Randomized Controlled Trial of an Integrated Family-Based Treatment for Adolescents Presenting to Community Mental Health Centers

Community Mental Health Journal - Most adolescents presenting to community mental health centers have one or more comorbidities (internalizing, externalizing, and substance use problems). We...     

Severe amygdala dysfunction in a MAPT transgenic mouse model of frontotemporal dementia

Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is a neurodegenerative tauopathy caused by mutations in the tau gene (MAPT). Individuals with FTDP-17 have deficits in learning, memory, and language, in addition to personality and behavioral changes that are often characterized by a lack of social inhibition. Several transgenic mouse models expressing tau mutations have been tested extensively for memory or motor impairments, though reports of amygdala-dependent behaviors are lacking. To this end, we tested the rTg4510 mouse model on a behavioral battery that included amygdala-dependent tasks of exploration. As expected, rTg4510 mice exhibit profound impairments in hippocampal-dependent learning and memory tests, including contextual fear conditioning. However, rTg4510 mice also display an abnormal hyperexploratory phenotype in the open-field assay, elevated plus maze, light-dark exploration, and cued fear conditioning, indicative of amygdala dysfunction. Furthermore, significant tau burden is detected in the amygdala of both rTg4510 mice and human FTDP-17 patients, suggesting that the rTg4510 mouse model recapitulates the behavioral disturbances and neurodegeneration of the amygdala characteristic of FTDP-17.     

Appendicular myological reconstruction of the forelimb of the giant titanosaurian sauropod dinosaur Dreadnoughtus schrani

Soft tissues are variably preserved in the fossil record with external tissues, such as skin and feathers, more frequently preserved than internal tissues (e.g. muscles). More commonly, soft tissues leave traces of their locations on bones and, for muscles, these clues can be used to reconstruct the musculature of extinct vertebrates, thereby enhancing our understanding of how these organisms moved and the evolution of their locomotor patterns. Herein we reconstruct the forelimb and shoulder girdle musculature of the giant titanosaurian sauropod Dreadnoughtus schrani based on observations of osteological correlates and dissections of taxa comprising the Extant Phylogenetic Bracket of non-avian dinosaurs (crocodilians and birds). Fossils of Dreadnoughtus exhibit remarkably well-preserved, well-developed, and extensive muscle scars. Furthermore, this taxon is significantly larger-bodied than any titanosaurian for which a myological reconstruction has previously been attempted, rendering this myological study highly informative for the clade. In total, 28 muscles were investigated in this study, for which 46 osteological correlates were identified; these osteological correlates allowed the reconstruction of 16 muscles on the basis of Level I or Level II inferences (i.e. not Level I' or Level II' inferences). Comparisons with other titanosaurians suggest widespread myological variation in the clade, although potential phylogenetic patterns are often obscured by fragmentary preservation, infrequent myological studies, and lack of consensus on the systematic position of many taxa. By identifying myological variations within the clade, we can begin to address specific evolutionary and biomechanical questions related to the locomotor evolution in these sauropods.     

Intravenously administered nanoparticles increase survival following blast trauma

Explosions account for 79% of combat-related injuries, leading to multiorgan hemorrhage and uncontrolled bleeding. Uncontrolled bleeding is the leading cause of death in battlefield traumas as well as in civilian life. We need to stop the bleeding quickly to save lives, but, shockingly, there are no treatments to stop internal bleeding. A therapy that halts bleeding in a site-specific manner and is safe, stable at room temperature, and easily administered is critical for the advancement of trauma care. To address this need, we have developed hemostatic nanoparticles that are administered intravenously. When tested in a model of blast trauma with multiorgan hemorrhaging, i.v. administration of the hemostatic nanoparticles led to a significant improvement in survival over the short term (1 h postblast). No complications from this treatment were apparent out to 3 wk. This work demonstrates that these particles have the potential to save lives and fundamentally change trauma care.On the battlefield, hemorrhage is a leading cause of preventable death (1). Blast injuries account for 79% of combat-related injuries and the majority of cases of traumatic brain injury (2). There are three classifications of blast injury: primary, secondary, and tertiary. Primary blast injuries refer to the direct effects of the overpressure wave, whereas secondary and tertiary insults result from objects propelled by the blast wind and the individual being thrown against other objects, respectively. Owing to the rapid change in pressure, blast traumas can involve hemorrhage in multiple organs, particularly the air-filled organs, brain, and spinal cord.Blast trauma is unique and difficult to treat because it can damage multiple organs and cause significant hemorrhaging. The shocking reality is that there are no treatments for internal bleeding, although early intervention is essential to minimizing the mortality associated with severe trauma (3). Uncontrolled bleeding is no less lethal beyond the battlefield, being the leading cause of death for civilians age 5–44 y (4, 5).We need a therapy that can be administered in the field to stop internal bleeding. This therapy must be extremely safe, stable at room temperature, and easily administered. Various therapies, ranging from platelets to recombinant factors to microparticles and nanoparticles, have been considered to date. Administration of allogeneic platelets confers a significant survival advantage in patients with massive trauma, but these platelets have a short shelf life, and administration can cause graft-versus-host disease, alloimmunization, and transfusion-associated lung injuries (6–8). These problems motivated the development of platelet substitutes. Typically, these nanoparticles and microparticles take advantage of the clotting cascade through peptide binding to receptors on activated platelets such as the glycoprotein IIb/IIIa receptor, which can bind fibrinogen, Arg-Gly-Asp (RGD), and dodecapeptide-H12 (HHLGGAKQAGDV). Early designs included RGD-conjugated red blood cells, which were effective in vitro and fibrinogen-coated albumin microparticles, which significantly reduced bleeding time and volume in thrombocytopenic rabbits (9, 10). Platelet-derived particles showed promising results in vitro and in thrombocytopenic rabbits, but did not significantly reduce prolonged bleeding times in thrombocytopenic primates (11, 12). Liposomal nanoparticles are also a potential synthetic core for particles, and particles decorated with RGD and the von Willebrand factor-binding peptide VBP promoted platelet aggregation in vivo and reduced bleeding time in a mouse tail bleeding model (13). Similarly, liposomes carrying the fibrinogen γ chain dodecapeptide (HHLGGAKQAGDV) (14, 15) were effective in thrombocytopenic rats, but might not be effective in healthy models.In addition to the platelet mimics, recombinant factor 7 (rFVIIa; NovoSeven) has been used to augment hemostasis by supplementing the coagulation cascade. Although rFVIIa can control or reduce massive bleeding in trauma patients, immunogenic and thromboembolic complications are unavoidable risks (16, 17). Nevertheless, rFVIIa is used in the clinic in trauma and surgical situations when bleeding cannot be controlled through other means (16). The data on rFVIIa’s efficacy is variable, and it is very expensive; a single dose costs approximately $10,000, and multiple doses are typically needed to impact hemostasis (16). We need an effective, safe therapy for the field.To address this need, we have developed hemostatic nanoparticles that can halt bleeding when delivered intravenously (18–20). We hypothesized that administration of these hemostatic nanoparticles could increase short-term and long-term survival following blast trauma. We developed a full-body blast model that replicates the injuries seen in personnel exposed to explosions, and tested the effects of administration of hemostatic nanoparticles, control nanoparticles, saline, and rFVIIa on survival, hemorrhaging, and behavioral outcomes following blast trauma.     

First Nations Health: The need for linked genomic surveillance of SARS-CoV-2

Genomic surveillance during the coronavirus disease 2019 (COVID-19) pandemic has been key to the timely identification of virus variants with important public health consequences, such as variants that can transmit among and cause severe disease in both vaccinated or recovered individuals. The rapid emergence of the Omicron variant highlighted the speed with which the extent of a threat must be assessed. Rapid sequencing and public health institutions’ openness to sharing sequence data internationally give an unprecedented opportunity to do this; however, assessing the epidemiological and clinical properties of any new variant remains challenging. Here we highlight a “band of four” key data sources that can help to detect viral variants that threaten COVID-19 management: 1) genetic (virus sequence) data; 2) epidemiological and geographic data; 3) clinical and demographic data; and 4) immunization data. We emphasize the benefits that can be achieved by linking data from these sources and by combining data from these sources with virus sequence data. The considerable challenges of making genomic data available and linked with virus and patient attributes must be balanced against major consequences of not doing so, especially if new variants of concern emerge and spread without timely detection and action.     

Smaller aortic dimensions do not fully account for the greater pulse pressure in elderly female hypertensives

This study examined the importance of aortic dimensions in determining pulse pressure in elderly hypertensives participating in the 2nd Australian National Blood Pressure Study, including a substantial number not previously receiving blood pressure lowering medication. Aortic dimensions were determined by ultrasound at the transverse arch and at the insertion of the aortic valve. Unadjusted data showed negative (P<0.001) correlations between central (carotid) and (brachial) peripheral pulse pressure and both arch (-0.200, -0.181) and outflow tract (-0.238, -0.238) diameters. Correlations were similar in those previously treated with blood pressure lowering medication and in the treatment na?ve. Central pulse pressure (84+/-26 versus 75+/-28 mm Hg, P<0.001) was higher and aortic dimensions (transverse arch 2.56+/-0.31 versus 2.88+/-0.35 mm, P<0.001) smaller in women than men. Women had greater aortic stiffness (beta index 29.4+/-36.1 versus 22.1+/-21.3, P<0.03). Other bivariate correlates of central pulse pressure were age, mean arterial pressure, height, heart rate, augmentation index, aortic stiffness (all P<0.001), and weight (P=0.027). In multivariate analyses gender remained a predictor of central pulse pressure (P<0.001) even with inclusion of aortic dimensions (P=0.013) height and weight. Other significant terms were age, heart rate, mean blood pressure, and aortic stiffness (all P<0.001). These findings demonstrate an independent inverse relation between aortic size and pulse pressure in older hypertensive subjects. Differences in aortic dimensions and stiffness between genders do not fully account for the observed blood pressure differences, suggesting that a contributory factor to gender differences in pulse pressure is an increased age-related mismatch in ventricular function and aortic stiffness in women compared with men.     

Pimecrolimus cream 1%: A new development in nonsteroid topical treatment of inflammatory skin diseases

Atopic dermatitis (AD) is one of a family of inflammatory skin diseases (psoriasis, irritant contact dermatitis, and allergic contact dermatitis). Dermal inflammation and production of proinflammatory cytokines by activated T cells is a prominent and defining characteristic in all of these conditions. Corticosteroids, though effective and potent immunosuppressants, are associated with a number of systemic and local adverse effects. The ascomycin derivative pimecrolimus (formerly ASM 981) is a nonsteroid with topical anti-inflammatory activity. Pimecrolimus cream 1% is minimally absorbed into the circulation; thus, it has a low bioavailability-reducing the risk for systemic adverse effects. The efficacy and safety of pimecrolimus cream 1% has been well shown in diverse patient populations with inflammatory skin diseases in several well-controlled trials. Significant and rapid amelioration of the signs and symptoms of AD was established in 3 studies lasting 6 weeks each, evaluating 589 pediatric patients. In a 1-year study, pimecrolimus was applied at the first signs and symptoms of eczema to prevent the progression of AD to flares. Flares were prevented in over 50% of patients who used pimecrolimus cream 1%, reducing or completely eliminating the need for topical corticosteroids during a 1-year treatment period. Results in pimecrolimus studies in chronic irritant hand dermatitis and chronic hand dermatitis of mixed causes indicate potential for use in these important diseases, and further study in these indications is warranted.     

Quality of anticoagulation care in patients discharged from a pharmacist-managed anticoagulation clinic after stabilization of warfarin therapy

STUDY OBJECTIVE: To determine if transitioning patients from a pharmacist- managed anticoagulation clinic after stabilization of warfarin therapy to physician-managed care alters the quality of anticoagulation care. DESIGN: Retrospective medical record review. SETTING: Pharmacist-managed, urban academic medical center-based outpatient anticoagulation clinic. PATIENTS: Forty patients who were stabilized on warfarin therapy. MEASUREMENTS AND MAIN RESULTS: Quality of anticoagulation care was measured by percentage of international normalized ratios (INRs) in target range, anticoagulation-related health care visits, and responses to satisfaction surveys. A significant decrease in anticoagulation control was observed on transition to physician-managed care. Before transition, 76% of all INRs were in target range versus 48% after transition (p<0.0001, chi(2) test). When performing paired analysis, a median 75% of each patient's INRs were therapeutic before transition compared with 36.5% after (p<0.0001, Wilcoxon signed rank test). Thirty-two percent of first INR values measured after transition from the clinic were in target range, and the median time to first follow-up INR was 41 days. The number of INR values above 4.5 and below 1.5 increased significantly after transition from the anticoagulation clinic (p<0.0001 and p=0.01, respectively, chi(2) test). Before transition from the anticoagulation clinic, two anticoagulation-related emergency department visits were reported in one patient. After transition, 13 cases of additional medical care were reported among seven patients; seven of the 13 cases required an office visit with the physician, and six resulted in emergency room evaluation. None of these cases resulted in hospitalization. Patient satisfaction with clinical care provided by the anticoagulation clinic was significantly higher before transition. CONCLUSION: Transition of patients from a pharmacist-managed anticoagulation clinic back to physician-managed anticoagulation care after stabilization of warfarin therapy was associated with a significant decrease in INR control, increased medical care related to anticoagulation, and decreased patient satisfaction.     

Injunctive norms for alcohol-related consequences and protective behavioral strategies: effects of gender and year in school

Perceived drinking norms have received increased attention as one determinant of high levels of college alcohol consumption and alcohol-related problems. Excessive drinking is widely visible on college campuses, and students may therefore assume that it is peer-supported (Kitts, 2003). Research into peer relations indicates that the perceived approval of important others predicts drinking behavior (Neighbors, Lee, Lewis, Fossos, & Larimer, 2007). Neither the use of alcohol-related protective behavioral strategies nor alcohol-related negative consequences have been investigated in terms of their perceived approval. The purpose of this study was to extend previous research on injunctive norms and assess self-other discrepancies in levels of approval for campus drinking patterns, negative alcohol-related consequences, and protective behavioral strategies. Undergraduate volunteers (n=324, 61% female, 67% Caucasian) completed an online survey of drinking patterns; they rated comfort with overall campus drinking, and the acceptability of alcohol-related consequences and protective strategies for themselves and their close friends. As predicted, students expressed lower acceptance of consequences than their friends, and higher acceptance of alcohol-related protective strategies. We observed main effects of gender and year in school. Males and upperclassmen expressed higher acceptance of negative consequences for both self and others, and lower acceptance of protective strategies for both self and others. Implications for prevention programs are discussed.     

Carbohydrate intake is the main determinant of growth in infants born <33 weeks' gestation when protein intake is adequate

OBJECTIVE: We investigated the relative contribution of macronutrients to postnatal growth in preterm infants born <33 wk of gestation. METHODS: An audit of daily parenteral and enteral intakes of protein, carbohydrate, fat, energy, and growth (daily weight, weekly length, and head circumference) from birth to discharge home in 138 infants at <33 wk of gestation admitted to an Australian tertiary hospital was done. A mixed-model analysis of variance with random effects (slope and intercept) for subject and controlling for time, sex, gestational age, and total energy was used to determine the relative contribution of macronutrients to growth. RESULTS: A higher energy intake (kilocalories per day) had a positive influence on growth. With total energy held constant, the contribution of carbohydrate to total energy had a positive relation to weight, length, and head circumference gains; protein had no relation and fat was negatively associated. For every 1% increase in energy from carbohydrate, there was a 2.3-g/d increase in weight (95% confidence interval 1.6-3.0, P < 0.0001), a 0.013-cm/d increase in length (95% confidence interval 0.003-0.022, P = 0.007), and a 0.015-cm/d increase in head circumference (95% confidence interval 0.009-0.022, P < 0.0001). CONCLUSION: A re-examination of the macronutrient balance in the diet of preterm infants is required in relation to optimizing growth.