for reliable monitoring and decision support. In CCSAT, we developed a retrospective seven-day moving window semantic map of county-level disease magnitude and acceleration that smoothed noisy daily variations. We also developed a novel Bayesian model that reliably forecasted county-level magnitude and acceleration for the upcoming week based on population and new case count data. Together these formed a robust operational update including county-level maps of new case rate changes, estimates of new cases in the upcoming week, and measures of model reliability. We found CCSAT provided stable, reliable estimates across the seven-day time window, with the greatest errors occurring in cases of anomalous, single day spikes. In this paper, we provide CCSAT details and apply it to a single week in June 2020.

The impact of heat on kidney stone presentations in South Carolina under two climate change scenarios.

The risk of kidney stone presentations increases after hot days, likely due to greater insensible water losses resulting in more concentrated urine and altered urinary flow. It is thus expected that higher temperatures from climate change will increase the global prevalence of kidney stones if no adaptation measures are put in place. This study aims to quantify the impact of heat on kidney stone presentations through 2089, using South Carolina as a model state. We used a time series analysis of historical kidney stone presentations (1997-2014) and distributed lag non-linear models to estimate the temperature dependence of kidney stone presentations, and then quantified the projected impact of climate change on future heat-related kidney stone presentations using daily projections of wet-bulb temperatures to 2089, assuming no adaptation or demographic changes. Two climate change models were considered-one assuming aggressive reduction in greenhouse gas emissions (RCP 4.5) and one representing uninibited greenhouse gas emissions (RCP 8.5). The estimated total statewide kidney stone presentations attributable to heat are projected to increase by 2.2% in RCP 4.5 and 3.9% in RCP 8.5 by 2085-89 (vs. 2010-2014), with an associated total excess cost of ~ $57 million and ~ $99 million, respectively.

Association of Social Distancing, Population Density, and Temperature With the Instantaneous Reproduction Number of SARS-CoV-2 in Counties Across the United States.

Importance: Local variation in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the United States has not been well studied. Objective: To examine the association of county-level factors with variation in the SARS-CoV-2 reproduction number over time. Design, Setting, and Participants: This cohort study included 211 counties, representing state capitals and cities with at least 100 000 residents and including 178 892 208 US residents, in 46 states and the District of Columbia between February 25, 2020, and April 23, 2020. Exposures: Social distancing, measured by percentage change in visits to nonessential businesses; population density; and daily wet-bulb temperatures. Main Outcomes and Measures: Instantaneous reproduction number (Rt), or cases generated by each incident case at a given time, estimated from daily case incidence data. Results: The 211 counties contained 178 892 208 of 326 289 971 US residents (54.8%). Median (interquartile range) population density was 1022.7 (471.2-1846.0) people per square mile. The mean (SD) peak reduction in visits to nonessential business between April 6 and April 19, as the country was sheltering in place, was 68.7% (7.9%). Median (interquartile range) daily wet-bulb temperatures were 7.5 (3.8-12.8) °C. Median (interquartile range) case incidence and fatality rates per 100 000 people were approximately 10 times higher for the top decile of densely populated counties (1185.2 [313.2-1891.2] cases; 43.7 [10.4-106.7] deaths) than for counties in the lowest density quartile (121.4 [87.8-175.4] cases; 4.2 [1.9-8.0] deaths). Mean (SD) Rt in the first 2 weeks was 5.7 (2.5) in the top decile compared with 3.1 (1.2) in the lowest quartile. In multivariable analysis, a 50% decrease in visits to nonessential businesses was associated with a 45% decrease in Rt (95% CI, 43%-49%). From a relative Rt at 0 °C of 2.13 (95% CI, 1.89-2.40), relative Rt decreased to a minimum as temperatures warmed to 11 °C, increased between 11 and 20 °C (1.61; 95% CI, 1.42-1.84) and then declined again at temperatures greater than 20 °C. With a 70% reduction in visits to nonessential business, 202 counties (95.7%) were estimated to fall below a threshold Rt of 1.0, including 17 of 21 counties (81.0%) in the top density decile and 52 of 53 counties (98.1%) in the lowest density quartile.2. Conclusions and Relevance: In this cohort study, social distancing, lower population density, and temperate weather were associated with a decreased Rt for SARS-CoV-2 in counties across the United States. These associations could inform selective public policy planning in communities during the coronavirus disease 2019 pandemic.

Clearing, immunofluorescence, and confocal microscopy for the three-dimensional imaging of murine testes and study of testis biology.

Optical clearing techniques provide unprecedented opportunities to study large tissue samples at histological resolution, eliminating the need for physical sectioning while preserving the three-dimensional structure of intact biological systems. There is significant potential for applying optical clearing to reproductive tissues. In testicular biology, for example, the study of spermatogenesis and the use of spermatogonial stem cells offer high-impact applications in fertility medicine and reproductive biotechnology. The objective of our study is to apply optical clearing, immunofluorescence, and confocal microscopy to testicular tissue in order to reconstruct its three-dimensional microstructure in intact samples. We used Triton-X/DMSO clearing in combination with refractive index matching to achieve optical transparency of fixed mouse testes. An antibody against smooth muscle actin was used to label peritubular myoid cells of seminiferous tubules while an antibody against ubiquitin C-terminal hydrolase was used to label Sertoli cells and spermatogonia in the seminiferous epithelium. Specimens were then imaged using confocal fluorescence microscopy. We were able to successfully clear testicular tissue and utilize immunofluorescent probes. Additionally, we successfully visualized the histological compartments of testicular tissue in three-dimensional reconstructions. Optical clearing combined with immunofluorescence and confocal imaging offers a powerful new method to analyze the cytoarchitecture of testicular tissue at histological resolution while maintaining the macro-scale perspective of the intact system. Considering the importance of the murine model, our developed method represents a significant contribution to the field of male reproductive biology, enabling the study of testicular function.

Genistein diet does not modify crypt morphology in the ob/ob mouse jejunum: a comparison of cryostat and clearing techniques.

INTRODUCTION: Diabetes is commonly associated with gastrointestinal dysfunction. We have previously shown that transepithelial short circuit current, Isc (chloride secretion), is significantly reduced in the jejunum from ob/ob mice vs lean controls, and consumption of 600 mg genistein/kg of diet (600 G) for 4 weeks significantly rescues Isc. We aimed to evaluate whether morphological changes in the jejunal crypts contribute to the rescue of Isc. METHODS: Male mice (ob/ob and lean controls) were fed either a genistein-free diet or genistein-containing diet (600 G). Comparisons of crypt morphology were made for crypt depth, length, and numbers of proliferative cells. Assessments of crypt measures using DAPI and 5-ethynyl-2'-deoxyuridine (EdU) were performed using traditional cryostat sectioning and an innovative 3D optical clearing method. RESULTS: We found that crypt length in the ob/ob genistein-fed group was significantly greater when measured with cleared tissue (85.19±4.73 µm, P<0.05, n=8) compared to lengths measured with cryostat (65.42±3.48 µm, n=8). In addition, proliferative EdU+ counts were approximately fivefold greater with clearing, compared to counts obtained via single plane images from cryostat sections for all groups measured. The average length to EdU+ ratio was unchanged between groups. CONCLUSION: Thus, we conclude that genistein diet does not affect overall cellular proliferation or crypt morphology, other than for the modest increased crypt length measured via clearing in the ob/ob genistein group. The increase in crypt length is likely indicative of the greater accuracy of the 3D measures compared to single plane. Genistein diet-induced increases in the intestinal Isc are therefore likely not attributed to changes in intestinal crypt morphology.

Nature, Mind, and Medicine: A Model for Mind-Body Healing.

OBJECTIVE: The human mind-body possesses a remarkable innate ability to heal. Grounded in the evolutionarily conserved systems of the brain and body, nature appears to function as the fundamental source of wellness along the two vectors of attention and relaxation. Yet, our species is moving away from nature at a time when humanity is just beginning to rediscover its benefits. CONCLUSIONS: Exposure to natural environments may provide a "window" of healing that can be extended through a continuum of intervention through the use of guided meditation and ultimately hypnotic suggestion. The result may be an improved ability to promote greater executive functioning and more robust immune regulation. The time has come for a more holistic medicine guided by the hand of nature.

Optical clearing of small intestine for three-dimensional visualization of cellular proliferation within crypts.

New methods on optical clearing provide a valuable alternative to traditional physical section histology. Optical clearing allows investigation of relatively large tissue samples at histological resolution while maintaining the three-dimensional architecture of the intact system. There is significant potential for applying optical clearing to gastrointestinal tissues. In particular, intestinal crypts contain high concentrations of stem cells, making these structures especially important for research on cellular proliferation in the intestinal epithelium. The objective of our study is to demonstrate an optical clearing method that is easy to implement and is compatible with mitotic fluorescent labeling. The optical clearing method we present utilizes a Triton/DMSO delipidization step followed by refractive index matching, rendering the tissue nearly transparent. We use EdU click chemistry to fluorescently label mitotic cell nuclei. Our results demonstrate successful clearing of jejunal samples with readily visible EdU staining by means of confocal microscopy. Three-dimensional reconstruction of labeled samples reveals preservation of intestinal cytoarchitecture including muscular, submucosal, and mucosal layers. Additionally, the morphology of intestinal crypts and individual EdU-positive mitotic nuclei are visible in sharp detail within their intact three-dimensional organization. In summary, we present an optical clearing method that is easy to implement and has the potential to provide more accurate assessment of cellular proliferation within the gastrointestinal tract in both healthy and disease states.

Manganese-enhanced MRI Offers Correlation with Severity of Spinal Cord Injury in Experimental Models.

BACKGROUND: Spinal cord injuries (SCI) are clinically challenging, because neural regeneration after cord damage is unknown. In SCI animal models, regeneration is evaluated histologically, requiring animal sacrifice. Noninvasive techniques are needed to detect longitudinal SCI changes. OBJECTIVE: To compare manganese-enhanced magnetic resonance imaging (MRI [MEMRI]) in hemisection and transection of SCI rat models with diffusion tensor imaging (DTI) and histology. METHODS: Rats underwent T9 spinal cord transection (n=6), hemisection (n=6), or laminectomy without SCI (controls, n=6). One-half of each group received lateral ventricle MnCl2 injections 24 hours later. Conventional DTI or T1-weighted MRI was performed 84 hours post-surgery. MEMRI signal intensity ratio above and below the SCI level was calculated. Fractional anisotropy (FA) measurements were taken 1 cm rostral to the SCI. The percentage of FA change was calculated 10 mm rostral to the SCI epicenter, between FA at the dorsal column lesion normalized to a lateral area without FA change. Myelin load (percentage difference) among groups was analyzed by histology. RESULTS: In transection and hemisection groups, mean MEMRI ratios were 0.62 and 0.87, respectively, versus 0.99 in controls (P<0.001 and P<0.001, respectively); mean FA decreases were 67.5% and 40.1%, respectively, compared with a 6.1% increase in controls (P=0.002 and P=0.019, respectively). Mean myelin load decreased by 38.8% (transection) and 51.8% (hemisection) compared to controls (99.1%) (P<0.001 and P<0.001, respectively). Pearson's correlation coefficients were -0.94 for MEMRI ratio and FA changes and 0.87 for MEMRI and myelin load. CONCLUSION: MEMERI results correlated to SCI severity measured by FA and myelin load. MEMRI is a useful noninvasive tool to assess neuronal damage after SCI.

Fish functional traits correlated with environmental variables in a temperate biodiversity hotspot.

The global biodiversity crisis has invigorated the search for generalized patterns in most disciplines within the natural sciences. Studies based on organismal functional traits attempt to broaden implications of results by identifying the response of functional traits, instead of taxonomic units, to environmental variables. Determining the functional trait responses enables more direct comparisons with, or predictions for, communities of different taxonomic composition. The North American freshwater fish fauna is both diverse and increasingly imperiled through human mediated disturbances, including climate change. The Tennessee River, USA, contains one of the most diverse assemblages of freshwater fish in North America and has more imperiled species than other rivers, but there has been no trait-based study of community structure in the system. We identified 211 localities in the upper Tennessee River that were sampled by the Tennessee Valley Authority between 2009 and 2011 and compiled fish functional traits for the observed species and environmental variables for each locality. Using fourth corner analysis, we identified significant correlations between many fish functional traits and environmental variables. Functional traits associated with an opportunistic life history strategy were correlated with localities subject to greater land use disturbance and less flow regulation, while functional traits associated with a periodic life history strategy were correlated with localities subject to regular disturbance and regulated flow. These are patterns observed at the continental scale, highlighting the generalizability of trait-based methods. Contrary to studies that found no community structure differences when considering riparian buffer zones, we found that fish functional traits were correlated with different environmental variables between analyses with buffer zones vs. entire catchment area land cover proportions. Using existing databases and fourth corner analysis, our results support the broad application potential for trait-based methods and indicate trait-based methods can detect environmental filtering by riparian zone land cover.

Brain volume of the newly-discovered species Rhynchocyon udzungwensis (Mammalia: Afrotheria: Macroscelidea): implications for encephalization in sengis.

The Gray-faced Sengi (Rhynchocyon udzungwensis) is a newly-discovered species of sengi (elephant-shrew) and is the largest known extant representative of the order Macroscelidea. The discovery of R. udzungwensis provides an opportunity to investigate the scaling relationship between brain size and body size within Macroscelidea, and to compare this allometry among insectivorous species of Afrotheria and other eutherian insectivores. We performed a spin-echo magnetic resonance imaging (MRI) scan on a preserved adult specimen of R. udzungwensis using a 7-Tesla high-field MR imaging system. The brain was manually segmented and its volume was compiled into a dataset containing previously-published allometric data on 56 other species of insectivore-grade mammals including representatives of Afrotheria, Soricomorpha and Erinaceomorpha. Results of log-linear regression indicate that R. udzungwensis exhibits a brain size that is consistent with the allometric trend described by other members of its order. Inter-specific comparisons indicate that macroscelideans as a group have relatively large brains when compared with similarly-sized terrestrial mammals that also share a similar diet. This high degree of encephalization within sengis remains robust whether sengis are compared with closely-related insectivorous afrotheres, or with more-distantly-related insectivorous laurasiatheres.

Social selection and peer influence in an online social network.

Disentangling the effects of selection and influence is one of social science's greatest unsolved puzzles: Do people befriend others who are similar to them, or do they become more similar to their friends over time? Recent advances in stochastic actor-based modeling, combined with self-reported data on a popular online social network site, allow us to address this question with a greater degree of precision than has heretofore been possible. Using data on the Facebook activity of a cohort of college students over 4 years, we find that students who share certain tastes in music and in movies, but not in books, are significantly likely to befriend one another. Meanwhile, we find little evidence for the diffusion of tastes among Facebook friends-except for tastes in classical/jazz music. These findings shed light on the mechanisms responsible for observed network homogeneity; provide a statistically rigorous assessment of the coevolution of cultural tastes and social relationships; and suggest important qualifications to our understanding of both homophily and contagion as generic social processes.

Selective reduction of Von Economo neuron number in agenesis of the corpus callosum.

Von Economo neurons (VENs) are large spindle-shaped neurons localized to anterior cingulate cortex (ACC) and fronto-insular cortex (FI). VENs appear late in development in humans, are a recent phylogenetic specialization, and are selectively destroyed in frontotemporal dementia, a disease which profoundly disrupts social functioning and self-awareness. Agenesis of the corpus callosum (AgCC) is a congenital disorder that can have significant effects on social and emotional behaviors, including alexithymia, difficulty intuiting the emotional states of others, and deficits in self- and social-awareness that can impair humor, comprehension of non-literal or affective language, and social judgment. To test the hypothesis that VEN number is selectively reduced in AgCC, we used stereology to obtain unbiased estimates of total neuron number and VEN number in postmortem brain specimens of four normal adult controls, two adults with isolated callosal dysgenesis, and one adult whose corpus callosum and ACC were severely atrophied due to a non-fatal cerebral arterial infarction. The partial agenesis case had approximately half as many VENs as did the four normal controls, both in ACC and FI. In the complete agenesis case the VENs were almost entirely absent. The percentage of neurons in FI that are VENs was reduced in callosal agenesis, but was actually slightly above normal in the stroke patient. These results indicate that the VEN population is selectively reduced in AgCC, but that the VENs do not depend on having an intact corpus callosum. We conclude that in agenesis of the corpus callosum the reduction in the number of VENs is not the direct result of the failure of this structure to develop, but may instead be another consequence of the genetic disruption that caused the agenesis. The reduction of the VEN population could help to explain some of the social and emotional deficits that are seen in this disorder.

Anatomical analysis of an aye-aye brain (Daubentonia madagascariensis, primates: Prosimii) combining histology, structural magnetic resonance imaging, and diffusion-tensor imaging.

This report presents initial results of a multimodal analysis of tissue volume and microstructure in the brain of an aye-aye (Daubentonia madagascariensis). The left hemisphere of an aye-aye brain was scanned using T2-weighted structural magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) prior to histological processing and staining for Nissl substance and myelinated fibers. The objectives of the experiment were to estimate the volume of gross brain regions for comparison with published data on other prosimians and to validate DTI data on fiber anisotropy with histological measurements of fiber spread. Measurements of brain structure volumes in the specimen are consistent with those reported in the literature: the aye-aye has a very large brain for its body size, a reduced volume of visual structures (V1 and LGN), and an increased volume of the olfactory lobe. This trade-off between visual and olfactory reliance is likely a reflection of the nocturnal extractive foraging behavior practiced by Daubentonia. Additionally, frontal cortex volume is large in the aye-aye, a feature that may also be related to its complex foraging behavior and sensorimotor demands. Analysis of DTI data in the anterior cingulum bundle demonstrates a strong correlation between fiber spread as measured from histological sections and fiber spread as measured from DTI. These results represent the first quantitative comparison of DTI data and fiber-stained histology in the brain.

Asymmetric regional cerebral blood flow in sedated baboons measured by positron emission tomography (PET).

The analysis of structural brain asymmetry has been a focal point in anthropological theories of human brain evolution and the development of lateralized behaviors. While physiological brain asymmetries have been documented for humans and animals presenting with pathological conditions or under certain activation tasks, published studies on baseline asymmetries in healthy individuals have produced conflicting results. We tested for the presence of cerebral blood flow asymmetries in 7 healthy, sedated baboons using positron emission tomography, a method of in vivo autoradiography. Five of the 7 baboons exhibited hemispheric asymmetries in which left-sided flow was significantly greater than right-sided flow. Furthermore, the degree of asymmetry in 8 of 24 brain regions was found to be significantly correlated with age; older individuals exhibited a higher degree of asymmetry than younger individuals. Cerebral blood flow itself was uncorrelated with age, and differences between males and females were not significant.