Protective Effects of Pear Extract on Skin from In Vitro and In Vivo UVA-Induced Damage.

The ancient Chinese medical book "Compendium of Materia Medica" records that pears can relieve symptoms of respiratory-related diseases. Previous research has shown that pear Pyrus Pyrifolia (Burm.f.) Nakai has antioxidant and anti-inflammatory properties. However, the anti-inflammatory, antioxidant, and anti-photoaging protective effects of Pyrus pyrifolia (Burm.f.) Nakai seed components have not been studied. Ultraviolet light (UV) causes skin inflammation, damages the skin barrier, and is an important cause of skin photoaging. Therefore, UV light with a wavelength of 365 nm was used to irradiate HaCaT and mice. Western blot, real-time quantitative polymerase chain reaction, and fluorescence imaging system were used to explore its anti-UVA mechanism. Dialysis membrane and nuclear magnetic resonance were used for the chemical constituent analysis of pear seed water extract (PSWE). We found that PSWE can significantly reduce UVA-induced skin cell death and mitogen-activated protein kinase phosphorylation and can inhibit the mRNA expression of UVA-induced cytokines (including IL-1ß, IL-6, and TNF-α). In addition, PSWE can also reduce the generation of oxidative stress within skin cells. In vivo experimental studies found that PSWE pretreatment effectively reduced transepidermal water loss, inflammation, redness, and dryness in hairless mice. The molecular weight of the active part of pear water extract is approximately 384. Based on the above results, we first found that pear seeds can effectively inhibit oxidative stress and damage caused by UVA. It is a natural extract with antioxidant properties and anti-aging activity that protects skin cells and strengthens the skin barrier.

Utilization of Split-Thickness Skin Graft as a Treatment Option Following Mohs Micrographic Surgery.

Split-thickness skin grafting (STSG) is a frontline treatment for challenging surgical wounds, including diabetic foot ulcers, venous leg ulcers, and post-surgical defects. This study explores the use of STSG employing the pinch graft technique for hard-to-heal surgical wounds following Mohs micrographic surgery (MMS). An 83-year-old patient with a non-improving post-MMS defect on the left lower leg underwent STSG from the right inner thigh using the pinch graft technique. The grafts were secured with a mesh dressing, adhesive strips, and compression bandaging. The patient experienced complete re-epithelialization and reduced pain within five weeks, emphasizing the efficacy of STSG for challenging cases. This case underscores the importance of considering STSG, especially in challenging locations, as a rapid and efficient treatment with improved quality of life. The pinch graft technique is presented as a useful option following MMS. This study encourages Mohs surgeons to consider STSG for reconstruction in challenging locations, especially on the lower leg.

Comparing the application of various engineered xenografts for skin defects: A systematic review.

INTRODUCTION: Xenografts are a now a cornerstone in the management of wound dressings. Promising results were achieved since 1960 in the application of skin substitute for skin defects. OBJECTIVE: The objective of this study was to evaluate the efficacy of various xenografts. METHODS: A literature research was conducted using the following query: 'Porcine skin dermatology substitute', 'bovine skin dermatology substitute', 'xenograft skin substitute dermatology', 'xenografts skin defect', 'porcine skin defect', 'bovine skin defect'. RESULTS: The review yielded 35 articles pertaining to the topic. Main indications for porcine and bovine xenograft application were burn wounds and post-traumatic wounds, respectively. Mean discharge date or length of stay was at the 6th day after porcine application, and the time of graft healing was reported for 33.7% (n = 510) of patients. Promising results were seen with Matriderm and split-thickness skin graft. Most wounds achieved an excellent cosmetic result with full range of motion and a smooth contour appearance. A great variety of tissue substitutes exist, and the choice of graft application should depend on a patient's factors, product availability, wound type, size, and physician's factors. CONCLUSION: In summary, xenografts are more economic and affordable but have higher risk of infections compared to allografts.

Evaluation of the Anti-Atopic Dermatitis Effects of α-Boswellic Acid on Tnf-α/Ifn-γ-Stimulated HaCat Cells and DNCB-Induced BALB/c Mice.

Boswellic acids, triterpenoids derived from the genus Boswellia (Burseraceae), are known for their anti-inflammatory and anti-tumor efficacy. Atopic dermatitis is a chronic, non-infectious inflammatory skin disease. However, the effects of α-boswellic acid on atopic dermatitis have not been studied. Therefore, in this study we examined the expression level of pro-inflammatory cytokines, histopathological analysis, and physiological data from BALB/c mice with atopic-like dermatitis induced by 2,4-dinitrochlorobenzene and TNF-α/IFN-γ-stimulated HaCaT cells to better understand the agent's anti-atopic dermatitis efficacy. First, we found that α-boswellic reduced the epidermal thickening, mast cell numbers, and dermal infiltration of 2,4-dinitrochlorobenzene-induced atopic-like dermatitis in BALB/c mice. Furthermore, we also found that α-boswellic acid can restore transepidermal water loss and skin reddening in mice. In human keratinocytes inflamed by TNF-α/IFN-γ, α-boswellic acid inhibited MAP kinase activation and showed a reduction in NF-κB nuclear translocation. Finally, α-boswellic acid can reduce the expression level of cytokines (IL-1ß, IL-6, and IL-8) following the stimulation of TNF-α/IFN-γ in HaCaT cells. Taken together, our study suggests that α-boswellic acids are a potential component for the development of anti-atopic dermatitis drugs.

Pathophysiology, clinical findings, and management of Fox-Fordyce disease: A systematic review.

BACKGROUND: Fox-Fordyce (FFD), also known as apocrine military, is an uncommon chronic inflammation of the apocrine sweat glands. It is characterized by pruritic, papular eruptions in apocrine-gland-bearing regions. FFD was described a century ago, but the exact pathogenesis of the disease and the management are not well understood. AIMS: This paper provides a wide understanding of the pathophysiology, clinical findings, and management of Fox-Fordyce disease. Its aim is to help the physician to diagnose and manage this entity accordingly. METHODS: A research was done using PubMed database on 12 April 12, 2020, and in order to retrieve all case reports, case series, cohort studies, randomized, and nonrandomized clinical trials were included describing FFD among patients. RESULTS: A total of 43 articles and 68 patients were included in the study. The majority of patients were young females. The disease was bilateral in 90%, affected the axillae and to a lesser extent the pubic and the periareolar areas and rarely the thoracic area, the abdominal area, and the face. FFD followed a relapsing and remitting course, and an evident improvement in disease course was noted after menopause. CONCLUSION: The typical FFD patient is a post-pubertal female and pre-menopause, presenting with pruritic papules in apocrine-gland-bearing regions. FFD can be sporadic or occurs in family, and it can be asymptomatic in 1/(3-4) of patients and can be triggered by laser hair removal and hormonal changes. Further randomized clinical trials assessing different treatment of FFD are now warranted.

A novel automated approach to rapid and precise in vivo measurement of hair morphometrics using a smartphone.

BACKGROUND: Although many hair disorders can be readily diagnosed based on their clinical appearance, their progression and response to treatment are often difficult to monitor, particularly in quantitative terms. We introduce an innovative technique utilizing a smartphone and computerized image analysis to expeditiously and automatically measure and compute hair density and diameter in patients in real time. METHODS: A smartphone equipped with a dermatoscope lens wirelessly transmits trichoscopy images to a computer for image processing. A black-and-white binary mask image representing hair and skin is produced, and the hairs are thinned into single-pixel-thick fiber skeletons. Further analysis based on these fibers allows morphometric characteristics such as hair shaft number and diameters to be computed rapidly. The hair-bearing scalps of fifty participants were imaged to assess the precision of our automated smartphone-based device in comparison with a specialized trichometry device for hair shaft density and diameter measurement. The precision and operation time of our technique relative to manual trichometry, which is commonly used by hair disorder specialists, is determined. RESULTS: An equivalence test, based on two 1-sided t tests, demonstrates statistical equivalence in hair density and diameter values between this automated technique and manual trichometry within a 20% margin. On average, this technique actively required 24 seconds of the clinician's time whereas manual trichometry necessitated 9.2 minutes. CONCLUSION: Automated smartphone-based trichometry is a rapid, precise, and clinically feasible technique which can significantly facilitate the assessment and monitoring of hair loss. Its use could be easily integrated into clinical practice to improve standard trichoscopy.

Inhibition of UVA Damage on Human Skin Dermis Fibroblasts by the Isoflavonoid Intermediate Deoxybenzoin-3A.

Ultraviolet rays are the main cause of skin aging. Isoflavone structures are good anti-ultraviolet natural compounds and have an especially strong anti-ultraviolet B (UVB) effect. However, the anti-ultraviolet A (UVA) effect of isoflavones is more controversial. Therefore, this study aims to discover which isoflavone analogue possesses a strong anti-ultraviolet A. We found the isoflavonoid intermediate deoxybenzoin-3A (DOB-3A) to be a similar isoflavone structural compound with strong anti-ultraviolet A effects. Ultraviolet rays with a wavelength of 350 nm are used to irradiate the fibroblasts of the human skin. Western blot, flow cytometry, and transmission electron microscope analyses were used to explore its anti-ultraviolet A mechanism. We established the results that DOB-3A (1) reduced the death of fibroblasts caused by ultraviolet A, (2) avoided the damage to the organelles and structures after UVA irradiation, (3) inhibited the generation of intracellular reactive oxygen species (ROS) and hydrogen peroxide-induced damage, and (4) decreased the phosphorylation of mitogen-activated protein kinases (MAPK) caused by UVA. Based on the above findings, DOB-3A is a very good anti-ultraviolet A isoflavone-related structure. Because it is simple to synthesize and has good effects, DOB-3A is a suitable anti-ultraviolet A product with an isoflavone structure. Moreover, DOB-3A's structure provides a reference for the synthesis of anti-UVA isoflavones.

An isoflavone extract from soybean cake suppresses 2,4-dinitrochlorobenzene-induced contact dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Numerous epidemiological and clinical studies have demonstrated the protective role of dietary isoflavones against development of several chronic diseases. ISO-1, one fraction of isoflavone powders derived from soybean cake, is reported to attenuate inflammation and photodamage. AIM OF THE STUDY: Contact dermatitis is a common inflammatory skin disease, which accounts for most occupational skin disorders. Instead of oral administration, we aimed to explore the effects of topical ISO-1 application on contact dermatitis by using 2,4-dinitrochlorobenzene (DNCB)-stimulated HaCaT keratinocytes and DNCB-induced mouse dermatitis as models. MATERIALS AND METHODS: In the in vitro study, we first evaluated the biologic effects of DNCB on HaCaT keratinocytes. HaCaT keratinocytes were treated with 2,4-dinitrochlorobenzene (DNCB), and cell viability was measured by MTT assay. Then, we detect the prominent induction of IL-8 mRNA expression after DNCB and ISO-1 treatment by reverse transcription polymerase chain reaction (RT-PCR), and release of IL-8 from HaCaT keratinocytes was measured by ELISA assay. HaCaT keratinocytes were pretreated with ISO-1 and then treated with DNCB, phosphorylation of JNK, p38, ERK and IκBα was analyzed by western blot. In the in vivo study, the hairless mice were used for an induced contact dermatitis model. The surface changes in the dorsal skin after DNCB and ISO-1 treatment were recorded using photography, and TEWL, erythema were measured using an MPA-580 cutometer. Blood was also collected from mice for measurement of white blood cell counts. RESULTS: Results showed ISO-1 inhibited DNCB-induced IL-8 production and also suppressed DNCB-induced phosphorylation of JNK and p38, and IκBα in HaCaT. In the animal model of DNCB-induced contact dermatitis, topical ISO-1 treatment significantly decreased DNCB-induced erythema and transepidermal water loss (TEWL) in mouse skin. ISO-1 also reduced DNCB-induced skin thickening and increase of white blood cell count. CONCLUSIONS: ISO-1 is promising for improvement of DNCB-induced inflammation and skin barrier impairment, suggesting the potential application of topical ISO-1 for inflammatory dermatoses.

Growth factor concentrations in platelet-rich plasma for androgenetic alopecia: An intra-subject, randomized, blinded, placebo-controlled, pilot study.

BACKGROUND: Platelet-rich plasma (PRP), processed from autologous peripheral blood, is used to treat androgenetic alopecia (AGA). OBJECTIVE: To determine the efficacy of PRP for hair growth promotion in AGA patients in a randomized, blinded, placebo-controlled, pilot clinical trial (NCT02074943). METHODS: The efficacy of an 8 week, five session, PRP treatment course was determined by measuring hair density and hair caliber changes in 10 AGA affected patients. For each PRP sample, the concentrations of selected growth factors were determined using a multiplex assay system. The clinical results were then correlated with the growth factor concentrations in PRP. RESULTS: At 16 weeks, 8 weeks after the last PRP injection, treated areas exhibited increased mean hair density (+12.76%) over baseline compared to placebo (+0.99%). Mean hair caliber decreased in both treated and placebo regions (-16.22% and -19.46%, respectively). Serial analysis of PRP significant variability in concentrations between patients. Overall, there was a positive correlation between GDNF concentration and hair density (P = .004). Trends, though not statistically significant, were also observed for FGF2 and VEGF. LIMITATIONS: Small sample size and lack of comparative cohorts receiving protocol variations limit confidence in the study data. CONCLUSIONS: This small pilot clinical trial suggests PRP treatment may be beneficial for AGA. However, the variable hair growth responses between patients indicate there is a significant opportunity to improve PRP therapy protocols for hair growth promotion. The variability in growth factor concentration in PRP suggests standardization of growth factors postprocessing might improve hair growth responses.

Incidence and outcomes of cutaneous angiosarcoma: A SEER population-based study.

BACKGROUND: Cutaneous angiosarcoma (CAS) is a rare, malignant tumor of vascular mesenchymal origin accounting for less than 1% of all sarcomas. OBJECTIVE: To examine epidemiologic trends and outcomes in CAS. METHODS: In this retrospective, population-based study, patients with CAS were identified from the Surveillance Epidemiology and End Results database. Age, sex, and race-standardized incidence rates (IRs) were calculated. Survival was assessed with Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 811 patients with CAS, 43% had a prior primary cancer. CAS IR for patients without prior primary cancers dropped from 5.88 per 100,000 in 1973 to 1984 to 2.87 per 100,000 in 2005 to 2014. In those with prior primary cancers, IR rose from 0.03 per 100,000 in 1973 to 1984 to 2.25 per 100,000 in 2005 to 2014. On multivariate analysis, patients older than 70 years of age had a higher risk of death compared with those younger than 50 years (hazard ratio, 2.16; 95% confidence interval 1.33-3.57; P = .002), and distant disease was associated with increased risk of death compared with localized disease (hazard ratio, 1.50; 95% confidence interval, 1.11-2.03; P = .008). Receipt of surgery and/or radiation therapy was not associated with survival. LIMITATIONS: Potential selection and miscoding bias, retrospective nature. CONCLUSION: CAS rates are rising among those with other prior primary cancers. Survival is not affected by current therapeutic strategies, highlighting the need for additional treatment options.

Intermittent Fasting and Its Effects on Athletic Performance: A Review.

Intermittent fasting (IFast) has been around for most of human history, and its proposed health benefits have been mentioned in ancient civilizations. However, recently, there has been a renewed public interest in IFast. Given the importance of nutrition in optimizing athletic performance, there is a concern about the effects of IFast on athletics. Most of the studies looking at performance and fasting are regarding athletes who observe Ramadan. Looking at high-intensity, endurance, and resistance exercises, studies have been varied but are uniform in showing that there is no benefit to athletic performance while fasting. More long-term studies need to be done to evaluate specific fasting protocols during sport.

Effects of foot progression angle adjustment on external knee adduction moment and knee adduction angular impulse during stair ascent and descent.

Foot progression angle adjustment was shown to reduce external knee adduction moment (EKAM) and knee adduction angular impulse (KAAI) during level ground walking. However, evidence on effects of foot progression angle adjustment on the above surrogate measures of medial knee loading during stair climbing is limited. Hence, this study examined the effects of toe-in and toe-out gait on EKAM and KAAI during stair ascent and descent. Kinematic and kinetic data were collected from thirty-two healthy adults during stair ascent and descent with toe-in, toe-out and natural gait. A repeated measures ANOVA indicated that toe-in gait significantly reduced the first EKAM peak (P < 0.001) and KAAI (P = 0.002), while toe-out gait significantly increased the first (P < 0.001) and second (P = 0.04) EKAM peaks and KAAI (P < 0.001) when compared with natural gait during stair ascent. During stair descent, toe-in gait significantly reduced the first (P < 0.001) and second (P = 0.032) EKAM peaks and KAAI (P < 0.001), whilst toe-out gait significantly increased the first EKAM peak (P = 0.022) and KAAI (P = 0.028) when compared with natural gait. In conclusion, toe-in gait was found to be a viable strategy in reducing medial knee loading during stair climbing.

The risk of venous thromboembolism during and after hospitalisation in patients with inflammatory bowel disease activity.

BACKGROUND: Inflammatory bowel disease (IBD) increases the risk of venous thromboembolism. AIMS: To determine when patients are at high risk of thromboembolic events, including after major surgery, and to guide timing of thromboprophylaxis. METHODS: Each IBD patient from Clinical Practice Research Datalink, linked with Hospital Episode Statistics, was matched to up to five non-IBD patients in this cohort study. We examined their risk of thromboembolism in hospital and within 6 weeks after leaving hospital, with or without undergoing major surgery, and while ambulant. Hazard ratios were estimated using Cox regression, with adjustment for age, sex, body mass index, smoking and history of malignancy or thromboembolism. RESULTS: Overall 23 046 IBD patients had a thromboembolic risk 1.74-times (95% CI = 1.55-1.96) higher than 106 795 non-IBD patients. Among ambulant patients, the thromboembolic risk was raised during acute (hazard ratio = 3.94, 2.79-5.57) or chronic disease activity (3.97, 2.90-5.45) but their absolute risk remained below 5/1000 person-years. The hazard ratio for thromboembolism among in-patients not undergoing major surgery was 1.13 (0.63-2.02), compared to 2.43 (1.20-4.92) among surgical patients, with a near doubling of absolute risk associated with surgery (59.5/1000 person-years, compared with 31.1 without surgery). The absolute risk remained elevated within 6 weeks after leaving hospital (18.6/1000 person-years in IBD patients after surgery). CONCLUSIONS: IBD patients are at an increased risk of venous thromboembolism. Absolute risks are raised during active disease, when in hospital, and after leaving hospital following major surgery.

How Do Biological Characteristics of Primary Intracranial Tumors Affect Their Clinical Presentation in Children and Young Adults?

We demonstrated the pattern in presentation of primary intracranial tumors in a population-based cohort of patients aged 0-24 years identified from the National Cancer Registry for England, using linked medical records from primary care and hospitals. We used generalized additive models to estimate temporal changes in presentation rates. Borderline and malignant tumors presented at a similar rate in primary care (6.4 and 6.6 consultations per 100 patients each month) and in hospital (3.4 and 3.6). Benign tumors presented earlier but less frequently (rate = 4.4 and rate ratio = 0.75, 95% CI = 0.60-0.93, in primary care; rate = 2.6 and rate ratio = 0.83, 95% CI = 0.77-0.89, in hospital). Many tumors began presenting shortly before their diagnosis, but less aggressive tumors were likely to present earlier in primary care. Earlier detection of less aggressive tumors in primary care may reduce the risk of complications and morbidity among survivors.

The Pattern of Underlying Cause of Death in Patients with Inflammatory Bowel Disease in England: A Record Linkage Study.

BACKGROUND AND AIMS: Numerous studies have established that mortality risk in inflammatory bowel disease [IBD] patients is higher than in the general population, but the causes of death have seldom been examined. We aimed to describe causes of death in IBD. METHODS: A matched cohort study using UK general practice data from Clinical Practice Research Datalink linked to death registration records. We described the distribution of causes of death among IBD patients by age at death and time since IBD diagnosis. We estimated age-specific mortality rates and hazard ratios of death in multivariable Cox proportional hazards models. RESULTS: 20293 IBD patients were matched to 83261 non IBD patients. The mortality rate was 40% higher in IBD patients [2005 deaths] than in non IBD patients [6024 deaths] (adjusted overall hazard ratio: = 1.4, 95% confidence interval [CI]: = 1.4-1.5], with greater risk of death in Crohn's disease [hazard ratio: = 1.6, 1.5-1.7] than in ulcerative colitis [1.3, 1.3-1.4]. Causes attributable to IBD constituted 3.7% of all deaths in ulcerative colitis and 8.3% in Crohn's disease. Among IBD patients, death was less likely to be due to circulatory, respiratory or neoplastic diseases than among non IBD patients. In both IBD and non IBD patients all these causes became more clinically important with advancing age, with the commonest neoplastic cause of death being lung cancer rather than gastrointestinal cancers. CONCLUSIONS: IBD patients have an additional risk of death. Most IBD patients die of circulatory or respiratory causes, and the contribution to mortality from long-term complications of IBD is clinically less important.

Where are the opportunities for an earlier diagnosis of primary intracranial tumours in children and young adults?

BACKGROUND: Childhood brain tumours have some of the longest time to diagnosis. A timely diagnosis may have a role in reducing anxiety in waiting for a diagnosis and subsequent morbidity and mortality. We investigated where the opportunities for an earlier diagnosis were, and for which anatomical locations this strategy will most likely to be effective. METHODS: A record-linkage cohort study of patients diagnosed aged 0-24 years with a primary intracranial tumour between 1989 and 2006 in England, using records from the National Cancer Registry linked to hospital admission records from Hospital Episode Statistics (HES, 1997-2006) and primary care consultation records from Clinical Practice Research Datalink (CPRD, 1989-2006). Relevant neurological presentations were extracted from HES and CPRD. Temporal changes in presentation rates were estimated in generalised additive models. RESULTS: Frequency of presentation began to increase six months before diagnosis in primary care and three months before diagnosis in hospital. Supratentorial and midline tumours had the longest presentation history before diagnosis. Peri-ventricular tumours presented frequently in hospital (rate ratio = 1.29 vs supratentorial tumours; 95% CI = 1.12-1.48) or as an emergency (1.24; 1.01-1.51), and in primary care (1.12; 0.62-1.85). CONCLUSIONS: Opportunities for an earlier diagnosis are greater in supratentorial, midline or cranial nerve tumours, which have a longer presentation history than peri-ventricular, cerebellar or brainstem tumours. Common features before diagnosis include headache, convulsions, and growth or endocrine disorders. Focal neurological deficits are uncommon and emerge late in the pre-diagnosis period.

Extra-Gastrointestinal Manifestations of Inflammatory Bowel Disease May Be Less Common Than Previously Reported.

BACKGROUND AND AIMS: Extra-intestinal manifestations are well recognized in inflammatory bowel disease (IBD). To what extent the commonly recognized extra-intestinal manifestations seen in IBD patients are attributable to IBD is, however, not clear due to the limited number of controlled studies published. METHODS: We have conducted a study of these manifestations using electronic primary care records. We have identified extra-intestinal manifestations in IBD and non-IBD patients and derived odds ratios (ORs) using conditional logistic regression. RESULTS: A total of 56,097 IBD patients (32.5 % Crohn's disease, 48.3 % ulcerative colitis (UC) and 19.2 % not classified) were matched to 280,382 non-IBD controls. We found records of pyoderma gangrenosum (OR = 29.24), erythema nodosum (OR = 5.95), primary sclerosing cholangitis (OR = 188.25), uveitis (OR = 2.81), ankylosing spondylitis (OR = 7.07), sacroiliitis (OR = 2.79) and non-rheumatoid inflammatory arthritides (OR = 2.66) to be associated with IBD. One or more of these was recorded in 8.1 % of IBD patients and 2.3 % of controls. Non-specific arthritides were present in many more patients, affecting 30 % of IBD patients and 23.8 % of controls overall. We also found weaker associations with a number of conditions not generally considered to be extra-intestinal manifestations including psoriasis, ischemic heart disease, multiple sclerosis and hay fever. CONCLUSION: Although "classical" extra-intestinal manifestations are strongly associated with IBD, most IBD patients remain unaffected. Arthropathies, perceived to be the commonest extra-intestinal manifestation, are not strongly associated with IBD, and the proportion of arthropathies attributable to IBD is likely to be small.