Virtual reality immerses you in your mind: the experience and stress-reduction benefits of VR mindfulness modules in persons with TBI.

OBJECTIVE: This pilot study tested the feasibility and stress reduction effectiveness of a one-time virtual reality mindfulness module (VRMM) in individuals with mild-to-moderate traumatic brain injury (TBI). METHODS: Thirty-eight participants participated in a pilot study utilizing a mixed methods convergent parallel design. Pretest and posttest stress levels were collected; participants engaged in a brief 4-question qualitative interview. Mann Whitney U and Wilcoxon Signed Rank Tests were used. Qualitative analysis utilized grounded theory. RESULTS: Post-VRMM, two-thirds (24) of participants had a statistically significant decrease in stress levels. A key qualitative finding indicated that participants found the immersiveness and realism of the VR environments helpful in compensating for cognitive deficits resulting from TBI. There were no adverse side effects reported, indicating that well-designed VRMMs that minimize motion-induced adverse effects are well tolerated in persons with TBI. CONCLUSION: A guided mindfulness activity in a VR environment was well tolerated, and participants overall found VRMM effective in reducing stress levels. VR-based environments have potential to harness guided mindfulness practice and may support persons with TBI to enhance concentration. Further application of this technology in TBI rehabilitation is promising and warrants future research to explore the benefit of VR in improving rehabilitation outcomes.

Management of Severe Botulinum-Induced Eyelid Ptosis With Pretarsal Botulinum Toxin and Oxymetazoline Hydrochloride 0.1.

BACKGROUND: Eyelid ptosis following periocular onabotulinumtoxinA (BoNT-A) treatment is a known complication that can be frustrating for both patients and practitioners. Iatrogenic blepharoptosis occurs due to local spread of the BoNT-A from the periocular region into the levator palpebrae superioris muscle. Although injectors should have a thorough understanding of the relevant anatomy in order to prevent it, BoNT-A induced ptosis can occur even in the most experienced hands. OBJECTIVES: The aim of this study was to describe a case series of patients treated effectively with topical oxymetazoline HCl 0.1% and pretarsal BoNT-A injections in the setting of botox-induced ptosis. METHODS: The study group consisted of 8 patients who had undergone recent cosmetic BoNT-A treatment preceding the sudden onset of unilateral upper eyelid ptosis. RESULTS: A diagnosis of severe ptosis (>3 mm) was made in all the cases in this series. Pretarsal BoNT-A injections alone or in association with topical administration of Upneeq eyedrops (Upneeq, Osmotica Pharmaceuticals, Marietta, GA) significantly reversed the ptosis in all treated cases. CONCLUSIONS: This is the first documented case series of patients treated effectively with topical oxymetazoline HCl 0.1% and pretarsal BoNT-A injections in the setting of botox-induced ptosis. This treatment combination is a safe and effective option in these cases.

Physical Activity and the Acute Hemodynamic Response to ACE Inhibition in Hypertension.

Introduction. Physical activity (PA) can reduce blood pressure (BP) in hypertensives through possibly interacting with the renin-angiotensin-aldosterone system (RAAS). We conducted a nested-cohort analysis to determine if self-reported PA was associated with BP responsiveness to acute angiotensin converting enzyme inhibition (ACEi). Methods. Data were extracted from the HyperPATH dataset, a cohort designed to identify mechanisms of cardiometabolic risk. Hypertensives that completed a self-assessed PA questionnaire, hormonal assessments (aldosterone [ALDO]), and BP to a single dose of an ACEi (captopril, 25 mg) were included. All participants (n = 144) were studied on a controlled diet for 7 days. PA was recorded as no PA, or little, moderate, or high amounts of exercise. Analyses were adjusted for age, sex, race, and body mass index. Results. Individuals who reported high amounts of PA displayed a greater BP lowering effect from ACEi compared to those who reported moderate (-14.8 ± 8.1 vs -8.4 ± 9.9 mm Hg, P < .01) or no additional PA (-14.8 ± 8.1 vs -2.6 ± 9.9 mm Hg, P < .001). Exploratory analyses indicated high amounts of PA were associated with a reduced heart rate (54 ± 8 vs 66 ± 10 bpm, P < .001) and blunted ALDO (ß = 0.44, 95% confidence interval = 0.19-0.70). Conclusions. Higher self-reported PA was associated with an augmented BP lowering effect to acute ACEi in hypertensive patients.

Evaluating hyaluronic acid dermal fillers: A critique of current characterization methods.

Soft-tissue augmentation has gained much popularity in recent years. Hyaluronic acid (HA) based dermal fillers; a non-permanent injectable device, can restore volume loss, fill fine lines and wrinkles and add curves and contours. HA based dermal fillers entered the non-surgical treatment market in the late 1990s, however there is a lack of data and literature comparing the range of products and detailing the complexities of these products and how it relates to tissue performance. Measuring the physico-chemical properties of these dermal fillers provide key parameters to predict their performance after injection into the body. This article reviews the currently reported methods and parameters used to characterize dermal fillers. The review of these methods and data from the literature provides a useful guide to clinicians and injectors in selecting the optimal product suitable for the needs of each patient.

Delayed-onset Nodules (DONs) and Considering their Treatment following use of Hyaluronic Acid (HA) Fillers.

Delayed-onset nodules (DONs) represent a poorly understood and generally neglected group of complications. It is not a diagnosis. The underlying pathologies and their incidences are largely unknown due to the lack of specificity in clinical signs and the challenges in accessing diagnostic tests, cost implications, or reluctance from patients to undergo them. A lack of presumptive clinical diagnosis, coupled with management ranging from "scatter-gun" polypharmacy to clinical inertia, is believed to result in chronicity and increased morbidity. This paper provides guidance on the identification and understanding of the underlying pathologies and encourages the increased utilization of a medical model of care. The more routine adoption of histopathology, inflammatory markers, and ultrasound will permit a more targeted management and a greater understanding of the incidences and evolution of the pathologies.

Guideline for the Safe Use of Hyaluronidase in Aesthetic Medicine, Including Modified High-dose Protocol.

Vascular occlusions can occur with injection of dermal fillers, causing devastating outcomes for the patient. Hyaluronidase is an enzyme that was first used in general medicine in 1949, but has gained widespread use in aesthetic medicine to dissolve hyaluronic acid (HA)-based dermal fillers. Knowledge of this drug and its use for other aesthetic indications is evolving, and there is often anxiety attached to the administration of animal-derived product due to fears of an allergic reaction. This paper provides guidance on the indications for use when dissolving HA filler with hyaluronidase. It discusses formulation differences, adverse events, allergy to wasp and bee stings, and how this increases risk of allergy to hyaluronidase. It also discusses incidence of allergy, which includes a discussion of types of allergic response and how this correlates to skin tests and a discussion on skin testing for allergy.

Acute effects of the food preservative propionic acid on glucose metabolism in humans.

INTRODUCTION: Propionic acid (PA) is a common food preservative generally recognized as safe by the US Food and Drug Administration; however, exogenous PA has effects on glucose metabolism that are not fully understood. Our preclinical studies demonstrated exogenous PA increases glucagon, norepinephrine, and endogenous glucose production (EGP). RESEARCH DESIGN AND METHODS: We performed a randomized, placebo-controlled, crossover study in 28 healthy men and women to determine the effect of PA (1500 mg calcium propionate) on these factors. Subjects had two study visits, each preceded by a 1 week, PA-free diet. During each visit, glucose, insulin, glucagon, norepinephrine, epinephrine, and EGP were assessed for 2 hours after oral administration of PA/placebo under resting conditions (protocol 1) and during either a euglycemic (~85-90 mg/dL) or hypoglycemic (~65-70 mg/dL) hyperinsulinemic clamp (protocol 2). RESULTS: PA, as compared with placebo, significantly increased: (1) glucagon and norepinephrine during protocol 1; (2) glucagon, norepinephrine, and epinephrine under euglycemic conditions in protocol 2; and (3) norepinephrine, epinephrine, and EGP under hypoglycemic conditions in protocol 2. CONCLUSION: Oral consumption of PA leads to inappropriate activation of the insulin counterregulatory hormonal network. This inappropriate stimulation highlights PA as a potential metabolic disruptor.

Guideline for the Management of Hyaluronic Acid Filler-induced Vascular Occlusion.

Vascular occlusions can occur with injection of dermal fillers causing devastating outcomes for the patient. The occurrence, and subsequent management, of these negative outcomes is a source of significant stress to the aesthetic clinician. Complications management is an essential component of clinical practice and professionals must develop competence and confidence in the identification and effective treatment of a vascular occlusion. The relatively rare occurrence of a vascular occlusion mandates that learning must be largely through the study of theory in addition to the sharing of learning experiences within a collaborative clinical community. The delivery of optimal care begins with an understanding of the underlying pathophysiology and the ability to assess and elicit clinical signs. Establishing a clinical diagnosis, targeted therapy can commence in a timely fashion. This paper provides guidance on how to identify and manage a vascular occlusion caused by cross-linked hyaluronic acid. It provides a detailed description of the pathological process of tissue ischemia, and introduces identifiable stages which will help to determine the extent of ischemia and the time frame since ischemic onset. The stages are particularly important as they highlight when wound support may be needed.

Facial Vascular Events and Tissue Ischemia: A Guide to Understanding and Optimizing Wound Care.

The Complications in Medical Aesthetics Collaborative (CMAC) is a nonprofit organization established to promote best patient outcomes through educating clinicians in the prevention, diagnosis, and management of complications that can arise following nonsurgical cosmetic procedures. The organization is a global community sharing information, learning, experience, and data to promote best practices. This article explores how dermal filler vascular events can cause tissue ischaemia leading to a facial wound. Ideally, vascular events will be diagnosed early and amenable to reversal with hyaluronidase if caused by a cross-linked hyaluronic acid. If there is significant and extensive hypoxia to the area, there is delayed diagnosis, or the injected product cannot be reversed, the management should center around optimizing wound care. Both simple and complex wounds will benefit from good care. Patients seek aesthetic treatments to improve how they look and can be vulnerable to poor outcomes. Wounds, if not treated appropriately, can result in permanent scarring or other sequalae, such as post-inflammatory hyperpigmentation. There are many publications addressing vascular events in aesthetic practice, but providing optimal care for facial wounds is not addressed.

Guideline for the Prevention, Diagnosis, and Management of Acute Bacterial Soft Tissue Infections Following Nonsurgical Cosmetic Procedures.

The Complications in Medical Aesthetics Collaborative (CMAC) is a nonprofit organization established to promote best patient outcomes through educating clinicians in the prevention, diagnosis, and management of complications that can arise following nonsurgical cosmetic procedures. The organization is a global community sharing information, learning, experience, and data to promote best practices. There is no reliable data on the risk or incidence of acute infection following a nonsurgical cosmetic procedure, but it is considered to be a rare complication. This article explores the evidence base for precautions and best practice standards, including an examination of the rational for standard aftercare advice and guidance on prevention, diagnosis, and management protocols.

Consensus Opinion for The Management of Soft Tissue Filler Induced Vision Loss.

There are multiple treatment strategies proposed for the management of vision loss related to the injection of soft tissue fillers. Currently, there is no internationally accepted consensus on the immediate management of soft tissue filler induced vision loss (STFIVL). A recent systematic review of the literature concluded that there is not enough evidence to support retrobulbar hyaluronidase, and alternative treatments require exploration. The available literature demonstrates the inconsistent and unproven success of retrobulbar and peribulbar hyaluronidase in reversal of soft filler induced vision loss. Various therapeutics have been used to aid the reversal of vision loss but with mixed outcomes. The current evidence base does not support the use of retrobulbar and peribulbar hyaluronidase. The use of retrobulbar hyaluronidase for reversing soft tissue filler induced vision loss is controversial. Its efficacy remains unproven and there is mixed evidence within the literature. The current evidence suggests that there may be an increased risk of introducing severe adverse events associated with retrobulbar hyaluronidase and may even exacerbate the problem for those clinicians who are not ophthalmology trained. Therefore, we recommend two alternative treatment pathways for ophthalmology and non-ophthalmology trained practitioners. The suggested goal of this publication is to understand the pathophysiology of STFIVL, recognize signs and symptoms, and to propose algorithms to manage vision loss for both non-ophthalmology and ophthalmology trained clinicians. Clinicians must act swiftly and arrange immediate transfer to an emergency department or ophthalmology specialist setting to give the patient the best chance of vision restoration. The focus of any intervention for non-ophthalmology trained clinicians should be based around the immediate use of non-invasive techniques.

Guideline for the Management Herpes Simplex 1 and Cosmetic Interventions.

The Complications in Medical Aesthetics Collaborative (CMAC) is a not-for-profit organization established to promote best patient outcomes through educating clinicians who perform nonsurgical cosmetic procedures in the prevention, diagnosis, and management of complications that can arise. The organization is a global community sharing information, learning, experience, and data to promote best practice. Herpes simplex is common in the general population. The risk of reactivation due to trauma is acknowledged in the literature. Reactivation of herpes simplex 1 following cosmetic procedures is considered rare, but there are no reliable data on the incidence. Although self-limiting, symptoms can be painful and distressing for patients who have undergone a procedure to improve their appearance. Clinicians should document the steps they've taken to avoid reactivation, and should be confident in their management plan and patient care if a patient suffers a reactivation. The authors have referred to the available literature and experience to provide a user-friendly guideline to reduce risk of herpes simplex 1 reactivation through appropriate patient screening, promote accurate diagnosis and an understanding of differentials, and provide management plans for prophylaxis to minimize adverse sequalae. In cases of post-procedure outbreak, the guideline explains the management options, including patient education and support when prescription medications are not indicated.

Interplay Between Statins, Cav1 (Caveolin-1), and Aldosterone.

Statin use is associated with lower aldosterone levels. We hypothesized that caveolin-1 may be important for the uptake of statins into the adrenal gland and would affect statin's aldosterone-lowering effects. The aim of this study was to test whether the caveolin-1 risk allele (rs926198) would affect aldosterone levels associated with statin use. The Hypertensive Pathotype database includes healthy and hypertensive individuals who have undergone assessment of adrenal hormones. Individuals were studied off antihypertensive medications but were maintained on statins if prescribed by their personal physician. Adrenal hormones were measured at baseline and after 1 hour of angiotensin II stimulation on both high- and low-sodium diets. A mixed-model repeated-measures analysis was employed with a priori selected covariates of age, sex, body mass index, and protocol (low versus high sodium, baseline versus angiotensin II stimulated aldosterone). A total of 250 individuals were included in the study; 31 individuals were taking statins (12.4%) and 219 were not. Among statin users, carrying a caveolin-1 risk allele resulted in a 25% (95% CI, 1-43.2) lower aldosterone level (P=0.04). However, among nonstatin users, carrying a caveolin-1 risk allele resulted in no significant effect on aldosterone levels (P=0.38). Additionally, the interaction between caveolin-1 risk allele and statin use on aldosterone levels was significant (P=0.03). These findings suggest caveolin-1 risk allele carrying individuals are likely to receive the most benefit from statin's aldosterone-lowering properties; however, due to the observational nature of this study, these findings need further investigation.

Primary Aldosteronism Decreases Insulin Secretion and Increases Insulin Clearance in Humans.

Primary aldosteronism is a frequent cause of resistant hypertension and is associated with an increased risk of developing diabetes mellitus. Aldosterone impairs insulin secretion in isolated islets, and insulin secretion is increased in aldosterone synthase-deficient mice. We hypothesized that treatment for primary aldosteronism increases insulin secretion and insulin sensitivity in humans. We conducted a prospective cohort study in patients with primary aldosteronism, with assessment of glucose metabolism before and 3 to 12 months after treatment. Participants underwent treatment for primary aldosteronism with adrenalectomy or a mineralocorticoid receptor antagonist at the discretion of their treating physician. We assessed insulin secretion and insulin sensitivity by hyperglycemic and hyperinsulinemic-euglycemic clamps, respectively, on 2 study days after a 5-day standardized diet. After treatment, the C-peptide and insulin response during the hyperglycemic clamp increased compared with pretreatment (ΔC-peptide at 90-120 minutes +530.5±384.1 pmol/L, P=0.004; Δinsulin 90-120 minutes +183.0±122.6, P=0.004). During hyperinsulinemic-euglycemic clamps, insulin sensitivity decreased after treatment (insulin sensitivity index 30.7±6.2 versus 18.5±4.7 nmol·kg-1·min-1·pmol-1·L; P=0.02). Insulin clearance decreased after treatment (872.8±207.6 versus 632.3±178.6 mL/min; P=0.03), and disposition index was unchanged. We conclude that the insulin response to glucose increases and insulin clearance decreases after treatment for primary aldosteronism, and these effects were not due to alterations in creatinine clearance or plasma cortisol. These studies may provide further insight into the mechanism of increased diabetes mellitus risk in primary aldosteronism.

Elements in the λ immunity region regulate phage development: beyond the 'Genetic Switch'.

Genetic elements in the bacteriophage λ immunity region contribute to stable maintenance and synchronous induction of the integrated Escherichia coli prophage. There is a bistable switch between lysogenic and lytic growth that is orchestrated by the CI and Cro repressors acting on the lytic (PL and PR ) and lysogenic (PRM ) promoters, referred to as the Genetic Switch. Other less well-characterized elements in the phage immunity region include the PLIT promoter and the immunity terminator, TIMM . The PLIT promoter is repressed by the bacterial LexA protein in λ lysogens. LexA repressor, like the λ CI repressor, is inactivated during the SOS response to DNA damage, and this regulation ensures that the PLIT promoter and the lytic PL and PR promoters are synchronously activated. Proper RexA and RexB protein levels are critical for the switch from lysogeny to lytic growth. Mutation of PLIT reduces RexB levels relative to RexA, compromising cellular energetics and causing a 10-fold reduction in lytic phage yield. The RexA and RexB proteins interact with themselves and each other in a bacterial two-hybrid system. We also find that the transcription terminator, TIMM , is a Rho-independent, intrinsic terminator. Inactivation of TIMM has minimal effect on λ lysogenization or prophage induction.

There's no cure for brain injury: work-related stress in brain injury rehabilitation professionals.

Objective: To explore the experience of work-related stress in brain injury professionals and to identify the contributing factors to work-related stress. Methods: 17 brain injury professionals participated in one-time interviews conducted either in person or utilising video conferencing. The data were analysed utilising a Grounded Theory approach. Results: Participants reported that working in brain injury rehabilitation is difficult due to the complex and unpredictable nature of brain injury. The impact of limited funding and resources was endorsed by all participants as the most stressful aspect of working in this field. Emotional experiences associated with treating survivors and organisational factors increase the risk for work-related stress. Brain injury professionals rely on support provided by coworkers and supervisors. Conclusion: This study provides a deeper understanding of work-related stress and challenges of working in the brain injury rehabilitation field, as well as appreciation for the personal and organisational strategies that may help to offset stress. The unpredictable nature of working in brain injury rehabilitation impacted professionals at the micro, mezzo, and macro levels of practice. Overall, it was apparent that the participants interviewed were highly resilient individuals, demonstrating acceptance and flexibility in the limitations they face working in the field of brain injury rehabilitation.

Serum Lipocalin 2 (Neutrophil Gelatinase-Associated Lipocalin) in Relation to Biomarkers of Inflammation and Cardiac Stretch During Activation of the Renin-Angiotensin-Aldosterone System in Human Immunodeficiency Virus.

PURPOSE: To evaluate the relationship of lipocalin 2 to inflammation and cardiac injury with increased aldosterone in human immunodeficiency virus (HIV). METHODS: A standardized 6-day low-sodium diet was used to stimulate renin-angiotensin-aldosterone system (RAAS) activation, and serum lipocalin 2 and biomarkers of inflammation and cardiac stretch were assessed among persons with or without HIV. RESULTS: Lipocalin 2 levels increased with RAAS activation compared with suppression in the HIV group (median level [interquartile range], 71.3 [59.2-99.7] vs 67.0 [51.8-86.3] ng/mL; P = .01). During RAAS activation, lipocalin 2 was related to biomarkers of inflammation (tumor necrosis factor α [P = .007]), monocyte/macrophage activation (soluble CD163 [P = .005] and chemokine [C-C motif] ligand 2 [P = .03]), and markers of cardiac stretch (brain natriuretic peptide [P < .001] and N-terminal fragment of the prohormone brain natriuretic peptide [P = .001]) in HIV. CONCLUSION: Lipocalin 2 may be important in modulating aldosterone-induced inflammation, monocyte activation, and cardiac stretch during RAAS activation in HIV. CLINICAL TRIAL REGISTRATION: NCT01407237.

In vivo molecular chronotyping, circadian misalignment, and high rates of depression in young adults.

BACKGROUND: Young adults are disproportionately affected by depression and related mental disorders. Circadian misalignment (a phase advance or delay in the body's internal clock timing) is thought to exert adverse effects on downstream physiological processes regulating mood. Circadian disruption may represent an additional, under-appreciated risk factor affecting young adults. Here, we test the hypothesis that depression in young adults is associated with circadian misalignment-the lack of concordance between an individual's endogenous rhythm and their external social and academic environment. METHODS: We screened 528 individuals for morningness-eveningness diurnal preference and sleep-wake chronotype. We selected individuals with extreme scores (n = 130) for estimation of circadian phase by measuring clock gene mRNA oscillations in hair follicles (a peripheral clock). Using an independent, data-driven cluster analysis, we define the circadian misalignment of both advanced- and delayed-phase individuals from clock gene mRNA expression levels. We compare depression (BDI-II), anxiety (STAI), social jetlag, sleep duration, and sleep disturbance (PROMIS) scores between misaligned individuals and control individuals of intermediate chronotype (n = 173). RESULTS: We demonstrate that depression scores in young adults are significantly higher in individuals with circadian phase delays and in individuals with a mismatch between circadian behavioral phenotypes and circadian molecular phase. Evening-type individuals with circadian phase delays are 20 times more likely and mismatched individuals are 5-8 times more likely to be depressed than control individuals. Sleep disturbance shows a similar relationship with circadian phenotypes, but the mood effects described in this study are independent of sleep duration, social jetlag and gender. LIMITATIONS: Our study examined peripheral clock genes that represents a circadian rhythm potentially influenced by both intrinsic and external, environmental factors. Our study population spanned a limited age-group and our results cannot distinguish between cause and effect of circadian, sleep and mood variables. CONCLUSIONS: Our study validates previous theoretical predictions of circadian effects on mood disorders and highlights a critical, hidden risk factor affecting mood in young adults-circadian disruption.

Circadian Effects on Performance and Effort in Collegiate Swimmers.

Although individual athletic performance generally tends to peak in the evening, individuals who exhibit a strong diurnal preference perform better closer to their circadian peak. Time-of-day performance effects are influenced by circadian phenotype (diurnal preference and chronotype-sleep-wake patterns), homeostatic energy reserves and, potentially, genotype, yet little is known about how these factors influence physiological effort. Here, we investigate the effects of time of day, diurnal preference, chronotype, and PER3 (a circadian clock gene) genotype on both effort and performance in a population of Division I collegiate swimmers (n = 27). Participants competed in 200m time trials at 7:00 and 19:00 and were sampled pre- and post-trial for salivary α-amylase levels (as a measure of physiological effort), allowing for per-individual measures of performance and physiological effort. Hair samples were collected for genotype analysis (a variable-number tandem-repeat (VNTR) and a single nucleotide polymorphism (SNP) in PER3). Our results indicate significant and parallel time-of-day by circadian phenotype effects on swim performance and effort; evening-type swimmers swam on average 6% slower with 50% greater α-amylase levels in the morning than they did in the evening, and morning types required 5-7 times more effort in the evening trial to achieve the same performance result as the morning trial. In addition, our results suggest that these performance effects may be influenced by gene (circadian clock gene PER3 variants) by environment (time of day) interactions. Participants homozygous for the PER34,4 length variant (rs57875989) or who possess a single G-allele at PER3 SNP rs228697 swam 3-6% slower in the morning. Overall, these results suggest that intra-individual variation in athletic performance and effort with time of day is associated with circadian phenotype and PER3 genotype.