Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers.

BACKGROUND: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. RESULTS: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. CONCLUSIONS: Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).

X-linked hypophosphataemia.

X-linked hypophosphataemia is a genetic disease caused by defects in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene and is characterised by X-linked dominant inheritance. The main consequence of PHEX deficiency is increased production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) in osteoblasts and osteocytes. Chronic exposure to circulating FGF23 is responsible for renal phosphate wasting and decreased synthesis of calcitriol, which decreases intestinal phosphate absorption. These mechanisms result in lifelong hypophosphataemia, impaired growth plate and bone matrix mineralisation, and diverse manifestations in affected children and adults, including some debilitating morbidities and possibly increased mortality. Important progress has been made in disease knowledge and management over the past decade; in particular, targeting FGF23 is a therapeutic approach that has substantially improved outcomes. However, patients affected by this complex disease need lifelong care and innovative treatment strategies, such as gene repair of PHEX, are necessary to further limit the disease burden.

Enzyme replacement therapy for hypophosphatasia-The current paradigm.

Hypophosphatasia (HPP) is a rare, inherited, and systemic disorder characterized by impaired skeletal mineralization and low tissue nonspecific serum alkaline phosphatase (TNSALP) activity. It is caused by either autosomal recessive or dominant-negative mutations in the gene that encodes TNSALP. The phenotype of HPP is very broad including abnormal bone mineralization, disturbances of calcium and phosphate metabolism, pain, recurrent fracture, short stature, respiratory impairment, developmental delay, tooth loss, seizures, and premature death. Other than supportive care, there has been no disease-specific treatment available for those with HPP. Asfotase alfa is a fully humanized, recombinant enzyme replacement therapy for the management of HPP. It is available in several countries for the treatment of the more severe forms of HPP, namely perinatal and infantile HPP. This review will summarize the preclinical data on asfotase alfa and highlight the data from clinical trials and case reports. These data show the transformative nature of asfotase alfa when administered as part of an interdisciplinary treatment model.

Crop rotational diversity can mitigate climate-induced grain yield losses.

Diversified crop rotations have been suggested to reduce grain yield losses from the adverse climatic conditions increasingly common under climate change. Nevertheless, the potential for climate change adaptation of different crop rotational diversity (CRD) remains undetermined. We quantified how climatic conditions affect small grain and maize yields under different CRDs in 32 long-term (10-63 years) field experiments across Europe and North America. Species-diverse and functionally rich rotations more than compensated yield losses from anomalous warm conditions, long and warm dry spells, as well as from anomalous wet (for small grains) or dry (for maize) conditions. Adding a single functional group or crop species to monocultures counteracted yield losses from substantial changes in climatic conditions. The benefits of a further increase in CRD are comparable with those of improved climatic conditions. For instance, the maize yield benefits of adding three crop species to monocultures under detrimental climatic conditions exceeded the average yield of monocultures by up to 553 kg/ha under non-detrimental climatic conditions. Increased crop functional richness improved yields under high temperature, irrespective of precipitation. Conversely, yield benefits peaked at between two and four crop species in the rotation, depending on climatic conditions and crop, and declined at higher species diversity. Thus, crop species diversity could be adjusted to maximize yield benefits. Diversifying rotations with functionally distinct crops is an adaptation of cropping systems to global warming and changes in precipitation.

Organellar phylogenomics at the epidendroid orchid base, with a focus on the mycoheterotrophic Wullschlaegelia.

BACKGROUND AND AIMS: Heterotrophic plants have long been a challenge for systematists, exemplified by the base of the orchid subfamily Epidendroideae, which contains numerous mycoheterotrophic species. METHODS: Here we address the utility of organellar genomes in resolving relationships at the epidendroid base, specifically employing models of heterotachy, or lineage-specific rate variation over time. We further conduct comparative analyses of plastid genome evolution in heterotrophs and structural variation in matK. KEY RESULTS: We present the first complete plastid genomes (plastomes) of Wullschlaegelia, the sole genus of the tribe Wullschlaegelieae, revealing a highly reduced genome of 37 kilobases, which retains a fraction of the genes present in related autotrophs. Plastid phylogenomic analyses recovered a strongly supported clade composed exclusively of mycoheterotrophic species with long branches. We further analyzed mitochondrial gene sets, which recovered similar relationships to those in other studies using nuclear data, but the placement of Wullschlaegelia remains uncertain. We conducted comparative plastome analyses among Wullschlaegelia and other heterotrophic orchids, revealing a suite of correlated substitutional and structural changes relative to autotrophic species. Lastly, we investigated evolutionary and structural variation in matK, which is retained in Wullschlaegelia and a few other 'late stage' heterotrophs and found evidence for structural conservation despite rapid substitution rates in both Wullschlaegelia and the leafless Gastrodia. CONCLUSIONS: Our analyses reveal the limits of what the plastid genome can tell us on orchid relationships in this part of the tree, even when applying parameter-rich heterotachy models. Our study underscores the need for increased taxon sampling across all three genomes at the epidendroid base, and illustrates the need for further research on addressing heterotachy in phylogenomic analyses.

Plastid genome evolution in leafless members of the orchid subfamily Orchidoideae, with a focus on Degranvillea dermaptera.

PREMISE: Leafless, heterotrophic plants are prime examples of organismal modification, the genomic consequences of which have received considerable interest. In particular, plastid genomes (plastomes) are being sequenced at a high rate, allowing continual refinement of conceptual models of reductive evolution in heterotrophs. However, numerous sampling gaps exist, hindering the ability to conduct comprehensive phylogenomic analyses in these plants. METHODS: Using floral tissue from an herbarium specimen, we sequenced and analyzed the plastome of Degranvillea dermaptera, a rarely collected, leafless orchid species from South America about which little is known, including its phylogenetic affinities. RESULTS: The plastome is the most reduced of those sequenced among the orchid subfamily Orchidoideae. In Degranvillea, it has lost the majority of genes found in leafy autotrophic species, is structurally rearranged, and has similar gene content to the most reduced plastomes among the orchids. We found strong evidence for the placement of Degranvillea within the subtribe Spiranthinae using models that explicitly account for heterotachy, or lineage-specific evolutionary rate variation over time. We further found evidence of relaxed selection on several genes and of correlations among substitution rates and several other "traits" of the plastome among leafless members of orchid subfamily Orchidoideae. CONCLUSIONS: Our findings advance knowledge on the phylogenetic relationships and paths of plastid genome evolution among the orchids, which have experienced more independent transitions to heterotrophy than any other plant family. This study demonstrates the importance of herbarium collections in comparative genomics of poorly known species of conservation concern.

Changes in cerebral vascular reactivity following mild repetitive head injury in awake rats: modeling the human experience.

The changes in brain function in response to mild head injury are usually subtle and go undetected. Physiological biomarkers would aid in the early diagnosis of mild head injury. In this study we used hypercapnia to follow changes in cerebral vascular reactivity after repetitive mild head injury. We hypothesized head injury would reduce vascular reactivity. Rats were maintained on a reverse light-dark cycle and head impacted daily at 24 h intervals over three days. All head impacts were delivered while rats were fully awake under red light illumination. There was no neuroradiological evidence of brain damage. After the 3rd impact rats were exposed to 5% CO2 and imaged for changes in BOLD signal. All imaging was done while rats were awake without the confound of anesthesia. The data were registered to a 3D MRI rat atlas with 171 segmented brain areas providing site specific information on vascular reactivity. The changes in vascular reactivity were not uniform across the brain. The prefrontal cortex, somatosensory cortex and basal ganglia showed the hypothesized decrease in vascular reactivity while the cerebellum, thalamus, brainstem, and olfactory system showed an increase in BOLD signal to hypercapnia.

Prevalence of suicidal and self-harm ideation in fathers during the perinatal and early parenting period: A systematic review and meta-analysis.

OBJECTIVE: Suicide is a leading cause of death in males aged 25-44 years, an age which often coincides with becoming a father. This review aims to synthesise the evidence of the prevalence of suicidal and self-harm ideation in fathers during the perinatal, postnatal and early parenting period. METHODS: Five databases were searched (PsycINFO, Medline, Web of Science, PubMed and the Cochrane Database of Systematic Reviews) to identify papers published between 1 January 2000 and 9 March 2023. A meta-analysis was conducted to estimate the prevalence of suicidality and self-harm ideation across the included studies. Subgroup and sensitivity analyses were conducted to explore potential sources of heterogeneity. RESULTS: A total of 4215 articles were identified, with 14 studies included in the review. The combined pooled prevalence of suicidal and self-harm ideation was 4.2% (95% CI [2.6%, 6.2%]). Prevalence estimates were higher for self-harm ideation at 5.1% (95% CI [2.6%, 6.2%]) than for suicidality at 3% (95% CI [0.9%, 6.1%]). CONCLUSIONS: This review found that a considerable proportion of fathers experience suicidal and self-harm ideation during the early years of parenting. However, the paucity of rigorous prevalence studies indicates that further research in this area is needed urgently.

The role of fathers in child development from preconception to postnatal influences: Opportunities for the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) program.

A growing body of literature highlights the important role of paternal health and socioemotional characteristics in child development, from preconception through adolescence. Much of this research addresses the indirect effects of fathers, for instance, their influence on maternal behaviors during the prenatal period or via the relationship with their partner. However, emerging evidence also recognizes the direct role of paternal health and behavior for child health and adjustment across development. This critical review presents evidence of biological and sociocultural influences of fathers on preconception, prenatal, and postnatal contributions to child development. The National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) program incorporates in its central conceptualization the impact of fathers on family and child outcomes. This critical synthesis of the literature focuses on three specific child outcomes in the ECHO program: health outcomes (e.g., obesity), neurodevelopmental outcomes (e.g., emotional, behavioral, psychopathological development), and positive health. We highlight the unique insights gained from the literature to date and provide next steps for future studies on paternal influences.

Stretching the Bisalkyne Raman Spectral Palette Reveals a New Electrophilic Covalent Motif.

Small heteroaryl-diyne (Het-DY) tags with distinct vibrational frequencies, and physiologically relevant cLog P were designed for multiplexed bioorthogonal Raman imaging. Pd-Cu catalyzed coupling, combined with the use of Lei ligand, was shown to improve overall yields of the desired heterocoupled Het-DY tags, minimizing the production of homocoupled side-products. Spectral data were in agreement with the trends predicted by DFT calculations and systematic introduction of electron- rich/poor rings stretched the frequency limit of aryl-capped diynes (2209-2243 cm-1 ). The improved Log P of these Het-DY tags was evident from their diffuse distribution in cellular uptake studies and functionalizing tags with organelle markers allowed the acquisition of location-specific biological images. LC-MS- and NMR-based assays showed that some heteroaryl-capped internal alkynes are potential nucleophile traps with structure-dependent reactivity. These biocompatible Het-DY tags, equipped with covalent reactivity, open up new avenues for Raman bioorthogonal imaging.

Surgical Management and Denosumab for Aneurysmal Bone Cysts of the Spine in an Australian Tertiary Paediatric Centre.

Aneurysmal bone cysts (ABC) are rare osteolytic, benign but often locally aggressive tumours of the long bones or vertebrae. For spinal ABC, surgical management, embolisation or sclerotherapy alone often carry high morbidity and/or high recurrence rates. Interruption of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling holds promise as an effective therapeutic strategy for these tumours. We aimed to review the approach to surgical management and evaluate the efficacy and safety of denosumab for ABC of the spine in children. Retrospective review of 7 patients treated with denosumab using a standardised protocol for ABC of the spine in a tertiary paediatric centre. Surgical intervention was only conducted if there was spinal instability or significant neurological impairment. Denosumab 70 mg/m2 was given 4-weekly for at least 6 months, followed by 2 doses of zoledronate 0.025 mg/kg, aiming to prevent rebound hypercalcaemia. All patients achieved stability of the spine and resolution of neurological impairment, if present. Six patients achieved metabolic remission and have ceased denosumab without recurrence to date; the other showed clinical and radiological improvement without complete metabolic remission. Three patients developed symptomatic hypercalcaemia 5-7 months after cessation of denosumab, requiring additional bisphosphonate treatment. We present our algorithm for the surgical and medical management of paediatric spinal ABC. Denosumab produced a radiological and metabolic response in all patients, with complete remission in most. Follow-up time was not long enough to evaluate the endurance of response after cessation in some patients. Incidence of rebound hypercalcaemia in this paediatric cohort was high, prompting a change to our protocol.

Expanding the phenotype of Bruck syndrome: Severe limb deformity, arthrogryposis, congenital cardiac disease and pulmonary hemorrhage.

Bruck syndrome is a rare collagen disorder with autosomal recessive inheritance caused by pathogenic variants in either FKBP10 or PLOD2 genes. It is characterized by bone fragility and fractures similar in severity and variability to osteogenesis-imperfecta as well as congenital joint contractures. This article describes an infant with a homozygous (partial) gene deletion of PLOD2 that includes the start codon and would be expected to lead to nonfunctional protein product. The infant had a severe phenotype of Bruck syndrome and is the only reported case of Bruck syndrome with congenital cardiac disease (triscuspid valve dysplasia with severe regurgitation, mitral valve prolapses with moderate regurgitation, and pulmonary hypertension) and pulmonary hemorrhage. We hypothesize that the additional feature of congenital cardiac disease in this case was due to the underlying defect in type I collagen, and that the pulmonary hemorrhage was multifactorial, with underlying vessel fragility, rib fractures, and high pulmonary pressures likely to be major contributing factors. Management was largely supportive with the use of bisphosphonates to assist in pain management. Care was complicated by comorbid cardiopulmonary compromise, limited evidence-base guiding care, and difficulties in discussing end-of-life care.

Frequency-dependent viscosity of salmon ovarian fluid has biophysical implications for sperm-egg interactions.

Gamete-level sexual selection of externally fertilising species is usually achieved by modifying sperm behaviour with mechanisms that alter the chemical environment in which gametes perform. In fish, this can be accomplished through the ovarian fluid, a substance released with the eggs at spawning. While the biochemical effects of ovarian fluid in relation to sperm energetics have been investigated, the influence of the physical environment in which sperm compete remains poorly explored. Our objective was therefore to gain insights on the physical structure of this fluid and potential impacts on reproduction. Using soft-matter physics approaches of steady-state and oscillatory viscosity measurements, we subjected wild Atlantic salmon ovarian fluids to variable shear stresses and frequencies resembling those exerted by sperm swimming through the fluid near eggs. We show that this fluid, which in its relaxed state is a gel-like substance, displays a non-Newtonian viscoelastic and shear-thinning profile, where the viscosity decreases with increasing shear rates. We concurrently find that this fluid obeys the Cox-Merz rule below 7.6 Hz and infringes it above this level, thus indicating a shear-thickening phase where viscosity increases provided it is probed gently enough. This suggests the presence of a unique frequency-dependent structural network with relevant implications for sperm energetics and fertilisation dynamics. This article has an associated ECR Spotlight interview with Marco Graziano.

Mental health as a family experience: Relationship of paternal characteristics with maternal perinatal depressive symptoms in a matched sample.

The present study investigates the relationship between perinatal maternal depressive symptoms and paternal factors using linked maternal-paternal survey data. From October 2018 to July 2019, among a representative sample and 2-6 months following the birth of an infant, mothers and fathers completed surveys and reported depressive symptoms. Results from the linked dyadic data (n = 243) show the prevalence of maternal depressive symptoms, both overall (16%) and by marital status and paternal health care involvement. Viewing mental health as a family experience may further understanding of postpartum maternal mental illness.

Imaging the effect of the circadian light-dark cycle on the glymphatic system in awake rats.

The glymphatic system functions in the removal of potentially harmful metabolites and proteins from the brain. Dynamic, contrast-enhanced MRI was used in fully awake rats to follow the redistribution of intraventricular contrast agent entrained to the light-dark cycle and its hypothetical relationship to the sleep-waking cycle, blood flow, and brain temperature in specific brain areas. Brain areas involved in circadian timing and sleep-wake rhythms showed the lowest redistribution of contrast agent during the light phase or time of inactivity and sleep in rats. Global brain redistribution of contrast agent was heterogeneous. The redistribution was highest along the dorsal cerebrum and lowest in the midbrain/pons and along the ventral surface of the brain. This heterogeneous redistribution of contrast agent paralleled the gradients and regional variations in brain temperatures reported in the literature for awake animals. Three-dimensional quantitative ultrashort time-to-echo contrast-enhanced imaging was used to reconstruct small, medium, and large arteries and veins in the rat brain and revealed areas of lowest redistribution overlapped with this macrovasculature. This study raises new questions and theoretical considerations of the impact of the light-dark cycle, brain temperature, and blood flow on the function of the glymphatic system.

Is Oxytocin "Nature's Medicine"?

Oxytocin is a pleiotropic, peptide hormone with broad implications for general health, adaptation, development, reproduction, and social behavior. Endogenous oxytocin and stimulation of the oxytocin receptor support patterns of growth, resilience, and healing. Oxytocin can function as a stress-coping molecule, an anti-inflammatory, and an antioxidant, with protective effects especially in the face of adversity or trauma. Oxytocin influences the autonomic nervous system and the immune system. These properties of oxytocin may help explain the benefits of positive social experiences and have drawn attention to this molecule as a possible therapeutic in a host of disorders. However, as detailed here, the unique chemical properties of oxytocin, including active disulfide bonds, and its capacity to shift chemical forms and bind to other molecules make this molecule difficult to work with and to measure. The effects of oxytocin also are context-dependent, sexually dimorphic, and altered by experience. In part, this is because many of the actions of oxytocin rely on its capacity to interact with the more ancient peptide molecule, vasopressin, and the vasopressin receptors. In addition, oxytocin receptor(s) are epigenetically tuned by experience, especially in early life. Stimulation of G-protein-coupled receptors triggers subcellular cascades allowing these neuropeptides to have multiple functions. The adaptive properties of oxytocin make this ancient molecule of special importance to human evolution as well as modern medicine and health; these same characteristics also present challenges to the use of oxytocin-like molecules as drugs that are only now being recognized. SIGNIFICANCE STATEMENT: Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug.

Genetic architecture of end-use quality traits in soft white winter wheat.

BACKGROUND: Genetic improvement of end-use quality is an important objective in wheat breeding programs to meet the requirements of grain markets, millers, and bakers. However, end-use quality phenotyping is expensive and laborious thus, testing is often delayed until advanced generations. To better understand the underlying genetic architecture of end-use quality traits, we investigated the phenotypic and genotypic structure of 14 end-use quality traits in 672 advanced soft white winter wheat breeding lines and cultivars adapted to the Pacific Northwest region of the United States. RESULTS: This collection of germplasm had continuous distributions for the 14 end-use quality traits with industrially significant differences for all traits. The breeding lines and cultivars were genotyped using genotyping-by-sequencing and 40,518 SNP markers were used for association mapping (GWAS). The GWAS identified 178 marker-trait associations (MTAs) distributed across all wheat chromosomes. A total of 40 MTAs were positioned within genomic regions of previously discovered end-use quality genes/QTL. Among the identified MTAs, 12 markers had large effects and thus could be considered in the larger scheme of selecting and fixing favorable alleles in breeding for end-use quality in soft white wheat germplasm. We also identified 15 loci (two of them with large effects) that can be used for simultaneous breeding of more than a single end-use quality trait. The results highlight the complex nature of the genetic architecture of end-use quality, and the challenges of simultaneously selecting favorable genotypes for a large number of traits. This study also illustrates that some end-use quality traits were mainly controlled by a larger number of small-effect loci and may be more amenable to alternate selection strategies such as genomic selection. CONCLUSIONS: In conclusion, a breeder may be faced with the dilemma of balancing genotypic selection in early generation(s) versus costly phenotyping later on.

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.

BACKGROUND: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients. METHODS: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry. RESULTS: When quintupling the dose of fluticasone (to 250 µg twice a day) was compared with adding salmeterol (50 µg twice a day) and doubling the fluticasone (to 100 µg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age. CONCLUSIONS: In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

A synthesis of senescence predictions for indeterminate growth, and support from multiple tests in wild lake trout.

Senescence-the deterioration of functionality with age-varies widely across taxa in pattern and rate. Insights into why and how this variation occurs are hindered by the predominance of laboratory-focused research on short-lived model species with determinate growth. We synthesize evolutionary theories of senescence, highlight key information gaps and clarify predictions for species with low mortality and variable degrees of indeterminate growth. Lake trout are an ideal species to evaluate predictions in the wild. We monitored individual males from two populations (1976-2017) longitudinally for changes in adult mortality (actuarial senescence) and body condition (proxy for energy balance). A cross-sectional approach (2017) compared young (ages 4-10 years) and old (18-37 years) adults for (i) phenotypic performance in body condition, and semen quality-which is related to fertility under sperm competition (reproductive senescence)-and (ii) relative telomere length (potential proxy for cellular senescence). Adult growth in these particular populations is constrained by a simplified foodweb, and our data support predictions of negligible senescence when maximum size is only slightly larger than maturation size. Negative senescence (aka reverse senescence) may occur in other lake trout populations where diet shifts allow maximum sizes to greatly exceed maturation size.

A Mobile Health Intervention to Support Parenting Self-Efficacy in the Neonatal Intensive Care Unit from Admission to Home.

OBJECTIVE: To test whether parents of premature infants less than 37 weeks of gestation provided with a unique smartphone app designed to support parents had greater parenting self-efficacy, a key element in parenting confidence, compared with controls. STUDY DESIGN: Using a quasiexperimental, time-lagged study design, parents were assigned to either usual care (control) or NICU2HOME app (intervention) groups. Both groups completed the validated Parenting Sense of Competence (PSOC) scale at 4 time points (approximately day of life 7, 1 day before discharge, and at 14 and 30 days after discharge) representing the neonatal intensive care unit, discharge, and home contexts. App use was described and categorized. Univariate group differences were assessed, and linear mixed effect regression models were used to assess treatment group effect on PSOC score across time, adjusted for covariates and controlling for overall family effect. RESULTS: We enrolled 298 parents (123 control, 175 intervention) with 256 completing 1 or more PSOC screenings. The intervention group had sustained higher PSOC scores than those of the control group (estimate, 4.3; P = .0042) from the first measurement onward with no significant change in PSOC score across time for either group. Average app use was 15 taps per average day; average and above-average users had significantly higher PSOC scores (estimate, 5.16; P = .0024; estimate, 5.16; P = .014) compared with controls or below-average users. CONCLUSIONS: Compared with controls, parents assigned to use the NICU2HOME app reported greater parenting self-efficacy while in the neonatal intensive care unit and this continued once discharged to home. Novel technologies such as point-of-care smartphone applications may hold promise for supporting parents in difficult and stressful situations. TRIAL REGISTRATION: ClincalTrials.gov: NCT03505424.