Search

Background Damage to hair by UV is relevant to most people, and for many, it is a major source of hair damage. Prevention of UV damage is of high interest to cosmetic companies. Objectives Describe UV damage mechanisms and link these mechanisms to measurable changes in hair protein composition and color changes resulting from breakdown of yellow-colored kynurenines. Test the power of botanical antioxidants, specifically Camellia sinensis (tea) extracts to prevent this protein damage and color change. Link specific phytochemistry of extract samples to hair performance. Methods Camellia sinensis (tea) extracts were analyzed by LC-MS to identify the key composition chemistries. ORAC (Oxygen Radical Antioxidant Capacity) was used to measure ability of the extract to react with a peroxyl radical via a hydrogen abstraction mechanism. Hair protein structural damage was measured by quantification of a biomarker peptide that is specific to UV-induced damage and hair color changes were measured with a spectrophotometer. Results Levels of key phytochemistry in the extracts, specifically the catechins, correlated with prevention of UV-induced protein damage and prevention of color changes due to kynurenine breakdown. Extracts with higher phytochemistry levels also had higher ORAC scores indicating that they were more effective antioxidants. Conclusions Camellia sinensis (tea) extracts can be used as effective protective treatments for hair protection but this efficacy is linked to extract concentrations of key chemistries (catechins).

Aims To assess the therapeutic potential of fatty acid synthase (FASN) inhibition with FT‐4101, a potent, selective, orally bioavailable, small‐molecule by (a) evaluating the dose−response of single FT‐4101 doses (3, 6 and 9 mg) on hepatic de novo lipogenesis (DNL) in healthy participants (Study 1) and (b) demonstrating the safety, tolerability and efficacy on hepatic steatosis after 12 weeks of FT‐4101 dosing in patients with non‐alcoholic fatty liver disease (NAFLD; Study 2). Materials and Methods In Study 1, three sequential cohorts of healthy men (n = 10/cohort) were randomized to receive a single dose of FT‐4101 (n = 5/cohort) or placebo (n = 5/cohort) followed by crossover dosing after 7 days. Hepatic DNL was assessed during fructose stimulation from 13C‐acetate incorporation. In Study 2, men and women with NAFLD (n = 14) randomly received 12 weeks of intermittent once‐daily dosing (four cycles of 2 weeks on‐treatment, followed by 1 week off‐treatment) of 3 mg FT‐4101 (n = 9) or placebo (n = 5). Steady‐state DNL based on deuterated water labelling, hepatic steatosis using magnetic resonance imaging‐proton density fat fraction and sebum lipids and circulating biomarkers were assessed. Results Single and repeat dosing of FT‐4101 were safe and well tolerated. Single FT‐4101 doses inhibited hepatic DNL dose‐dependently. Twelve weeks of 3 mg FT‐4101 treatment improved hepatic steatosis and inhibited hepatic DNL. Decreases in sebum sapienate content with FT‐4101 at week 11 were not significant compared to placebo and rebounded at week 12. Biomarkers of liver function, glucose and lipid metabolism were unchanged. Conclusions Inhibition of FASN with 3 mg FT‐4101 safely reduces hepatic DNL and steatosis in NAFLD patients.

To determine the prevalence of antibodies to Brucella melitensis, Brucella abortus and Coxiella burnetii in animals on Caribbean islands we obtained sera from convenience samples of cattle (C), sheep (S), goats (G) and cats (F) from Dominica (C, S, G), Grenada (C, S, G), Montserrat (C, S, G), Puerto Rico (C), Nevis (C, S, G), St Kitts (C, S, G, F) and St Lucia (C, G). The sera were tested for antibodies against the Brucella spp. using commercial ELISA kits. Some sera were also tested at 1/80 for antibodies to C. burnetii using an indirect fluorescent antibody test. Positive sera were also tested at 1/640. None of 599 cattle, 462 sheep or 434 goats were positive in the Brucella ELISAs. None of 230 cattle had antibodies against C. burnetii, but one of 299 sheep was positive at 1/80 (Dominica – 1/54, 2%, 95% CI (0%–5.6%)), as were two of 314 goats, at 1/80 (Grenada – 1/53, 2%, 95% CI (0%–7.5%)) and 1/640 (St Kitts − 1/18, 5.6%, 95% CI (0%–16.7%)), and one of 34 cats, at 1/80 (St Kitts − 1/34; 3%, 95% CI (0%–8.8%)). Our data suggests that there is a very low prevalence or absence of B. melitensis and B. abortus on Caribbean islands. Coxiella burnetii, however, is present but it appears to be present on only some islands and then only at low levels. Overall, there appears to be a low threat to human and animal health from these organisms in the Caribbean., A serosurvey of animals from Caribbean islands showed little evidence of exposure to Coxiella burnetii and Brucella spp., the agents of Q fever and brucellosis in animals and people, respectively. The findings indicate that there appears to be a low threat to human and animal health from these organisms in the region.

Duvelisib (IPI‐145) is an oral dual inhibitor of phosphoinositide‐3‐kinase (PI3K)‐δ and ‐γ in clinical development for the treatment of hematologic malignancies, including indolent non‐Hodgkin lymphoma (iNHL). In a Phase 1, open‐label study to determine the maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, clinical activity, and safety of duvelisib monotherapy in patients with advanced hematologic malignancies, duvelisib was administered at eight dose levels (8‐100 mg BID) in a dose‐escalation phase (n = 31 evaluable patients). Two dose‐limiting toxicities (DLTs), Grade 3 transaminase elevations and Grade 3 rash, occurred at 100 mg BID, and the MTD was determined to be 75 mg BID. Across all doses, 58.1% of iNHL patients had a response (19.4% complete, 35.5% partial, and 3.2% minor); median time to response was 1.84 months and duration of response was 16.9 months. Median progression‐free survival was 14.7 months, and the probability of overall survival at 24 months was 71.7%. Severe (Grade ≥ 3) adverse events included elevated liver enzymes (38.7%), diarrhea (25.8%), and neutropenia (29.0%). Three patients, all in the 75 mg BID cohort, experienced fatal AEs: E. coli sepsis, acute respiratory failure, and fungal pneumonia. No iNHL patients experienced Pneumocystis pneumonia. Duvelisib demonstrated favorable clinical activity and an acceptable safety profile in these high‐risk, heavily pretreated, relapsed/refractory iNHL patients, with 25 mg BID selected for further clinical development.

Habitat loss and fragmentation negatively impact the size and diversity of many natural populations. Woodland amphibians require connected aquatic and terrestrial habitats to complete their life cycle, and often rely on metapopulation structure for long-term persistence. Wetland loss and deforestation fragment amphibian populations, which may result in population isolation and its negative effects. The aim of this research was to analyze the population genetic structure of small-mouthed salamanders (Ambystoma texanum) in western Ohio, where agriculture is now the dominant land use. Salamander tail tissue was collected from eight breeding pools. Three pools occur in the same forest; the other five are in forest patches at distances ranging from 250 m to 20 km from one another. Eight microsatellite loci were amplified by PCR and genotyped for allele size. Observed heterozygosities were lower than expected in all sampled populations; the two most isolated sites (Ha1, Ha2) had the highest inbreeding coefficients. Ha2 also had the lowest mean number of alleles and was found to be genetically differentiated from populations to which our data analysis indicates it was historically connected by gene flow. The most distant site (Ha1) had the highest number of private alleles and showed genetic differentiation from other populations both historically and currently. Geographic distance between pools was strongly correlated with the number of private alleles in a population. The results suggest that population isolation results in decreased genetic diversity and that a breakdown of metapopulation structure due to landscape change may contribute to differentiation between once-connected populations.

Purpose Infant formulas are often supplemented with medium-chain triglycerides (MCTs) to optimize calories for small for gestational age or preterm infants. High amounts of MCTs have been associated with an increase in dicarboxylic acid (DCA) in the urine. Elevated DCA in the urine is also a clinical indicator for fatty acid metabolism disorders. The purpose of this study was to identify if there is an amount of MCTs that can be provided without elevating urinary DCA excretion. Methods A metabolic screening laboratory provided urinary DCA excretion data for 175 infants. It was verified that no infants were diagnosed with metabolic disorders and therefore were considered "metabolically normal." All infants were either formula fed or breastfed at the time of screening. The type and volume of formula provided at the time of urine screening was documented. The exact amount of MCTs provided to each infant was calculated. Results The mean age of the infants was 3.09 months. The mean total DCA was determined for both the breastfeeding and formula groups. Within the formula group, the means were 32.07, 13.36, and 5.77 mmol/mol creatinine for adipic, suberic, and sebacic acids, respectively. Spearman correlation coefficient indicated correlations of r = 0.0693, r = 0.0166, and r = -0.0128 between percent MCT and adipic, suberic, and sebacic acids, respectively. No value was statistically significant. DCA excretion amounts did not vary between breastfed and formula-fed infants. Our data suggest that clinicians should not expect elevated dicarboxylic aciduria in infants who are fed a standard formula without added MCT oil.

Limited functional expression of the viral envelope receptor is a recognized barrier to efficient oncoretroviral mediated gene transfer. To circumvent this barrier we evaluated a number of envelope proteins with respect to gene transfer efficiency into primitive human hematopoietic stem cell populations. We observed that oncoretroviral vectors pseudotyped with the envelope protein of feline endogenous virus (RD114) could efficiently transduce human repopulating cells capable of establishing multilineage hematopoiesis in immunodeficient mice after a single exposure to RD114-pseudotyped vector. Comparable rates of gene transfer with amphotropic and GALV-pseudotyped vectors have been reported, but only after multiple exposures to the viral supernatant. Oncoretroviral vectors pseudotyped with the RD114 or the amphotropic envelopes had similar stability in vitro, indicating that the increased efficiency in gene transfer is at the receptor level likely due to increased receptor expression or an increased receptor affinity for the RD114 envelope. We also found that RD114-pseudotype vectors can be efficiently concentrated, thereby removing any adverse effects of the conditioned media to the long-term repopulating potential of the target human hematopoietic stem cell. These studies demonstrate the potential of RD114-pseudotyped vectors for clinical use.

Over the last 20 years, advances in molecular techniques have greatly facilitated the identification of the members of the Rickettsiales, and numerous new species and diseases have been described. In this paper, we review taxonomic rules and appropriate approaches to valid naming of rickettsial species and the diseases they cause.

Langerhans cell histiocytosis (LCH) is a disorder characterized by proliferation of activated Langerhans cells. Immune dysregulation is believed to be part of the pathogenesis. Although current therapies are very effective at inducing remission, multiple recurrences and long-term sequelae are common for patients with low-risk disease, and a significant proportion of young patients die of their disease. More effective therapies based on the pathogenesis of LCH are needed. We investigated the use of 2-chloro-deoxyadenosine (2-CdA), a purine analogue with an antiproliferative effect on histiocytes and lymphocytes, in patients with recurrent or high-risk LCH. Six patients with recurrent LCH received 2-CdA (5-7 mg/m(2)/day for 5 days, repeated every 21-28 days). All patients achieved remission. With a median follow-up of 15 months (range, 3-25 months), 5 patients remain in remission. A patient with multisystem disease who recurred after 13 months, achieved a second remission with 2-CdA. Hematologic toxicity was minimal, and no infectious complications were documented. 2-CdA is among the most effective drugs for the treatment of LCH, and this is probably due to both its anti-proliferative and immunomodulatory effects. 2-CdA needs to be considered for the treatment of recurrent LCH. However, its incorporation into front-line treatment of patients with multi-system LCH needs further study.

INTRODUCTION: Reconstruction after wide local excision of melanomas in the head and neck can be formidable. Many tumors lie close to vital structures, and excision must carefully balance preservation of form and function. For small defects, primary closure or skin grafting is satisfactory. However, it has become increasingly evident that more advanced reconstructive procedures can improve the outcome in terms of both function and aesthetics. This study was undertaken to determine the effectiveness of flap closure after wide local excision of melanomas in the head and neck and to develop a set of surgical recommendations on the basis of our experience. METHOD: We reviewed 35 patients who underwent 39 flap closures at The University of Texas, M. D. Anderson Cancer Center after wide local excision of head and neck melanomas. Local flaps were primarily used to close defects after the resection of superficial or intermediate-thickness melanomas. Pedicle and free flaps were used to cover larger defects resulting from the excision of extensive tumors. The flap closures were compared with an analogous database of 560 melanoma resections that underwent primary closure or skin grafting. RESULTS: The mean age of the patient population was 57 years. The most common location for tumor presentation was the cheek, followed by the ear, forehead, and lip. Pathologic findings most commonly demonstrated superficial spreading melanoma, and the average defect size was 30.7 cm(2). Local flaps were used most often for reconstruction. The only variable that significantly predicted local recurrence was the depth of the tumor. Local, pedicle, or free flaps did not decrease the ability of detecting local recurrence or increase this number compared with primary closure and skin grafting. Major postoperative complications were detected in seven patients. We found flap closure to achieve excellent functional and aesthetic results. CONCLUSION: Although primary closure is the ideal method of reconstruction for small defects, flap closure provides a versatile and safe alternative when simple closure would yield unsatisfactory results. With careful planning, flap closure offers an exceptional functional and aesthetic result and may even enhance contour defects after extensive neck or parotid dissections. Moreover, our experience with flap closure did not appear to delay the detection of local recurrence and may have even served to decrease the incidence of local failure after wide local excision of head and neck melanomas. Copyright 2000 John Wiley & Sons, Inc. Head Neck 23: 8-15, 2001.

Information technology can be helpful in supporting advice, guidance, and student learning services, but its successful use demands constant attention to learners' realities and a skeptical enthusiast's attitude.