Energetic differences between bacterioplankton trophic groups and coral reef resistance.

Coral reefs are among the most productive and diverse marine ecosystems on the Earth. They are also particularly sensitive to changing energetic requirements by different trophic levels. Microbialization specifically refers to the increase in the energetic metabolic demands of microbes relative to macrobes and is significantly correlated with increasing human influence on coral reefs. In this study, metabolic theory of ecology is used to quantify the relative contributions of two broad bacterioplankton groups, autotrophs and heterotrophs, to energy flux on 27 Pacific coral reef ecosystems experiencing human impact to varying degrees. The effective activation energy required for photosynthesis is lower than the average energy of activation for the biochemical reactions of the Krebs cycle, and changes in the proportional abundance of these two groups can greatly affect rates of energy and materials cycling. We show that reef-water communities with a higher proportional abundance of microbial autotrophs expend more metabolic energy per gram of microbial biomass. Increased energy and materials flux through fast energy channels (i.e. water-column associated microbial autotrophs) may dampen the detrimental effects of increased heterotrophic loads (e.g. coral disease) on coral reef systems experiencing anthropogenic disturbance.

Intimate partner sexual violence: a comparison of foreign- versus US-born physically abused Latinas.

Men's violence against women-particularly intimate partner sexual violence (IPSV)-is associated with the transmission of HIV. Men who physically abuse their female intimate partners often also sexually abuse them. Latinas are one of the fastest growing populations in the USA and at high-risk for contracting HIV, though little is known about IPSV against physically abused Latinas, including whether there is an association between nativity of the victim and the likelihood of sexual violence by intimate partners. This study examined the (1) prevalence of recent (past 6 months) IPSV against 555 physically abused, help-seeking Latinas and (2) relationship of nativity to recent IPSV. This study used data collected in 2002­2003 from participants in one major city on the East Coast and one West Coast county, who were involved in the Risk Assessment Validation (RAVE) Study. The RAVE Study assessed the accuracy of four different methods for predicting risk of future intimate partner violence. IPSV was defined as an abusive male partner physically forcing sex (rape) or making the woman have sex without a condom. Recent IPSV was reported by 38 % of the sample. Among those reporting recent IPSV, multiple assaults were common: 30%of women were raped and 51%were made to have unprotected sex six or more times during the past 6 months. IPSV was significantly associated with nativity. Physically abused Latinas who were foreign born had two times greater odds of reporting recent IPSV than physically abused Latinas born in the USA, after controlling for other demographic covariates. Exploratory post hoc analyses examining all pairwise comparisons of IPSV against Latinas born in the USA, Mexico, Central America, South America, and the Caribbean also revealed some significant differences that warrant further study with larger samples. HIV prevention efforts aimed at reducing IPSV in this population are needed.

Microorganisms and dissolved metabolites distinguish Florida's Coral Reef habitats.

As coral reef ecosystems experience unprecedented change, effective monitoring of reef features supports management, conservation, and intervention efforts. Omic techniques show promise in quantifying key components of reef ecosystems including dissolved metabolites and microorganisms that may serve as invisible sensors for reef ecosystem dynamics. Dissolved metabolites are released by reef organisms and transferred among microorganisms, acting as chemical currencies and contributing to nutrient cycling and signaling on reefs. Here, we applied four omic techniques (taxonomic microbiome via amplicon sequencing, functional microbiome via shotgun metagenomics, targeted metabolomics, and untargeted metabolomics) to waters overlying Florida's Coral Reef, as well as microbiome profiling on individual coral colonies from these reefs to understand how microbes and dissolved metabolites reflect biogeographical, benthic, and nutrient properties of this 500-km barrier reef. We show that the microbial and metabolite omic approaches each differentiated reef habitats based on geographic zone. Further, seawater microbiome profiling and targeted metabolomics were significantly related to more reef habitat characteristics, such as amount of hard and soft coral, compared to metagenomic sequencing and untargeted metabolomics. Across five coral species, microbiomes were also significantly related to reef zone, followed by species and disease status, suggesting that the geographic water circulation patterns in Florida also impact the microbiomes of reef builders. A combination of differential abundance and indicator species analyses revealed metabolite and microbial signatures of specific reef zones, which demonstrates the utility of these techniques to provide new insights into reef microbial and metabolite features that reflect broader ecosystem processes.

Characterization of Active MMP9 in Chronic Inflammatory Diseases Using a Novel Anti-MMP9 Antibody.

Matrix metalloproteinase 9 (MMP9), a protease implicated in multiple diseases, is secreted as an inactive zymogen and requires proteolytic removal of the pro-domain for activation. The relative levels and functionality of the pro- and active-MMP9 isoforms in tissues are not characterized. We generated a specific antibody that distinguishes an active form of MMP9, F107-MMP9, from the inactive pro-MMP9 isoform. Using multiple in vitro assays and specimen types, we show that F107-MMP9 expression is localized and disease-specific compared with its more abundant parental pro-form. It is detected around sites of active tissue remodeling, including fistulae of inflammatory bowel and dermal fissures in hidradenitis suppurativa, and is expressed by myeloid cells, including macrophages and neutrophils. Together, our findings provide insights into the distribution and potential role of MMP9 in inflammatory diseases.

Uterine artery embolization during pregnancy.

Uterine artery pseudoaneurysms are very rare but serious malformations that can occur during pregnancy or postpartum. It is crucial to identify and treat them due to the morbid consequences associated with rupture. We present a case of a 27-year-old primigravid at 22 weeks 4 days with placenta previa and recent right salpingo-oophorectomy who presented with hematuria and right lower quadrant pain. A left uterine artery pseudoaneurysm was found on computed tomography, which grew from 1.3 to 1.8 cm over 2 days. During therapeutic endovascular embolization, the pseudoaneurysm was identified and the uterine artery was successfully embolized. The fetus was carried to 34 weeks 4 days. There is no medical treatment for pseudoaneurysms and the risk of rupture vs complication of embolization must be weighed on an individual basis. As shown in this case, interventions are generally recommended to prevent harm to both mother and fetus.

Using GenBank and SRA.

GenBank® and the Sequence Read Archive (SRA) are comprehensive databases of publicly available DNA sequences. GenBank contains data for 480,000 named organisms, more than 176,000 within the embryophyta, obtained through submissions from individual laboratories and batch submissions from large-scale sequencing projects. SRA contains reads from next-generation sequencing studies from over 110,000 species. Daily data exchange with the European Nucleotide Archive (ENA) in Europe and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage for both databases. GenBank and SRA data are accessible through the NCBI Entrez retrieval system that integrates these data with other data at NCBI, such as genomes, taxonomy, and the biomedical literature. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. Usage scenarios for both GenBank and SRA ranging from local and cloud analyses to online analyses supported by the NCBI web-based tools are discussed. Both GenBank and SRA, along with their related retrieval and analysis services, are available from the NCBI homepage at www.ncbi.nlm.nih.gov .

Radiographic prevalence of juvenile osteochondral conditions of the proximal interphalangeal joint of Australian Thoroughbred racehorse yearlings and associations with sales results and race performance.

Objectives: Ascertain the radiographic prevalence and variation in characteristics of juvenile osteochondral conditions (JOC) in the proximal interphalangeal joint (PIPJ) of Australian Thoroughbred racehorse yearlings. Establish whether there are any significant associations with public auction sale results and racing performance. Methods: Retrospective evaluation of 1,098 yearling repository radiograph sets. Comparison of sales results and whole career racing performance of the case group with two control groups: maternal siblings (N = 397) and yearlings without PIP JOC (N = 391). Results: 6.3% of yearlings had at least one PIPJ JOC lesion with 4.8% having subchondral lucencies of the proximal phalanx (P1SC), 0.6% with subchondral lucencies of the middle phalanx (P2SC) and 0.8% with osteochondral fragmentation (OCF). P1SC were more prevalent in forelimbs and P2SC and OCF were more commonly located in the hindlimbs. 51% of PIPJ JOC were not identified on a lateromedial projection (LM). A significantly lower proportion of horses with OCF were successfully sold at public auction (p ≤ 0.05) but there was no significant difference in sales price between the case group and controls. A lower proportion of horses with PIPJ JOC made it to the racetrack to race, although this was not statistically significant. There was no significant difference in racing performance between the case group and controls, although there was a trend toward case horses earning lower career prize money and lower prize money per race (p ≤ 0.1). Lesions located in a dorsal or palmar/plantar location on the LM projection earned a lower average prize money per race (p ≤ 0.05) than those in a central location, and showed a trend toward earning lower total prize money (p ≤ 0.1) and number of places (p ≤ 0.1). There was no significant difference in performance for horses with lesions at the medial, axial or lateral aspects of the articular surface. Clinical importance: Overall, the findings of this study indicate that the presence of PIPJ JOC in radiographs of Thoroughbred yearlings should be attributed a low to moderate risk to future racing performance, however certain lesion characteristics may be associated with decreased performance.

Implanted microvessels progress through distinct neovascularization phenotypes.

We have previously demonstrated that implanted microvessels form a new microcirculation with minimal host-derived vessel investment. Our objective was to define the vascular phenotypes present during neovascularization in these implants and identify post-angiogenesis events. Morphological, functional and transcriptional assessments identified three distinct vascular phenotypes in the implants: sprouting angiogenesis, neovascular remodeling, and network maturation. A sprouting angiogenic phenotype appeared first, characterized by high proliferation and low mural cell coverage. This was followed by a neovascular remodeling phenotype characterized by a perfused, poorly organized neovascular network, reduced proliferation, and re-associated mural cells. The last phenotype included a vascular network organized into a stereotypical tree structure containing vessels with normal perivascular cell associations. In addition, proliferation was low and was restricted to the walls of larger microvessels. The transition from angiogenesis to neovascular remodeling coincided with the appearance of blood flow in the implant neovasculature. Analysis of vascular-specific and global gene expression indicates that the intermediate, neovascular remodeling phenotype is transcriptionally distinct from the other two phenotypes. Therefore, this vascular phenotype likely is not simply a transitional phenotype but a distinct vascular phenotype involving unique cellular and vascular processes. Furthermore, this neovascular remodeling phase may be a normal aspect of the general neovascularization process. Given that this phenotype is arguably dysfunctional, many of the microvasculatures present within compromised or diseased tissues may not represent a failure to progress appropriately through a normally occurring neovascularization phenotype.

Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts.

Cardiomyocytes derived from human embryonic stem (hES) cells potentially offer large numbers of cells to facilitate repair of the infarcted heart. However, this approach has been limited by inefficient differentiation of hES cells into cardiomyocytes, insufficient purity of cardiomyocyte preparations and poor survival of hES cell-derived myocytes after transplantation. Seeking to overcome these challenges, we generated highly purified human cardiomyocytes using a readily scalable system for directed differentiation that relies on activin A and BMP4. We then identified a cocktail of pro-survival factors that limits cardiomyocyte death after transplantation. These techniques enabled consistent formation of myocardial grafts in the infarcted rat heart. The engrafted human myocardium attenuated ventricular dilation and preserved regional and global contractile function after myocardial infarction compared with controls receiving noncardiac hES cell derivatives or vehicle. The ability of hES cell-derived cardiomyocytes to partially remuscularize myocardial infarcts and attenuate heart failure encourages their study under conditions that closely match human disease.

High-flow Nasal Oxygen Versus Standard Oxygen During Flexible Bronchoscopy in Lung Transplant Patients: A Randomized Controlled Trial.

BACKGROUND: Diagnostic and interventional flexible bronchoscopy (FB) is increasingly utilized in complex and high-risk patients. Patients are often sedated for comfort and procedure facilitation and hypoxia is commonly observed in this setting. We hypothesized that high-flow nasal oxygen (HFNO) would reduce the incidence of patients experiencing oxygen desaturation. METHODS: In this randomized controlled trial, postlung transplant patients booked for FB with transbronchial lung biopsy were assigned to either HFNO or low-flow nasal oxygen (LFNO). The patient and bronchoscopist were blinded to group allocation. The primary endpoint was the proportion of patients experiencing mild desaturation [peripheral oxygen saturation (SpO2)<94%]. Secondary endpoints included desaturation (SpO2<90%), the number of airway interventions required and procedure interruptions, the duration of oxygen desaturation and patient, bronchoscopist and anesthesiologist satisfaction scores. RESULTS: The trial analyzed data from 76 patients (LFNO, n=39; HFNO, n=37). HFNO reduced the proportion of patients experiencing SpO2<94% (43.2% vs. 89.7%, P<0.001) and SpO2<90% (16.2% vs. 69.2%, P<0.001). The FB was interrupted 11 times in 9 patients in the LFNO group, whereas there were no interruptions in the HFNO group. There were no differences in patient and bronchoscopist satisfaction scores between groups, anesthesiologists had higher satisfaction scores when using HFNO (P<0.001). CONCLUSION: Hypoxia occurred less commonly in postlung transplant patients receiving HFNO during FB. Further studies are warranted in other high-risk populations undergoing longer duration FB.

Transcriptional profiling of human cavernosal endothelial cells reveals distinctive cell adhesion phenotype and role for claudin 11 in vascular barrier function.

To determine specific molecular features of endothelial cells (ECs) relevant to the physiological process of penile erection we compared gene expression of human EC derived from corpus cavernosum of men with and without erectile dysfunction (HCCEC) to coronary artery (HCAEC) and umbilical vein (HUVEC) using Affymetrix GeneChip microarrays and GeneSifter software. Genes differentially expressed across samples were partitioned around medoids to identify genes with highest expression in HCCEC. A total of 190 genes/transcripts were highly expressed only in HCCEC. Gene Ontology classification indicated cavernosal enrichment in genes related to cell adhesion, extracellular matrix, pattern specification and organogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed high expression of genes relating to ECM-receptor interaction, focal adhesions, and cytokine-cytokine receptor interaction. Real-time PCR confirmed expression differences in cadherins 2 and 11, claudin 11 (CLDN11), desmoplakin, and versican. CLDN11, a component of tight junctions not previously described in ECs, was highly expressed only in HCCEC and its knockdown by siRNA significantly reduced transendothelial electrical resistance in HCCEC. Overall, cavernosal ECs exhibited a transcriptional profile encoding matrix and adhesion proteins that regulate structural and functional characteristics of blood vessels. Contribution of the tight junction protein CLDN11 to barrier function in endothelial cells is novel and may reflect hemodynamic requirements of the corpus cavernosum.

Intestinal permeability and effects of Lactobacillus rhamnosus therapy in children with short bowel syndrome.

BACKGROUND: The present study was conducted to investigate the effects of Lactobacillus rhamnosus (also known as LGG) on intestinal permeability (IP) in children with short bowel syndrome (SBS). PATIENTS AND METHODS: In a double-blind, placebo-controlled crossover clinical trial, baseline IP (ie, lactulose-to-mannitol ratio) was measured in subjects with SBS and healthy control subjects. Subjects with SBS received LGG or placebo for 4 weeks, followed by a 3-week washout before therapy was crossed over for another 4 weeks. IP, quantitative fecal cultures for Lactobacillus species (in colony-forming units [cfu] per gram of stool) and hydrogen breath test (HBT) were performed during LGG and placebo phases of therapy. RESULTS: Twenty-one children (SBS, n = 9; control, n = 12) with a median age of 4.5 years (range 1.6-16.4 years) enrolled. Baseline IP measurements were similar in patients with SBS and control subjects: 0.08 +/- 0.06 (mean +/- SD) versus 0.07 +/- 0.05 (P = 1.0). IP was correlated with age in control subjects (r = -0.83, P = 0.001) but not among patients with SBS (r = -0.55, P = 0.16). Fecal colonization with Lactobacillus species did not differ during LGG versus placebo therapy (median 1.4 x 10(9) cfu/g [range 4.0 x 10(5) to 4.0 x 10(9) cfu/g] vs 6.0 x 10(9) cfu/g [1.0 x 10(3) to 1.0 x 10(10) cfu/g], respectively; P = 0.83). LGG therapy had no consistent effects on IP (P = 0.58) or its relationship with age (r = -0.40, P = 0.29), and was associated with conversion to positive HBT results in 1 subject. CONCLUSIONS: In this sample of children with SBS, the IP was within normal limits but did not correlate with age. LGG therapy had no consistent effects on IP. These findings do not support empiric LGG therapy to enhance IP in children with SBS.

MMP-9 inhibition promotes anti-tumor immunity through disruption of biochemical and physical barriers to T-cell trafficking to tumors.

Matrix metalloproteinase-9 (MMP-9), whose expression is frequently dysregulated in cancer, promotes tumor growth, invasion, and metastasis by multiple mechanisms, including extracellular matrix remodeling and growth-factor and cytokine activation. We developed a monoclonal antibody against murine MMP-9, which we found decreased growth of established primary tumors in an orthotopic model of HER2-driven breast cancer (HC11-NeuT) in immunocompetent mice. RNA sequencing (RNAseq) profiling of NeuT tumors and additional mouse model tumors revealed that anti-MMP-9 treatment resulted in upregulation of immune signature pathways associated with cytotoxic T-cell response. As there is a need to boost the low response rates observed with anti-PDL1 antibody treatment in the clinical setting, we assessed the potential of anti-MMP-9 to improve T-cell response to immune checkpoint inhibitor anti-PDL1 in NeuT tumors. Anti-MMP-9 and anti-PDL1 cotreatment reduced T-cell receptor (TCR) clonality and increased TCR diversity, as detected by TCR sequencing of NeuT tumors. Flow cytometry analyses of tumors showed that the combination treatment increased the frequency of CD3+ T cells, including memory/effector CD4 and CD8 T cells, but not regulatory T cells, among tumor-infiltrating leukocytes. Moreover, in vitro enzymatic assays corroborated that MMP-9 cleaves key T-cell chemoattractant CXC receptor 3 ligands (CXC ligand [CXCL] 9, CXCL10, and CXCL11) and renders them inactive in T-cell migration assays. Consistent with our in vitro experiments, analysis of NeuT tumor protein lysates showed that anti-MMP-9 treatment increases expression of CXCL10 and other T cell-stimulating factors, such as interleukin (IL)-12p70 and IL-18. We show that inhibition of MMP-9, a key component of the tumor-promoting and immune-suppressive myeloid inflammatory milieu, increases T-helper cell 1 type cytokines, trafficking of effector/memory T cells into tumors, and intratumoral T-cell diversity.

Are Abused Women's Protective Actions Associated With Reduced Threats, Stalking, and Violence Perpetrated by Their Male Intimate Partners?

Victims of intimate partner violence may take various actions to protect themselves from their partner. This research examined the association between abused women's ( N = 755) protective strategies at baseline and her partner's threats, stalking, and moderate and severe violence 8 months later. Emergency domestic violence shelter and orders of protection significantly reduced subsequent abuse. Receiving medical treatment was associated with a significant increase in violence, and security devices (e.g., mace, changing locks) with an increase in stalking. Safety planning and other strategies had no statistical association with abuse at follow-up. Future research should continue to examine the efficacy of safety strategies.

Human embryonic stem cell-derived cardiomyocytes can be maintained in defined medium without serum.

Current procedures for the maintenance of cardiomyocytes from human embryonic stem (hES) cells rely on either co-culture with mouse cells or medium containing fetal bovine serum (FBS). Due to exposure to animal products, these methods carry the risk of potential pathogen contamination and increased immunogenicity. Additionally, FBS introduces inherent variability in the cultures due to the inevitable differences in serum lots. Here we investigated whether a defined serum-free medium containing creatine, carnitine, taurine, and insulin (CCTI) could maintain hES cell-derived cardiomyocytes. We show that hES cell-derived cardiomyocytes maintained in the CCTI medium in the absence of any feeders exhibit similar phenotypes to those maintained in serum, as indicated by the following observations: (1) comparable levels of cardiac gene transcription were found in cells grown in serum-containing medium versus those in the CCTI medium; (2) cardiomyocyte-associated proteins were expressed in cells cultured in the CCTI medium; (3) beating cells in the CCTI medium responded to pharmacological agents in a dose-dependent manner; and (4) the vast majority of the beating embryoid bodies displayed ventricular-like action potentials (APs), and the ventricular cells in serum-containing medium and the CCTI medium had indistinguishable AP properties. Therefore, culturing hES cell-derived cardiomyocytes in serum-free medium as described here should facilitate the use of the cells for in vitro and in vivo applications.

Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats.

To investigate the full range of molecular changes associated with erectile dysfunction (ED) in Type 1 diabetes, we examined alterations in penile gene expression in streptozotocin-induced diabetic rats and littermate controls. With the use of Affymetrix GeneChip arrays and statistical filtering, 529 genes/transcripts were considered to be differentially expressed in the diabetic rat cavernosum compared with control. Gene Ontology (GO) classification indicated that there was a decrease in numerous extracellular matrix genes (e.g., collagen and elastin related) and an increase in oxidative stress-associated genes in the diabetic rat cavernosum. In addition, PubMatrix literature mining identified differentially expressed genes previously shown to mediate vascular dysfunction [e.g., ceruloplasmin (Cp), lipoprotein lipase, and Cd36] as well as genes involved in the modulation of the smooth muscle phenotype (e.g., Kruppel-like factor 5 and chemokine C-X3-C motif ligand 1). Real-time PCR was used to confirm changes in expression for 23 relevant genes. Further validation of Cp expression in the diabetic rat cavernosum demonstrated increased mRNA levels of the secreted and anchored splice variants of Cp. CP protein levels showed a 1.9-fold increase in tissues from diabetic rats versus controls. Immunohistochemistry demonstrated localization of CP protein in cavernosal sinusoids of control and diabetic animals, including endothelial and smooth muscle layers. Overall, this study broadens the scope of candidate genes and pathways that may be relevant to the pathophysiology of diabetes-induced ED as well as highlights the potential complexity of this disorder.

Flow-dependent remodeling in the carotid artery of fibroblast growth factor-2 knockout mice.

OBJECTIVE: Fibroblast growth factor-2 (FGF2) has been implicated as a mediator in the structural remodeling of arteries. Chronic changes in blood flow are known to cause reorganization of the vessel wall, resulting in permanent changes in artery size (flow-dependent remodeling). Using FGF2 knockout (Fgf2(-/-)) mice, we tested the hypothesis that FGF2 is required during flow-dependent remodeling of the carotid arteries. METHODS AND RESULTS: All branches originating from the left common carotid artery (LCCA), except for the left thyroid artery, were ligated to reduce flow in the LCCA and increase flow in the contralateral right common carotid artery (RCCA). Age- and sex-matched control animals did not undergo ligation of the LCCA branches. Morphometric analysis showed that by day 7, vessel diameter was significantly greater in the high-flow RCCA of FGF2 wild-type (Fgf2(+/+)) and Fgf2(-/-) mice versus the respective control RCCA, demonstrating outward remodeling. In contrast, vessel diameter was decreased by day 7 in the low-flow LCCA of both genotypes compared with the control LCCA, showing inward remodeling. No differences were observed between Fgf2(+/+) and Fgf2(-/-) mice in either high-flow or low-flow remodeling. CONCLUSIONS: Given these results, we demonstrate that FGF2 is not essential for flow-dependent remodeling of the carotid arteries.

Outcomes of custody and visitation petitions when fathers are restrained by protection orders: the case of the New York family courts.

A random sample of custody and visitation petitions filed in New York City Family Courts in 1995 was used to examine outcomes of mothers' Order of Protection (OP) Petitions in relation to parents' custody and visitation petitions. Fathers restrained by OPs were more likely to secure visitation orders (64%) than not. In contrast, 80.8% of fathers' custody petitions were dismissed when they were restrained by OPs. Fathers' custody petitions were most likely to be ordered when mothers' OP petitions were withdrawn. Mothers were most likely to secure custody when their OP petitions were ordered or withdrawn. Courts rarely denied petitions. Those that did not result in court orders were either withdrawn by the petitioner or dismissed by the court (most likely because of failure of the petitioner to appear in court). This pattern has negative implications for battered women who may be vulnerable to pressure or threats from abusive ex-partners.