Illuminating the landscape of sibling relationship quality: An evidence and gap map.

This paper used an evidence and gap map (EGM) to advance the scientific understanding of sibling relationship quality among children aged 2 to 18 years by synthesizing literature on 277 empirical studies from 1985 to 2022 to delineate patterns of study design, sampling, and measurement. Most existing research has utilized majority of White, middle-to-upper class, and/or two-caregiver family samples. Nearly 85% (n = 235) of studies used quantitative methods to measure sibling relationship quality across eight domains: conflict, warmth/affection, quality, cohesion, hostility, power/control, positive engagement, and conflict management. A total of 122 studies used a measure of sibling relationship quality as a predictor of sibling behavior, social, psychological, cognitive, health, or physiological outcomes. Future directions for research are discussed.

Examination of protective factors that promote prosocial skill development among children exposed to intimate partner violence.

This retrospective cohort study examined prosocial skills development in child welfare-involved children, how intimate partner violence (IPV) exposure explained heterogeneity in children's trajectories of prosocial skill development, and the degree to which protective factors across children's ecologies promoted prosocial skill development. Data were from 1,678 children from the National Survey of Child and Adolescent Well-being I, collected between 1999 and 2007. Cohort-sequential growth mixture models were estimated to identify patterns of prosocial skill development between the ages of 3 to 10 years. Four diverse pathways were identified, including two groups that started high (high subtle-decreasing; high decreasing-to-increasing) and two groups that started low (low stable; low increasing-to-decreasing). Children with prior history of child welfare involvement, preschool-age IPV exposure, school-age IPV exposure, or family income below the federal poverty level had higher odds of being in the high decreasing-to-increasing group compared with the high subtle-decreasing group. Children with a mother with greater than high school education or higher maternal responsiveness had higher odds of being in the low increasing-to-decreasing group compared with the low stable group. The importance of maternal responsiveness in fostering prosocial skill development underlines the need for further assessment and intervention. Recommendations for clinical assessment and parenting programs are provided.

Ontogenetic changes in bite force and gape in tufted capuchins.

Bite force and gape are two important performance metrics of the feeding system, and these metrics are inversely related for a given muscle size because of fundamental constraints in sarcomere length-tension relationships. How these competing performance metrics change in developing primates is largely unknown. Here, we quantified in vivo bite forces and gapes across ontogeny and examined these data in relation to body mass and cranial measurements in captive tufted capuchins, Sapajus spp. Bite force and gape were also compared across geometric and mechanical properties of mechanically challenging foods to investigate relationships between bite force, gape and food accessibility (defined here as the ability to breach shelled nuts). Bite forces at a range of gapes and feeding behavioral data were collected from a cross-sectional ontogenetic series of 20 captive and semi-wild tufted capuchins at the Núcleo de Procriação de Macacos-Prego Research Center in Araçatuba, Brazil. These data were paired with body mass, photogrammetric measures of jaw length and facial width, and food geometric and material properties. Tufted capuchins with larger body masses had absolutely higher in vivo bite forces and gapes, and animals with wider faces had absolutely higher bite forces. Bite forces and gapes were significantly smaller in juveniles compared with subadults and adults. These are the first primate data to empirically demonstrate the gapes at which maximum active bite force is generated and to demonstrate relationships to food accessibility. These data advance our understanding of how primates meet the changing performance demands of the feeding system during development.

Corticosteroid Receptors in Cardiac Health and Disease.

Nuclear receptors play a central role in both energy metabolism and cardiomyocyte death and survival in the heart. Recent evidence suggests they may also influence cardiomyocyte endowment. Although several members of the nuclear receptor family play key roles in heart maturation (including thyroid hormone receptors) and cardiac metabolism, here, the focus will be on the corticosteroid receptors, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). The heart is an important target for the actions of corticosteroids, yet the homeostatic role of GR and MR in the healthy heart has been elusive. However, MR antagonists are important in the treatment of heart failure, a condition associated with mitochondrial dysfunction and energy failure in cardiomyocytes leading to mitochondria-initiated cardiomyocyte death (Ingwall and Weiss, Circ Res 95:135-145, 2014; Ingwall , Cardiovasc Res 81:412-419, 2009; Zhou and Tian , J Clin Invest 128:3716-3726, 2018). In contrast, animal studies suggest GR activation in cardiomyocytes has a cardioprotective role, including in heart failure.

A preventable, life-altering case of fluoroquinolone-associated tendonitis.

ABSTRACT: Fluoroquinolones, such as ciprofloxacin and levofloxacin, are broad-spectrum antibacterial agents that have historically been widely used for urinary tract infections, pneumonia, and intra-abdominal infections but are associated with several serious adverse reactions, including tendinopathy and tendon rupture, peripheral neuropathy, and aortic aneurysm. These drugs should not be used for uncomplicated infections unless no other antimicrobial treatment is feasible. This article describes a patient who experienced life-altering disability from a fluoroquinolone, reviews the adverse reactions of this drug class, and discusses recommended treatment for acute uncomplicated cystitis and asymptomatic bacteriuria.

Fiber-type phenotype of the jaw-closing muscles in Gorilla gorilla, Pan troglodytes, and Pan paniscus: A test of the Frequent Recruitment Hypothesis.

Skeletal muscle fiber types are important determinants of the contractile properties of muscle fibers, such as fatigue resistance and shortening velocity. Yet little is known about how jaw-adductor fiber types correlate with feeding behavior in primates. Compared with chimpanzees and bonobos, gorillas spend a greater percentage of their daily time feeding and shift to herbaceous vegetation when fruits are scarce. We thus used the African apes to test the hypothesis that chewing with unusually high frequency is correlated with the expression in the jaw adductors of a high proportion of type 1 (slow, fatigue-resistant) fibers at the expense of other fiber types (the Frequent Recruitment Hypothesis). We used immunohistochemistry to determine the presence and distribution of the four major myosin heavy chain (MHC) isoforms in the anterior superficial masseter (ASM), superficial anterior temporalis, and deep anterior temporalis of four Gorilla gorilla, two Pan paniscus, and four Pan troglodytes. Serial sections were stained against slow (MHC-1/-α-cardiac) and fast (MHC-2/-M) fibers. Fibers were counted and scored for staining intensity, and fiber cross-sectional areas (CSAs) were measured and used to estimate percentage of CSA of each MHC isoform. Hybrid fibers accounted for nearly 100% of fiber types in the masseter and temporalis of all three species, resulting in three main hybrid phenotypes. As predicted, the gorilla ASM and deep anterior temporalis comprised a greater percentage of CSA of the slower, fatigue-resistant hybrid fiber type, significantly so for the ASM (p = 0.015). Finally, the results suggest that fiber phenotype of the chewing muscles contributes to behavioral flexibility in ways that would go undetected in paleontological studies relying solely on morphology of the bony masticatory apparatus.

11ß-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action.

Glucocorticoid action on target tissues is determined by the density of "nuclear" receptors and intracellular metabolism by the two isozymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11ß-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11ß-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11ß-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11ß-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11ß-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11ß-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11ß-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11ß-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11ß-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental "programming." The role of 11ß-HSD2 as a marker of programming is being explored. The 11ß-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

The Role of 11ß-Hydroxy Steroid Dehydrogenase Type 2 in Glucocorticoid Programming of Affective and Cognitive Behaviours.

Developmental exposure to stress hormones, i.e. glucocorticoids, is central to the process of prenatal programming of later-life health. Glucocorticoid overexposure, through stress or exogenous glucocorticoids, results in a reduced birthweight, as well as affective and neuropsychiatric outcomes in adults, combined with altered hypothalamus-pituitary-adrenal (HPA) axis activity. As such, glucocorticoids are tightly regulated during development through the presence of the metabolizing enzyme 11ß-hydroxysteroid dehydrogenase type 2 (HSD2). HSD2 is highly expressed in 2 hubs during development, i.e. the placenta and the fetus itself, protecting the fetus from inappropriate glucocorticoid exposure early in gestation. Through manipulation of HSD2 expression in the mouse placenta and fetal tissues, we are able to determine the relative contribution of glucocorticoid exposure in each compartment. Feto-placental HSD2 deletion resulted in a reduced birthweight and the development of anxiety- and depression-like behaviours in adult mice. The placenta itself is altered by glucocorticoid overexposure, which causes reduced placental weight and vascular arborisation. Furthermore, altered flow and resistance in the umbilical vessels and modification of fetal heart function and development are observed. However, brain-specific HSD2 removal (HSD2BKO) also generated adult phenotypes of depressive-like behaviour and memory deficits, demonstrating the importance of fetal brain HSD2 expression in development. In this review we will discuss potential mechanisms underpinning early-life programming of adult neuropsychiatric disorders and the novel therapeutic potential of statins.

The Source and the Course of the Articular Branches to the T4-T8 Zygapophysial Joints.

OBJECTIVE: To define the source and the course of the articular branches to the midthoracic zygapophysial ("z") joints. DESIGN: Cadaveric dissection. SETTING: The Gross Anatomy Laboratory of the Duke University School of Medicine. SUBJECTS: Ten human cadaveric thoraces. METHODS: Gross and stereoscopic dissection of dorsal rami T4-T8 was performed bilaterally on 10 adult embalmed cadavers. The medial and lateral branches were traced to their origins from the dorsal rami, and the course of the articular nerves was documented through digital photography. Radio-opaque wire (20 gauge) was applied to the nerves. Fluoroscopic images were obtained to delineate their radiographic course with respect to osseous landmarks. RESULTS: Forty-eight inferior articular branches were identified. Three (6.3%) originated from the medial branch and 44 (91.7%) from the dorsal ramus. One was indeterminate. Fifty-one superior articular branches were identified. Eight (15.7%) originated from the medial branch and 43 (84.3%) from the dorsal ramus. In 12% of cases (6/50), there was side-to-side asymmetry in the origins of the articular branches. Nerves were commonly suspended in the intertransverse space. The articular branches contacted an osseous structure in only 39% of cases. As previously reported, a "descending branch" was not identified in any specimen. CONCLUSIONS: Articular branches to the T4-T8 z-joints have substantial inter- and intraspecimen variability of origin. They typically arise from the dorsal ramus rather than the medial branch and frequently do not contact any osseous structure to allow percutaneous needle placement.

Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11ß-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11ß-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.