The thermoneutral zone in women takes an "arctic" shift compared to men.

Conventionally, women are perceived to feel colder than men, but controlled comparisons are sparse. We measured the response of healthy, lean, young women and men to a range of ambient temperatures typical of the daily environment (17 to 31 °C). The Scholander model of thermoregulation defines the lower critical temperature as threshold of the thermoneutral zone, below which additional heat production is required to defend core body temperature. This parameter can be used to characterize the thermoregulatory phenotypes of endotherms on a spectrum from "arctic" to "tropical." We found that women had a cooler lower critical temperature (mean ± SD: 21.9 ± 1.3 °C vs. 22.9 ± 1.2 °C, P = 0.047), resembling an "arctic" shift compared to men. The more arctic profile of women was predominantly driven by higher insulation associated with more body fat compared to men, countering the lower basal metabolic rate associated with their smaller body size, which typically favors a "tropical" shift. We did not detect sex-based differences in secondary measures of thermoregulation including brown adipose tissue glucose uptake, muscle electrical activity, skin temperatures, cold-induced thermogenesis, or self-reported thermal comfort. In conclusion, the principal contributors to individual differences in human thermoregulation are physical attributes, including body size and composition, which may be partly mediated by sex.

Women are Not at Higher Risk for Reintervention or Major Amputation after Lower Extremity Atherectomy for Peripheral Artery Disease.

BACKGROUND: Our objective was to compare short-term and long-term differences in reintervention-free and major amputation-free survival between female and male patients undergoing lower extremity atherectomy for peripheral artery disease. METHODS: We analyzed lower extremity atherectomy procedures performed on 294 patients between January 2014 and September 2019. Reintervention was defined as either open bypass or endovascular procedure to the same region following the index operation. Kaplan-Meier (KM) survival analysis was performed to compare reintervention-free and major amputation-free survival between sexes. Multivariate logistic regression analyses were performed to determine the adjusted odds of reintervention and major amputation based on sex. We conducted subgroup analyses by anatomic region (femoropopliteal vs. tibial), indication (claudication vs. chronic limb-threatening ischemia (CLTI)), and balloon type (drug-coated balloon (DCB) versus plain balloon angioplasty (POBA)) across sexes. RESULTS: Of the 294 patients, 125 (42.5%) were female. Compared to men, women receiving atherectomy were more likely to be Black (28.0% vs. 16.6%; P = 0.018), a nonsmoker (44.8% vs. 21.3%; P < 0.001), and present with CLTI (55.2% vs. 43.2%; P = 0.042). There were no differences in atherectomy region, lesion type, or balloon type between sexes. KM analysis showed similar 4-year reintervention-free survival (68.8% vs. 75.1%; P = 0.88) and major amputation-free survival (97.6% vs. 97.6%; P = 0.41) between sexes. Women and men had similar reintervention-free survival when grouped by femoropopliteal (67.9% vs. 70.8%; P = 0.69) or tibial (76.2% vs. 83.9%; P = 0.68) atherectomy region. Indication (claudication versus CLTI) did not affect reintervention-free survival in either women (64.5% vs. 69.6%; P = 0.28) or men (68.5% vs. 76.7%; P = 0.84). KM curves for DCB versus POBA were also similar between sexes and showed an early benefit in reintervention rate favoring DCB, which dissipated in both women (65.4% vs. 72.7%; P = 0.61) and men (75.5% vs. 78.4%; P = 0.18) by 3 years. CONCLUSIONS: Compared to men, women demonstrate commensurate benefit from atherectomy for lower extremity revascularization. There were no differences seen in long-term reintervention or major amputation between sexes.

Activating Human Adipose Tissue with the ß3-Adrenergic Agonist Mirabegron.

An appealing strategy for treatment of metabolic disease in humans is activation of brown adipose tissue (BAT), a thermogenic organ best visualized through 18F-FDG PET/CT. BAT has been activated to varying degrees by mild cold exposure. However, this approach can cause undesirable stress, and there remains no consensus protocol. Here, we describe standardized methods for both acute and chronic activation of BAT using the orally administered ß3-adrenergic receptor (AR) agonist, mirabegron. Acute pharmacological stimulation has enabled quantification of whole-body BAT volume and metabolic activity using PET/CT imaging, and chronic stimulation increases these properties of BAT over time.

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity.

The current obesity pandemic results from a physiological imbalance in which energy intake chronically exceeds energy expenditure (EE), and prevention and treatment strategies remain generally ineffective. Approaches designed to increase EE have been informed by decades of experiments in rodent models designed to stimulate adaptive thermogenesis, a long-term increase in metabolism, primarily induced by chronic cold exposure. At the cellular level, thermogenesis is achieved through increased rates of futile cycling, which are observed in several systems, most notably the regulated uncoupling of oxidative phosphorylation from ATP generation by uncoupling protein 1, a tissue-specific protein present in mitochondria of brown adipose tissue (BAT). Physiological activation of BAT and other organ thermogenesis occurs through ß-adrenergic receptors (AR), and considerable effort over the past 5 decades has been directed toward developing AR agonists capable of safely achieving a net negative energy balance while avoiding unwanted cardiovascular side effects. Recent discoveries of other BAT futile cycles based on creatine and succinate have provided additional targets. Complicating the current and developing pharmacological-, cold-, and exercise-based methods to increase EE is the emerging evidence for strong physiological drives toward restoring lost weight over the long term. Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.

"Smart" polymer enhances the efficacy of topical antimicrobial agents.

The delivery of antimicrobial agents to surface wounds has been shown to be of central importance to the wound healing process. In this work, we prepared film forming wound care formulations containing 3 polymers (FTP) that provide broad-spectrum antimicrobial protection for prolonged periods. FTP formulations comprises of a smart gel matrix comprising of pH-degradable and temperature responsive polyacetals (smart polymer) which allow for the FTP films to be hydrophobic at room temperature, preventing accidental rubbing off, and hydrophilic at lower temperatures, allowing for easy removal. Two FTP smart-antimicrobial films were evaluated in this work: FTP-AgSD (Silver sulfadiazine actives), and FTP-NP (Neosporin actives). The in vitro and ex vivo antimicrobial efficacy studies show that FTP-AgSD films are significantly more effective for longer durations against Staphylococcus aureus (3 days), Candida albicans (9 days) and Pseudomonas aeruginosa (4 days) when compared to the cream formulations containing antimicrobials. FTP-NP films showed significantly improved antimicrobial activity for a minimum of 3 days for all pathogens tested. Moreover, when tested ex vivo in porcine skin, FTP-AgSD and FTP-NP showed average improvements of 0.89 log10 and 1.66 log10 respectively over standard cream counterparts. Dermal toxicity studies were carried out in a rat skin excision model which showed a similar wound healing pattern to that in rats treated with standard cream formulations as represented by reduction in wound size, and increase in wound healing markers.