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Background Sensitive skin is a highly prevalent problem. The objective of the study was to assess whether the tested products are effective and safe in terms of improving the symptoms of sensitive skin. Methods A clinical randomized split‐face study was carried out on 24 healthy female subjects. Three cosmetic combinations were tested versus vehicle: product A (Solía Thermal Spring Water–TSW–from Cantabria, Spain + diatom algae–P. tricornutum–extract), product B (Solía TSW + diatom algae extract + Annona cherimola Fruit Extract) and product C (Solía TSW + diatom algae extract + Annona cherimola Fruit Extract + niacinamide). Prior to each application of the study Product (A, B, or C)/vehicle, 10% of aqueous solution of capsaicin to induce skin irritation was applied, mimicking the symptoms of sensitive skin. Stinging and burning sensations were evaluated at different time points. Results All three tested products A, B, and C showed to act better in calming the symptoms induced by capsaicin when compared to the vehicle. Conclusions The tested products would be an interesting option for treating stinging and burning sensations in sensitive skin patients.

Intravenous vesicants are commonly infused via peripheral intravenous catheters (PIVC) despite guidelines recommending administration via central route. The impact of these medications on PIVC failure is unclear. We aimed to assess dose-related impact of these caustic medications on ultrasound-guided (US) PIVC survivorship. We performed a secondary analysis of a randomized control trial that compared survival of two catheters: a standard long (SL) and an ultra-long (UL) US PIVC. This study involved reviewing and recording all vesicants infusions through the PIVCs. Type and number of vesicants doses were extracted and characterized as one, two or multiple. The most commonly used vesicants were individually categorized for further analysis. The primary outcome was PIVC failure accounting for use and timing of vesicant infusates. Between October 2018 and March 2019, 257 subjects were randomized with 131 in the UL group and 126 in the SL group. Vesicants were infused in 96 (37.4%) out of 257 study participants. In multivariable time-dependent extended Cox regression analysis, there was no significant increased risk of failure due to vesicant use [adjusted hazard ratio, aHR 1.71 (95% CI 0.76-1.81) p = 0.477]. The number of vesicant doses was not significantly associated with the increased risk of PIVC failure [(1 vs 0) aHR 1.20 (95% CI 0.71-2.02) p = 0.500], [(2 vs 0) aHR 1.51 (95% CI 0.67-3.43) p = 0.320] and [(≥ 3 vs 0) aHR 0.98 (95% CI 0.50-1.92) p = 0.952]. Vesicant usage did not significantly increase the risk of PIVC failure even when multiple doses were needed in this investigation. Ultrasound-guided PIVCs represent a pragmatic option when vesicant therapy is anticipated. Nevertheless, it is notable that overall PIVC failure rates remain high and other safety events related to vesicant use should be considered when clinicians make vascular access decisions for patients.

Objective Main objective of this study was to examine the chemosensory effects of formaldehyde on hyposensitive and hypersensitive males at concentrations relevant to the workplace. Attention focused on objective effects on and subjective symptoms of the mucous membranes of the eyes, the nose, the upper respiratory tract and olfactory function. Methods Forty-one male volunteers were exposed for 5 days (4 h per day) in a randomised schedule to the control condition (0 ppm) and to formaldehyde concentrations of 0.5 and 0.7 ppm and to 0.3 ppm with peak exposures of 0.6 ppm, and to 0.4 ppm with peak exposures of 0.8 ppm, respectively. Peak exposures were carried out four times a day over a 15-min period of time. Subjective pain perception induced by nasal application of carbon dioxide served as indicator for sensitivity to sensory nasal irritation. The following parameters were examined before and after exposure: subjective rating of symptoms and complaints (Swedish Performance Evaluation System), conjunctival redness, eye-blinking frequency, self-reported tear film break-up time and nasal flow rates. In addition, the influence of personality factors on the volunteer’s subjective scoring was examined (Positive And Negative Affect Schedule). Results Formaldehyde exposures to 0.7 ppm for 4 h and to 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min caused no significant sensory irritation of the measured conjunctival and nasal parameters. No differences between hypo- and hypersensitive subjects were seen. Nevertheless, statistically significant differences were noted for olfactory symptoms, especially for the ‘perception of impure air’. These subjective complaints were more pronounced in hypersensitive subjects. Conclusions Formaldehyde concentrations of 0.7 ppm for 4 h and of 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min did not cause adverse effects related to irritation, and no differences between hypo- and hypersensitive subjects were observed.

Law enforcement officers use conducted electrical weapons (CEW) such as the TASER X26 ® to control violently resistive subjects. There are no studies in the medical literature examining the effects of these weapons on the human stress response. This is the first study to compare the human stress response to conducted electrical weapons, oleoresin capsicum (O.C.), a cold-water tank immersion, and a defensive tactics drill. Subjects were randomized to one of the four interventions studied. Subjects received either a 5-s exposure from the TASER X26 CEW with the probes fired into the back from 7 ft, a 5-s spray of O.C., a skin and mucous membrane irritant, to the eyes, a 45-s exposure of the hand and forearm in a 0 °C cold water tank, or a 1-min defensive tactics drill. Alpha-amylase had the greatest increase from baseline at 10–15 min with the defensive tactics drill. Cortisol had the greatest increase at 15–20 min with O.C. Cortisol remained most elevated at 40–60 min in the defensive tactics drill group. Our preliminary data suggests that physical exertion during custodial arrest may be most activating of the human stress response, particularly the sympathetic–adrenal–medulla axis. This may suggest that techniques to limit the duration of this exertion may be the safest means to apprehend subjects, particularly those at high-risk for in-custody death. Conducted electrical weapons were not more activating of the human stress response than other uses of force.

A good patch test system should have good adhesion and contact, and minimal leakage; Finn and IQ patch test system have these properties but are expensive. To develop a new cost-effective occlusive patch test system that had good contact with the skin and was non-irritant. The system (designated Chamber X) was fabricated using a semi-permeable tape and a flexible virgin plastic chamber. Chamber X was developed by (i) selecting adhesive tape based on its non irritancy and adhesive potential (ii) testing plastic chamber material for its skin irritancy (iii) testing the assembled system against Finn, IQ and locally available chambers for irritancy, contact, leakage and occlusivity. Chamber X showed better occlusion than IQ, Finn and locally available chambers and was comparable to, (P > 0.05) IQ and Finn in terms of irritancy, contact and leakage. The results demonstrate that the Chamber X offers a cost effective patch test system comparable to IQ and Finn chambers in terms of safety, adhesion, leakage and occlusivity.

Allergen-specific responses in atopic dermatitis (AD) are skewed toward a Th2 profile. However, individuals with AD have been shown to make effective virus-specific Th1 responses, raising the possibility that the skin itself contributes to driving the AD Th2 immunophenotype. Therefore, to explore the programming of immunological sensitization by the skin, we examined the outcome of sensitization through non-lesional skin of individuals with AD and healthy controls. Volunteers (controls, AD individuals with filaggrin gene (FLG) mutations (ADFM), and AD individuals without FLG mutations (ADWT)) were sensitized by cutaneous application of 2,4-dinitrochlorobenzene (DNCB), a small, highly lipophilic chemical sensitizer. At the doses tested, DNCB showed equal penetration into skin of all groups. Clinical reactions to DNCB were significantly reduced in AD. Although both controls and AD made systemic DNCB-specific Th1 responses, these were reduced in AD and associated with significantly Th2-skewed DNCB-specific T-cell responses. Th2 skewing was seen in both ADFM and ADWT, with no difference between these groups. After 3 months, DNCB-specific Th2 responses were persistent in individuals with AD, and Th1 responses persisted in controls. These data provide evidence that when antigen penetration is not limiting, AD skin has a specific propensity to Th2 programming, suggesting the existence of altered skin immune signaling that is AD-specific and independent of FLG status.

Background Compounded cantharidin has been used for decades to treat molluscum contagiosum but lacks rigorous clinical evidence to support its safety and efficacy. VP-102 is a shelf-stable drug–device combination product that contains topical cantharidin (0.7% weight/volume [w/v]) and is being evaluated for the treatment of molluscum. Objectives Our objective was to present pooled safety and efficacy analyses of VP-102 in the treatment of molluscum compared with vehicle. Methods Participants aged ≥ 2 years were randomized 3:2 to topical administration of VP-102 or vehicle in two randomized, double-blind, vehicle-controlled phase III trials. Study drug was applied to all baseline and new lesions once every 21 days until clear or for a maximum of four applications. Assessors blinded to treatment counted all lesions at each study visit. All adverse events (AEs) were documented. Data were pooled for analyses. Results In total, 310 participants received VP-102 and 218 received vehicle. Mean age was 7.5 years (range 2–60) for VP-102 and 6.8 (2–54) for vehicle. Complete clearance of all molluscum lesions at day 84 occurred in 50% of VP-102 participants and 15.6% of vehicle recipients ( p  < 0.0001). Mean molluscum lesion counts decreased 76% for VP-102 and 0.3% for vehicle at day 84 ( p  < 0.0001). The most common AEs in the VP-102 group were application site blistering, pruritus, pain, and erythema, which were generally mild or moderate in severity. Conclusions Pooled analyses showed a significantly higher percentage of participants with complete molluscum lesion clearance and larger reductions in lesion counts with VP-102 than with vehicle. AEs were anticipated because of the pharmacodynamic properties of cantharidin. Trial Registration ClinicalTrials.gov identifiers: NCT03377790 (first posted 19 December 2017) and NCT03377803 (first posted 19 December 2017). AUUyPmXRLmH-tSjyurtwWb Video abstract: Pooled Results of Two Randomized Phase III Trials Evaluating VP 102, a Drug Device Combination Product Containing Cantharidin 0.7% (w/v) for the Treatment of Molluscum Contagiosum (MP4 131293 KB)

Information on the acute effects associated with the handling of 1,4-dioxane is sparse. Our aim was to evaluate the acute effects of 1,4-dioxane vapours. In a screening study, six healthy volunteers rated symptoms on a visual analogue scale (VAS), while exposed to stepwise increasing levels of 1,4-dioxane, from 1 to 20 ppm. The initial study indicated no increased ratings at any of the exposure levels; we decided to use 20 ppm (72 mg/m3) as a tentative no observed adverse effect level (NOAEL). In the main study, six female and six male healthy volunteers were exposed to 0 (control exposure) and 20 ppm 1,4-dioxane vapour, for 2 hours at rest. The volunteers rated 10 symptoms on VAS before, during, and after the exposure. Blink frequency was monitored during exposure. Pulmonary function, and nasal swelling, was measured before, and at 0 and 3 hours after exposure. Inflammatory markers in plasma (C-reactive protein, and interleukin-6) were measured before and at 3 hours after exposure. In conclusion, exposure to 20 ppm 1,4-dioxane for 2 hours did not significantly affect symptom ratings, blink frequency, pulmonary function, nasal swelling, or inflammatory markers in the plasma of the 12 volunteers in our study.

Capsaicin, a topical analgesic used in the treatment of chronic pain, has irritant properties that frequently interrupt its use. In this work, the effect of nanoencapsulation of the main capsaicinoids (capsaicin and dihydrocapsaicin) on skin irritation was tested in humans. Skin tolerance of a novel vehicle composed of chitosan hydrogel containing nonloaded nanocapsules (CH-NC) was also evaluated. The chitosan hydrogel containing nanoencapsulated capsaicinoids (CH-NC-CP) did not cause skin irritation, as measured by an erythema probe and on a visual scale, while a formulation containing free capsaicinoids (chitosan gel with hydroalcoholic solution [CH-ET-CP]) and a commercially available capsaicinoids formulation caused skin irritation. Thirty-one percent of volunteers reported slight irritation one hour after application of CH-NC-CP, while moderate (46% [CH-ET-CP] and 23% [commercial product]) and severe (8% [CH-ET-CP] and 69% [commercial product]) irritation were described for the formulations containing free capsaicinoids. When CH-NC was applied to the skin, erythema was not observed and only 8% of volunteers felt slight irritation, which demonstrates the utility of the novel vehicle. A complementary in vitro skin permeation study showed that permeation of capsaicinoids through an epidermal human membrane was reduced but not prevented by nanoencapsulation.

Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone) and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8), the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may promote smoking initiation and nicotine addiction.