Como tirar o mau cheiro dos sapatos

Sabia que é possível usar a aromaterapia até para tirar o mau cheiro dos sapatos? No Saúde Zen, desta segunda-feira (4), você aprende a fazer um sachê para colocar dentro dos sapatos, gavetas e armários. ▶️​Dê play no vídeo e confira!

Retrospective text and qualitative analyses of patient experience and management of vasomotor symptoms due to menopause: voices from the PatientsLikeMe community.

OBJECTIVE: Vasomotor symptoms (VMS) due to menopause cause substantial burden and distress. Some women join online communities to share experiences and treatment outcomes through peer-to-peer interactions. This study describes women's experiences with VMS and symptom management on the PatientsLikeMe online support group. METHODS: Mixed-methods research included women aged 40 to 65 years in the PatientsLikeMe community who were recruited using convenience sampling. Text from online posts by members was analyzed retrospectively using natural language processing. Relevant data, including numbers and percentages of women and frequencies of mentions, were summarized descriptively. Qualitative semistructured interviews were conducted; data, notes, and recordings were transcribed and deidentified and thematic analyses were performed. RESULTS: Demographic information was available from 1,614 accounts included in retrospective text analyses. Women had a mean age of 56.7 years; most were White (87.8%) and not Hispanic/Latino (90.2%). Hot flashes and night sweats were most commonly mentioned symptoms (n = 146). Of 16 women who were interviewed, 14 met the inclusion criteria, and their responses were included in the analysis. VMS impacted life quality in terms of physical (43%) and mental well-being (36%), social activities (21%), and productivity (14%). Symptom management included temperature regulation (43%), lifestyle changes (36%), over-the-counter Estroven (29%), hormone therapy (21%), and contraceptives (21%). Half of the women were surprised by symptom intensity and duration; many felt unheard by their healthcare providers. CONCLUSIONS: VMS have a substantial negative impact on multiple aspects of women's life. Management strategies for these symptoms vary widely, and many women feel unprepared for navigating the complex challenges of menopause.

Pretreatment of microneedles enhances passive transdermal administration of pilocarpine and pilocarpine-induced sweat production in humans.

The development of an effective transdermal drug delivery protocol to eccrine sweat glands is important for the advancement of research on the human sweating response. We investigated whether microneedle treatment prior to the application of pilocarpine, a hydrophilic and sudorific agent that does not induce sweating due to a limited percutaneous passive diffusion by skin application alone, augments sweat production. We applied three microneedle arrays to forearm skin sites simultaneously (n = 20). Upon removal of the microneedles, 1 % pilocarpine was applied to each site for 5-, 15-, and 30-min for the assessment of sweat gland function. In parallel, pilocarpine was administered by transdermal iontophoresis (5-min) at a separate site. Sweat rate was assessed continuously via the ventilated capsule technique. Pilocarpine augmented sweat rate at the 15- and 30-min periods as compared to the application at 5-min. The sweating responses induced by the 15- and 30-min application of pilocarpine were equivalent to âˆ¼ 80 % of that measured at the iontophoretically treated sites. Notably, we observed a correlation in sweat rate between these two transdermal drug delivery methods. Altogether, our findings show that pre-treatment of microneedle arrays can enhance transdermal delivery efficiency of pilocarpine to human eccrine sweat glands.

Reduced unilateral sweating caused by varicella zoster virus infection: a case report.

BACKGROUND: Herpes zoster is an infectious skin disease caused by the reactivation of the varicella zoster virus (VZV), which has been latent in the posterior root ganglia of the spinal cord or cranial ganglia for an extended period. Neurological complications caused by herpes zoster include aseptic meningitis, white matter disease, peripheral motor neuropathy, and Guillain-Barré syndrome. However, reduced unilateral sweating caused by the VZV is very rare. CASE PRESENTATION: This article reports the case of a 34-year-old woman who was admitted to our hospital with sore throat, dizziness, and reduced sweating on the left side of her body. Physical examination found herpes lesions on the left upper lip and left external ear canal (scabbed) and reduced sweating on the left side of the body. Head magnetic resonance imaging (MRI) with contrast showed no abnormalities. After a lumbar puncture, the patient was diagnosed with viral meningitis by VZV infection. The electromyographic skin sympathetic reflex indicated damage to the left sympathetic nerve. CONCLUSIONS: Secondary unilateral sweating reduction is a rare neurological complication of herpes zoster, caused by damage to the autonomic nervous system. Literature review and comprehensive examination indicated that the reduced unilateral sweating was due to the activation of latent herpes zoster virus in the autonomic ganglia which has damaged the autonomic nervous system. For patients who exhibit acute hemibody sweat reduction, doctors should consider the possibility of secondary autonomic nervous system damage caused by herpes zoster.

Involvement of TRPV4 in temperature-dependent perspiration in mice.

Reports indicate that an interaction between TRPV4 and anoctamin 1 (ANO1) could be widely involved in water efflux of exocrine glands, suggesting that the interaction could play a role in perspiration. In secretory cells of sweat glands present in mouse foot pads, TRPV4 clearly colocalized with cytokeratin 8, ANO1, and aquaporin-5 (AQP5). Mouse sweat glands showed TRPV4-dependent cytosolic Ca2+ increases that were inhibited by menthol. Acetylcholine-stimulated sweating in foot pads was temperature-dependent in wild-type, but not in TRPV4-deficient mice and was inhibited by menthol both in wild-type and TRPM8KO mice. The basal sweating without acetylcholine stimulation was inhibited by an ANO1 inhibitor. Sweating could be important for maintaining friction forces in mouse foot pads, and this possibility is supported by the finding that wild-type mice climbed up a slippery slope more easily than TRPV4-deficient mice. Furthermore, TRPV4 expression was significantly higher in controls and normohidrotic skin from patients with acquired idiopathic generalized anhidrosis (AIGA) compared to anhidrotic skin from patients with AIGA. Collectively, TRPV4 is likely involved in temperature-dependent perspiration via interactions with ANO1, and TRPV4 itself or the TRPV4/ANO 1 complex would be targeted to develop agents that regulate perspiration.

Stress, spicy foods and elevated temperatures can all trigger specialized gland cells to move water to the skin ­ in other words, they can make us sweat. This process is one of the most important ways by which our bodies regulate their temperature and avoid life-threatening conditions such as heatstroke. Disorders in which this function is impaired, such as AIGA (acquired idiopathic generalized anhidrosis), pose significant health risks. Finding treatments for sweat-related diseases requires a detailed understanding of the molecular mechanisms behind sweating, which has yet to be achieved. Recent research has highlighted the role of two ion channels, TRPV4 and ANO1, in regulating fluid secretion in glands that produce tears and saliva. These gate-like proteins control how certain ions move in or out of cells, which also influences water movement. Once activated by external stimuli, TRPV4 allows calcium ions to enter the cell, causing ANO1 to open and chloride ions to leave. This results in water also exiting the cell through dedicated channels, before being collected in ducts connected to the outside of the body. TRPV4, which is activated by heat, is also present in human sweat gland cells. This prompted Kashio et al. to examine the role of these channels in sweat production, focusing on mice as well as AIGA patients. Probing TRPV4, ANO1 and AQP5 (a type of water channel) levels using fluorescent antibodies confirmed that these channels are all found in the same sweat gland cells in the foot pads of mice. Further experiments highlighted that TRPV4 mediates sweat production in these animals via ANO1 activation. As rodents do not regulate their body temperature by sweating, Kashio et al. explored the biological benefits of having sweaty paws. Mice lacking TRPV4 had reduced sweating and were less able to climb a slippery slope, suggesting that a layer of sweat helps improve traction. Finally, Kashio et al. compared samples obtained from healthy volunteers with those from AIGA patients and found that TRPV4 levels are lower in individuals affected by the disease. Overall, these findings reveal new insights into the underlying mechanisms of sweating, with TRPV4 a potential therapeutic target for conditions like AIGA. The results also suggest that sweating could be controlled by local changes in temperature detected by heat-sensing channels such as TRPV4. This would depart from our current understanding that sweating is solely controlled by the autonomic nervous system, which regulates involuntary bodily functions such as saliva and tear production.

Effects of hot bath therapy on cholinergic urticaria with hypohidrosis or anhidrosis.

Cholinergic urticaria with hypohidrosis or anhidrosis (CUHA) can impair quality of life due to itching, tingling, and reduced sweating. Current treatment options for CUHA include antihistamines, pulsed steroids, and sweat-promoting therapies such as exercise or hot baths. However, the efficacy of these therapies, particularly hot bath therapy, has yet to be established. We evaluated the efficacy of hot bath therapy in patients with CUHA. We enrolled eight patients who underwent hot bath therapy between January 2010 and August 2022. Patients had a half-body bath in a bathtub filled with hot water (40-43°C) for 30-60 minutes daily for 3-7 days. After treatment, pain improved in three (42.9%) patients, urticaria improved in four (50%) patients, and anhidrosis improved in five (62.5%) patients without any severe adverse events. Because hot bath therapy is easily performed, it should be considered a treatment option for patients with CUHA.

Questions and questionnaires about acute climacteric syndrome.

The acute climacteric syndrome has a large scale of symptoms. Main symptoms are hot flashes and night sweats. Each symptom could be presented alone or commonly in combination with other symptoms. The acute climacteric syndrome is induced by decrease and fluctuations of estrogen and neurosteroids levels. Therapy could be focused on hormone replacement. Changes of quality of life and especially effects of the therapy could be measured by standardized questionaries.

Bioinspired Multilayered Knitted Fabric with Directional Water Transport and Collection for Personal Sweat Management.

Effective sweat management fabric for sportswear facilitates sweat removal from the skin and elevates the comfort for human. However, when the body is in a strong hot and humid environment or after strenuous exercise, the sweat management fabric will be totally wetted and saturated quickly. As a result, excess sweat cannot be absorbed effectively by the garment, which creates obvious stickiness and heaviness. In this paper, a directional water transport and collection multilayered knitted fabric (DWTCF) is prepared by plasma pretreatment technology and screen coating. The treelike water transport network inspired from nature is designed in order to drive the liquid flow along the channels. By surface modification, branched hydrophilic flow paths are fabricated, and other regions are hydrophobic. As a demonstration, DWTCF has been injected with water to observe the liquid transport behavior. During the experiment, 76.7% liquid is collected by DWTCF, but there is just 0.06% collected by an ordinary knitted fabric. The weight increase of the ordinary fabric is 555.4% larger than that of DWTCF. Specifically, DWTCF utilizes the wetting and pressure-gradient-induced interfacial tension as well as the gravitational effect to facilitate the fluid motion along the hydrophilic channel, in addition to the capillarity present in the fabric structure. This study provides a new idea to develop directional water transport and collection fabric to solve the moisture absorption saturation problem of the fabric, especially for conditions requiring intense sweating.

Zinc fever in a painter and varnisher: a case report.

BACKGROUND: Zinc fever is well described in medical literature, particularly in workers after handling zinc-containing materials at high temperatures e.g., in the welding of hot-dip galvanized steel sheets. It is not known whether zinc fever also occurs at low temperatures. CASE PRESENTATION: We present the case of a 33-year-old Caucasian atopic painter and varnisher with work-related dyspnea, sweating, as well as multiple occurrences of fever. He was sent to Institute for Prevention and Occupational medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA) for the evaluation of isocyanate asthma, but an inhalative challenge with hexamethylene diisocyanate was negative. Since symptoms were closely related to the use of zinc coatings at room temperature without adequate protective measures, the diagnosis of zinc fever was made. After exposure cessation the worker immediately became symptom-free. The work as painter and varnisher may be associated with various exposures to hazardous substances. Besides solvents, epoxy compounds and isocyanates, which can cause obstructive respiratory diseases; additionally, zinc-containing agents should be considered as health hazards. CONCLUSIONS: This case demonstrates that zinc fever may occur also after application of zinc coatings by spray painting at low temperatures.

The effect of female breast surface area on heat-activated sweat gland density and output.

Female development includes significant morphological changes across the breast. Yet, whether differences in breast surface area (BrSA) modify sweat gland density and output remains unclear. The present study investigated the relationship between BrSA and sweat gland density and output in 22 young to middle-aged women (28 ± $\ \pm \ $ 10 years) of varying breast sizes (BrSA range: 147-561 cm2) during a submaximal run in a warm environment (32  ± $ \pm \ $ 0.6°C; 53  ± $ \pm \ $ 1.7% relative humidity). Local sweat gland density and local sweat rate (LSR) above and below the nipple and at the bra triangle were measured. Expired gases were monitored for the estimation of evaporative requirements for heat balance (Ereq, in W/m2). Associations between BrSA and (i) sweat gland density; (ii) LSR; and (iii) sweat output per gland for the breast sites were determined via correlation and regression analyses. Our results indicated that breast sweat gland density decreased linearly as BrSA increased (r = -0.76, P < 0.001), whereas sweat output per gland remained constant irrespective of BrSA (r = 0.29, P = 0.28). This resulted in LSR decreasing linearly as BrSA increased (r = -0.62, P = 0.01). Compared to the bra triangle, the breast had a 64% lower sweat gland density (P < 0.001), 83% lower LSR (P < 0.001) and 53% lower output per gland (P < 0.001). BrSA (R2 = 0.33, P = 0.015) explained a greater proportion of variance in LSR than Ereq (in W/m2) (R2 = 0.07, P = 0.538). These novel findings extend the known relationship between body morphology and sweat gland density and LSR, to the female breast. This knowledge could innovate user-centred design of sports bras by accommodating breast size-specific needs for sweat management, skin wetness perception and comfort.

Autonomic impairment in primary lateral sclerosis.

PURPOSE: Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis. METHODS: Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable). Patients with other potential causes of autonomic failure and patients with autonomic testing results compromised by artifact were excluded. RESULTS: A total of 17 patients reported autonomic symptoms. Orthostatic lightheadedness was most frequent (8 patients), followed by bladder (7), bowel (5), and erectile dysfunction (3). The autonomic reflex screens of 33 patients were reviewed; 20 patients had abnormal studies. The thermoregulatory sweat tests of 19 patients were reviewed; 11 patients had abnormal studies. Composite Autonomic Severity Score was calculated for 33 patients and found abnormal in 20/33 patients (60.6%): 15/20 patients (75%) had mild impairment, and 5/20 patients (25%) had moderate impairment. The frequencies of testing abnormalities were: sudomotor 18/20 (90%), cardiovagal 9/20 (45%), and adrenergic 6/20 (30%). Sweat loss pattern analysis showed global, regional, and mixed patterns to be more common than length-dependent and distal patterns. CONCLUSION: We found evidence of frequent autonomic dysfunction in primary lateral sclerosis, which is generally of modest severity akin to prior reports for amyotrophic lateral sclerosis, but more commonly in a pattern consistent with preganglionic/ganglionic localization. This suggests that primary lateral sclerosis, as with amyotrophic lateral sclerosis, is a multisystem disease that affects the autonomic nervous system.

A case report on the physiological responses to extreme heat during Sicily's July 2023 heatwave.

July 2023 has been confirmed as Earth's hottest month on record, and it was characterized by extraordinary heatwaves across southern Europe. Field data collected under real heatwave periods could add important evidence to understand human adaptability to extreme heat. However, field studies on human physiological responses to heatwave periods remain limited. We performed field thermo-physiological measurements in a healthy 37-years male undergoing resting and physical activity in an outdoor environment in the capital of Sicily, Palermo, during (July 21; highest level of local heat-health alert) and following (August 10; lowest level of local heat-health alert) the peak of Sicily's July 2023 heatwave. Results indicated that ~40 min of outdoor walking and light running in 33.8°C Wet Bulb Globe Temperature (WBGT) conditions (July 21) resulted in significant physiological stress (i.e., peak heart rate: 209 bpm; core temperature: 39.13°C; mean skin temperature: 37.2°C; whole-body sweat losses: 1.7 kg). Importantly, significant physiological stress was also observed during less severe heat conditions (August 10; WBGT: 29.1°C; peak heart rate: 190 bpm; core temperature: 38.48°C; whole-body sweat losses: 2 kg). These observations highlight the physiological strain that current heatwave conditions pose on healthy young individuals. This ecologically-valid empirical evidence could inform more accurate heat-health planning.

Single Session Intermittent Heat Exposure With More Frequent and Shorter Cooling Breaks Facilitates Greater Training Intensity and Elicits Physiological Responses Comparable to Continuous Heat Exposure.

PURPOSE: To investigate the influence of shorter, more frequent rest breaks with per-cooling as an alternative heat-acclimation session on physiological, perceptual, and self-paced maximal cycling performance, compared with continuous heat exposure. METHODS: Thirteen participants completed 1 continuous and 3 intermittent-heat-exposure (IHE) maximal self-paced cycling protocols in a random order in heat (36 °C, 80% relative humidity): 1 × 60-minute exercise (CON), 3 × 20-minute exercise with 7.5-minute rest between sets (IHE-20), 4 × 15-minute exercise with 5-minute rest between sets (IHE-15), and 6 × 10-minute exercise with 3-minute rest between sets (IHE-10). Mixed-method per-cooling (crushed-ice ingestion and cooling vest) was applied during rest periods of all IHE protocols. RESULTS: Total distance completed was greater in IHE-10, IHE-15, and IHE-20 than in CON (+11%, +9%, and +8%, respectively), with no difference observed between IHE protocols. Total time spent above 38.5 °C core temperature was longer in CON compared with IHE-15 and IHE-20 (+62% and +78%, respectively) but similar to IHE-10 (+5%). Furthermore, a longer time above 38.5 °C core temperature occurred in IHE-10 versus IHE-15 and IHE-20 (+54% and +69%, respectively). Sweat loss did not differ between conditions. CONCLUSION: IHE with per-cooling may be a viable alternative heat-acclimation protocol in situations where training quality takes precedence over thermal stimulus or when both factors hold equal priority.

Nature-Inspired Superhydrophilic Biosponge as Structural Beneficial Platform for Sweating Analysis Patch.

Perspiration plays a pivotal role not only in thermoregulation but also in reflecting the body's internal state and its response to external stimuli. The up-to-date skin-based wearable platforms have facilitated the monitoring and simultaneous analysis of sweat, offering valuable physiological insights. Unlike conventional passive sweating, dynamic normal perspiration, which occurs during various activities and rest periods, necessitates a more reliable method of collection to accurately capture its real-time fluctuations. An innovative microfluidic patch incorporating a hierarchical superhydrophilic biosponge, poise to significantly improve the efficiency capture of dynamic sweat is introduced. The seamlessly integrated biosponge microchannel showcases exceptional absorption capabilities, efficiently capturing non-sensitive sweat exuding from the skin surface, mitigating sample loss and minimizing sweat volatilization. Furthermore, the incorporation of sweat-rate sensors alongside a suite of functional electrochemical sensors endows the patch of uninterrupted monitoring and analysis of dynamic sweat during various activities, stress events, high-energy intake, and other scenarios.

Personalized Hydration Strategy to Improve Fluid Balance and Intermittent Exercise Performance in the Heat.

Sweat rate and electrolyte losses have a large inter-individual variability. A personalized approach to hydration can overcome this issue to meet an individual's needs. This study aimed to investigate the effects of a personalized hydration strategy (PHS) on fluid balance and intermittent exercise performance. Twelve participants conducted 11 laboratory visits including a VO2max test and two 5-day trial arms under normothermic (NOR) or hyperthermic (HYP) environmental conditions. Each arm began with three days of familiarization exercise followed by two random exercise trials with either a PHS or a control (CON). Then, participants crossed over to the second arm for: NOR+PHS, NOR+CON, HYP+PHS, or HYP+CON. The PHS was prescribed according to the participants' fluid and sweat sodium losses. CON drank ad libitum of commercially-available electrolyte solution. Exercise trials consisted of two phases: (1) 45 min constant workload; (2) high-intensity intermittent exercise (HIIT) until exhaustion. Fluids were only provided in phase 1. PHS had a significantly greater fluid intake (HYP+PHS: 831.7 ± 166.4 g; NOR+PHS: 734.2 ± 144.9 g) compared to CON (HYP+CON: 369.8 ± 221.7 g; NOR+CON: 272.3 ± 143.0 g), regardless of environmental conditions (p < 0.001). HYP+CON produced the lowest sweat sodium concentration (56.2 ± 9.0 mmol/L) compared to other trials (p < 0.001). HYP+PHS had a slower elevated thirst perception and a longer HIIT (765 ± 452 s) compared to HYP+CON (548 ± 283 s, p = 0.04). Thus, PHS reinforces fluid intake and successfully optimizes hydration status, regardless of environmental conditions. PHS may be or is an important factor in preventing negative physiological consequences during high-intensity exercise in the heat.

Whole body sweat rate prediction: outdoor running and cycling exercise.

Our aim was to develop and validate separate whole body sweat rate prediction equations for moderate to high-intensity outdoor cycling and running, using simple measured or estimated activity and environmental inputs. Across two collection sites in Australia, 182 outdoor running trials and 158 outdoor cycling trials were completed at a wet-bulb globe temperature ranging from ∼15°C to ∼29°C, with ∼60-min whole body sweat rates measured in each trial. Data were randomly separated into model development (running: 120; cycling: 100 trials) and validation groups (running: 62; cycling: 58 trials), enabling proprietary prediction models to be developed and then validated. Running and cycling models were also developed and tested when locally measured environmental conditions were substituted with participants' subjective ratings for black globe temperature, wind speed, and humidity. The mean absolute error for predicted sweating rate was 0.03 and 0.02 L·h-1 for running and cycling models, respectively. The 95% confidence intervals for running (+0.44 and -0.38 L·h-1) and cycling (+0.45 and -0.42 L·h-1) were within acceptable limits for an equivalent change in total body mass over 3 h of ±2%. The individual variance in observed sweating described by the predictive models was 77% and 60% for running and cycling, respectively. Substituting measured environmental variables with subjective assessments of climatic characteristics reduced the variation in observed sweating described by the running model by up to ∼25%, but only by ∼2% for the cycling model. These prediction models are publicly accessible (https://sweatratecalculator.com) and can guide individualized hydration management in advance of outdoor running and cycling.NEW & NOTEWORTHY We report the development and validation of new proprietary whole body sweat rate prediction models for outdoor running and outdoor cycling using simple activity and environmental inputs. Separate sweat rate models were also developed and tested for situations where all four environmental parameters are not available, and some must be subsequently estimated by the user via a simple rating scale. All models are freely accessible through an online calculator: https://sweatratecalculator.com. These models, via the online calculator, will enable individualized hydration management for training or recreational cycling or running in an outdoor environment.

Validation and Application of Thresholds to Define Meaningful Change in Vasomotor Symptoms Frequency: Analysis of Pooled SKYLIGHT 1 and 2 Data.

INTRODUCTION: Vasomotor symptoms (VMS), the characteristic symptoms of menopausal transition, are often the primary reason women seek treatment. Current treatment options for VMS include fezolinetant, a nonhormonal, selective neurokinin 3 receptor antagonist. This study aimed to define a clinically meaningful threshold for reduction of moderate-to-severe VMS in postmenopausal women treated with fezolinetant and then apply it in a responder analysis of the pooled trial data. METHODS: This analysis pooled data from two identical phase 3, double-blind, placebo-controlled studies that randomized women with moderate-to-severe VMS to once-daily fezolinetant 30 mg, 45 mg, or placebo (SKYLIGHT 1 and 2). The frequency of VMS was collected daily using an electronic diary. Patients completed the Patient Global Impression of Change in VMS (PGI-C VMS) instrument, which assessed changes in hot flushes/night sweats at weeks 4 and 12 compared with baseline using a seven-point Likert scale. VMS frequency data were anchored to PGI-C VMS data; the anchor level for meaningful within-patient change in PGI-C VMS was "moderately better." RESULTS: In the pooled population (N = 1022), the mean (standard deviation) estimated thresholds for a meaningful within-patient change in moderate-to-severe VMS frequency were - 5.73 (3.47) at week 4 and - 6.20 (5.18) at week 12. Applying the thresholds for meaningful within-patient change to responder analyses ("missing as non-responder" imputation method) indicated a favorable clinical benefit: greater proportions of responders were observed in the fezolinetant 30-mg and 45-mg groups compared with placebo at week 4 (odds ratio range 2.48-2.91; P < 0.001) and week 12 (odds ratio range 1.908-2.68; P < 0.001). CONCLUSION: PGI-C VMS is sensitive to change and correlates with VMS frequency: a reduction of approximately six VMS episodes per day from baseline to week 12 was meaningful at the individual patient level. Fezolinetant provides a meaningful clinical benefit for women with moderate-to-severe VMS associated with menopause and represents an important nonhormonal treatment option. TRIAL REGISTRATION NUMBER: NCT04003155 and NCT04003142.