Variations of skin thermal diffusivity on different skin regions.

BACKGROUND AND OBJECTIVE: Skin thermal diffusivity plays a crucial role in various applications, including laser therapy and cryogenic skin cooling.This study investigates the correlation between skin thermal diffusivity and two important skin parameters, melanin content and erythema, in a cohort of 102 participants. METHODS: An in-house developed device based on transient temperature measurement was used to assess thermal diffusivity at different body locations. Melanin content and erythema were measured using a colorimeter. Statistical analysis was performed to examine potential correlations. RESULTS: The results showed that the measured thermal diffusivity values were consistent with previous reports, with variations observed among subjects. No significant correlation was found between thermal diffusivity and melanin content or erythema. This suggests that other factors, such as skin hydration or epidermis thickness, may have a more dominant influence on skin thermal properties. CONLCUSION: This research provides valuable insights into the complex interplay between skin thermal properties and physiological parameters, with potential implications for cosmetic and clinical dermatology applications.

A Simple Non-Contact Optical Method to Quantify In-Vivo Sweat Gland Activity and Pulsation.

OBJECTIVE: Most methods for monitoring sweat gland activity use simple gravimetric methods, which merely measure the average sweat rate of multiple sweat glands over a region of skin. It would be extremely useful to have a method which could quantify individual gland activity in order to improve the treatment of conditions which use sweat tests as a diagnostic tool, such as hyperhidrosis, cystic fibrosis, and peripheral nerve degeneration. METHODS: An optical method using an infrared camera to monitor the skin surface temperature was developed. A thermodynamics computer model was then implemented to utilize these skin temperature values along with other environmental parameters, such as ambient temperature and relative humidity, to calculate the sweat rates of individual glands using chemically stimulated and unstimulated sweating. The optical method was also used to monitor sweat pulsation patterns of individual sweat glands. RESULTS: In this preliminary study, the feasibility of the optical approach was demonstrated by measuring sweat rates of individual glands at various bodily locations. Calculated values from this method agree with expected sweat rates given values found in literature. In addition, a lack of pulsatile sweat expulsion was observed during chemically stimulated sweating, and a potential explanation for this phenomenon was proposed. CONCLUSION: A simple, non-contact optical method to quantify sweat gland activity in-vivo was presented. SIGNIFICANCE: This method allows researchers and clinicians to investigate several sweat glands simultaneously, which has the potential to provide more accurate diagnoses and treatment as well as increase the potential utility for wearable sweat sensors.

Development of a diffusion-weighed mathematical model for intradermal drainage quantification.

The quantitative assessment of lymphatic dermal clearance using NIR fluorescent tracers is particularly important for the early diagnosis of several potential disabling diseases. Currently, half-life values are computed using a mono-exponential mathematical model, neglecting diffusion of the tracer within the dermis after injection. The size and position of the region of interest are subjectively manually selected around the point of injection on the skin surface where the fluorescence signal intensity is averaged, neglecting any spatial information contained in the image. In this study we present and test a novel mathematical model allowing the objective quantification of dermal clearance, taking into consideration potential dermal diffusion. With only two parameters, this "clearance-diffusion" model is simple enough to be applied in a variety of settings and requires almost no prior information about the system. We demonstrate that if dermal diffusion is low, the mono-exponential approach is suitable but still lacking objectivity. However, if dermal diffusion is substantial, the clearance-diffusion model is superior and allows the accurate calculation of half-life values.

A Naked Eye-Invisible Ratiometric Fluorescent Microneedle Tattoo for Real-Time Monitoring of Inflammatory Skin Conditions.

The field of portable healthcare monitoring devices has an urgent need for the development of real-time, noninvasive sensing and detection methods for various physiological analytes. Currently, transdermal sensing techniques are severely limited in scope (i.e., measurement of heart rate or sweat composition), or else tend to be invasive, often needing to be performed in a clinical setting. This study proposes a minimally invasive alternative strategy, consisting of using dissolving polymeric microneedles to deliver naked eye-invisible functional fluorescent ratiometric microneedle tattoos directly to the skin for real-time monitoring and quantification of physiological and pathological parameters. Reactive oxygen species are overexpressed in the skin in association with various pathological conditions. Here, one demonstrates for the first time the microneedle-based delivery to the skin of active fluorescent sensors in the form of an invisible, ratiometric microneedle tattoo capable of sensing reactive oxygen species in a reconstructed human-based skin disease model, as well as an in vivo model of UV-induced dermal inflammation. One also elaborates a universal ratiometric quantification concept coupled with a custom-built, multiwavelength portable fluorescence detection system. Fully realized, this approach presents an opportunity for the minimally invasive monitoring of a broad range of physiological parameters through the skin.

Development and Clinical Validation of the LymphMonitor Technology to Quantitatively Assess Lymphatic Function.

Current diagnostic methods for evaluating the functionality of the lymphatic vascular system usually do not provide quantitative data and suffer from many limitations including high costs, complexity, and the need to perform them in hospital settings. In this work, we present a quantitative, simple outpatient technology named LymphMonitor to quantitatively assess lymphatic function. This method is based on the painless injection of the lymphatic-specific near-infrared fluorescent tracer indocyanine green complexed with human serum albumin, using MicronJet600TM microneedles, and monitoring the disappearance of the fluorescence signal at the injection site over time using a portable detection device named LymphMeter. This technology was investigated in 10 patients with unilateral leg or arm lymphedema. After injection of a tracer solution into each limb, the signal was measured over 3 h and the area under the normalized clearance curve was calculated to quantify the lymphatic function. A statistically significant difference in lymphatic clearance in the healthy versus the lymphedema extremities was found, based on the obtained area under curves of the normalized clearance curves. This study provides the first evidence that the LymphMonitor technology has the potential to diagnose and monitor the lymphatic function in patients.

Modeling Stratum Corneum Swelling for the Optimization of Electrode-Based Skin Hydration Sensors.

We present a novel computational model of the human skin designed to investigate dielectric spectroscopy electrodes for stratum corneum hydration monitoring. The multilayer skin model allows for the swelling of the stratum corneum, as well as the variations of the dielectric properties under several hydration levels. According to the results, the stratum corneum thickness variations should not be neglected. For high hydration levels, swelling reduces the skin capacitance in comparison to a fixed stratum corneum thickness model. In addition, different fringing-field electrodes are evaluated in terms of sensitivity to the stratum corneum hydration level. As expected, both conductance and capacitance types of electrodes are influenced by the electrode geometry and dimension. However, the sensitivity of the conductance electrodes is more affected by dimension changes than the capacitance electrode leading to potential design optimization.

Rational design of a fluorescent microneedle tattoo for minimally invasive monitoring of lymphatic function.

The monitoring of lymphatic drainage is of great importance, particularly in the context of the early detection and diagnosis of several diseases. Existing methods of imaging and monitoring lymphatic drainage can be costly and require trained personnel, posing problems for at-home or point-of-care monitoring. Recently, an alternative approach has been proposed, consisting of using microneedles to deliver a near-infrared (NIR) fluorescent tattoo to the skin, which can be monitored with traditional laboratory-based fluorescence detectors. In this work, we present further development of this approach, using a specifically designed NIR-fluorescent probe and rational optimization of microneedle properties and the spatial location of the NIR dye within the microneedles. Moreover, we demonstrate that this method is compatible with a custom-made portable fluorescence measurement device and able to discriminate between drainage and lack of drainage in vivo in rats.

Minimally invasive method for the point-of-care quantification of lymphatic vessel function.

Current clinical methods for the evaluation of lymphatic vessel function, crucial for early diagnosis and evaluation of treatment response of several pathological conditions, in particular of postsurgical lymphedema, are based on complex and mainly qualitative imaging techniques. To address this unmet medical need, we established a simple strategy for the painless and quantitative assessment of cutaneous lymphatic function. We prepared a lymphatic-specific tracer formulation, consisting of the clinically approved near-infrared fluorescent dye, indocyanine green, and the solubilizing surfactant Kolliphor HS15. The tracer was noninvasively delivered to the dermal layer of the skin using MicronJet600 hollow microneedles, and the fluorescence signal decay at the injection site was measured over time using a custom-made, portable detection device. The decay rate of fluorescence signal in the skin was used as a direct measure of lymphatic vessel drainage function. With this method, we could quantify impaired lymphatic clearance in transgenic mice lacking dermal lymphatics and distinguish distinct lymphatic clearance patterns in pigs in different body locations and under manual stimulus. Overall, this method has the potential for becoming a noninvasive and quantitative clinical "office test" for lymphatic function assessment.

Endometriosis doubles odds for miscarriage in patients undergoing IVF or ICSI.

OBJECTIVE: To identify and estimate the importance of risk factors on pregnancy loss until the end of the second trimester after clinical pregnancy was achieved by either in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI). STUDY DESIGN: Retrospective cohort study including 588 cycles with fresh embryo transfers and 150 cycles with frozen-thawed embryo transfers using logistic regression. RESULTS: The rate of miscarriages subsequent to a fresh embryo transfer was significantly increased by a diagnosis of endometriosis (p=0.02), as well as significantly influenced by the age of the female patient at the time of oocyte retrieval (p<0.01) and the serum level of testosterone (p=0.02). The time between freezing and thawing of the pronuclear stages for a frozen-thawed embryo transfer revealed a trend to a higher rate of miscarriages (p=0.06). CONCLUSION: Endometriosis significantly decreases the chance of having a baby even with IVF or ICSI.

Relationship between anti-Müllerian hormone and antral follicle count across the menstrual cycle using the Beckman Coulter Access assay in comparison with Gen II manual assay.

BACKGROUND: The study aim was to validate Beckman Coulter's fully automated Access Immunoassay System (BC Access assay) for anti-Müllerian hormone (AMH) and compare it with Beckman Coulter's Modified Manual Generation II assay (BC Mod Gen II), with regard to cycle AMH fluctuations and antral follicle counts. METHODS: During one complete menstrual cycle, transvaginal ultrasound was performed on regularly menstruating women (n=39; 18-40years) every 2 days until the dominant ovarian follicle reached 16mm, then daily until observed ovulation; blood samples were collected throughout the cycle. Number and size of antral follicles was determined and AMH levels measured using both assays. RESULTS: AMH levels measured by the BC Access assay vary over ovulatory menstrual cycles, with a statistically significant pre-ovulatory decrease from -5 to +2 days around objective ovulation. Mean luteal AMH levels were significantly lower (-7.99%) than mean follicular levels but increased again towards the end of the luteal phase. Antral follicle count can be estimated from AMH (ng/mL, BC Access assay) concentrations on any follicular phase day. BC Access assay-obtained AMH values are considerably lower compared with the BC Mod Gen II assay (-19% on average); conversion equation: AMH BC Access (ng/mL)=0.85 [AMH BC Mod Gen II (ng/mL)]0.95. CONCLUSIONS: AMH levels vary throughout the cycle, independently of assay utilised. A formula can be used to convert BC Access assay-obtained AMH levels to BC Mod Gen II values. The number of antral follicles can be consistently estimated from pre-ovulatory AMH levels using either assay.

Prospective study into the value of the automated Elecsys antimüllerian hormone assay for the assessment of the ovarian growing follicle pool.

OBJECTIVE: To evaluate a new fully automated assay measuring antimüllerian hormone (AMH; Roche Elecsys) against antral follicle count in women of reproductive age. DESIGN: Prospective cohort study. SETTING: Hospital infertility clinics and academic centers. PATIENT(S): Four hundred fifty-one women aged 18 to 44 years, with regular menstrual cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): AMH and antral follicle count (AFC) determined at a single visit on day 2-4 of the menstrual cycle. RESULT(S): There was a statistically significant variance in AFC but not in AMH between centers. Both AFC and AMH varied by age (overall Spearman rho -0.50 for AFC and -0.47 for AMH), but there was also significant between-center variation in the relationship between AFC and age but not for AMH. There was a strong positive correlation between AMH and AFC (overall spearman rho 0.68), which varied from 0.49 to 0.87 between centers. An agreement table using AFC cutoffs of 7 and 15 showed classification agreement in 63.2%, 56.9% and 74.5% of women for low, medium, and high groups, respectively. CONCLUSION(S): The novel fully automated Elecsys AMH assay shows good correlations with age and AFC in women of reproductive age, providing a reproducible measure of the growing follicle pool.

GaPP: a pilot randomised controlled trial of the efficacy of action of gabapentin for the management of chronic pelvic pain in women: study protocol.

INTRODUCTION: Chronic pelvic pain (CPP) affects >1 million UK women. Annual healthcare costs are estimated at >£150 million. Proven interventions for CPP are limited, and treatment is often unsatisfactory. Gabapentin is increasingly prescribed due to reports of effectiveness in other chronic pain conditions, but there are insufficient data supporting value in CPP specifically. The mechanism by which gabapentin exerts its analgesic action is unknown. Given the prevalence and costs of CPP, the authors believe that a large, multicentre, placebo-controlled, double-blind randomised controlled trial to evaluate the efficacy of gabapentin in management of CPP is required. The focus of this study is a pilot to inform planning of a future randomised controlled trial. METHODS AND ANALYSIS: The authors plan to perform a two-arm, parallel, randomised controlled pilot trial. The authors aim to recruit 60 women with CPP in NHS Lothian and NHS Grampian (UK) and randomise them to gabapentin or placebo. Response to treatment will be monitored by questionnaire compared at 0, 3 and 6 months. The primary objective is to assess recruitment and retention rates. The secondary objectives are to determine the effectiveness and acceptability to participants of the proposed methods of recruitment, randomisation, drug treatments and assessment tools and to perform a pretrial cost-effectiveness assessment of treatment with gabapentin. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Scotland A Research Ethics Committee (LREC 12/SS/0005). Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN70960777.

Modifications of laparoscopic supracervical hysterectomy technique significantly reduce postoperative spotting.

STUDY OBJECTIVE: The aim of this study was to estimate the benefit of excision of the endocervix during laparoscopic supracervical hysterectomy (LSH) with regard to postoperative cyclical bleeding. DESIGN: Cohort study from 2 centers (Canadian Task Force classification II-2). SETTING: Two surgical teams at the University of Duesseldorf Medical Center and PAN Clinic, Cologne, Germany. PATIENTS: Women with menstrual bleeding disorders resistant to medical treatment, symptomatic leiomyomata, dysmenorrhea. INTERVENTION: Laparoscopic supracervical hysterectomy. The uterus was transsected from the cervix with 2 techniques with and without excision of cervical canal. MEASUREMENTS AND MAIN RESULTS: We evaluated 300 patients who underwent consecutive LSH procedures. In 150 patients the uterus was transsected from the cervix using a monopolar loop. In a second series of 150 patients a unipolar needle electrode was used for the uterine amputation and the excision of cervical canal. The mean duration of the transsection was 65 seconds (monopolar loop) versus 168 seconds (monopolar needle). The excision of the endocervix was performed without any complications in 148 procedures. Histologic examination of the removed tissue revealed endocervical tissue in 83.3% (n = 125), endometrium in 9.4% (n = 14), cervicoisthmic mucosa in 3.3% (n = 5), and myometrium only in 4% (n = 4). All 300 patients were contacted 12 months after surgery to inquire about bleeding status, and 282 (94%) responded. In patients who underwent excision of the endocervix, postoperative cyclical bleeding was significantly reduced compared with the control group (1.4% vs 10.7%). CONCLUSION: The results of this study indicate that the routine excision of the endocervix is a quick safe procedure which allows a significant reduction of postoperative cyclical bleeding in patients who undergo LSH.

A novel, tissue occlusive poly(ethylene glycol) hydrogel material.

The use of guided bone regeneration (GBR) techniques requires new materials meeting the needs of clinical application. Design criteria for GBR devices are biocompatibility, tissue occlusion, space provision, and clinical manageability. This study evaluates a novel biodegradable poly (ethylene glycol) (PEG) based material as tissue occlusive membrane. A subcutaneous implant model in rats was developed to test the barrier function of the PEG hydrogels over time. Fourteen rats received three membrane implants and two positive controls each. Explants were collected over a period of 7 months. Histological analysis revealed that for at least 4 months cellular infiltration in the membrane explants was lower than 1% of that of the positive controls. Therefore, the PEG based hydrogel can be regarded as tissue occlusive during this period of time. A barrier function seems to be maintained for up to 6 months. In vitro degradation studies performed with the same PEG constructs confirm the in vivo result. In conclusion, our results indicate that this novel PEG-based material has potential for use as a GBR barrier membrane.

BMI1 is a target gene of E2F-1 and is strongly expressed in primary neuroblastomas.

The oncogene BMI1 encodes a polycomb group transcription factor that is required for embryonic development and self-renewal of stem cells. Despite these important functions little is known about the regulation of BMI1 expression. A cDNA microarray based search for target genes of E2F-1 in neuroblastoma cells expressing a 4-OHT-regulated E2F-1-ER fusion protein identified many hitherto unknown E2F-1 regulated genes. A total of 10% of these genes, including BMI1, encode proteins that function primarily in the regulation of gene expression. The BMI1 promoter contains a putative E2F binding site that was required for the activation of a BMI1 promoter-dependent reporter construct by E2F-1. Chromatin immunoprecipitation revealed 4-OHT-dependent binding of E2F-1-ER and binding of endogenous E2F-1 to the BMI1 promoter in tumor cells. We have previously shown activation of the oncogene MYCN by E2F. Thus, in neuroblastomas deregulated E2F-1 can activate two oncogenes, MYCN and BMI1 that are known to co-operate in tumor formation. Consistent with a role of Bmi1 in neuroblastoma tumorigenesis we found strong Bmi1 expression in primary neuroblastomas. Our results reveal a novel link between E2F and polycomb transcription factors and suggest a role of Bmi1 in neuroblastomas.