Recent Advances in Phytochemical-Based Topical Applications for the Management of Eczema: A Review.

Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments.

Product labeling accuracy and contamination analysis of commercially available cannabidiol product samples.

Background and objective: Commercially available cannabidiol (CBD) products are increasingly being used for medicinal purposes, including for the treatment of various neurological conditions, but there are growing concerns around adherence to quality control measures that protect consumers. This study was conducted to assess the purity and label accuracy of commercially available CBD products. Methods: Commercially available CBD products were chosen from the open stream of commerce in the United States based on formulations as a tincture, gummy, vape, or topical product. Cannabinoid concentrations were analyzed to verify label accuracy including "full spectrum," "broad spectrum," and "CBD isolate" claims on the product label. Analysis for the presence of contaminants included evaluation for heavy metals, pesticides, and residual solvents. Labeled and actual total amounts of CBD and levels of impurities such as heavy metals, residual solvents, and pesticides were measured. Results: A total of 202 CBD products (100 tinctures, 48 gummies, 34 vape products, and 20 topicals) were chosen to represent a broad sample in the United States. Of the products tested (full spectrum, n = 84; broad spectrum, n = 28; CBD isolate, n = 37), 26% did not meet the definition for product type claimed on the packaging. The majority of products (74%) deviated from their label claim of CBD potency by at least 10%. Heavy metals were detected 52 times across 44 of the 202 products tested, with lead being the most prevalent heavy metal. Residual solvents were detected 446 times across 181 of 202 products, with the highest concentrations reported for hexane, m/p-xylene, methanol, and o-xylene. Of 232 pesticides tested, 26 were found 55 times across 30 products. A total of 3% of heavy metals, 1% of residual solvents, and 1% of pesticides violated >1 regulatory threshold. Discussion: This study demonstrated that the majority of commercially available CBD products tested within the current study are inaccurately labeled. Heavy metals, residual solvents, and pesticides were found in several products, some of which violated regulatory thresholds. Thus, uniform compliance with CBD quality control measures is lacking and raises consumer protection concerns. Improved regulatory oversight of this industry is recommended.

Zonisamide: A Comprehensive, Updated Review for the Clinician.

Purpose of Review: Zonisamide (ZNS) was first approved in the United States in 2000 for the adjunctive treatment of patients aged 16 years or older with partial (focal) seizures. Although ZNS has been proven to treat multiple seizure types, it has been largely underutilized in US clinical practice. Recent Findings: Published literature demonstrated that antiseizure medications (ASMs) acting on Na+ and Ca2+ channels may add beneficial effects in many seizure types by reducing seizure frequency and leading to overall improvements. In addition, effects of ZNS may lead to clinical improvements in Parkinson disease, alcohol and sleep disorders, pain, and migraine. ZNS is available in multiple formulations and is a safe and effective, broad spectrum ASM. Summary: The purpose of this review was to provide an update to what is known about the efficacy of ZNS and where it shows benefits in the treatment of patients with epilepsy and other CNS disorders through its many unique mechanisms of action.

CyberKnife Stereotactic Radiosurgery for Growing Vestibular Schwannoma: Longitudinal Tumor Control, Hearing Outcomes, and Predicting Post-Treatment Hearing Status.

OBJECTIVES: (1) To determine tumor control rates for treating growing vestibular schwannoma (VS) with CyberKnife stereotactic radiosurgery (CK SRS); (2) to determine hearing outcomes after CK SRS; (3) to propose a set of variables that could be used to predict hearing outcomes for patients receiving CK SRS for VS. STUDY DESIGN: Retrospective case series review. METHODS: 127 patients who received CK SRS for radiographically documented growing VS were reviewed. Tumors were monitored for post-procedure growth radiographically with linear measurements and three-dimensional segmental volumetric analysis (3D-SVA). Hearing outcomes were reviewed for 109 patients. Cox proportional hazard modeling was used to identify variables correlated with hearing outcomes. RESULTS: Tumor control rate was 94.5% for treating VS with CK SRS. Hearing outcomes were categorized using the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) classification system. As of their last available audiogram, 33.3% of patients with pre-treatment class A and 26.9% of patients with class B retained their hearing in that class. 15.3% of patients starting with class A or B with extended follow-up (>60 months), maintained hearing within this same grouping. Our final model proposed to predict hearing outcomes included age, fundal cap distance (FCD), tumor volume, and maximum radiation dose to the cochlea; however, FCD was the only statistically significant variable. CONCLUSION: CK SRS is an effective treatment for control of VS. Hearing preservation by class was achieved in a third of patients. Finally, FCD was found to be protective against hearing loss. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:S1-S12, 2024.

Cardiac Abnormalities in Hispanic/Latina Women With Prior De Novo Hypertensive Disorders of Pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with long-term maternal risks for cardiovascular disease for reasons that remain incompletely understood. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos), a multi-center community-based cohort of Hispanic/Latino adults recruited 2008 to 2011, was used to evaluate the associations of history of de novo HDP (gestational hypertension, preeclampsia, eclampsia) with echocardiographic measures of cardiac structure and function in Hispanic/Latina women with ≥1 prior pregnancy and the proportion of association mediated by current hypertension (>140/90 mm Hg or antihypertensive therapy). RESULTS.: The study cohort included 5168 Hispanic/Latina women with an average age (SD) of 58.7 (9.7) years at time of echocardiogram. Prior de novo HDP was reported by 724 (14%) of the women studied and was associated with lower left ventricle (LV) ejection fraction -0.66 (95% confidence interval [CI], -1.21 to -0.11), higher LV relative wall thickness 0.09 (95% CI, 0-0.18), and 1.39 (95% CI, 1.02-1.89) higher risk of abnormal LV geometry after adjusting for blood pressure and other confounders. The proportion of the association mediated by current hypertension between HDP and LV ejection fraction was 0.09 (95% CI, 0.03-0.45), LV relative wall thickness was 0.28 (95% CI, 0.16-0.51), abnormal LV geometry was 0.14 (95% CI, 0.12-0.48), concentric left ventricular hypertrophy was 0.31 (95% CI, 0.19-0.86), and abnormal LV diastolic dysfunction was 0.58 (95% CI, 0.26-0.79). CONCLUSIONS.: In a large cohort of Hispanic/Latina women those with history of de novo HDP had detectable and measurable subclinical alterations in cardiac structure and both systolic and diastolic dysfunction that were only partially mediated by current hypertension.

Lamotrigine use and potential for adverse cardiac effects: A retrospective evaluation in a Veteran population.

OBJECTIVE: To identify the impact of lamotrigine (LTG) on cardiac rhythm and conduction abnormalities for Veterans, an especially vulnerable population. BACKGROUND: In October 2020 the US Food and Drug Administration (FDA) added a new warning to the label of lamotrigine (Lamictal™) regarding its potential to cause cardiac rhythm and conduction abnormalities [1]. This warning came following in vitro data which suggested Class IB antiarrhythmic effects occurring at clinically achievable concentrations of lamotrigine [2]. However, it is unclear whether the in vitro findings will result in adverse clinical outcomes. Our objective was to assess for evidence for adverse clinical outcomes in a vulnerable population and examine for subtler signs of an association between lamotrigine and cardiac rhythm disturbances. METHODS: A retrospective chart review was conducted using records between 10-01-2017 and 07-06-2021, identifying patients at the William S. Middleton Memorial Veterans Hospital who were prescribed lamotrigine. Data collected included: dates of lamotrigine initiation or discontinuation, lamotrigine dosing over the time of the prescription and maximum lamotrigine dose, any cardiac-related ICD-10-CM codes or a history of a cardiology appointment, EKGs with any abnormalities or changes, any concomitantly prescribed medications with known potential to cause cardiac abnormalities, any cardiac deaths. This retrospective chart review was approved by the University of Wisconsin-Madison Institutional Review Board. RESULTS: Two hundred and thirty-three (189 male) patients with a lamotrigine prescription and 41.2 % (n = 96) of these patients had an EKG performed while prescribed lamotrigine. The average age of patients was 64.3 ± 13.0 (range 29 to 90) years and mean maximum lamotrigine daily dose was 250.8 ± 148.2 mg (range 25 to 800 mg). Nearly half (47.9 %, 46/96) of the patients were prescribed a concomitant sodium channel blocking medication in addition to lamotrigine. Eighty-four of the patients (87.5 %, 84/96) had a cardiac diagnosis, while 12 (12.5 %, 12/96) did not. A total of 12 deaths occurred within the review period, with two cardiac deaths from congestive heart failure. Four cases did not have information on cause of death. No LTG-associated cardiac adverse effects were noted as part of clinical care, though rash was noted in 5 cases. A total of 7 (7.3 %, 7/96) patients were found to have EKG abnormalities potentially related to lamotrigine, including 7.1 % (6/84) of those with a cardiac diagnosis and 8.3 % (1/12) of those without a cardiac diagnosis. CONCLUSIONS: While recent FDA warnings have suggested caution regarding cardiac complications associated with lamotrigine based on in vitro studies, the clinical implications are uncertain. Despite selecting a particularly vulnerable population, this retrospective chart review did not identify any deaths due to cardiac rhythm or conduction causes, nor demonstrate unambiguous cardiac complications related to lamotrigine. Even using permissive criteria (including any prolonged PR or QTc) to examine for subtle effects, only a low incidence (<10 %) of potential complications was found. Broader implications of this study are limited by the number of patients included and the retrospective nature of the study. Therefore, further studies are warranted to evaluate a link between cardiac complications and the use of lamotrigine, including the role of concomitant medications such as other sodium channel blocking agents and psychotropic medications.

Cross-modal exposure restores multisensory enhancement after hemianopia.

Hemianopia is a common consequence of unilateral damage to visual cortex that manifests as a profound blindness in contralesional space. A noninvasive cross-modal (visual-auditory) exposure paradigm has been developed in an animal model to ameliorate this disorder. Repeated stimulation of a visual-auditory stimulus restores overt responses to visual stimuli in the blinded hemifield. It is believed to accomplish this by enhancing the visual sensitivity of circuits remaining after a lesion of visual cortex; in particular, circuits involving the multisensory neurons of the superior colliculus. Neurons in this midbrain structure are known to integrate spatiotemporally congruent visual and auditory signals to amplify their responses, which, in turn, enhances behavioral performance. Here we evaluated the relationship between the rehabilitation of hemianopia and this process of multisensory integration. Induction of hemianopia also eliminated multisensory enhancement in the blinded hemifield. Both vision and multisensory enhancement rapidly recovered with the rehabilitative cross-modal exposures. However, although both reached pre-lesion levels at similar rates, they did so with different spatial patterns. The results suggest that the capability for multisensory integration and enhancement is not a pre-requisite for visual recovery in hemianopia, and that the underlying mechanisms for recovery may be more complex than currently appreciated.

The formin DAAM1 regulates the deubiquitinase activity of USP10 and integrin homeostasis.

The differentiation of fibroblasts into pathological myofibroblasts during wound healing is characterized by increased cell surface expression of αv-integrins. Our previous studies found that the deubiquitinase (DUB) USP10 removes ubiquitin from αv-integrins, leading to cell surface integrin accumulation, subsequent TGFß1 activation, and pathological myofibroblast differentiation. In this study, a yeast two-hybrid screen revealed a novel binding partner for USP10, the formin, DAAM1. We found that DAAM1 binds to and inhibits USP10's DUB activity through the FH2 domain of DAAM1 independent of its actin functions. The USP10/DAAM1 interaction was also supported by proximity ligation assay (PLA) in primary human corneal fibroblasts. Treatment with TGFß1 significantly increased USP10 and DAAM1 protein expression, PLA signal, and co-localization to actin stress fibers. DAAM1 siRNA knockdown significantly reduced co-precipitation of USP10 and DAAM1 on purified actin stress fibers, and ß1- and ß5-integrin ubiquitination. This resulted in increased αv-, ß1-, and ß5-integrin total protein levels, αv-integrin recycling, and extracellular fibronectin (FN) deposition. Together, our data demonstrate that DAAM1 inhibits USP10's DUB activity on integrins subsequently regulating cell surface αv-integrin localization and FN accumulation.

Patterns of psychotropic drug use in veterans with epilepsy: Do drug interactions matter?

RATIONALE: Patients with epilepsy are likely to suffer from psychiatric comorbidities, including depression and anxiety. They often require treatment with multiple psychotropic drugs (PDs). While it is clear that CYP-inducing ASMs (EIASMs) can increase the oral clearance of multiple medications (thus lowering systemic exposure), it is less clear that all PK interactions are clinically meaningful (e.g. lower efficacy). As a first step in addressing this issue, this study sought to quantify the potential impact of ASM choice, whether EIASM or non-inducer (NIASM), on surrogate markers of suggestive of clinical use, including resultant antidepressant (AD) or antipsychotic (AP) dose, frequency of combination use of AD & AP, and number of multiple drug switches of PDs. Our hypothesis is that because of PK interactions, EIAED treatment would be associated with higher psychotropic drug doses, more frequent Rx adjustments and poly psychotropic comedication, all in order to optimize therapeutic response. METHODS: Using VA pharmacy and national encounter databases, veterans with epilepsy were identified based on having a seizure diagnosis and being prescribed concomitantly an ASM and a psychotropic drug for at least 365 days between 10/1/2010 and 9/30/2014. Patients for whom psychotropic drugs were prescribed any time between beginning and end prescriptions dates of ASMs were considered. Among those, patients receiving both an EIASM + NEIASM concomitantly were categorized with the EIASM group. Patients were evaluated for AD only, AP only and both (AD & AP). To compute average drug doses per day, averages for each patient were computed and averaged again. Multiple drug switches were defined to be for patients who had been prescribed more than three psychotropic drugs during the observation period. Pearson's Chi-Square test was used to compare relative proportions of AD, AP and AD + AP in both groups. RESULTS: In all, 16,188 patients were identified (57.0% on EIASM, 43.0% on NIASM) with a mean age of 58.7 years (91.2% male). A larger proportion of patients on EIASM received mono treatment with any psychotropic drug, as compared to NIASM (42.0% vs 36.1%). Among all, 59.6% received AD only, 6.5% received AP only, and 33.8% received both concurrently. Of EIASM, 62.5% were on AD, 5.9% on AP, and 31.7% on both AP & AD. For NIASM, 55.9% received AD, 7.4% AP, and 36.7% on AD & AP.Chi-square showed that the distribution of PD was statistically different between EIASM and NIASM groups. Z tests showed that each difference (AD, AP and both) in proportions was statistically significant (p values (4 tests, one Chi-square, 3 Z tests <0.001) between EIASM vs NIASM. Interestingly, mean doses of AD or AP did not appear to differ between ASM groups. CONCLUSIONS: Concurrent psychotropic drug use is quite common in the VA population with epilepsy, and a large number of patients still receive enzyme-inducing ASMs that may complicate other medical therapies. Interestingly, in seeming contradiction to our hypothesis, mean daily doses of either AD or AP did not appear to differ between inducers vs non-inducers. Similarly, use of polytherapy, and/or multiple trials of various psychotropic drugs did not appear increased in the CYP-induced group. In fact, combination therapy of AD + AP was higher in NIASM than EIASM. These data suggest that perhaps these types of PK interactions may not in fact result in meaningful clinical differences. Since the present analyses did not include clinical psychiatric measures, future analyses examining direct clinical outcomes are clearly warranted.

Estrogen-Based Gender-Affirming Hormone Therapy and Subclinical Cardiovascular Disease in Transgender Women with HIV.

Purpose: Transgender women (TW) are disproportionately affected by HIV infection and cardiovascular disease (CVD). This study evaluated whether estrogen-based gender-affirming hormone therapy (GAHT) in TW with HIV (TWH-GAHT) is associated with indices of subclinical CVD. Methods: Of the 40 HIV-seropositive persons enrolled, 20-60 years of age, on antiretroviral treatment with undetectable viral load, assessments were performed on 15 TWH; of these persons, 11 were GAHT treated. These TWH-GAHT were matched with HIV+ cisgender men and women based on age, ethnicity/race, body mass index, and antihypertensive medication use. Sex hormones, and cardiometabolic (waist circumference, blood pressure, insulin resistance, lipid profile, and C-reactive protein), vascular (flow-mediated dilation [FMD] and arterial stiffness), and proinflammatory measures were obtained. Results: TWH-GAHT displayed elevated estradiol and suppressed testosterone levels relative to normative ranges. Analyses indicated the TWH-GAHT displayed lower low-density lipoprotein compared with cisgender groups (p < 0.05). Although no difference was seen on FMD, the central augmentation index of aortic stiffness was higher in cisgender HIV+ women than cisgender HIV+ men (p < 0.05). No other group difference on subclinical CVD markers was observed. For TWH, partial correlations indicated associations of certain sex hormones with selected cardiometabolic outcomes and the inflammatory cytokine, interleukin-8. Conclusion: When well matched to HIV+ cisgender men and women, subclinical CVD pathophysiology did not appear elevated in TWH-GAHT, although tendencies emerged suggesting that some subclinical CVD indices may be higher, but others lower than cisgender groups. Longitudinal studies of TWH are needed to more precisely evaluate the moderating effect of GAHT on cardiometabolic pathophysiology.

Acute inhalation of tungsten particles results in early signs of cardiac injury.

Epidemiological studies have established that exposure to tungsten increases the risk of developing cardiovascular diseases. However, no studies have investigated how tungsten affects cardiac function or the development of cardiovascular disease. Inhalation of tungsten particulates is relevant in occupational settings, and inhalation of particulate matter has a known causative role in driving cardiovascular disease. This study examined if acute inhalation to tungsten particulates affects cardiac function and leads to heart tissue alterations. Female BALB/c mice were exposed to Filtered Air or 1.5 ± 0.23 mg/m3 tungsten particles, using a whole-body inhalation chamber, 4 times over the course of two weeks. Inhalation exposure resulted in mild pulmonary inflammation characterized by an increased percentage and number of macrophages and metabolomic changes in the lungs. Cardiac output was significantly decreased in the tungsten-exposed group. Additionally, A', an indicator of the amount of work required by the atria to fill the heart was elevated. Cardiac gene expression analysis revealed, tungsten exposure increased expression of pro-inflammatory cytokines, markers of remodeling and fibrosis, and oxidative stress genes. These data strongly suggest exposure to tungsten results in cardiac injury characterized by early signs of diastolic dysfunction. Functional findings are in parallel, demonstrating cardiac oxidative stress, inflammation, and early fibrotic changes. Tungsten accumulation data would suggest these cardiac changes are driven by systemic consequences of pulmonary damage.

Predictability alters multisensory responses by modulating unisensory inputs.

The multisensory (deep) layers of the superior colliculus (SC) play an important role in detecting, localizing, and guiding orientation responses to salient events in the environment. Essential to this role is the ability of SC neurons to enhance their responses to events detected by more than one sensory modality and to become desensitized ('attenuated' or 'habituated') or sensitized ('potentiated') to events that are predictable via modulatory dynamics. To identify the nature of these modulatory dynamics, we examined how the repetition of different sensory stimuli affected the unisensory and multisensory responses of neurons in the cat SC. Neurons were presented with 2HZ stimulus trains of three identical visual, auditory, or combined visual-auditory stimuli, followed by a fourth stimulus that was either the same or different ('switch'). Modulatory dynamics proved to be sensory-specific: they did not transfer when the stimulus switched to another modality. However, they did transfer when switching from the visual-auditory stimulus train to either of its modality-specific component stimuli and vice versa. These observations suggest that predictions, in the form of modulatory dynamics induced by stimulus repetition, are independently sourced from and applied to the modality-specific inputs to the multisensory neuron. This falsifies several plausible mechanisms for these modulatory dynamics: they neither produce general changes in the neuron's transform, nor are they dependent on the neuron's output.

Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex® (cannabidiol) in patients with refractory epilepsy.

OBJECTIVE: Epidiolex® (CBD) is FDA-approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). Phase III studies suggest that certain adverse effects (AEs), possibly linked to pharmacokinetic/pharmacodynamic (PK/PD) interactions may be therapy-limiting. We sought to identify these factors that contribute to treatment success and retention of therapy. METHODS: A single-center, retrospective review of patients with refractory epilepsy taking Epidiolex® was performed. Kaplan-Meier analysis was performed to describe Epidiolex® retention, as a measure of overall effectiveness. RESULTS: One hundred and twelve patients were screened; 4 were excluded due to loss to follow-up or never starting Epidiolex®. Of 108 patients, mean age was 20.3 years (13.1, range 2 to 63), and 52.8% were female. Mean initial and maintenance doses were 5.3 mg/kg/day (1.3) and 15.3 mg/kg/day (5.8), respectively. At the final evaluation, 75% of patients remained on Epidiolex®. The 25th percentile for discontinuation was 19 months. 46.3% of patients experienced at least one treatment-emergent adverse effect (TEAE) with 14.5% d/c Epidiolex® due to treatment emerging adverse effects (TEAE). The most common reasons for discontinuation were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). One out of 27 discontinuations was due to liver function test (LFT) elevations (3.7%). At initiation, 47.2% were concurrently taking clobazam, and 39.2% of those patients had an initial clobazam dose decrease. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication. SIGNIFICANCE: Epidiolex® is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials, however gastrointestinal complaints, and significant LFT elevations were less common. Our data suggest most patients discontinue within the first several months of treatment and suggest that further studies designed to evaluate early identification and potential mitigation of adverse effects and including drug interactions are warranted.

Developing a stress induction tool relevant to relationships in a health context.

Concerns pertaining to health and to problems in close relationships are both known to be major stressors, yet existing tools are inadequate to assess individual reactions to such stressors. Thus, we sought to develop and preliminarily validate a stress-inducing task for use in a laboratory setting that pertains to the sorts of health-related concerns people face in close relationships. Heterosexual dating couples (44 individuals: mean age 22) were randomized to be paired with their own partner or a stranger and to play a role of speaker or listener. Participants were asked to imagine a scenario in which one person is hit by a car (listener role) and the partner has no means to provide or seek out help for the victim (speaker role). The session consisted of baseline, speech preparation, stress task, and recovery phases. General linear modeling results revealed that the task induced stress, evidenced in cardiovascular activities and self-reported negative affect. Giving a brief speech about the stressful situation creates physiological and psychological strains, regardless of pairing with one's own partner or stranger. Furthermore, cardiovascular and negative affect reactivity to the STress Induction Tool for Close relationships and Health (STITCH) task tended to vary by individual characteristics that reflect one's sensitivity to close relationship-and health-related stress. This tool is intended to be used for testing relationship theory-driven phenomenon and longer-term implications of physiological and affective reactivities in the quality of life and health outcomes of those who experienced a medically stressful circumstance personally or in the family.

Ameliorating Hemianopia with Multisensory Training.

Hemianopia (unilateral blindness), a common consequence of stroke and trauma to visual cortex, is a debilitating disorder for which there are few treatments. Research in an animal model has suggested that visual-auditory stimulation therapy, which exploits the multisensory architecture of the brain, may be effective in restoring visual sensitivity in hemianopia. It was tested in two male human patients who were hemianopic for at least 8 months following a stroke. The patients were repeatedly exposed to congruent visual-auditory stimuli within their blinded hemifield during 2 h sessions over several weeks. The results were dramatic. Both recovered the ability to detect and describe visual stimuli throughout their formerly blind field within a few weeks. They could also localize these stimuli, identify some of their features, and perceive multiple visual stimuli simultaneously in both fields. These results indicate that the multisensory therapy is a rapid and effective method for restoring visual function in hemianopia.SIGNIFICANCE STATEMENT Hemianopia (blindness on one side of space) is widely considered to be a permanent disorder. Here, we show that a simple multisensory training paradigm can ameliorate this disorder in human patients.

Noise-rearing precludes the behavioral benefits of multisensory integration.

Concordant visual-auditory stimuli enhance the responses of individual superior colliculus (SC) neurons. This neuronal capacity for "multisensory integration" is not innate: it is acquired only after substantial cross-modal (e.g. auditory-visual) experience. Masking transient auditory cues by raising animals in omnidirectional sound ("noise-rearing") precludes their ability to obtain this experience and the ability of the SC to construct a normal multisensory (auditory-visual) transform. SC responses to combinations of concordant visual-auditory stimuli are depressed, rather than enhanced. The present experiments examined the behavioral consequence of this rearing condition in a simple detection/localization task. In the first experiment, the auditory component of the concordant cross-modal pair was novel, and only the visual stimulus was a target. In the second experiment, both component stimuli were targets. Noise-reared animals failed to show multisensory performance benefits in either experiment. These results reveal a close parallel between behavior and single neuron physiology in the multisensory deficits that are induced when noise disrupts early visual-auditory experience.

Complementary and Alternative Medicines in the Management of Heart Failure: A Scientific Statement From the American Heart Association.

Complementary and alternative medicines (CAM) are commonly used across the world by diverse populations and ethnicities but remain largely unregulated. Although many CAM agents are purported to be efficacious and safe by the public, clinical evidence supporting the use of CAM in heart failure remains limited and controversial. Furthermore, health care professionals rarely inquire or document use of CAM as part of the medical record, and patients infrequently disclose their use without further prompting. The goal of this scientific statement is to summarize published efficacy and safety data for CAM and adjunctive interventional wellness approaches in heart failure. Furthermore, other important considerations such as adverse effects and drug interactions that could influence the safety of patients with heart failure are reviewed and discussed.

Circulating endothelial and angiogenic cells predict hippocampal volume as a function of HIV status.

Circulating endothelial cells (CECs) and myeloid angiogenic cells (MACs) have the capacity to stabilize human blood vessels in vivo. Evidence suggests that these cells are depleted in dementia and in persons living with HIV (PWH), who have a higher prevalence of dementia and other cognitive deficits associated with aging. However, the associations of CECs and MACs with MRI-based measures of aging brain health, such as hippocampal gray matter volume, have not been previously demonstrated. The present study examined differences in these associations in 51 postmenopausal women with and without HIV infection. Gray matter volume was quantified using MRI. CECs and MACs were enumerated using fluorescence-activated cell sorting. Analyses examined the association of these cell counts with left and right hippocampal gray matter volume while controlling for age and hypertension status. The main finding was an interaction suggesting that compared to controls, postmenopausal PWH with greater levels of CECs and MACs had significantly greater hippocampus GMV. Further research is necessary to examine potential underlying pathophysiological mechanisms in HIV infection linking morpho-functional circulatory reparative processes with more diminished hippocampal volume in postmenopausal women.

An 8-year pragmatic observation evaluation of the benefits of allogeneic HCT in older and medically infirm patients with AML.

We designed a prospective, observational study enrolling patients presenting for treatment of acute myeloid leukemia (AML) at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), and function in: the entire cohort, those aged ≥65 years, those with high comorbidity burden, intermediate cytogenetic risk, adverse cytogenetic risk, and first complete remission with or without measurable residual disease. Patient were assessed 8 times over 2 years. Time-dependent regression models were used. Among 692 patients that were evaluable, 46% received HCT with a 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in most subgroups. Although function, social life, performance status, and depressive symptoms were better for those selected for HCT, these health advantages were lost after receiving HCT. Recipients and nonrecipients of HCT similarly ranked and expected cure as main goal of therapy, whereas physicians had greater expectations for cure than the former. Accounting for health impairments negates survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is mostly owing to selection of the healthier candidates. Considering patients' overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT. This trial was registered at www.clinicaltrials.gov as #NCT01929408.

Light-Guided Percutaneous Neck Rejuvenation With Division of Platysma Bands and Suture Suspension: A Multicenter Retrospective Study.

BACKGROUND: Traditional invasive suture suspension techniques have proven efficacy and durability. A previously described percutaneous placement of a neck suspension suture with light guidance has transformed this into a minimally invasive technique. This novel technique provides a major advance for minimally invasive neck rejuvenation. OBJECTIVES: The authors sought to describe their experience with light-guided percutaneous neck rejuvenation over the past 4.5 years, including technique, patient selection, safety profile, and expected outcomes. METHODS: Data were retrospectively reviewed for all patients who underwent the procedure with 5 surgeons across 4 aesthetic plastic surgery practices from January 2018 through May 2022. Inclusion criteria were mild to moderate neck laxity, prominent anterior platysma bands, and desire to improve neck contour. Patients undergoing concurrent skin incision >5 mm (ie, open rhytidectomy or platysmaplasty) were excluded. RESULTS: A total of 391 patients meeting criteria were identified during the study period. No hematomas were documented. Four patients (1%) developed infection at the suture site, 1 resolving on antibiotics and 3 requiring suture removal. Eighteen (4.6%) developed recurrent platysmal bands, and 7 (1.8%) had residual loose skin. Four (1%) experienced transient marginal mandibular neuropraxia. Mean length of follow-up time was 240 days. CONCLUSIONS: Light-guided percutaneous suture suspension is a safe and viable option for improving neck contours. Although it does not address extensive skin laxity or excess submental fat, it can be combined with energy-based tissue tightening, submental liposuction, or skin excision. In selected patients, this minimally invasive procedure provides predictable results with a low risk of complications.