The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into ...circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT
-Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT
-Cre mouse line, generated with the internal ribosome entry site (IRES) method. ChAT
-Cre transgenic and wild-type mice did not differ in general locomotor behavior, anxiety measures, drug-induced cataplexy, nicotine-mediated hypolocomotion, or operant food training. However, ChAT
-Cre transgenic mice did exhibit significant deficits in intravenous nicotine self-administration, which paralleled an increase in vesicular acetylcholine transporter and choline acetyltransferase (ChAT) hippocampal expression. For the ChAT
-Cre line, transgenic mice exhibited deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant food training compared with wild-type and hemizygous littermates. No differences among ChAT
-Cre wild-type, hemizygous, and transgenic littermates were found in anxiety measures, drug-induced cataplexy, and nicotine self-administration. Given that increased cre expression was present in the ChAT
-Cre transgenic mice, as well as a decrease in ChAT expression in the hippocampus, altered neuronal function may underlie behavioral phenotypes. In contrast, ChAT
-Cre hemizygous mice were more similar to wild-type mice in both protein expression and the majority of behavioral assessments. As such, interpretation of data derived from ChAT-Cre rodents must consider potential limitations dependent on the line and/or genotype used in research investigations.
Altered baseline and/or nicotine-mediated behavioral profiles were discovered in transgenic mice from the ChAT
-Cre and ChAT
-Cre lines. Given that these cre-expressing mice have become increasingly used by the scientific community, either independently with chemicogenetic and optogenetic viral vectors or crossed with other transgenic lines, the current studies highlight important considerations for the interpretation of data from previous and future experimental investigations. Moreover, the current findings detail the behavioral effects of either increased or decreased baseline cholinergic signaling mechanisms on locomotor, anxiety, learning/memory, and intravenous nicotine self-administration behaviors.
Melasma is a common, therapeutically challenging, and universally relapsing disorder of hyperpigmentation that is most often observed in women and individuals with Fitzpatrick Skin Types III through ...VI. The pathogenesis of melasma is complex and protean. Contributing factors that are often implicated in the etiopathogenesis of this condition include a genetic predisposition, intense ultraviolet radiation exposure, and hormonal influences. Therapeutic interventions for melasma include a multimodality approach incorporating photoprotection agents, topical and oral skin lighteners, and resurfacing procedures. Given our expanding knowledge of the pathogenesis of melasma, new and effective treatments are expanding our therapeutic armamentarium. This article reviews new and emerging oral and topical treatments for melasma.
We have analyzed FUSE (905-1187 A) spectra of a sample of 16 local starburst galaxies. These galaxies cover almost three orders of magnitude in star-formation rates and over two orders of magnitude ...in stellar mass. Absorption features from the stars and interstellar medium are observed in all the spectra. The strongest interstellar absorption features are generally blue-shifted by ~ 50-300 km s-1, implying the almost ubiquitous presence of starburst-driven galactic winds in this sample. The outflow velocites increase with both the star-formation rate and the star-formation rate per unit stellar mass, consistent with a galactic wind, driven by the population of massive stars. We find outflowing coronal-phase gas (T ~105.5 K) detected via the O VI absorption line in nearly every galaxy. The O VI absorption-line profile is optically thin, is generally weak near the galaxy-systemic velocity, and has a higher mean outflow velocity than seen in the lower ionization lines. The relationship between the line width and column density for the O VI absorbing gas is in good agreement with expectations for radiatively cooling and outflowing gas. Such gas will be created in the interaction of the hot out-rushing wind seen in X-ray emission and cool dense ambient material. O VI emission is not generally detected in our sample, suggesting that radiative cooling by the coronal gas is not dynamically significant in draining energy from galactic winds. We find that the measured outflow velocities in the H I and H II phases of the interstellar gas in a given galaxy increase with the strength (equivalent width) of the absorption feature and not with the ionization potential of the species. The strong lines often have profiles consisting of a broad and optically-thick component centered near the galaxy-systemic velocity and weaker but highly blue-shifted absorption. This suggests that the outflowing gas with high velocity has a lower column density than the more quiescent gas, and can only be readily detected in the strongest absorption lines. From direct observations below the Lyman edge in the galaxy rest frame, we find no evidence of Lyman continuum radiation escaping from any of the galaxies in the sample. Moreover, the small escape fraction of light in the center of the strong C II absorption feature confirms the high opacity below the Lyman limit in the neutral ISM. The absolute fraction of escaping Lyman continuum photons is typically <1%. This sample provides a unique window on the global properties of local star-forming galaxies as observed in the far-UV and also provides a useful comparison sample for understanding spectra of high-redshift star-forming galaxies.
The safety of hydroquinone Nordlund, JJ; Grimes, PE; Ortonne, JP
Journal of the European Academy of Dermatology and Venereology,
August 2006, Letnik:
20, Številka:
7
Journal Article
Recenzirano
Hydroquinone is one of the most effective molecules for the treatment of hyperpigmentary disorders, with over 40 years of efficacy and safety data. Concerns over its safety have been raised because ...of the fact that it is a derivative of benzene and because of the long‐term side‐effects observed with cosmetic products containing high concentrations of hydroquinone. However, despite 40–50 years use of hydroquinone for medical conditions, there has not been a single documented case of either a cutaneous or internal malignancy associated with this drug. This article reviews the evidence for the safety of hydroquinone in the treatment of hyperpigmentation conditions.
Vitiligo is a relatively common disorder that is characterized by depigmented patches of skin. Multiple studies characterize the overwhelming psychological burden that is experienced by many patients ...around the globe. This review examines personal patient stories and the impacts of age, culture, sex, race, and ethnicity in relationship to altered self-esteem and quality of life in patients who live with vitiligo.
Summary
Background
There is no cure or firm clinical recommendations for the treatment of vitiligo. One of the main issues is the heterogeneity of outcome measures used in randomized controlled ...trials for vitiligo.
Objectives
To define successful repigmentation from the patients’ point of view and to propose how and when repigmentation should be evaluated in clinical trials in vitiligo.
Methods
We conducted three workshops with patients with vitiligo and their parents or caregivers. Workshop 1 was held at World Vitiligo Day (Detroit, MI), workshop 2 at the University of Texas Southwestern Medical Center and workshop 3 at the Vitiligo and Pigmentation Institute of Southern California, University of California.
Results
Seventy‐three participants were recruited. Consensus on the following questions was achieved unanimously: (i) the definition of ‘successful repigmentation’ was 80–100% of repigmentation of a target lesion and (ii) both an objective and a subjective scale to measure repigmentation should be used.
Conclusions
This was the largest patients’ outcomes workshop. We followed the guidance from the CSG‐COUSIN and the Vitiligo Global Issues Consensus Group. Our recommendations to use percentage of repigmentation quartiles (0–25%, 26–50%, 51–79%, 80–100%) and the Vitiligo Noticeability Scale are based on the best available current evidence. A limitation of the research is that the workshops were conducted only in the U.S.A., due to pre‐existing organisational support and the availability of funding.
What's already known about this topic?
There are no firm clinical recommendations for the treatment of vitiligo.
One of the main issues is the heterogeneity of outcome measures used in randomized controlled trials for vitiligo.
What does this study add?
Based on international consensus and the best available evidence, repigmentation should be assessed by measuring the percentage of repigmentation in quartiles (0–25%, 26–50%, 51–79%, 80–100%).
The cosmetic acceptability of results should also be assessed, for example using the Vitiligo Noticeability Scale.
Respond to this article
Linked Comment: Wolkerstorfer. Br J Dermatol 2019; 180:454–455.
Plain language summary available online
There is a perception that the standard of care is to repair hip fractures surgically within 24 hours of hospitalization. However, it is unclear whether this reduces mortality or morbidity.
We ...performed a retrospective study in consecutive hip fracture patients, aged 60 years or older, who underwent surgical repair. Patients with metastatic cancer, trauma, or a fracture occurring >48 hours before admission were excluded. The primary outcome was long-term (up to 18 years) mortality. Secondary outcomes included 30-day mortality and decubitus ulcers, serious bacterial infections, myocardial infarction, and thromboembolism. Analyses were adjusted for medical conditions; the comparison group comprised patients who underwent surgery for hip fracture repair within 24 to 48 hours because there were no patients with active medical problems who underwent surgery within 24 hours.
Of the 8383 patients, surgery was delayed for more than 24 hours in 2464 patients (29%) for medical reasons and in 1341 patients (16%) without active medical problems. Compared with those who underwent surgery 24 to 48 hours after admission to the hospital, patients who underwent surgery more than 96 hours after admission did not have increased long-term mortality (hazard ratio = 1.07; 95% confidence interval CI: 0.95 to 1.21), although the risk of decubitus ulcer was increased (odds ratio = 2.2; 95% CI: 1.6 to 3.1). There were no associations between time-to-surgery and the other secondary outcomes.
Time-to-surgery in hip fracture patients was not associated with short- or long-term mortality after adjusting for active medical problems. Other than increasing the risk of decubitus ulcer formation, waiting did not appear to affect patients' outcomes adversely.
We have analyzed observations with the Chandra X-Ray Observatory of the diffuse emission by hot gas in seven dwarf starburst galaxies, six edge-on starburst galaxies, and nine ultraluminous infrared ...galaxies. These systems cover ranges of similar to 10 super(4) in X-ray luminosity, and several thousand in star formation rate and K-band luminosity (a proxy for stellar mass). Despite this range in fundamental parameters, we find that the properties of the diffuse X-ray emission are very similar in all three classes of starburst galaxies. The spectrum of the diffuse emission is well fitted by thermal emission from gas with kT similar to 0.25-0.8 keV and with several times solar abundance ratios of alpha -elements to Fe. The ratio of the thermal X-ray to far-infrared luminosity is roughly constant, as is the characteristic surface brightness of the diffuse X-ray emission. The size of the diffuse X-ray source increases systematically with both far-infrared and K-band luminosity. All three classes show strong morphological relationships between the regions of hot gas probed by the diffuse X-ray emission and the warm gas probed by optical line emission. These findings suggest that the same physical mechanism is producing the diffuse X-ray emission in the three types of starbursts. These results are consistent with that mechanism being shocks driven by a galactic "superwind," which is powered by the kinetic energy collectively supplied by stellar winds and supernovae in the starburst.
It has been generally believed that the four main causes of melasma are pregnancy, hormonal contraception, family history and sun exposure; however, there are few published comprehensive studies that ...confirm these assertions. The Pigmentary Disorders Academy - an international group of experts in pigmentary disorders - designed and conducted a global survey of women to investigate the effect of these factors on onset and chronicity of melasma and the course of the disease in order to gain a better understanding of the causative factors associated with this disorder, with a particular focus on hormonal factors and UV exposure in females.
A 40-item largely self-administered questionnaire was completed by 324 women being treated for melasma in nine clinics worldwide.
The mean age at onset of melasma was 34 years, and 48% of subjects questioned had a family history of melasma (97% in a first-degree relative). Subjects with family history of melasma tended to have darker skin (90% types III-VI) compared to those without (77% types III-VI). The most common time of onset was after pregnancy (42%), often years after the last pregnancy, with 29% appearing pre-pregnancy and 26% during pregnancy. Onset was related to darker skin type post-pregnancy (P = 0.002). Risk of onset during pregnancy was associated with having spent more time outdoors (an extra 10 h per week spent working outside increases the odds of onset of melasma during pregnancy by approximately 27%) and an increased maternal age at pregnancy (increased by approximately 8% for each year of age at first pregnancy; P = 0.02). The odds of melasma occurring for the first time during a pregnancy were also increased with multiple pregnancies (twice the odds if 2 vs. 1 pregnancies, three times higher if 3 or more vs. 1 pregnancy). Of the women, 25% who had used hormonal contraception claimed that melasma appeared for the first time after its use, the rate being higher for those without vs. with a family history.
The results suggest that, whilst accepted causes do affect onset of melasma, a combination of these factors often triggers this disorder. These factors may provide further insights into how physicians can manage individual melasma cases, support recommendation of preventative measures and even anticipate treatment results and recurrence.
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