Abstract Marrow adipose tissue (MAT), associated with skeletal fragility and hematologic insufficiency, remains poorly understood and difficult to quantify. We tested the response of MAT to high fat ...diet (HFD) and exercise using a novel volumetric analysis, and compared it to measures of bone quantity. We hypothesized that HFD would increase MAT and diminish bone quantity, while exercise would slow MAT acquisition and promote bone formation. Eight week-old female C57BL/6 mice were fed a regular (RD) or HFD, and exercise groups were provided voluntary access to running wheels (RD-E, HFD-E). Femoral MAT was assessed by μCT (lipid binder osmium) using a semi-automated approach employing rigid co-alignment, regional bone masks and was normalized for total femoral volume (TV) of the bone compartment. MAT was 2.6-fold higher in HFD relative to RD mice. Exercise suppressed MAT in RD-E mice by more than half compared with RD. Running similarly inhibited MAT acquisition in HFD mice. Exercise significantly increased bone quantity in both diet groups. Thus, HFD caused significant accumulation of MAT; importantly running exercise limited MAT acquisition while promoting bone formation during both diets. That MAT is exquisitely responsive to diet and exercise, and its regulation by exercise appears to be inversely proportional to effects on exercise induced bone formation, is relevant for an aging and sedentary population.
Interprofessional student hotspotting involves experiential and longitudinal learning about team-based care for patients with complex medical and social needs. As an emerging strategy for ...interprofessional education, there have been few research studies to examine student perspectives.
This study used a descriptive qualitative approach to examine the experiences and perspectives of health professions students who participated in a six-month interprofessional student hotspotting program.
At the end of the program, focus group interviews were conducted with 24 health professions students from medicine, social work, pharmacy, nursing, and health psychology.
Thematic analysis revealed four themes: Observed benefits of interprofessional collaboration; Gained skills for collaborative care; Experienced difficulty managing group dynamics; and Learned approaches to caring for complex patients.
The hotspotting program helped deepen students' appreciation for interprofessional team-based care. Repeated practice of teamwork skills during the six-month clinical learning experience resulted in students feeling more prepared to provide collaborative care for complex patients.
•Student hotspotting is a strategy for providing longitudinal and experiential IPE.•Students observed the benefits of interprofessional collaborative care.•Collaboration skills were practiced while providing team-based care to patients.•Faculty guidance can assist students to grow their ability to manage team conflict.•Hotspotting promotes learning the care of medically and socially complex patients.
To identify factors associated with prolonged maternal breast milk (BM) provision in very low birth weight (VLBW) infants.
This was a cohort study of VLBW infants who initially received maternal BM ...and were born at one of 197 neonatal intensive care units managed by the Pediatrix Medical Group from 2010 to 2012. We used multivariable logistic regression to identify demographic, clinical, and maternal factors associated with provision of maternal BM on day of life (DOL) 30 and at discharge.
Median gestational age for all infants was 28 weeks (25th, 75th percentiles: 26, 30), and median maternal age was 28 years (23, 33). Of 8806 infants, 6261 (71%) received maternal BM on DOL 30, and 4003 of 8097 (49%) received maternal BM at discharge to home. Predictors of maternal BM provision at DOL 30 included increased maternal age, white maternal race, absence of history of necrotizing enterocolitis or late-onset sepsis, higher household income, lower education level, lack of donor BM exposure, and lower gestational age.
Our results suggest that maternal-infant demographic and clinical factors and household neighborhood socioeconomic characteristics were associated with provision of maternal BM at 30 postnatal days to VLBW infants. Identification of these factors allows providers to anticipate mothers' needs and develop tailored interventions designed to improve rates of prolonged maternal BM provision and infant outcomes.
causes the sexually transmitted infection gonorrhea, which is highly prevalent worldwide and has a major impact on reproductive and neonatal health. The superbug status of
necessitates the ...development of drugs with different mechanisms of action. Here, we focused on targeting the nitrite reductase AniA, which is a pivotal component of
anaerobic respiration and biofilm formation. Our studies showed that gonococci expressing AniA containing the altered catalytic residues D137A and H280A failed to grow under anaerobic conditions, demonstrating that the nitrite reductase function is essential. To facilitate the pharmacological targeting of AniA, new crystal structures of AniA were refined to 1.90-Å and 2.35-Å resolutions, and a phage display approach with libraries expressing randomized linear dodecameric peptides or heptameric peptides flanked by a pair of cysteine residues was utilized. Biopanning experiments led to the identification of 29 unique peptides, with 1 of them, C7-3, being identified multiple times. Evaluation of their ability to interact with AniA using enzyme-linked immunosorbent assay and computational docking studies revealed that C7-3 was the most promising inhibitor, binding near the type 2 copper site of the enzyme, which is responsible for interaction with nitrite. Subsequent enzymatic assays and biolayer interferometry with a synthetic C7-3 and its derivatives, C7-3m1 and C7-3m2, demonstrated potent inhibition of AniA. Finally, the MIC
value of C7-3 and C7-3m2 against anaerobically grown
was 0.6 mM. We present the first peptide inhibitors of AniA, an enzyme that should be further exploited for antigonococcal drug development.
The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening.
We performed a retrospective cohort ...study of neonates born to mothers with negative antenatal GBS screening between 2002 and 2012. Our primary outcome was EOGBS infection. We used multivariable logistic regression to assess factors associated with EOGBS.
EOGBS was confirmed in 492 of the 179 818 neonates that met the study inclusion criteria. Risk factors for EOGBS included black race (reference: white, odds ratio (OR) =1.81 (95% confidence interval: 1.43, 2.31)), maternal age <18 years (reference: >35 years, OR=2.63 (1.54, 4.51)) and maternal age 18 to 35 years (reference: >35 years, OR=1.94 (1.30, 2.88)).
Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.
The impact of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) on pediatric antibacterial or antifungal drug trials is unknown. Our objective was to ...identify and characterize trials conducted under the BPCA and/or the PREA.
Pediatric antibacterial and antifungal drug trials with industry or US federal funding registered in clinicaltrials.gov from 2007 to 2017 were identified. Those conducted under BPCA and/or PREA were identified through US Food and Drug Administration and National Institute of Child Health and Human Development databases.
Of 17 495 pediatric trials registered on clinicaltrials.gov between October 2007 and September 2017, 122 systemic antibacterial or antifungal drug trials with industry or US federal funding were identified. Of these 122 trials, 98 (80%) involved antibacterials only, 23 (19%) antifungals only, and 1 (1%) both antibacterials and antifungals. These represented <1% (122 of 17 495) of pediatric trials. Neither pediatric antibacterial nor antifungal drug trials commonly enrolled neonates 0 to 30 days old (30% 30 of 99 vs 42% 10 of 24, respectively). Pediatric antibacterial and antifungal trials were commonly industry funded (79% 78 of 99 and 83% 20 of 24, respectively). In total, 65% (79 of 122) of pediatric antibacterial and/or antifungal drug trials were conducted under BPCA and/or PREA. Researchers in trials conducted under BPCA and/or PREA, relative to non-BPCA and/or PREA trials, more often collected pharmacokinetic data (70% 55 of 79 vs 26% 11 of 43).
Although the majority of pediatric antibacterial and/or antifungal drug trials were conducted under BPCA and/or PREA, the overall number was low. Greater effort is needed to stimulate such trials.
Abstract Background Histamine-2 receptor (H2 ) blockers are often used in very low birth weight infants despite lack of population specific efficacy and safety data. Aims We sought to describe safety ...and temporal trends in histamine-2 receptor (H2 ) blocker use in hospitalized very low birth weight (VLBW) infants. Study design We conducted a retrospective cohort study using a clinical database populated by an electronic health record shared by 348 neonatal intensive care units in the United States. Subjects We included all VLBW infants without major congenital anomalies. Outcome measures We used multivariable logistic regression with generalizing estimating equations to evaluate the association between days of H2 blocker exposure and risk of: 1) death or necrotizing enterocolitis (NEC); 2) death or sepsis; and 3) death, NEC, or sepsis. Results Of 127,707 infants, 20,288 (16%) were exposed to H2 blockers for a total of 6,422,352 days. Median gestational age for infants exposed to H2 blockers was 27 weeks (25th 75th percentile 26, 29). H2 blocker use decreased from 18% of infants in 1997 to 8% in 2012 (p < 0.001). On multivariable analysis, infants were at increased risk of the combined outcome of death, NEC, or sepsis on days exposed to H2 blockers (odds ratio = 1.14) (95% confidence interval 1.08, 1.19). Conclusions H2 blocker use is associated with increased risk of the combined outcome of death, NEC, or sepsis in hospitalized VLBW infants.
As head injuries in American football have received increasing publicity, the safety of the sport has become a great concern for parents nationwide. The purpose of this study was to examine perceived ...safety concerns in youth football using Eccles’ expectancy-value model (Eccles et al., 1983). We hypothesized perceived safety concerns to moderate relationships between parent perceptions of parent cost/benefit, child cost/benefit, and child motivation and enjoyment outcomes for football. Youth football parents (
N
= 105,
M
age
= 42) completed valid and reliable online assessments of study variables. Regression analyses revealed child safety concerns (as rated by parents) to mediate, rather than moderate, the relationship between parent safety concerns and child cost perceptions (as rated by parents). Furthermore, safety concerns did not significantly associate with child achievement outcomes of motivation and enjoyment. Results provide valuable insight into parent and child attitudes toward youth football safety. Such knowledge may inform future educational interventions targeting sport safety promotion.
Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies ...(GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
Objectives
Tracheoplasty or tracheal resection and are essential components of the care of patients with severe tracheal stenosis. We aimed to study the perioperative outcomes of patients after ...tracheoplasty or resection using a national surgical registry.
Methods
We analyzed the 2014 to 2016 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) participant use file for patients who underwent tracheal resection or tracheoplasty (CPT codes 31750, 31760, 31780, and 31781). We analyzed the perioperative outcomes including length of stay (LOS), dehiscence, unplanned reintubations, unplanned surgeries, and 30‐day readmission rates. A random 4:1 sample of non‐tracheoplasty patients served as the control group.
Results
From 2014 to 2016, 126 patients underwent tracheoplasty. The median age was 56 years (IQR = 45–63). There were 93 (74%) females, 88 (70%) white, and 3.2% (4/126) Hispanic. The median LOS was 7 days (IQR = 5–10 days). Of these, 4.8% (6/126) developed wound infections and 3/126 (2.4%) developed wound dehiscence. Five out of 126 required unplanned reintubation (4.0%) and 16/126 (13%) had an unplanned reoperation. The 30‐day unplanned readmission rate was 16% (20/126). The wound infection, unplanned intubations, and readmission rates were significantly higher (P < .005) than the control group.
Conclusions
The 30‐day perioperative outcomes of adult patients undergoing tracheoplasty showed that adverse events are common, but severe adverse events such as death are rare. Continued research into risk mitigation among these patients is warranted.
Level of Evidence
NA Laryngoscope, 130:1514–1519, 2020
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