Long-Term Mortality in Patients With Severe Hypercholesterolemia Phenotype From a Racial and Ethnically Diverse US Cohort.

BACKGROUND: Tools for mortality prediction in patients with the severe hypercholesterolemia phenotype (low-density lipoprotein cholesterol ≥190 mg/dL) are limited and restricted to specific racial and ethnic cohorts. We sought to evaluate the predictors of long-term mortality in a large racially and ethnically diverse US patient cohort with low-density lipoprotein cholesterol ≥190 mg/dL. METHODS: We conducted a retrospective analysis of all patients with a low-density lipoprotein cholesterol ≥190 mg/dL seeking care at Montefiore from 2010 through 2020. Patients <18 years of age or with previous malignancy were excluded. The primary end point was all-cause mortality. Analyses were stratified by age, sex, and race and ethnicity. Patients were stratified by primary and secondary prevention. Cox regression analyses were used to adjust for demographic, clinical, and treatment variables. RESULTS: A total of 18 740 patients were included (37% non-Hispanic Black, 30% Hispanic, 12% non-Hispanic White, and 2% non-Hispanic Asian patients). The mean age was 53.9 years, and median follow-up was 5.2 years. Both high-density lipoprotein cholesterol and body mass index extremes were associated with higher mortality in univariate analyses. In adjusted models, higher low-density lipoprotein cholesterol and triglyceride levels were associated with an increased 9-year mortality risk (adjusted hazard ratio [HR], 1.08 [95% CI, 1.05-1.11] and 1.04 [95% CI, 1.02-1.06] per 20-mg/dL increase, respectively). Clinical factors associated with higher mortality included male sex (adjusted HR, 1.31 [95% CI, 1.08-1.58]), older age (adjusted HR, 1.19 per 5-year increase [95% CI, 1.15-1.23]), hypertension (adjusted HR, 2.01 [95% CI, 1.57-2.57]), chronic kidney disease (adjusted HR, 1.68 [95% CI, 1.36-2.09]), diabetes (adjusted HR, 1.79 [95% CI, 1.50-2.15]), heart failure (adjusted HR, 1.51 [95% CI, 1.16-1.95]), myocardial infarction (adjusted HR, 1.41 [95% CI, 1.05-1.90]), and body mass index <20 kg/m2 (adjusted HR, 3.36 [95% CI, 2.29-4.93]). A significant survival benefit was conferred by lipid-lowering therapy (adjusted HR, 0.57 [95% CI, 0.42-0.77]). In the primary prevention group, high-density lipoprotein cholesterol <40 mg/dL was independently associated with higher mortality (adjusted HR, 1.49 [95% CI, 1.06-2.09]). Temporal trend analyses showed a reduction in statin use over time (P<0.001). In the most recent time period (2019-2020), 56% of patients on primary prevention and 85% of those on secondary prevention were on statin therapy. CONCLUSIONS: In a large, diverse cohort of US patients with the severe hypercholesterolemia phenotype, we identified several patient characteristics associated with increased 9-year all-cause mortality and observed a decrease in statin use over time, in particular for primary prevention. Our results support efforts geared toward early recognition and consistent treatment for patients with severe hypercholesterolemia.

Mechanisms regulating the initiation of porcine conceptus elongation.

Significant increases in litter size within commercial swine production over the past decades have led to increases in preweaning piglet mortality due to increase within-litter birthweight variation, typically due to mortality of the smallest littermate piglets. Therefore, identifying mechanisms to reduce variation in placental development and subsequent fetal growth are critical to normalizing birthweight variation and improving piglet survivability in high-producing commercial pigs. A major contributing factor to induction of within-litter variation occurs during the peri-implantation period as the pig blastocyst elongates from spherical to filamentous morphology in a short period of time and rapidly begins superficial implantation. During this period, there is significant within-litter variation in the timing and extent of elongation among littermates. As a result, delays and deficiencies in conceptus elongation not only contribute directly to early embryonic mortality, but also influence subsequent within-litter birthweight variation. This study will highlight key aspects of conceptus elongation and provide some recent evidence pertaining to specific mechanisms from -omics studies (i.e., metabolomics of the uterine environment and transcriptomics of the conceptus) that may specifically regulate the initiation of conceptus elongation to identify potential factors to reduce within-litter variation and improve piglet survivability.

Secreted metabolome of porcine blastocysts encapsulated within in vitro 3D alginate hydrogel culture systems undergoing morphological changes provides insights into specific mechanisms involved in the initiation of porcine conceptus elongation.

CONTEXT: The exact mechanisms regulating the initiation of porcine conceptus elongation are not known due to the complexity of the uterine environment. AIMS: To identify contributing factors for initiation of conceptus elongation in vitro , this study evaluated differential metabolite abundance within media following culture of blastocysts within unmodified alginate (ALG) or Arg-Gly-Asp (RGD)-modified alginate hydrogel culture systems. METHODS: Blastocysts were harvested from pregnant gilts, encapsulated within ALG or RGD or as non-encapsulated control blastocysts (CONT), and cultured. At the termination of 96h culture, media were separated into blastocyst media groups: non-encapsulated control blastocysts (CONT); ALG and RGD blastocysts with no morphological change (ALG- and RGD-); ALG and RGD blastocysts with morphological changes (ALG+ and RGD+) and evaluated for non-targeted metabolomic profiling by liquid chromatography (LC)-mass spectrometry (MS) techniques and gas chromatography-(GC-MS). KEY RESULTS: Analysis of variance identified 280 (LC-MS) and 1 (GC-MS) compounds that differed (P <0.05), of which 134 (LC-MS) and 1 (GC-MS) were annotated. Metabolites abundance between ALG+ vs ALG-, RGD+ vs RGD-, and RGD+ vs ALG+ were further investigated to identify potential differences in metabolic processes during the initiation of elongation. CONCLUSIONS: This study identified changes in phospholipid, glycosphingolipid, lipid signalling, and amino acid metabolic processes as potential RGD-independent mechanisms of elongation and identified changes in lysophosphatidylcholine and sphingolipid secretions during RGD-mediated elongation. IMPLICATIONS: These results illustrate changes in phospholipid and sphingolipid metabolic processes and secretions may act as mediators of the RGD-integrin adhesion that promotes porcine conceptus elongation.

Elevated red cell distribution width and cardiovascular mortality in ASCVD risk cohorts: National Health and Nutrition Examination Survey (NHANES III).

BACKGROUND: Although red cell distribution width (RDW) is associated with increased cardiovascular mortality, the relationship between an elevated RDW and cardiovascular mortality among various ASCVD risk groups is unknown. METHODS: We utilized the National Health and Nutrition Examination Survey (NHANES) III, which uses a complex, multistage, clustered design to represent the civilian, community-based US population. Out of 30,818 subjects whose data were entered during the 1988-1994 period, 8884 subjects over 40 years of age, representing a weighted sample of 85,323,902 patients, were selected after excluding missing variables. The ACC/AHA pooled cohort equation (PCE) was used to calculate atherosclerotic cardiovascular disease (ASCVD) risk, and low (<7.5%), intermediate (7.5-20%), and high (>20%) risk groups were created. The primary endpoint was cardiovascular mortality. A multivariate proportional hazard regression was performed using the Fine and Gray (sub-distribution) method. Red cell distribution (RDW), C-reactive protein (CRP), age, sex, race, diabetes, smoking status, high-density lipoprotein (HDL), and chronic kidney disease (CKD) were used as covariates in each of the ACC/AHA pooled cohort risk groups. RESULTS: The adjusted hazard ratios for RDW >14 (Normal range 12.5-14.5 %) as compared to <13 were 2.79 (95% confidence intervals (95% CI) 2.77-2.81, p < 0.01), 2.02 (95% CI 2.01-2.02, p < 0.01), 1.18 (95% CI 1.18-1.18, p < 0.01) in the low, intermediate and high-risk groups respectively. The 20-year cumulative cardiovascular mortality (RDW >14 vs. <13) was 4% vs. 1.3% low, 17.7% vs. 7.7% in intermediate and 28.1% vs. 24.6% in high ASCVD risk groups respectively. CONCLUSION: Our findings support that measurement of RDW in the intermediate ASCVD group may be clinically valuable for further risk stratification and prognostication in the general population of people aged more than 40 years of age with regards to identifying those at an increased risk for cardiovascular mortality.

Global analysis of differential gene expression within the porcine conceptus transcriptome as it transitions through spherical, ovoid, and tubular morphologies during the initiation of elongation.

This study aimed to identify transcriptome differences between distinct or transitional stage spherical, ovoid, and tubular porcine blastocysts throughout the initiation of elongation. We performed a global transcriptome analysis of differential gene expression using RNA-Seq with high temporal resolution between spherical, ovoid, and tubular stage blastocysts at specific sequential stages of development from litters containing conceptus populations of distinct or transitional blastocysts. After RNA-Seq analysis, significant differentially expressed genes (DEGs) and pathways were identified between distinct morphologies or sequential development stages. Overall, 1898 significant DEGs were identified between distinct spherical and ovoid morphologies, with 311 total DEGs between developmental stages throughout this first morphological transition, while 15 were identified between distinct ovoid and tubular, with eight total throughout these second morphological transition developmental stages. The high quantity of DEGs and pathways between conceptus stages throughout the spherical to ovoid transition suggests the importance of gene regulation during this first morphological transition for initiating elongation. Further, extensive DEG coverage of known elongation signaling pathways was illustrated from spherical to ovoid, and regulation of lipid signaling and membrane/ECM remodeling across these early conceptus stages were implicated as essential to this process, providing novel insights into potential mechanisms governing this rapid morphological change.

A Cluster of Nontuberculous Mycobacterial Tenosynovitis Following Hurricane Relief Efforts.

BACKGROUND: Nontuberculous mycobacteria (NTM) are a rare cause of infectious tenosynovitis of the upper extremity. Using molecular methods, clinical microbiology laboratories are increasingly reporting identification down to the species level. Improved methods for speciation are revealing new insights into the clinical and epidemiologic features of rare NTM infections. METHODS: We encountered 3 cases of epidemiologically linked upper extremity NTM tenosynovitis associated with exposure to hurricane-damaged wood. We conducted whole-genome sequencing to assess isolate relatedness followed by a literature review of NTM infections that involved the upper extremity. RESULTS: Despite shared epidemiologic risk, the cases were caused by 3 distinct organisms. Two cases were rare infections caused by closely related but distinct species within the Mycobacterium terrae complex that could not be differentiated by traditional methods. The third case was caused by Mycobacterium intracellulare. An updated literature review that focused on research that used modern molecular speciation methods found that several species within the M. terrae complex are increasingly reported as a cause of upper extremity tenosynovitis, often in association with environmental exposures. CONCLUSIONS: These cases illustrate the importance of molecular methods for speciating phenotypically similar NTM, as well as the limitations of laboratory-based surveillance in detecting point-source outbreaks when the source is environmental and may involve multiple organisms.

A Systematic Review of the Incidence and Outcomes of In-Hospital Cardiac Arrests in Patients With Coronavirus Disease 2019.

OBJECTIVES: To investigate the incidence, characteristics, and outcomes of in-hospital cardiac arrest in patients with coronavirus disease 2019 and to describe the characteristics and outcomes for patients with in-hospital cardiac arrest within the ICU, compared with non-ICU patients with in-hospital cardiac arrest. Finally, we evaluated outcomes stratified by age. DATA SOURCES: A systematic review of PubMed, EMBASE, and preprint websites was conducted between January 1, 2020, and December 10, 2020. Prospective Register of Systematic Reviews identification: CRD42020203369. STUDY SELECTION: Studies reporting on consecutive in-hospital cardiac arrest with a resuscitation attempt among patients with coronavirus disease 2019. DATA EXTRACTION: Two authors independently performed study selection and data extraction. Study quality was assessed with the Newcastle-Ottawa Scale. Data were synthesized according to the Preferred Reporting Items for Systematic Reviews guidelines. Discrepancies were resolved by consensus or through an independent third reviewer. DATA SYNTHESIS: Eight studies reporting on 847 in-hospital cardiac arrest were included. In-hospital cardiac arrest incidence varied between 1.5% and 5.8% among hospitalized patients and 8.0-11.4% among patients in ICU. In-hospital cardiac arrest occurred more commonly in older male patients. Most initial rhythms were nonshockable (83.9%, [asystole = 36.4% and pulseless electrical activity = 47.6%]). Return of spontaneous circulation occurred in 33.3%, with a 91.7% in-hospital mortality. In-hospital cardiac arrest events in ICU had higher incidence of return of spontaneous circulation (36.6% vs 18.7%; p < 0.001) and relatively lower mortality (88.7% vs 98.1%; p < 0.001) compared with in-hospital cardiac arrest in non-ICU locations. Patients greater than or equal to 60 years old had significantly higher in-hospital mortality than those less than 60 years (93.1% vs 87.9%; p = 0.019). CONCLUSIONS: Approximately, one in 20 patients hospitalized with coronavirus disease 2019 received resuscitation for an in-hospital cardiac arrest. Hospital survival after in-hospital cardiac arrest within the ICU was higher than non-ICU locations and seems comparable with prepandemic survival for nonshockable rhythms. Although the data provide guidance surrounding prognosis after in-hospital cardiac arrest, it should be interpreted cautiously given the paucity of information surrounding treatment limitations and resource constraints during the pandemic. Further research is into actual causative mechanisms is needed.

Metabolic compounds within the porcine uterine environment are unique to the type of conceptus present during the early stages of blastocyst elongation.

The objective of this study was to identify metabolites within the porcine uterine milieu during the early stages of blastocyst elongation. At Days 9, 10, or 11 of gestation, reproductive tracts of White cross-bred gilts (n = 38) were collected immediately following harvest and flushed with Roswell Park Memorial Institute-1640 medium. Conceptus morphologies were assessed from each pregnancy and corresponding uterine flushings were assigned to one of five treatment groups based on these morphologies: (a) uniform spherical (n = 8); (b) heterogeneous spherical and ovoid (n = 8); (c) uniform ovoid (n = 8); (d) heterogeneous ovoid and tubular (n = 8); and (e) uniform tubular (n = 6). Uterine flushings from these pregnancies were submitted for nontargeted profiling by gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography (UPLC)-MS techniques. Unsupervised multivariate principal component analysis (PCA) was performed using pcaMethods and univariate analysis of variance was performed in R with false discovery rate (FDR) adjustment. PCA analysis of the GC-MS and UPLC-MS data identified 153 and 104 metabolites, respectively. After FDR adjustment of the GC-MS and UPLC-MS data, 38 and 59 metabolites, respectively, differed (p < .05) in uterine flushings from pregnancies across the five conceptus stages. Some metabolites were greater (p < .05) in abundance for uterine flushings containing earlier stage conceptuses (i.e., spherical), such as uric acid, tryptophan, and tyrosine. In contrast, some metabolites were greater (p < .05) in abundance for uterine flushings containing later stage conceptuses (i.e., tubular), such as creatinine, serine, and urea. These data illustrate several putative metabolites that change within the uterine milieu during early porcine blastocyst elongation.

Integrated Compression Screw Stabilization of the Dorsal Lunate Facet in Intra-Articular Distal Radius Fractures.

PURPOSE: To evaluate outcomes of intra-articular distal radius fractures with displaced dorsal lunate facet fragments treated with a combination of volar plating and the use of a dorsal screw that integrates into the plate. METHODS: We reviewed a retrospective cohort of 22 patients who underwent open reduction and internal fixation of an intra-articular distal radius fracture with a volar plate in conjunction with the Frag-Loc Compression screw. Patient charts and radiographs were reviewed for clinical and radiographic outcomes. RESULTS: A total of 12 patients with a minimum 6-month follow-up who met all eligibility criteria were included in this study. There were 8 women and 4 men. The mean age was 55.2 years. Mean follow-up was 11.5 months (range, 6-21 months). The most common mechanism of injury was a fall from standing (75.0%). At final follow-up, all patients were able to return to their previous level of function. Bony union was achieved in all patients at the time of final follow-up. Average radiographic parameters at final follow-up were radial inclination 24.2° ± 5.3°, volar tilt 1.3° ± 5.2°, and ulnar variance 0.9 ± 1.7 mm. During the follow-up period, transient median nerve paresthesias were observed in 4 patients, with spontaneous resolution in 3 of 4 patients. Loss of articular reduction was not observed in any case. CONCLUSIONS: This study demonstrates satisfactory clinical and radiographic results and minimal complications with utilization of a new fixation device for distal radius fractures with displaced dorsal lunate facet fragments. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Neonatal lactocrine deficiency affects the adult porcine endometrial transcriptome at pregnancy day 13.

Reproductive performance of female pigs that do not receive sufficient colostrum from birth is permanently impaired. Whether lactocrine deficiency, reflected by low serum immunoglobulin immunocrit (iCrit), affects patterns of endometrial gene expression during the periattachment period of early pregnancy is unknown. Here, objectives were to determine effects of low iCrit at birth on the adult endometrial transcriptome on pregnancy day (PxD) 13. On the first day of postnatal life, gilts were assigned to high or low iCrit groups. Adult high (n = 8) and low (n = 7) iCrit gilts were bred (PxD 0), and humanely slaughtered on PxD 13 when tissues and fluids were collected. The endometrial transcriptome was defined for each group using mRNAseq and microRNAseq. Reads were mapped to the Sus scrofa 11.1 genome build. Mature microRNAs were annotated using miRBase 21. Differential expression was defined based on fold change (≥ ±1.5). Lactocrine deficiency did not affect corpora lutea number, uterine horn length, uterine wet weight, conceptus recovery, or uterine luminal fluid estrogen content on PxD 13. However, mRNAseq revealed 1157 differentially expressed endometrial mRNAs in high versus low iCrit gilts. Differentially expressed genes had functions related to solute transport, endometrial receptivity, and immune response. Six differentially expressed endometrial microRNAs included five predicted to target 62 differentially expressed mRNAs, affecting similar biological processes. Thus, lactocrine deficiency on the first day of postnatal life can alter uterine developmental trajectory with lasting effects on endometrial responses to pregnancy as reflected at the level of the transcriptome on PxD 13.

Impact of seasonality, storage of semen, and sperm head-shape on whole tissue methylation and expression of methylation responsive candidate genes in swine placenta and fetal livers from summer and winter breedings.

Epigenetics includes the study of external factors that can influence the expression of genes by altering the accessibility of DNA through methylation. To investigate the epigenetic influence of season, sperm head shape, and semen storage on placental and fetal tissues, pregnancies were generated in the summer or winter using boar semen from either least or most sperm head shape change, collected during cool or warm seasons, and stored as cooled-extended or cryopreserved. The lowest (p < 0.05) ratios of 5-methylcytosine to 5-hydroxymethylcytosine activity (5mC:5hmC) in fetal liver were from summer breedings and in placental tissues from winter breedings. The relative expression of placental CDH1 tended ( p < 0.10) to be greater in placenta generated from cryopreserved semen or semen collected during cool periods. The relative expression of placental GNAS was affected ( p < 0.05) by the interaction of breeding and semen collection seasons. Cryopreserved semen increased ( p < 0.05) the placental relative expression of GNAS. Placental MEST and RHOBTB3 tended ( p < 0.10) to have a greater relative expression from pregnancies generated using semen collected during cool periods used during winter breedings. Within fetal liver, the relative expression of GNAS and HGF was greater ( p < 0.05) from winter breedings. Interaction of winter breedings and least sperm head shape change tended ( p < 0.10) to have the greatest fetal liver expression of CDH1. Seasonality of semen collection, breeding, and the effect on sperm head shape change had an influence on the expression of genes with known differentially methylated regions or response to methylation activity from embryonic and extraembryonic tissues.

Sleepy Teens and Energy Drink Use: Results From an Ethnically Diverse Sample of Youth.

This study examines the association between use of energy drinks or products (EP), EP expectancies, and the association between EP use and sleep in a racially and ethnically diverse sample (N = 2,485) of adolescents. Prevalence of EP use was approximately 18%, with no statistically significant racial or ethnic differences in prevalence. There were significant racial and ethnic differences in EP expectancies; Hispanic and Multiracial or Other groups endorsed less positive expectancies than Whites and Asians. EP use was significantly associated with later weekend bedtimes, shorter weekend total sleep time (TST), a smaller weekend-weekday difference in TST, and more trouble sleeping, even after adjusting for covariates. There were no significant race or ethnicity interactions between EP use and sleep. EP use is an independent correlate of sleep problems in adolescents across racial or ethnic groups.

Predictors of Retention in an Alcohol and Risky Sex Prevention Program for Homeless Young Adults.

Homeless young adults are at risk for alcohol and other drug (AOD) use and risky sexual behavior. Interventions are needed to help these young people reduce their risky behavior, but this population is often difficult to engage and retain in services. We offered a four-session AOD and risky sex reduction program to 100 participants and examined if retention in the program was predicted by a number of factors: demographics, homelessness severity, other service use, AOD behaviors, mental health symptoms, sexual risk behaviors, and readiness to change AOD and condom use. Nearly half (48%) of participants completed all sessions. In bivariate analyses, participants were significantly less likely to be retained in the program if they had slept outdoors in the past month, engaged in more alcohol and marijuana use, experienced more alcohol-related consequences, and received the program in an urban drop-in center (as opposed to a drop-in center near the beach). When controlling for all significant bivariate relationships, only sleeping outdoors and receipt of the program in the urban setting predicted fewer sessions completed. The most endorsed reasons for program non-completion were being too busy to attend and inconvenient day/time of the program. Findings can help outreach staff and researchers better prepare methods to engage higher risk homeless youth and retain them in services. Finding unique ways to help youth overcome barriers related to location of services appears especially necessary, perhaps by bringing services to youth where they temporarily reside or offering meaningful incentives for program attendance.

Association of Transthoracic Echocardiography Findings and Long-Term Outcomes in Patients Undergoing Workup of Stroke.

BACKGROUND: Transthoracic echocardiography (TTE) has become routine as part of initial stroke workup to assess for sources of emboli. Few studies have looked at other TTE findings such as ejection fraction, wall motion abnormalities, valve disease, pulmonary hypertension and left ventricular hypertrophy and their association with various subtypes of stroke, long-term outcomes of recurrent stroke, and all-cause mortality. METHODS AND RESULTS: Computed tomography and magnetic resonance imaging brain imaging and TTE reports were reviewed for 2464 consecutive patients referred for TTE as part of a workup for acute stroke between 1/1/01 and 9/30/07. Study patients were 67 ± 15years, 60% female, 75% minorities and had hypertension (76%), diabetes (41%), chronic kidney disease (27%) and atrial fibrillation (18%). On TTE, a mass, thrombus, or vegetation was identified in only 4 cases (0.2%), whereas a clinically significant abnormality (ejection fraction < 50%, left ventricle or right ventricle wall motion abnormalities, severe valve disease, pulmonary hypertension, or left ventricular hypertrophy) was identified in 16%. Those with an abnormal TTE had increased risk for death at 10years (hazard ratio [HR] 1.8; 95% confidence interval [CI]: 1.6, 2.0; P < .01), although risk for readmission with stroke was not increased. Abnormal TTE remained associated with increased risk of death at 10years after adjustment for age, sex, race, and cardiovascular risk factors (HR 1.4; 95% CI: 1.2, 1.7; P < .01). CONCLUSIONS: TTE performed as part of an initial workup for stroke had minimal yield for identifying sources of embolism. Clinically important abnormalities found on TTE were independently associated with increased long-term mortality, but not recurrent stroke.

Sources of Care for Alcohol and Other Drug Problems: The Role of the African American Church.

African Americans experience significant disparities in treatment access, retention, and quality of care for alcohol and drug use (AOD) problems. Religious congregations, often the first point of contact for help with AOD problems, can play an integral role in improving access to treatment. However, little is known about the role of African American churches in addressing AOD problems. We administered a survey to a faith-based collaborative of 169 African American churches in Los Angeles to examine how AOD problems are identified in congregations, the types of support provided, barriers to providing treatment referrals, and factors associated with the provision of treatment referrals. Seventy-one percent of churches reported caring often for individuals with AOD problems. AOD problems came to the attention of congregations most commonly via a concerned family member (55%) and less frequently through individuals with AOD problems directly approaching clergy (30%). In addition to providing spiritual support, a substantial proportion of churches reported linking individuals to AOD services through referrals (62%) and consultation with providers (48%). Barriers to providing treatment referrals included lack of affordable programs (50%), stigma (50%), lack of effective treatments (45%), and insufficient resources or staff (45%). The likelihood of providing treatment referrals was greater among mid-sized versus smaller-size congregations (OR 3.43; p < .05) and among congregations with clergy that had attended seminary (OR 3.93; p < .05). Knowing how to effectively coordinate informal sources of care provided by African American churches with the formal service sector could make a significant impact on AOD treatment disparities.

In vitro porcine blastocyst development in three-dimensional alginate hydrogels.

Appropriate embryonic and fetal development significantly impact pregnancy success and, therefore, the efficiency of swine production. The pre-implantation period of porcine pregnancy is characterized by several developmental hallmarks, which are initiated by the dramatic morphological change that occurs as pig blastocysts elongate from spherical to filamentous blastocysts. Deficiencies in blastocyst elongation contribute to approximately 20% of embryonic loss, and have a direct influence on within-litter birth weight variation. Although factors identified within the uterine environment may play a role in blastocyst elongation, little is known about the exact mechanisms by which porcine (or other species') blastocysts initiate and progress through the elongation process. This is partly due to the difficulty of replicating elongation in vitro, which would allow for its study in a controlled environment and in real-time. We developed a three dimensional (3-D) culture system using alginate hydrogel matrices that can encapsulate pig blastocysts, maintain viability and blastocyst architecture, and facilitate reproducible morphological changes with corresponding expression of steroidogenic enzyme transcripts and estrogen production, consistent with the initiation of elongation in vivo. This review highlights key aspects of the pre-implantation period of porcine pregnancy and the difficulty of studying blastocyst elongation in vivo or by using in vitro systems. This review also provides insights on the utility of 3-D hydrogels to study blastocyst elongation continuously and in real-time as a complementary and confirmatory approach to in vivo analysis.

A systematic review of modifiable risk factors in the progression of multiple sclerosis.

BACKGROUND: The presenting symptoms and rate of progression of multiple sclerosis (MS) are very heterogeneous. The diverse clinical manifestations and the clinical course of the disease may vary with modifiable risk factors. OBJECTIVE: To systematically review modifiable risk factors and exposures associated with MS progression. METHODS: We searched six databases till March 2015, reference-mined reviews, and consulted with experts (PROSPERO 2015:CRD42015016461). Two reviewers screened and extracted data. We used random meta-analysis models and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the quality of evidence. RESULTS: In total, 59 studies met inclusion criteria. Lower vitamin D levels were associated with higher Expanded Disability Status Scale (EDSS) scores ( r = -0.22; confidence interval (CI) = -0.32, -0.12; 11 studies; I2 = 66%), smokers had an increased risk of MS progression (hazard ratio (HR) = 1.55; CI = 1.10, 2.19; I2 = 72%; seven studies), and there was no association of MS progression with the use of epidural analgesics during childbirth delivery (three studies). There was insufficient evidence to draw conclusions for 11 risk factors due to conflicting results or use of different predictor and outcome measures. CONCLUSION: MS progression was consistently associated with low vitamin D levels, and smoking was associated with a more rapid decline in MS disability. Studies used a variety of methods, predictors, and outcomes making it difficult to draw conclusions. Future studies should focus on prospective assessments.

A systematic review of the effects of modifiable risk factor interventions on the progression of multiple sclerosis.

BACKGROUND: Several risk factors are associated with multiple sclerosis (MS) progression and may be amenable to intervention. OBJECTIVE: To systematically review the evidence for interventions targeting risk factors for MS progression. METHODS: We searched six databases and existing reviews till March 2015 and consulted with experts to identify randomized controlled trials (RCTs) of interventions targeting MS risk factors (PROSPERO 2015:CRD42015016461). RESULTS: In total, 37 RCTs met inclusion criteria. Expanded Disability Status Scale (EDSS) scores after exercise interventions did not differ compared with untreated controls (standardized mean differences (SMDs): 0.02; confidence interval (CI): -0.40, 0.44; I2: 0%; seven RCTs; very low quality of evidence (QoE)). Dietary interventions did not show a statistically significant effect on the relative risk (RR) of progression (RR: 0.86; CI: 0.67, 1.05; I2: 0%; four RCTs; moderate QoE) compared to placebo. EDSS scores after vitamin D supplementation were not significantly different from placebo (SMD: -0.15; CI: -0.33, 0.02; I2: 0%; five RCTs; very low QoE). CONCLUSION: We did not identify any risk factor interventions with significant effects on MS progression, but the overall QoE was limited. More adequately powered trials are needed on vitamin D supplementation, long-term exercise, and smoking cessation.

Neighborhood, Family and Peer-Level Predictors of Obesity-Related Health Behaviors Among Young Adolescents.

Objective: This longitudinal study examines peer social functioning (PSF), familism, and neighborhood socioeconomic status (NSES) on adolescents' obesity risk. Methods: Participants ( N = 2,144) were originally sampled from 16 middle schools in Southern California (45% male; 45% Hispanic) as part of an alcohol and other drug use prevention program (CHOICE). Multilevel regression modeling tested main effects and interaction terms of PSF, familism, and NSES assessed at Wave 5 ( M age = 14.15) on body mass index and risk of obesity-related behaviors at Wave 6. Results: Higher PSF predicted healthier eating habits, less screen time, and more physical activity. Higher familism also predicted more physical activity. The positive effect of PSF on healthy eating was stronger among youth who reported higher familism. PSF also moderated the associations of NSES with healthy eating and physical activity. Conclusion: Findings emphasize the importance of targeting both peer and family factors, which may be more amenable to change than NSES.

Development of pre-implantation porcine blastocysts cultured within alginate hydrogel systems either supplemented with secreted phosphoprotein 1 or conjugated with Arg-Gly-Asp Peptide.

Although deficiencies in porcine blastocyst elongation play a significant role in early embryonic mortality and establishment of within-litter developmental variation, the exact mechanisms of elongation are poorly understood. Secreted phosphoprotein 1 (SPP1) is increased within the uterine milieu during early porcine pregnancy and contains an Arg-Gly-Asp (RGD) peptide sequence that binds to cell surface integrins on the uterine endometrium and trophectoderm, promoting cell adhesion and migration. The aim of the present study was to evaluate the development of preimplantation porcine blastocysts encapsulated and cultured within alginate hydrogels either supplemented with SPP1 or conjugated with RGD. Blastocysts encapsulated within alginate hydrogels supplemented with SPP1 or conjugated with RGD had increased survival compared with non-encapsulated control blastocysts. In addition, the percentage of blastocysts encapsulated within RGD hydrogels that underwent morphological changes was greater than that of blastocysts encapsulated within standard alginate hydrogels or SPP1-supplemented hydrogels. Finally, only blastocysts encapsulated within RGD hydrogels had both increased expression of steroidogenic and immune responsiveness transcripts and increased 17ß-oestradiol production, consistent with blastocysts undergoing elongation in vivo. These results illustrate the importance of the integrin-binding RGD peptide sequence for stimulating the initiation of blastocyst elongation.