Pressure Building Against the Clock: The Impact of Circadian Misalignment on Blood Pressure.

PURPOSE OF REVIEW: Misalignment between the endogenous biological timing system and behavioral activities (i.e., sleep/wake, eating, activity) contributes to adverse cardiovascular health. In this review, we discuss the effects of recurring circadian misalignment on blood pressure regulation and the implications for hypertension development. Additionally, we highlight emerging therapeutic approaches designed to mitigate the negative cardiovascular consequences elicited by circadian disruption. RECENT FINDINGS: Circadian misalignment elicited by work schedules that require individuals to be awake during the biological night (i.e., shift work) alters 24-h blood pressure rhythms. Mechanistically, circadian misalignment appears to alter blood pressure via changes in autonomic nervous system balance, variations to sodium retention, dysregulation of endothelial vasodilatory responsiveness, and activation of proinflammatory mechanisms. Recurring circadian misalignment produced by a mismatch in sleep timing on free days vs. work days (i.e., social jetlag) appears to have no direct effects on prevailing blood pressure levels in healthy adults; though, circadian disruptions resulting from social jetlag may increase the risk of hypertension through enhanced sympathetic activation and/or obesity. Furthermore, social jetlag assessment may be a useful metric in shift work populations where the magnitude of circadian misalignment may be greater than in the general population. Circadian misalignment promotes unfavorable changes to 24-h blood pressure rhythms, most notably in shift working populations. While light therapy, melatonin supplementation, and the timing of drug administration may improve cardiovascular outcomes, interventions designed to target the effects of circadian misalignment on blood pressure regulation are warranted.

A Long-Term Study of the Safety and Efficacy of a Nutraceutical Supplement for Promoting Hair Growth in Perimenopausal, Menopausal, and Postmenopausal Women.

The prevalence of female hair loss and hair thinning increases with advancing age and is most common among post-menopausal women. Recent statistics show that by age 60, an estimated 80% of women experience hair loss. A previous publication detailing the results of the 6-month randomized, double-blind, placebo-controlled phase of this study demonstrated the ability of a nutraceutical supplement to significantly improve hair growth and shedding compared to placebo. Here, we present results from a subsequent 6-month, open-label extension phase assessing the continued safety and efficacy of this nutraceutical for promoting and improving hair growth and evaluate potential long-term benefits on quality of life and menopausal symptoms. After a total of 12 months with the active nutraceutical, subjects had progressive improvements in hair growth, quality, and shedding. Quality of life measures and menopausal symptoms also improved over the duration of the study. When transitioned to daily intake of the supplement, subjects previously treated with placebo achieved significant increases in all hair counts, a significant decrease in shedding, and significant improvement in blinded investigator global hair growth and quality assessments. The results of this long-term study demonstrate that continued use of a novel nutraceutical provides significant incremental improvement over the beneficial effects achieved during the initial 6-month randomized, placebo-controlled phase. Continued use may provide ongoing improvements in hair growth and exert a positive effect on secondary symptoms of menopause, and quality of life in perimenopausal, menopausal, and postmenopausal women with selfperceived thinning hair (ClinicalTrials.gov Identifier: NCT04048031). J Drugs Dermatol. 2022;21(7):776-783. doi:10.36849/JDD.6912.

A Prospective Six-month Single-blind Study Evaluating Changes in Hair Growth and Quality Using a Nutraceutical Supplement in Men and Women of Diverse Ethnicities.

Objective: The goal of this study was to assess the perceived efficacy of a standardized nutraceutical to improve hair growth and quality in men and women of various ethnicities with self-perceived hair thinning. Methods: This prospective, single-blind study enrolled healthy men aged 20 to 55 years (n=47) and premenopausal women aged 20 to 45 years (n=51) with self-perceived, mild-to-moderate hair thinning and included African American, Asian, Hispanic Caucasian and Non-Hispanic Caucasian participants. The nutraceutical supplement (Nutrafol® Men or Women Capsules, Nutraceutical Wellness Inc., New York, New York) was taken daily for six months. Subjects were evaluated in the clinic at baseline and Weeks 12 and 24 with two self-assessments at Weeks 4 and 8. Study endpoints were standardized digital imaging and investigator rated assessments. Self-assessment questionnaires rated hair growth, hair satisfaction, and lifestyle factors. Results: Investigator ratings for baseline hair growth, coverage, density, and volume were significant at Weeks 12 and 24 for all subjects (for each, p<0.001). These significant improvements were seen in 83.7 percent of men and 79.5 percent of women at Week 24. Results were similar across ethnic subgroups with significant benefit at Weeks 12 and 24 (for each, p<0.05). All subjects reported significant improvements in baseline hair appearance/quality, volume/fullness, scalp coverage, thickness, and shedding at Weeks 4, 8, 12 and 24 (for each, p<0.01). Conclusion: A standardized nutraceutical supplement improved visible hair growth with less notable shedding based on subjects' and investigators' overall perception of treatment benefit for men and women of various ethnic backgrounds.

A Randomized, Double-Blind, Placebo-Controlled Study of a Nutraceutical Supplement for Promoting Hair Growth in Perimenopausal, Menopausal, and Postmenopausal Women With Thinning Hair.

Hair loss is a complex and multi-factorial problem that is associated with significant psychological morbidity in women. Menopausal women represent a significant percentage of those affected, since the menopausal hormonal transition can be a contributing factor. A novel nutraceutical supplement has been specifically formulated with phytoactives to improve hair growth and quality in menopausal women (Nutrafol® Women’s Balance Capsules). The objective of this 6-month, randomized, double-blind, placebo-controlled study was to assess the safety and efficacy of this oral supplement to promote hair growth in perimenopausal, menopausal, and postmenopausal women with self-perceived thinning. Subjects were randomized to the study supplement (n=40) or placebo (n=30). The primary endpoint was a statistically significant increase in the number of terminal and vellus hairs based on phototrichogram analysis. Daily intake of the nutraceutical supplement resulted in progressive and significant increase in terminal and total hair counts on days 90 (P<0.01) and 180 (P<0.01) compared to placebo. The vellus hair counts significantly increased for the active treatment group (P<0.05) by day 180 while significantly decreasing for the placebo group subjects. Hair shedding progressively and significantly decreased for the active group compared to placebo, culminating in a reduction of 32.41% by day 180 (P<0.01). The study supplement was well-tolerated. ClinicalTrials.gov Identifier: NCT04048031 J Drugs Dermatol. 2021;20(1):55-61. doi:10.36849/JDD.5701 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

The impact of inflammation on neurocognition and risk for psychosis: a critical review.

Neurocognitive difficulties are highly prevalent among people with schizophrenia and have been linked to increased inflammation, as well as dysfunction and disability. Poor neurocognitive functioning has also been documented in individuals at clinical high risk for psychosis (CHR) and a burgeoning literature point to alterations in inflammation markers in this population. However, there is limited information regarding the putative link between inflammation and neurocognition in CHR individuals, and the potential role of inflammation in the development of cognitive difficulties and psychosis. As previous reports indicate that early treatment in schizophrenia is associated with better outcomes, there is an urgent need to identify neurobiological mechanisms underlying cognitive deterioration and psychosis in CHR individuals to provide them with care prior to significant cognitive and functional declines. To address this gap in the literature, we review and summarize the relevant literatures on inflammation and neurocognitive dysfunction in schizophrenia and CHR individuals, point to remaining gaps, and suggest directions for future research.

Inflammation in individuals with schizophrenia - Implications for neurocognition and daily function.

Individuals with schizophrenia display substantial deficits in neurocognition, resulting in poor daily functioning and disability. Recent reports have suggested that neurocognitive dysfunction in this population is linked to increased inflammation. However, there is paucity of evidence supporting this link, as well as lack of information about the putative link of inflammation to daily functioning. We examined neurocognition (MCCB) and daily functioning (SLOF), as well as inflammatory markers (TNF-α, IL-6, IL-1ß, and IL-12p70) in 41 individuals with schizophrenia. Poor neurocognition was significantly associated with increased peripheral TNF-α and IL-12p70 (r = -0.44 and r = -0.38, respectively, controlling for BMI, depression and antipsychotic medication). Notably, difficulties with daily functioning were significantly associated with increased peripheral TNF-α (r = -0.51) and a trend with increased IL-12p70. Our findings support previous hypotheses linking neurocognitive impairment to increased inflammation in individuals with schizophrenia. Our results extend these associations in this population, linking inflammation to poor daily functioning in this population.

A Six-Month, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of a Nutraceutical Supplement for Promoting Hair Growth in Women With Self-Perceived Thinning Hair.

Hair loss is a complex problem that generates significant concern for those who are affected. Patients seeking medical treatments have limited options, and are increasingly turning to natural therapies. A novel nutraceutical product containing a proprietary Synergen Complex® composed of standardized, active botanicals with potent anti-inflammatory, adaptogenic (anti-stress), antioxidant, and dihydrotestosterone-inhibiting properties has been developed to improve hair growth and hair quality. The objective of this 6-month randomized, double-blind, placebo-controlled study was to assess the ability of this oral supplement (Nutrafol® Women's Capsules) to strengthen and promote the growth of hair in adult women with self-perceived thinning. Enrolled subjects were randomized to receive active treatment (n=26) or placebo (n=14). The primary endpoint in this study was a statistically significant increase in the number of terminal and vellus hairs based on phototrichograms obtained through macrophotography analysis. Daily intake of the nutraceutical supplement resulted in a significant increase in the number of terminal and vellus hairs in the target area at day 90 and day 180 vs placebo (P less than 0.009). Blinded Investigator Global Hair Assessments revealed significant improvements in hair growth (P equals 0.016) and overall hair quality (P equals 0.005). A significant percentage of subjects receiving active treatment also reported improvement in hair growth, volume, thickness, and hair growth rate, as well as decreased anxiety and other wellness parameters. There were no reported adverse events. CONCLUSION: This nutraceutical supplement safely and effectively promoted hair growth in women with self-perceived thinning. It provides a multi-targeted therapeutic approach to hair loss by addressing micro-inflammation, stress, and oxidative damage with clinically tested, standardized, and bio-optimized phytoactive ingredients. ClinicalTrials.gov: NCT03206567 J Drugs Dermatol. 2018;17(5):558-565.

New Insight Into the Pathophysiology of Hair Loss Trigger a Paradigm Shift in the Treatment Approach.

Hair loss affects millions of men and women of all ages and ethnicities, impacting appearance, social interactions, and psycho-emotional well-being. Although a number of options are available, they are limited, carry a potential risk of side effects, and none have proven to be comprehensive for treatment of hair loss. Across the spectrum of hair loss disorders, there has long been a segmentation into distinct mechanisms, driving the main trend in current therapeutics to focus on targeting single molecules or pathways. However, research points to similar dysregulation of intrinsic signaling pathways within follicle physiology that span the hair loss disorder spectrum - with a common inflammatory component identified in most hair loss pathogenesis, including that of androgenetic alopecia (AGA).

J Drugs Dermatol. 2017;16(11 Suppl):s135-140.

A Novel Multi-Targeting Approach to Treating Hair Loss, Using Standardized Nutraceuticals.

Hair loss is a complicated problem that causes significant concern for those who are affected. Patients seeking medical treatment have limited options that include topical minoxidil and oral finasteride. While these treatments are backed by long term clinical use and research outcomes, many patients find topical minoxidil difficult to incorporate into their daily routine and some are concerned with the side effects associated with finasteride. In the office setting, patients may be treated with more invasive procedures such as platelet-rich plasma injections (PRP) and hair transplantation, treatments that often must be repeated and can lead to a costly investment. Consumers are increasingly interested in natural treatments for hair loss. Many turn to basic supplements only to be disappointed when they fail to deliver due to lack of standardization and efficacy. In this paper we review the benefits of a nutraceutical containing a specific blend of highly purified, standardized, bio-optimized, and bioavailable botanical extracts to treat hair loss. These phytoactives were selected because of their diverse multi-modal biologic activity against inflammation, DHT, stress mediators, oxidative damage, and intermediary signaling cascades. This supplement represents a paradigm shift as it addresses not only the factors that trigger hair loss but the downstream mediators of inflammation as well. Multi-center clinical studies are currently underway to confirm the efficacy and benefits of this unique nutraceutical.

J Drugs Dermatol. 2017;16(11 Suppl):s141-148.

CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance.

The pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation in adipose tissue and liver. The CD40 receptor and its ligand CD40L initiate immune cell signaling promoting inflammation, but conflicting data on CD40L-null mice confound its role in obesity-associated insulin resistance. Here, we demonstrate that CD40 receptor-deficient mice on a high-fat diet display the expected decrease in hepatic cytokine levels but paradoxically exhibit liver steatosis, insulin resistance, and glucose intolerance compared with their age-matched wild-type controls. Hyperinsulinemic-euglycemic clamp studies also demonstrated insulin resistance in glucose utilization by the CD40-null mice compared with wild-type mice. In contrast to liver, adipose tissue in CD40-deficient animals harbors elevated cytokine levels and infiltration of inflammatory cells, particularly macrophages and CD8(+) effector T cells. In addition, ex vivo explants of epididymal adipose tissue from CD40(-/-) mice display elevated basal and isoproterenol-stimulated lipolysis, suggesting a potential increase of lipid efflux from visceral fat to the liver. These findings reveal that 1) CD40-null mice represent an unusual model of hepatic steatosis with reduced hepatic inflammation, and 2) CD40 unexpectedly functions in adipose tissue to attenuate its inflammation in obesity, thereby protecting against hepatic steatosis.

Procedures and drugs in pediatric dermatology: iatrogenic risks and situations of concern.

Over the past several decades, improved technologies used in the care of hospitalized and outpatient pediatric populations have resulted in a decreased but still significant number of iatrogenic injuries. Children at the highest risk for cutaneous injury include those with the most immature skin barriers, such as neonates younger than 32 weeks of gestational age. Additional risk factors include low birth weight, increased length of hospital stay, and indwelling instrumentation. Also at risk are older children with compromised skin barriers owing to infectious disease (staphylococcal scalded skin syndrome), inflammatory disease (atopic dermatitis), drug eruptions, and inherited or acquired blistering disorders. This review highlights the presentation, course, and management of iatrogenic skin injury events in children.

Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation.

Thoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and the metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea, and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared with white adipose tissue (WAT), PVAT and BAT from C57BL6/J mice fed a high-fat diet for 13 wk had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80 and CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b(+)/CD11c(+) macrophages in BAT (1.0%) compared with WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from inflammatory stress.

Integrins in prostate cancer progression.

Integrins, which are transmembrane receptors for extracellular matrix proteins, play a key role in cell survival, proliferation, migration, gene expression, and activation of growth factor receptors. Their functions and expression are deregulated in several types of cancer, including prostate cancer. In this article, we review the role of integrins in prostate cancer progression and their potential as therapeutic targets.

Attenuated liver fibrosis in the absence of B cells.

Analysis of mononuclear cells in the adult mouse liver revealed that B cells represent as much as half of the intrahepatic lymphocyte population. Intrahepatic B cells (IHB cells) are phenotypically similar to splenic B2 cells but express lower levels of CD23 and CD21 and higher levels of CD5. IHB cells proliferate as well as splenic B cells in response to anti-IgM and LPS stimulation in vitro. VDJ gene rearrangements in IHB cells contain insertions of N,P region nucleotides characteristic of B cells maturing in the adult bone marrow rather than in the fetal liver. To evaluate whether B cells can have an impact on liver pathology, we compared CCl4-induced fibrosis development in B cell-deficient and wild-type mice. CCl4 caused similar acute liver injury in mutant and wild-type mice. However, following 6 weeks of CCl4 treatment, histochemical analyses showed markedly reduced collagen deposition in B cell-deficient as compared with wild-type mice. By analyzing mice that have normal numbers of B cells but lack either T cells or immunoglobulin in the serum, we established that B cells have an impact on fibrosis in an antibody- and T cell-independent manner.