Physiological impacts of atmospheric pollution: Effects of environmental air pollution on exercise.

In this review, we discuss some of the recent advances in our understanding of the physiology of the air pollution and exercise. The key areas covered include the effect of exercise intensity, the effects of pre-exposure to air pollution, acclimation to air pollution, and the utility of masks during exercise. Although higher intensity exercise leads to an increase in the inhaled dose of pollutants for a given distance traveled, the acute effects of (diesel exhaust) air pollution do not appear to be more pronounced. Second, exposure to air pollution outside of exercise bouts seems to have an effect on exercise response, although little research has examined this relationship. Third, humans appear to have an ability to acclimate to ground level ozone, but not other pollutants. And finally, masks may have beneficial effects on certain outcomes at low intensity exercise in pollution with significant levels of particles, but more study is required in realistic conditions.

Evaluation of Mental Health First Aid in New York City.

More than 155,000 New Yorkers were trained in Mental Health First Aid (MHFA) between 2016 and 2020. Free citywide trainings were made available to all New Yorkers and were disseminated through city agencies and community-based settings. RAND Corporation researchers conducted a mixed-methods study that included a web-based survey of past trainees and a series of focus groups with leaders of community-based organizations and city agency staff to assess the impact of the MHFA trainings and needs for future training. In this article, the authors describe the evaluation activities that took place; the methods behind them; and the results at the individual, agency, and community levels. They also offer recommendations for ways to improve future mental health education efforts. Respondents applied MHFA skills extensively and broadly across their social networks. Nine in ten respondents had contact with an individual with a mental health problem in the past six months. Among those who had contact, 84 percent indicated using their MHFA skills to help a friend or family member, and nearly half reported applying skills with a co-worker, neighbor, or acquaintance. Because MHFA was offered through city agency workplaces and community-based settings, tens of thousands of New Yorkers were given tools to come to the aid of individuals in their personal and professional lives. MHFA may be a promising approach to building supportive social networks, organizations, and communities that are primed to recognize and assist those experiencing mental health challenges.

Personal strategies to mitigate the effects of air pollution exposure during sport and exercise: a narrative review and position statement by the Canadian Academy of Sport and Exercise Medicine and the Canadian Society for Exercise Physiology.

Air pollution is among the leading environmental threats to health around the world today, particularly in the context of sports and exercise. With the effects of air pollution, pollution episodes (eg, wildfire conflagrations) and climate change becoming increasingly apparent to the general population, so have their impacts on sport and exercise. As such, there has been growing interest in the sporting community (ie, athletes, coaches, and sports science and medicine team members) in practical personal-level actions to reduce the exposure to and risk of air pollution. Limited evidence suggests the following strategies may be employed: minimising all exposures by time and distance, monitoring air pollution conditions for locations of interest, limiting outdoor exercise, using acclimation protocols, wearing N95 face masks and using antioxidant supplementation. The overarching purpose of this position statement by the Canadian Academy of Sport and Exercise Medicine and the Canadian Society for Exercise Physiology is to detail the current state of evidence and provide recommendations on implementing these personal strategies in preventing and mitigating the adverse health and performance effects of air pollution exposure during exercise while recognising the limited evidence base.

The diverse pleiotropic effects of spliceosomal protein PUF60: A case series of Verheij syndrome.

Verheij syndrome (VRJS) is a rare craniofacial spliceosomopathy presenting with craniofacial dysmorphism, multiple congenital anomalies and variable neurodevelopmental delay. It is caused by single nucleotide variants (SNVs) in PUF60 or interstitial deletions of the 8q24.3 region. PUF60 encodes a splicing factor which forms part of the spliceosome. To date, 36 patients with a sole diagnosis of VRJS due to disease-causing PUF60 SNVs have been reported in peer-reviewed publications. Although the depth of their phenotyping has varied greatly, they exhibit marked phenotypic heterogeneity. We report 10 additional unrelated patients, including the first described patients of Khmer, Indian, and Vietnamese ethnicities, and the eldest patient to date, with 10 heterozygous PUF60 variants identified through exome sequencing, 8 previously unreported. All patients underwent deep phenotyping identifying variable dysmorphism, growth delay, neurodevelopmental delay, and multiple congenital anomalies, including several unique features. The eldest patient is the only reported individual with a germline variant and neither neurodevelopmental delay nor intellectual disability. In combining these detailed phenotypic data with that of previously reported patients (n = 46), we further refine the known frequencies of features associated with VRJS. These include neurodevelopmental delay/intellectual disability (98%), axial skeletal anomalies (74%), appendicular skeletal anomalies (73%), oral anomalies (68%), short stature (66%), cardiac anomalies (63%), brain malformations (48%), hearing loss (46%), microcephaly (41%), colobomata (38%), and other ocular anomalies (65%). This case series, incorporating three patients from previously unreported ethnic backgrounds, further delineates the broad pleiotropy and mutational spectrum of PUF60 pathogenic variants.

COVID-19 Pandemic and Exercise (COPE) trial: a multigroup pragmatic randomised controlled trial examining effects of app-based at-home exercise programs on depressive symptoms.

BACKGROUND: The number of adults across the globe with significant depressive symptoms has grown substantially during the COVID-19 pandemic. The extant literature supports exercise as a potent behaviour that can significantly reduce depressive symptoms in clinical and non-clinical populations. OBJECTIVE: Using a suite of mobile applications, at-home exercise, including high intensity interval training (HIIT) and/or yoga, was completed to reduce depressive symptoms in the general population in the early months of the pandemic. METHODS: A 6-week, parallel, multiarm, pragmatic randomised controlled trial was completed with four groups: (1) HIIT, (2) Yoga, (3) HIIT+yoga, and (4) waitlist control (WLC). Low active, English-speaking, non-retired Canadians aged 18-64 years were included. Depressive symptoms were measured at baseline and weekly following randomisation. RESULTS: A total of 334 participants were randomised to one of four groups. No differences in depressive symptoms were evident at baseline. The results of latent growth modelling showed significant treatment effects in depressive symptoms for each active group compared with the WLC, with small effect sizes (ESs) in the community-based sample of participants. Treatment groups were not significantly different from each other. Effect sizes were very large (eg, week 6 ES range=-2.34 to -2.52) when restricting the analysis only to participants with high depressive symptoms at baseline. CONCLUSIONS: At-home exercise is a potent behaviour to improve mental health in adults during the pandemic, especially in those with increased levels of depressive symptoms. Promotion of at-home exercise may be a global public health target with important personal, social and economic implications as the world emerges scathed by the pandemic. TRIAL REGISTRATION NUMBER: NCT04400279.

Eteplirsen Use in a Boy with Duchenne Muscular Dystrophy and Sickle Cell Anemia.

Eteplirsen is an antisense oligonucleotide used in the treatment of Duchenne muscular dystrophy (DMD). The safety of eteplirsen use in individuals with rare comorbid conditions is not known. We present the case of a 4-year-old boy with a DMD exon deletion amenable to treatment with eteplirsen and comorbid sickle cell anemia. He has received eteplirsen treatment for 3 years with no clear adverse effects, including no increase in sickle cell crises.

Viscoelastic and Deformation Characteristics of Structurally Different Commercial Topical Systems.

Rheological characteristics and shear response have potential implication in defining the pharmaceutical equivalence, therapeutic equivalence, and perceptive equivalence of commercial topical products. Three creams (C1 and C3 as oil-in-water and C2 as water-in-oil emulsions), and two gels (G1 and G2 carbomer-based) were characterized using the dynamic range of controlled shear in steady-state flow and oscillatory modes. All products, other than C3, met the Critical Quality Attribute criteria for high zero-shear viscosity (η0) of 2.6 × 104 to 1.5 × 105 Pa∙s and yield stress (τ0) of 55 to 277 Pa. C3 exhibited a smaller linear viscoelastic region and lower η0 (2547 Pa∙s) and τ0 (2 Pa), consistent with lotion-like behavior. All dose forms showed viscoelastic solid behavior having a storage modulus (G') higher than the loss modulus (G″) in the linear viscoelastic region. However, the transition of G' > G″ to G″ > G' during the continual strain increment was more rapid for the creams, elucidating a relatively brittle deformation, whereas these transitions in gels were more prolonged, consistent with a gradual disentanglement of the polymer network. In conclusion, these analyses not only ensure quality and stability, but also enable the microstructure to be characterized as being flexible (gels) or inelastic (creams).

Evaluation of the Connections to Care (C2C) Initiative: Interim Report.

At least one in five adult New Yorkers is likely to meet the criteria for a mental health diagnosis, yet most do not receive mental health services to treat these problems. Mental health problems, such as depression and anxiety, disproportionately affect historically underserved segments of the population, such as racial/ethnic minority and low-income individuals, and these groups are least likely to receive mental health services. The Connections to Care (C2C) Collaborative developed the C2C program, which integrates mental health support into the work of nonclinical community-based organizations (CBOs) through task shifting; task shifting is an approach extending evidence-informed health care skills to community-based partners under the oversight of trained professionals to expand the health care workforce. This study uses data from interviews, surveys, and CBO-provided progress indicators to describe how C2C has been implemented within and across the 15 CBOs. This study also describes study methods and a description of the baseline sample for the impact evaluation at the time of writing.

Posterior calvarial distraction for complex craniosynostosis and cerebellar tonsillar herniation.

OBJECTIVE: Children with syndromic, multisuture, and lambdoid craniosynostosis undergoing calvarial surgery often have Chiari malformation type I (CM-I) (or cerebellar tonsillar herniation). The optimal management of this patient group, including the surgical techniques and timing of surgery, remains uncertain. Posterior calvarial distraction (PCD) is an effective method to increase the supratentorial cranial volume and improve raised intracranial pressure in children with complex craniosynostosis. This study investigated the efficacy of PCD in posterior fossa (PF) volume expansion and treatment of CM-I and associated syringomyelia (syrinx) in this group of children. METHODS: This retrospective study included patients who were surgically treated between 2006 and 2015. Over 10 years, 16 patients with multisuture synostosis, lambdoid synostosis, or craniosynostosis associated with a confirmed genetic syndrome, and a concurrent CM-I, were included. The mean age at the time of surgery was 5.1 years (range 8 months-18 years). Fourteen patients had pansynostosis and 2 had lambdoid synostosis. Eight had a confirmed syndromic diagnosis (Crouzon in 8, Apert in 4, Pfeiffer in 1, and Saethre-Chotzen in 1). Ten patients had raised intracranial pressure; 4 had syringomyelia. RESULTS: The average clinical follow-up was 50 months (range 9-116 months). Clinically, 9 patients improved, 7 remained stable, and none deteriorated. The average distraction distance was 23 mm (range 16-28 mm). The PF anterior-posterior (AP) distance/width ratio increased from 0.73 to 0.80 mm (p = 0.0004). Although an osteotomy extending inferior to the torcula (compared with superior) was associated with a larger absolute PF AP distance increase (13 vs 6 mm, p = 0.028), such a difference was not demonstrable when the PF AP distance/width ratio was calculated. Overall, the mean tonsillar herniation improved from 9.3 to 6.0 mm (p = 0.011). Syrinx dimensions also improved in the AP (from 7.9 to 3.1 mm) and superior-inferior (from 203 to 136 mm) dimensions. No patients required further foramen magnum decompression for CM. Of the 16 patients, 2 had subsequent frontoorbital advancement and remodeling, of which 1 was for volume expansion and 1 was for cosmetic purposes. Two patients required CSF shunt insertion after PCD. CONCLUSIONS: Following PCD, PF volume increased as well as supratentorial volume. This morphometric change was observed in osteotomies both inferior and superior to the torcula. The PF volume increase resulted in improvement of cerebellar tonsillar herniation and syrinx. PCD is an efficacious first-line, single-stage treatment for concurrent pansynostosis and lambdoid craniosynostosis, CM-I, and syrinx.

Vascular effects of physical activity are not modified by short-term inhaled diesel exhaust: Results of a controlled human exposure study.

BACKGROUND: The combined effects of physical activity and air pollution exposure on vascular function are insufficiently understood, particularly after the inhalation of a ß2-agonist, a vasodilating agent. OBJECTIVE: To assess the micro- and macrovascular response to physical activity after ß2-agonist use while breathing diesel exhaust (DE) in individuals with exercise-induced bronchoconstriction. METHODS: On four exposure visits, eighteen adults inhaled either 400 µg of the ß2-agonist salbutamol or placebo before resting for 60 min, followed by a 30-min cycling bout. During rest and cycling, participants inhaled filtered air (FA) or DE (300 µg/m3 of PM2.5). Microvascular (central retinal arteriolar and venular equivalents, CRAE and CRVE, respectively) and macrovascular parameters (blood pressure (BP)) and heart rate (HR)) were assessed at baseline (T1), 10 min (T2) and 70 min (T3) after cycling. RESULTS: The cycling bout increased CRAE (T2-T1 difference (95th % confidence interval): 4.88 µm (4.73, 5.00 µm), p < 0.001; T3-T1 difference: 2.10 µm (1.62, 2.58 µm), p = 0.031) and CRVE (T2-T1 difference: 3.78 µm (3.63, 3.92 µm), p < 0.001; T3-T1 difference: 3.73 µm (3.63, 3.92 µm), p < 0.001). The exposure to DE had no effect on CRAE (FA-DE difference at T2: 0.46 µm (-0.02, 0.92 µm); p = 0.790; FA-DE difference at T3: 1.76 µm (1.36, 2.16 µm), p = 0.213) and CRVE (FA-DE difference at T2: 0.26 µm (-0.35, 0.88 µm), p = 0.906; FA-DE difference at T3: 0.55 µm (0.05, 1.06 µm), p = 0.750). Compared to T1, systolic BP was decreased at T2 by 2.5 mmHg (2.8, 2.3 mmHg, p = 0.047), independent of inhaled exposure. Heart rate at T2 was significantly increased by 3 bpm (2, 3 bpm, p = 0.025) after the DE-exposure when compared to FA. DISCUSSION: Acute physical activity induces a vasodilatory response in the micro- and macrovasculature in healthy adults by increasing CRAE and CRVE, and by reducing systolic BP post exercise, despite breathing DE. The DE-associated increase in HR might be indicative of an increased sympathetic response to physical activity while breathing DE.

Measurement of Hansen Solubility Parameters of Human Stratum Corneum.

Hansen Solubility Parameters (HSP) of human stratum corneum (SC) represent its polarity and are very important for design and optimization of dermatological formulations. However, there is no directly measured data available in the literature for such a crucial property, which is the subject of the present investigation. HSP of the SC was measured by solvent uptake here. 18 solvents/mixtures with different HSP values were selected and their uptake by the SC was measured at 32 °C. The solvents were then divided into good and bad solvents according to their uptake into the SC. The HSP discrete parts of "atomic dispersion forces (δD)", "dipolar intermolecular forces (δP)", and "hydrogen bonding (δH)" were then calculated using uptake data and HSPiP software. Results showed that δD, δP, and δH values of the SC at 32 °C are 16.5, 12, 7.7 respectively. The obtained HSP values, which were measured for the first time here, were then used to interpret enhancement effects of permeation enhancers and the uptake of vehicles by the SC using Relative Energy Difference (RED), with good correlations. SC HSP values can be further used in transdermal drug delivery, cosmetic formulations, safety issues, etc.

Journal impact factor: a bumpy ride in an open space.

The journal impact factor (IF) is the leading method of scholarly assessment in today's research world. An important question is whether or not this is still a constructive method. For a specific journal, the IF is the number of citations for publications over the previous 2 years divided by the number of total citable publications in these years (the citation window). Although this simplicity works to an advantage of this method, complications arise when answers to questions such as 'What is included in the citation window' or 'What makes a good journal impact factor' contain ambiguity. In this review, we discuss whether or not the IF should still be considered the gold standard of scholarly assessment in view of the many recent changes and the emergence of new publication models. We will outline its advantages and disadvantages. The advantages of the IF include promoting the author meanwhile giving the readers a visualization of the magnitude of review. On the other hand, its disadvantages include reflecting the journal's quality more than the author's work, the fact that it cannot be compared across different research disciplines, and the struggles it faces in the world of open access. Recently, alternatives to the IF have been emerging, such as the SCImago Journal & Country Rank, the Source Normalized Impact per Paper and the Eigenfactor Score, among others. However, all alternatives proposed thus far are associated with their own limitations as well. In conclusion, although IF contains its cons, until there are better proposed alternative methods, IF remains one of the most effective methods for assessing scholarly activity.

Craniofacial Approaches to Pediatric Orbital Tumors.

Primary pediatric orbital tumors requiring surgery are uncommon and often require multidisciplinary management. Commonly used surgical approaches to the orbit include transconjunctival, transcutaneous (eyelid), transcranial, or extracranial osteotomies. This paper reviews a 10-year experience of cases that required a transcranial or extracranial surgical approach at the Birmingham Children's Hospital. A total of 9 patients were identified between the years 2008 to 2017. Pathologies included rhabdomyosarcoma, juvenile ossifying fibroma, optic nerve glioma, and retinoblastoma. Surgical approaches to the orbit included supraorbital bar osteotomy (transcranial) or lateral orbitotomy (extracranial). Surgical team members included neurosurgery, craniofacial surgery, and ophthalmology. This study aims to review the role of surgery in management as well as the specific indications for performing transcranial or extracranial osteotomies. It also highlights the excellent access achieved with the use of these osteotomies in certain cases, especially when compared with transconjunctival or transcutaneous approaches.

Topical sirolimus as an effective treatment for a deep neurofibroma in a patient with neurofibromatosis type I.

A 14-year-old boy with neurofibromatosis type I (NF1) presented with a painful neurofibroma on his right palm. The lesion was treated with topical sirolimus, resulting in decreased size and pain and improvement in motor function of his hand. This case demonstrates the efficacy of topical sirolimus in the management of neurofibromas in NF1.

Needs of Male Sexual Assault Victims in the U.S. Armed Forces.

In the National Defense Authorization Act for Fiscal Year 2016, Congress included a requirement to improve prevention of and response to sexual assaults in which the victim is a male member of the U.S. armed forces. To support this effort, RAND researchers reviewed previous research on male sexual assault and specifically considered research on male sexual assault in the U.S. military. The researchers also conducted interviews with individuals who provide support services to U.S. military personnel and with civilian experts who study male sexual assault or provide services to male victims. Although research considering the needs of and services for male sexual assault victims is more limited than research addressing female victims of sexual assault, the available research provides initial information on the prevalence, characteristics, consequences, and public perceptions of male sexual assault. This literature-along with the results of interviews that addressed needs of male sexual assault victims, reporting and help-seeking among victims, and knowledge and perceptions about such assaults-suggests potential avenues for the U.S. Department of Defense to pursue to better address the needs of male sexual assault victims in the U.S. military. These avenues include improvements to reporting procedures, counseling services, outreach, and education and training of service providers and servicemembers.

Connections to Care (C2C): The Perspectives of Leaders at Community-Based Organizations That Are Integrating Mental Health Supports.

The mental health system often does not reach all individuals who need mental health services. The Connections to Care (C2C) program, a $30 million public-private partnership under the federal Social Innovation Fund, with oversight from the C2C Collaborative, aims to address this problem by reaching up to 40,000 New Yorkers over five years by encouraging formal collaborations between community-based organizations (CBOs) and mental health providers (MHPs). In the C2C task-shifting model, mental health specialists equip non-specialist direct service staff at CBOs with the skills to deliver nonmedical mental health services while also facilitating referrals for more intensive care, if needed. By the end of the first year of C2C implementation, CBOs had contracted with MHPs, and together they developed operational plans, and delivered C2C services to over 4,000 CBO clients. The RAND Corporation is evaluating the results of the C2C program from three vantage points: the effect of C2C on participating clients, relative to a comparison group of New Yorkers not receiving C2C services (impact); the program's implementation across different CBOs; and the effects of the program on government and CBO spending. The purpose of this brief research study is to present preliminary key findings from interviews with CBO leadership, conducted between June and August of 2017, which focused on CBO leaders' experiences launching C2C at their organizations. We share these findings to support CBOs and additional stakeholders in decisionmaking for C2C during the implementation phase. Other findings from the evaluation will be released as data become available.

Alternative Methods to Animal Studies for the Evaluation of Topical/ Transdermal Drug Delivery Systems.

It is critical to develop an effective understanding of the interaction between the drug, delivery system and skin in order to predict and assess skin penetration and permeation. Experimental models for the assessment of topical and transdermal delivery systems must permit evaluation of these complex interactions. Whilst in the past, animal models were commonly used, recent regulatory guidelines, based on 3R principles (refinement, reduction, replacement), encourage the rational use of animals. Alternative methods have been proposed for use in the development of topical and transdermal delivery systems which are often used in combination. We will review the current state of the art in alternative methods for topical and transdermal delivery systems development, including technologies that can assist in the characterization of skin penetration/permeation studies.