Evaluation of mortality among Marines, Navy personnel, and civilian workers exposed to contaminated drinking water at USMC base Camp Lejeune: a cohort study.

BACKGROUND: Drinking water at U.S. Marine Corps Base (MCB) Camp Lejeune, North Carolina was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985. METHODS: A cohort mortality study was conducted of Marines/Navy personnel who, between 1975 and 1985, began service and were stationed at Camp Lejeune (N = 159,128) or MCB Camp Pendleton, California (N = 168,406), and civilian workers employed at Camp Lejeune (N = 7,332) or Camp Pendleton (N = 6,677) between October 1972 and December 1985. Camp Pendleton's drinking water was not contaminated with industrial solvents. Mortality follow-up was between 1979 and 2018. Proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) comparing mortality rates between Camp Lejeune and Camp Pendleton cohorts. The ratio of upper and lower 95% confidence interval (CI) limits, or CIR, was used to evaluate the precision of aHRs. The study focused on underlying causes of death with aHRs ≥ 1.20 and CIRs ≤ 3. RESULTS: Deaths among Camp Lejeune and Camp Pendleton Marines/Navy personnel totaled 19,250 and 21,134, respectively. Deaths among Camp Lejeune and Camp Pendleton civilian workers totaled 3,055 and 3,280, respectively. Compared to Camp Pendleton Marines/Navy personnel, Camp Lejeune had aHRs ≥ 1.20 with CIRs ≤ 3 for cancers of the kidney (aHR = 1.21, 95% CI: 0.95, 1.54), esophagus (aHR = 1.24, 95% CI: 1.00, 1.54) and female breast (aHR = 1.20, 95% CI: 0.73, 1.98). Causes of death with aHRs ≥ 1.20 and CIR > 3, included Parkinson disease, myelodysplastic syndrome and cancers of the testes, cervix and ovary. Compared to Camp Pendleton civilian workers, Camp Lejeune had aHRs ≥ 1.20 with CIRs ≤ 3 for chronic kidney disease (aHR = 1.88, 95% CI: 1.13, 3.11) and Parkinson disease (aHR = 1.21, 95% CI: 0.72, 2.04). Female breast cancer had an aHR of 1.19 (95% CI: 0.76, 1.88), and aHRs ≥ 1.20 with CIRs > 3 were observed for kidney and pharyngeal cancers, melanoma, Hodgkin lymphoma, and chronic myeloid leukemia. Quantitative bias analyses indicated that confounding due to smoking and alcohol consumption would not appreciably impact the findings. CONCLUSION: Marines/Navy personnel and civilian workers likely exposed to contaminated drinking water at Camp Lejeune had increased hazard ratios for several causes of death compared to Camp Pendleton.

Myositis ossificans - Another condition with USP6 rearrangement, providing evidence of a relationship with nodular fasciitis and aneurysmal bone cyst.

Myositis ossificans is defined as a self-limiting pseudotumor composed of reactive hypercellular fibrous tissue and bone. USP6 rearrangements have been identified as a consistent genetic driving event in aneurysmal bone cyst and nodular fasciitis. It is therefore an integral part of the diagnostic workup when dealing with (myo)fibroblastic lesions of soft tissue and bone. Two cases of myositis ossificans with USP6 rearrangement were published so far. We determine herein the incidence of USP6 rearrangement in myositis ossificans using USP6 fluorescence in situ hybridization analysis (FISH). Of the 11 cases included, seven patients were female and four were male. Age ranged from 6 to 56 years (mean 27 years). Lesions were located in the thigh (n = 5), knee (n = 1), lower leg (n = 1), lower arm (n = 1), perineum (n = 1), gluteal (n = 1) and thoracic wall (n = 1). All assessable cases except one (8/9) showed rearrangement of USP6 providing evidence that myositis ossificans is genetically related to nodular fasciitis and aneurysmal bone cyst.

An effective night slimming topical treatment.

So-called 'sex-specific fat' appears to be physiologically advantageous, but it has a cosmetic downside as well. A pool of functional ingredients, principally represented by botanical extracts, was selected to treat this condition, specifically for people intimidated by other more invasive approaches. The topical product was formulated using ingredients aimed at two specific actions; adipolysis and microcirculation stimulation [1-4]. The product was conceived for night-time application because during the night the body releases Growth Hormone, which activates adipolysis and blood flow, and the skin barrier function and metabolic rate are also more active. We aimed at assessing the effect of the topical product vs. placebo through an in vivo evaluation protocol, performed using a skin bioengineering method, namely ultrasonography, and clinical evaluation. The protocol was conducted as a double-blind, active vs. placebo trial (form. N°690 vs. form. N°1362), on 100 subjects enrolled by two research centres (Pavia and Rome, Italy), over a 4 week period, during which volunteers were checked four times, both clinically and instrumentally. At the end of the trial, both centres agreed on the slimming effects of the topical product. Tolerability was good. The enrolled volunteers expressed their full satisfaction regarding the product under study.

The influence of a non-occlusive bi-layer composite membrane on skin barrier properties. A non-invasive evaluation with a right-left intra-individual pre/post comparison study.

The purpose of this placebo-controlled right-left intra-individual pre/post comparison study was to evaluate the efficacy of a new bi-layer composite membrane, composed of a layer of knitted cotton and a layer of semi-permeable polyurethane, developed in order to improve skin hydration. Eighteen healthy subjects entered the study. A T-shirt, dedicated to this study, was prepared and it was worn for 8 h, mimicking overnight wearing. Before and at the removal of the T-shirt an objective quantification of skin parameters was performed by measuring hydration, transepidermal water loss (TEWL) and skin surface pH, bilaterally, on the inner side of the forearm. Measurements were performed both at the interface between the skin and the bi-layer composite membrane or cotton and on the outer side of the membrane (to assess permeation of water and occlusive properties of the product) with and without a single application of a moisturizer. A statistically significant improvement of skin hydration, recorded on the stratum corneum underneath the bi-layer membrane versus cotton alone, was measured both with (p < 0.0001) and without application of the moisturizer (p < 0.002). TEWL was shown to decrease significantly on the side of the bi-layer membrane, if compared with cotton (p < 0.008), after application of the moisturizer. TEWL through the membrane showed no significant differences as compared to placebo, confirming the permeability of the fabric. Our data suggest that this bi-layer composite membrane can promote the hydration process of the stratum corneum, increasing the hydrating properties of the moisturizer agent.

Efficacy of oleuropein against UVB irradiation: preliminary evaluation.

Oleuropein, a phenolic compound derived from olive leaves and oil, is known to possess several biological properties, many of which may be attributed to its antioxidant and free radical-scavenging activities. Nevertheless, up to now, the cosmetic activity of this molecule has not been extensively investigated. The aim of this work was to evaluate the cosmetic properties of oleuropein against UVB-induced erythema. To this end, an emulsion and an emulgel containing oleuropein were prepared, applied and evaluated on healthy volunteers who had undergone UVB irradiation to investigate its protective and/or lenitive activity. Protective effect was assayed by application of topical preparations before irradiation and lenitive effect was evaluated after erythema induction. Vitamin E was used as the reference compound. Our study was carried out by using noninvasive techniques to assess specific skin parameters: barrier function, skin colour and microcirculation. Results clearly showed that oleuropein formulations highlighted lenitive efficacy by reducing erythema, transepidermal water loss and blood flow of about 22%, 35% and 30% respectively. The study allowed us to point out the lenitive property of oleuropein, opening the way to further trials to deepen our specific knowledge about this natural molecule, which could be used in association with other active ingredients in cosmetics to repair UV damages.

Testing anticellulite products.

Cellulite represents the most common lipodystrophic disease. It affects more likely women than men and it usually develops in particular anatomic sites such as lateral thighs and buttocks. In these areas skin resembles 'orange peel' surface. The pathophysiological aspects of cellulite are still not clear. Many predisposing factors seem to influence cellulite onset, including gender, heredity, race, body weight and age. Hormones and impairment of both microvascular and lymphatic circulation are considered the most important etiological factors. The evaluation of cellulite is based principally on clinical observation, thigh circumference measurements, body mass index and thermography but for testing anticellulite products, more objective and non-invasive methods of evaluation are requested.

Non-invasive evaluation of tacalcitol plus puva versus tacalcitol plus UVB-NB in the treatment of psoriasis: "right-left intra-individual pre/post comparison design".

Photochemotherapy with psoralen plus ultraviolet A(PUVA) and phototherapy with UVB narrow band (UVB-NB) are used in the treatment of psoriasis. Numerous studies have shown that the additional administration of either topical or systemic antipsoriatic agents may effectively increase the efficacy of these therapies. This study aimed to compare through objective data the efficacy of topical tacalcitol in combination with PUVA or UVB-NB versus PUVA and UVB-NB monotherapy in the treatment of mild to moderate chronic plaque psoriasis. Modified Psoriasis Area and Severity Index (PASI) score, transepidermal water loss (TEWL) and stratum corneum hydration were used to monitor the restoration of skin barrier in the psoriatic plaques of 40 patients during photochemotherapy. The study was a right-left, intra-individual, pre/post comparison trial. PUVAand UVB-NB treatments were given three times a week. On those plaques localized on the right side of the body tacalcitol ointment was applied once a day, in the evening. Corneometry, TEWL and modified PASI score were used to evaluate the response to the treatment at baseline, one month and two months. Thirty-six of the forty enrolled subjects completed the study. The comparison between combination treatments and the PUVA/UVB-NB monotherapy showed no significant differences with regard to modified PASI index. However, significant differences were recorded with regard to TEWL and corneometry. The combination of tacalcitol plus PUVA or tacalcitol plus UVB-NB restored epidermal barrier functions as well as skin hydration faster than PUVA or UVB-NB monotherapy (TEWL: p=0.0050 and corneometry: p=0.003). The combination of tacalcitol plus UVB-NB allowed a better restoration of skin barrier functions than tacalcitol plus PUVA (p=0.013). In conclusion, the combination of tacalcitol plus PUVA or plus UVB-NB improves the therapeutic result. In addition, the data from TEWL and skin hydration suggest a means in which tacalcitol plus UVB-NB induces a better normalization of skin biophysical parameters.

JAK2 and AMP-kinase inhibition in vitro by food extracts, fractions and purified phytochemicals.

We have identified a range of food phytochemicals that inhibit Janus Kinase 2 (JAK2) and Adenosine Monophosphate Kinase (AMPK). A mutated and dysregulated form of JAK2, a tyrosine kinase, is associated with several diseases including Crohn's disease. Using an in vitro, time-resolved fluorescence (TR-FRET) assay, we tested 49 different types of food extracts, plus 10 concentrated fractions of increasing hydrophobicity from each extract, to find foods containing JAK2 inhibitors. The food extracts tested included grains, meat, fish, shellfish, dairy products, herbs, mushrooms, hops, fruits and vegetables. Several fruits were potent inhibitors of JAK2: blackberry, boysenberry, feijoa, pomegranate, rosehip and strawberry, which all contain ellagitannins, known inhibitors of kinases. These fruits are in the Rosales and Myrtales plant orders. No other foods gave >1% of the maximal JAK2 inhibitory activities of these fruits. AMPK, a sensor and regulator of energy metabolism in cells, is a serine-threonine kinase which is reported to be activated by various flavonoid phytochemicals. Using a TR-FRET assay, we tested various fruit extracts for AMPK activation and inhibition. Ellagitannin containing foods scored highly as AMPK inhibitors. Despite several reports of AMPK activation in whole cells by phytochemicals, no extracts or pure compounds activated AMPK in our assay.

Oral fish cartilage polysaccharides in the treatment of photoageing: biophysical findings.

The topically applied cosmetic products can be helpful in improving the aged skin condition. The present study shows how oral fish-cartilage food supplementation can be helpful in improving the treatment of ageing skin. A total of 30 healthy women with signs of skin ageing were studied. Fifteen of the women were treated with a food supplement based on polysaccharides derived from the fish cartilage and a natural mix of antioxidants for 2 months and the other 15 with a placebo. Clinical evaluation and biophysical parameters related to skin function and wrinkle severity, such as silicone replica, skin thickness, mechanical properties, skin colour and capacitance, were measured. The results showed statistically significant changes in the active-treated group in comparison to the placebo. In particular, dermal thickness (treatment: from 1.13 to 1.23 mm; P < 0.001), skin wrinkling (treatment: from 9.5 to 3.5 R(a); P< 0.002), skin colour (treatment: brighter and less pigmented; P < 0.02) and viscoelasticity (treatment: from 0.70 to 0.97%; P < 0.02) showed considerable improvement. Most of these parameters are related to changes occurring within the dermal matrix, which is improved after the treatment, whereas most of the topically applied cosmetic products have a short-term effect on superficial structures. A combination treatment (oral and topical) can be more effective in reducing the signs of skin-ageing.

A PPARγ ligand present in Actinidia fruit (Actinidia chrysantha) is identified as dilinolenoyl galactosyl glycerol.

Activity-guided fractionation of Actinidia fruit species, including Kiwifruit, has identified DLGG (dilinolenoyl galactosyl glycerol) as a potent PPARγ (peroxisome-proliferator-activated receptor γ) ligand. DLGG is a type of MGDG (monogalactosyl diacylglycerol) and is present in all chloroplasts, and therefore all green fruits and vegetables. PPARγ is a ligand-activated transcription factor that regulates glucose metabolism and inflammation. An ethyl acetate extract of Actinidia chrysantha was fractionated by HPLC and the PPARγ-binding activity was detected by FP (fluorescence polarization). Linoleic and α-linolenic acids in A. chrysantha were readily detected as PPARγ ligands. Slow-binding PPARγ ligands were detected in several hydrophobic fractions. High-resolution MS identified DLGG as one of these ligands and confirmed that its binding is non-covalent. DLGG is a slow-binding PPARγ ligand with an IC50 of 1.64 µM, ±0.093 achieved after 45 min equilibration. DLGG is the first example of a form of DAG (diacylglycerol) that is a PPARγ ligand. In addition, DLGG is the first reported glycolipid ligand for PPARγ and also the first non-covalent, slow-binding PPARγ ligand.

The combination of analytical-scale HPLC separation with a TR-FRET assay to investigate JAK2 inhibitory compounds in a Boysenberry drink.

We report the detection of JAK2 inhibitory activity in a Boysenberry (Rubus loganbaccus x R. baileyanus Britt.) drink using a combination of analytical-scale high performance liquid chromatography (HPLC) with a high-sensitivity time-resolved fluorescence coupled with fluorescence resonance energy transfer (TR-FRET) method. Phytochemical components of a Boysenberry drink were separated by reversed phase HPLC , and 84 separate fractions were collected. HPLC fractions corresponding to the ellagitannin and ellagic acid peaks observed in the chromatogram inhibited JAK2 activity. Anthocyanins, while they were the major phytochemical components of the Boysenberry drink, had no JAK2 inhibitory activity even though anthocyanins have previously been shown to be anti-inflammatory. This study demonstrates the usefulness of combining rapid analytical-scale HPLC separation with a highly sensitive fluorescence bioassay for characterising bioactivity in complex plant extracts. Ellagic acid was found to have an IC(50) of 92 nM against JAK2 and complete inhibition of JAK2 activity was observed in HPLC fractions of Boysenberry extract which had been diluted several hundred fold. To the best of our knowledge, this is the first demonstration that ellagitannins and other natural ellagic acid analogues are potent inhibitors of JAK2. Thus a drink containing Boysenberry juice concentrate may have anti-inflammatory properties.

Apple peels, from seven cultivars, have lipase-inhibitory activity and contain numerous ursenoic acids as identified by LC-ESI-QTOF-HRMS.

Apple peel contains numerous phytochemicals, many of which show bioactivity. This study investigated the identity of triterpenoid compounds contained in ethanolic extracts of peel from seven apple cultivars. Using HPLC-ESI-QTOF-HRMS, accurate mass information was obtained for 43 compounds, and chemical identity was inferred from the calculated elemental composition, fragment masses, ms/ms, and a limited set of authentic standards. Compounds were identified as triterpene acids and tentatively identified as ursenoic (or oleanoic) acid derivatives containing hydroxyl, oxo, and coumaroyloxy groups. These apple skin extracts exhibited lipase-inhibitory activity, which may be linked to the ursenoic acid content. Furthermore, both triterpene content and lipase-inhibitory activity varied by cultivar.

A long-term time course of colorimetric assessment of the effects of imatinib mesylate on skin pigmentation: a study of five patients.

BACKGROUND: Imatinib mesylate (IM), the first-line treatment of chronic myeloid leukaemia (CML), is a tyrosine kinase inhibitor that targets those proteins involved in BCR-ABL signal transduction in CML, c-kit (KIT) and platelet-derived growth-factor (PDGFR) receptor. The use of IM has been associated with cutaneous reactions. In the last 2 years numerous studies have focused the attention on hypopigmentations, depigmentations and photosensitivity developing after the initiation of IM therapy. OBJECTIVE: The aim of this study is to evaluate the effects of IM therapy on the skin pigmentation of five patients affected by CML. METHODS: Skin pigmentation measurements were performed with a Minolta CR-200 Chromameter. results: All the studied patients show the gradual lightening of the skin on unexposed areas over the treatment with IM. In particular, this explorative colorimetric study indicates the association between IM and skin depigmentation with a significant increase of luminance value (L*) (P = 0.001) and a significant decrease of the pigmentation value (b*) (P = 0.028). CONCLUSION: Even if we do not know the clinical significance of the skin depigmentation caused by IM, the regulatory role of KIT and its ligand stem cell factor in melanocyte development and survival seems to suggest an objective mechanism of action for IM in the pathogenesis of this cutaneous depigmentation.

The cosmetic treatment of wrinkles.

Wrinkles now have a greater social impact because people live longer. Science and hedonism overlap in the search for causes, treatments and prevention of wrinkles. The cosmetic approach to wrinkles includes: i Cleansing ii Photoprotection iii Active ingredients Active ingredients go well beyond simple moisturisers and exert a more complex activity in protecting skin from external injuries, nourishing it and removing its superficial layers. Transport systems and excipients are increasingly effective. Functional agents currently include alpha hydroxy acids (AHAs), poly-AHAs, complex poly-AHAs, retinoids, fish polysaccharides, anti-enzymatic agents, antioxidants (including ascorbic acid, pycnogenol, ursolic acid, vegetable isoflavones, vitamin E, coenzyme Q10, lipoic acid, resveratorol, l-carnosine and taurine) as well as agaricic acid and various plant extracts. All are reviewed in this text. Most are topical, some can be given by mouth, even as food supplements. Cosmetics are becoming closer to drugs in preventing and treating wrinkles. Included amongst the cosmeceuticals are the anti-wrinkle agents described herein.

Detection of skin irritation potential of cosmetics by non-invasive measurements.

This study analyses the ability of four non-invasive techniques (laser Doppler velocimetry, evaporimetry, chromametry and corneometry) to discriminate between irritant and non-irritant products, when compared to appropriate controls, and to detect subliminal changes in barrier function and erythema. These changes, which remain undetectable in the traditional visual and palpable clinical assessment, can be used as early reactions that are followed by the development of overt skin irritation. Laser Doppler velocimetry and evaporimetry were good discriminators between irritant and non-irritant substances, whereas corneometry and chromametry did not clearly distinguish between them. Laser Doppler velocimetry and evaporimetry detected early stages in the development of an irritant reaction before it became visible, but chromametry was not able to detect an early irritant response. It was concluded that non-invasive measurements could improve the quality and relevance of data obtained from human irritation testing, since the data they provide are objective, quantitative and sometimes subclinical, which also allows the concentration of a positive control to be reduced, resulting in the induction of less skin damage in human volunteers and reducing the ethical concerns related to the deliberate induction of an irritant response in a 'healthy' volunteer.

Predicting visual assessment of allergic patch test reactions by non-invasive measurements.

The quantification of allergic patch test reactions to several compounds was evaluated on patients using laser Doppler velocimetry (LDV), transepidermal water loss and colorimetry. The correlation between visual scores and instrumental measurements was investigated by the implementation of a modern statistical method: a classification tree. The LDV showed the highest correlation with the severity of the reaction. The best prediction model was obtained when the data of the three instruments were considered together. Using the classification tree methodology, a model of classification, independent of human observation, was developed. The technique can not only predict an allergic reaction for a new patient, but can also give a measure of how reliable its predictions are. This new method, when entirely standardised and approved, could help in the harmonisation of patch test reactions in different laboratories, thus allowing a more homogenous interpretation of these reactions.