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Mutation or loss of collagen VI has been linked to a variety of musculoskeletal abnormalities, particularly muscular dystrophies, tissue ossification and/or fibrosis, and hip osteoarthritis. However, the role of collagen VI in bone and cartilage structure and function in the knee is unknown. In this study, we examined the role of collagen VI in the morphology and physical properties of bone and cartilage in the knee joint of Col6a1(-/-) mice by micro-computed tomography (microCT), histology, atomic force microscopy (AFM), and scanning microphotolysis (SCAMP). Col6a1(-/-) mice showed significant differences in trabecular bone structure, with lower bone volume, connectivity density, trabecular number, and trabecular thickness but higher structure model index and trabecular separation compared to Col6a1(+/+) mice. Subchondral bone thickness and mineral content increased significantly with age in Col6a1(+/+) mice, but not in Col6a1(-/-) mice. Col6a1(-/-) mice had lower cartilage degradation scores, but developed early, severe osteophytes compared to Col6a1(+/+) mice. In both groups, cartilage roughness increased with age, but neither the frictional coefficient nor compressive modulus of the cartilage changed with age or genotype, as measured by AFM. Cartilage diffusivity, measured via SCAMP, varied minimally with age or genotype. The absence of type VI collagen has profound effects on knee joint structure and morphometry, yet minimal influences on the physical properties of the cartilage. Together with previous studies showing accelerated hip osteoarthritis in Col6a1(-/-) mice, these findings suggest different roles for collagen VI at different sites in the body, consistent with clinical data.

As the nonprofessional theatre continues to grow in popularity, its technology expands at a dizzying rate, presenting exciting new opportunities and challenges for all nonprofessional theatre craftsmen. This new edition of a stage manager’s old friend takes into account many aspects of the new theatre technology, insuring the book’s lasting place in college, high school, and community theatres everywhere. It is a book more likely to be found backstage on a stepladder than on a library shelf, and this is exactly what the author has intended. The emphasis is on simplicity, economy, and practicability. It is a book that can help now to put any play into production.

ObjectiveTo examine whether changes in survival without moderate or severe neurodevelopmental impairment (NDI) at 18–26 months’ corrected age from 1999 to 2018 differed between male and female infants.DesignThis retrospective cohort study used data from the NICHD Neonatal Research Network hospitals. Robust Poisson regression models were used to estimate adjusted relative risks (aRRs) and 95% CIs for survival without moderate or severe NDI between males and females. Interactions between sex and time were assessed to evaluate temporal differences in the outcome by sex. Variables adjusted for included centre, maternal age, ethnicity/race, gestational age and small for gestational age.PatientsInborn infants with gestational age of 22–26 weeks at NICHD Neonatal Research Network hospitals from 1999 to 2018.Main outcome measureChange over time in survival without moderate or severe NDI at 18–26 months’ corrected age between male and female infants.ResultsOf 26 307 infants, 13 045 (49.6%) were male. Survival without moderate or severe NDI declined for both sexes over time, from 32.9% to 30.6% for males and from 47.4% to 40.0% for females, between 1999–2003 and 2014–2018. Males were less likely than females to survive without moderate or severe NDI (aRR=0.80; 95% CI 0.78 to 0.83). Changes in survival without moderate or severe NDI did not differ between males and females.ConclusionThere were no differential changes in survival without moderate or severe NDI between male and female infants.

ObjectiveExtremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.Study designBlinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.ResultsWe assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56–2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001).Difficulty recruiting TR patients at 2 years extended the study by 14 months and affected their demographics.ConclusionImpairment rates among EP infants appear to be substantially underestimated from Bayley III norms. These rates may be best assessed by comparison with healthy term infants followed with minimal attrition from birth in the same centers.ClinicalTrials.gov IDTerm Reference (under the Generic Database Study): NCT00063063

ObjectivesTo compare serum ferritin and RET-He values among extremely low gestational age neonates ELGANs with other markers of iron-deficient erythropoiesis.Study DesignThis is a secondary analysis of the NICHD Darbepoetin Trial. Study data from placebo recipients who had a serum ferritin, a RET-He, and a mean corpuscular volume (MCV) measurement within a 24-hour period were analyzed for correlation.ResultsMixed linear regression models showed no association between ferritin and RET-He at both early (β = 0.0016, p = 0.40) and late (β = −0.0001, p = 0.96) time points. Positive associations were observed between RET-He and MCV at baseline, early, and late time points (p < 0.01, =0.01, <0.001, respectively), while ferritin was not associated with MCV at any time point.ConclusionsOur study shows that RET-He is better correlated with MCV as a marker of iron-limited erythropoiesis than ferritin. The results suggest that ferritin is limited as a marker of iron sufficiency in premature infants.Study IdentificationFDA IND Number 100138; ClinicalTrials.gov number NCT03169881; NRN ID number NICHD-NRN-0058 (Darbe).

The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials. To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal steroids at 22 6/7 weeks' gestation or less vs no exposure to antenatal steroids. This cohort study enrolled infants born at GA 22 0/7 to 23 6/7 weeks between January 1, 2016, and December 31, 2019, at centers in the National Institute of Child Health and Human Development Neonatal Research Network. Infants who did not receive intensive care and infants with antenatal steroid exposure after GA 22 6/7 weeks were excluded. Infants were classified as having no, partial, or complete exposure to antenatal steroids. The primary outcome was survival to discharge. The main secondary outcome was survival without major neonatal morbidity. The associations of differential exposures to antenatal steroids with outcomes were evaluated using logistic regression, adjusting for GA, sex, race, maternal education, small for GA status, mode of delivery, multiple birth, prolonged rupture of membranes, year of birth, and Neonatal Research Network center. A total of 431 infants (mean [SD] GA, 22.6 [0.5] weeks; 232 [53.8%] boys) were included, with 110 infants (25.5%) receiving no antenatal steroids, 80 infants (18.6%) receiving partial antenatal steroids, and 241 infants (55.9%) receiving complete antenatal steroids. Seventeen infants were exposed to antenatal steroids at GA 21 weeks. Among infants exposed to complete antenatal steroids, 130 (53.9%) survived to discharge, compared with 30 infants (37.5%) with partial antenatal steroid exposure and 239 infants (35.5%) with no antenatal steroids. Infants born after complete antenatal steroid exposure, compared with those without antenatal steroid exposure, were more likely to survive to discharge (adjusted odds ratio [aOR], 1.95 [95% CI, 1.07-3.56]) and to survive without major morbidity (aOR, 2.74 [95% CI, 1.19-6.30]). In this retrospective cohort study, among infants born between GA 22 0/7 and 23 6/7 weeks who received intensive care, exposure to a complete course of antenatal steroids at GA 22 6/7 weeks or less was independently associated with greater odds of survival and survival without major morbidity. These data suggest that the use of antenatal steroids in patients at GA 22 6/7 weeks or less could be beneficial when active treatment is considered.

Hypothesis Increased social distancing was associated with a lower incidence of extremely preterm live births (EPLB) during the initial COVID-19 pandemic period. Study design Prospective study at the NICHD Neonatal Research Network sites comparing EPLB (22 0/7 –28 6/7 weeks) and extremely preterm intrapartum stillbirths (EPIS) rates during the pandemic period (March-July, weeks 9–30 of 2020) with the reference period (same weeks in 2018 and 2019), correlating with state-specific social distancing index (SDI). Results EPLB and EPIS percentages did not significantly decrease (1.58–1.45%, p  = 0.07, and 0.08–0.06%, p  = 0.14, respectively). SDI was not significantly correlated with percent change of EPLB (CC = 0.29, 95% CI = −0.12, 0.71) or EPIS (CC = −0.23, 95% CI = −0.65, 0.18). Percent change in mean gestational age was positively correlated with SDI (CC = 0.49, 95% CI = 0.07, 0.91). Conclusions Increased social distancing was not associated with change in incidence of EPLB but was associated with a higher gestational age of extremely preterm births. ClinicalTrials.gov ID Generic Database: NCT00063063.

BACKGROUND: Cancer treatment has a significant impact on a patient's sexual health and function. However, numerous communication barriers deter healthcare professionals from initiating a sexual health conversation with patients.OBJECTIVES: This study assessed the effects of a nurse-focused sexual health education workshop on change in knowledge of sexual concerns, barriers to discussing sexuality, and frequency of bringing up sexual concerns.METHODS: A train-the-trainer approach was used to educate oncology nurse managers, who then trained oncology nurses (N = 65) at 10 education workshops. Each workshop provided four hours of content on sexual health and incorporated roleplay and lecture.FINDINGS: Mean knowledge scores were improved, and barriers to discussing sexuality at the three- and six-month follow-ups were reduced. Frequency in discussing sexual concerns increased at three months and was sustained at six months.

Importance Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended. Objective To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks’ postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years’ corrected age in extremely preterm infants. Design, Setting, and Participants This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks’ gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022. Exposure Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth. Main Outcomes and Measures The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years’ corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years’ corrected age. Results A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%). Conclusions and Relevance Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

Cancer treatment has a significant impact on a patient's sexual health and function. However, numerous communication barriers deter healthcare professionals from initiating a sexual health conversation with patients. This study assessed the effects of a nurse-focused sexual health education workshop on change in knowledge of sexual concerns, barriers to discussing sexuality, and frequency of bringing up sexual concerns. A train-the-trainer approach was used to educate oncology nurse managers, who then trained oncology nurses (N = 65) at 10 education workshops. Each workshop provided four hours of content on sexual health and incorporated role-play and lecture. Mean knowledge scores were improved, and barriers to discussing sexuality at the three- and six-month follow-ups were reduced. Frequency in discussing sexual concerns increased at three months and was sustained at six months.