Post-stroke Intranasal (+)-Naloxone Delivery Reduces Microglial Activation and Improves Behavioral Recovery from Ischemic Injury

Peer reviewe

Sex and the Single Gametophyte: Revising the Homosporous Vascular Plant Life Cycle in Light of Contemporary Research

Homosporous vascular plants are typically depicted as extreme inbreeders, with bisexual gametophytes that produce strictly homozygous sporophytes. This view is promulgated in textbook life cycles despite ample evidence that natural populations of most species regularly outcross. We review research on a variety of mechanisms, including genetic load, asynchronous production of eggs and sperm, and pheromonal control of gamete production, that actively promote heterozygosity in ferns and lycophytes. Evolution of the land plants cannot be reconstructed without accurate depictions of the unique life cycle that has helped make ferns the second most diverse lineage of vascular plants on Earth. With revised illustrations and definitions, we provide scientists, educators, and students with a contemporary understanding of fern and lycophyte reproduction, revealing them as evolutionarily dynamic and exploiting a wide range of mating systems

WISE/NEOWISE observations of Active Bodies in the Main Belt

We report results based on mid-infrared photometry of 5 active main belt objects (AMBOs) detected by the Wide-field Infrared Survey Explorer (WISE) spacecraft. Four of these bodies, P/2010 R2 (La Sagra), 133P/Elst-Pizarro, (596) Scheila, and 176P/LINEAR, showed no signs of activity at the time of the observations, allowing the WISE detections to place firm constraints on their diameters and albedos. Geometric albedos were in the range of a few percent, and on the order of other measured comet nuclei. P/2010 A2 was observed on April 2-3, 2010, three months after its peak activity. Photometry of the coma at 12 and 22 {\mu}m combined with ground-based visible-wavelength measurements provides constraints on the dust particle mass distribution (PMD), dlogn/dlogm, yielding power-law slope values of {\alpha} = -0.5 +/- 0.1. This PMD is considerably more shallow than that found for other comets, in particular inbound particle fluence during the Stardust encounter of comet 81P/Wild 2. It is similar to the PMD seen for 9P/Tempel 1 in the immediate aftermath of the Deep Impact experiment. Upper limits for CO2 & CO production are also provided for each AMBO and compared with revised production numbers for WISE observations of 103P/Hartley 2.Comment: 32 Pages, including 5 Figure

Centaurs and Scattered Disk Objects in the Thermal Infrared: Analysis of WISE/NEOWISE Observations

The Wide-field Infrared Survey Explorer (WISE) observed 52 Centaurs and scattered disk objects (SDOs) in the thermal infrared, including 15 new discoveries. We present analyses of these observations to estimate sizes and mean optical albedos. We find mean albedos of 0.08 ± 0.04 for the entire data set. Thermal fits yield average beaming parameters of 0.9 ± 0.2 that are similar for both SDO and Centaur sub-classes. Biased cumulative size distributions yield size-frequency distribution power law indices of ~–1.7 ± 0.3. The data also reveal a relation between albedo and color at the 3σ level. No significant relation between diameter and albedos is found

Maternal and neonatal outcomes in patients with hepatitis C and intrahepatic cholestasis of pregnancy: The sum of the parts.

ObjectiveHepatitis C virus and intrahepatic cholestasis of pregnancy (ICP) are well-known independent risk factors for adverse outcomes in pregnancy. In addition, it is well-established that there is an association between Hepatitis C and ICP. This study's objective was to describe the impact of having both Hepatitis C and ICP on maternal and obstetric outcomes compared to patients having either Hepatitis C or ICP.MethodsWe conducted a retrospective cohort study of the Nationwide Readmissions Database, an all-payor sample of discharges from approximately 60% of US hospitalizations. Deliveries at 24-42+ weeks between 10/2015 and 12/2020 were included. Diagnosis of Hepatitis C and ICP, and outcomes related to severe maternal morbidity were identified using International Classification of Disease-10 codes. Patients were categorized based on Hepatitis C and ICP status. Weighted logistic and negative binomial regression analyses were used to evaluate the association between Hepatitis C and ICP status and outcomes, adjusting for patient and hospital characteristics. The primary outcome was any severe maternal morbidity; secondary outcomes included acute respiratory distress syndrome, acute kidney injury, sepsis, gestational diabetes, cesarean delivery, preterm birth, and hospital length of stay. We modeled interaction terms between ICP and Hepatitis C to assess whether there was a greater or lesser effect from having both conditions on outcomes than we would expect from additive combination of the individual components (i.e., synergy or antagonism).ResultsA total of 10,040,850 deliveries between 24-42+ weeks were identified. Of these, 45,368 had Hepatitis C only; 84,582 had ICP only; and 1,967 had both Hepatitis C and ICP. Patients with both Hepatitis C and ICP had 1.5-fold higher odds of developing severe maternal morbidity compared to having neither. There was an also an increased odds of severe maternal morbidity in patients with both Hepatitis C and ICP compared to patients with only Hepatitis C or ICP. Having both was also associated with higher odds of preterm birth and length of stay compared to having only Hepatitis C, only ICP, or neither (preterm birth: aOR 5.09, 95% CI 4.87-5.33 vs. neither; length of stay: 46% mean increase, 95% CI 35-58% vs. neither). Associations were additive-no significant interactions between hepatitis C and cholestasis were found on rates of severe maternal morbidity, acute respiratory distress syndrome, acute kidney injury, sepsis, cesarean section, or preterm birth (all p>0.05), and was minimal for gestational diabetes and length of stay.ConclusionHepatitis C and ICP are independent, additive risk factors for adverse maternal and obstetric outcomes. Despite physiologic plausibility, no evidence of a synergistic effect of these two diagnoses on outcomes was noted. These data may be useful in counseling patients regarding their increased risk of adverse outcomes when ICP presents in association with Hepatitis C versus ICP alone

Combining RNAscope and immunohistochemistry to visualize inflammatory gene products in neurons and microglia

A challenge for central nervous system (CNS) tissue analysis in neuroscience research has been the difficulty to codetect and colocalize gene and protein expression in the same tissue. Given the importance of identifying gene expression relative to proteins of interest, for example, cell-type specific markers, we aimed to develop a protocol to optimize their codetection. RNAscope fluorescent in situ hybridization (FISH) combined with immunohistochemistry (IHC) in fixed (CNS) tissue sections allows for reliable quantification of gene transcripts of interest within IHC-labeled cells. This paper describes a new method for simultaneous visualization of FISH and IHC in thicker (14-μm), fixed tissue samples, using spinal cord sections. This method’s effectiveness is shown by the cell-type-specific quantification of two genes, namely the proinflammatory cytokine interleukin-1beta (IL-1b) and the inflammasome NLR family pyrin domain containing 3 (NLRP3). These genes are challenging to measure accurately using immunohistochemistry (IHC) due to the nonspecificity of available antibodies and the hard-to-distinguish, dot-like visualizations of the labeled proteins within the tissue. These measurements were carried out in spinal cord sections after unilateral chronic constriction injury of the sciatic nerve to induce neuroinflammation in the spinal cord. RNAscope is used to label transcripts of genes of interest and IHC is used to label cell-type specific antigens (IBA1 for microglia, NeuN for neurons). This combination allowed for labeled RNA transcripts to be quantified within cell-type specific boundaries using confocal microscopy and standard image analysis methods. This method makes it easy to answer empirical questions that are intractable with standard IHC or in situ hybridization alone. The method, which has been optimized for spinal cord tissue and to minimize tissue preparation time and costs, is described in detail from tissue collection to image analysis. Further, the relative expression changes in inflammatory genes NLRP3 and IL-1b in spinal cord microglia vs. neurons of somatotopically relevant laminae are described for the first time

Prioritizing Health-Sector Interventions for Noncommunicable Diseases and Injuries in Low- and Lower-Middle Income Countries: National NCDI Poverty Commissions

Health sector priorities and interventions to prevent and manage noncommunicable diseases and injuries (NCDIs) in low- and lower-middle-income countries (LLMICs) have primarily adopted elements of the World Health Organization Global Action Plan for NCDs 2013–2020. However, there have been limited efforts in LLMICs to prioritize among conditions and health-sector interventions for NCDIs based on local epidemiology and contextually relevant risk factors or that incorporate the equitable distribution of health outcomes. The Lancet Commission on Reframing Noncommunicable Diseases and Injuries for the Poorest Billion supported national NCDI Poverty Commissions to define local NCDI epidemiology, determine an expanded set of priority NCDI conditions, and recommend cost-effective, equitable health-sector interventions. Fifteen national commissions and 1 state-level commission were established from 2016–2019. Six commissions completed the prioritization exercise and selected an average of 25 NCDI conditions; 15 conditions were selected by all commissions, including asthma, breast cancer, cervical cancer, diabetes mellitus type 1 and 2, epilepsy, hypertensive heart disease, intracerebral hemorrhage, ischemic heart disease, ischemic stroke, major depressive disorder, motor vehicle road injuries, rheumatic heart disease, sickle cell disorders, and subarachnoid hemorrhage. The commissions prioritized an average of 35 health-sector interventions based on cost-effectiveness, financial risk protection, and equity-enhancing rankings. The prioritized interventions were estimated to cost an additional US$4.70–US$13.70 per capita or approximately 9.7%–35.6% of current total health expenditure (0.6%–4.0% of current gross domestic product). Semistructured surveys and qualitative interviews of commission representatives demonstrated positive outcomes in several thematic areas, including understanding NCDIs of poverty, informing national planning and implementation of NCDI health-sector interventions, and improving governance and coordination for NCDIs. Overall, national NCDI Poverty Commissions provided a platform for evidence-based, locally driven determination of priorities within NCDIs.publishedVersio