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.

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.

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.

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.

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.