What causes alopecia areata?

The pathobiology of alopecia areata (AA), one of the most frequent autoimmune diseases and a major unsolved clinical problem, has intrigued dermatologists, hair biologists and immunologists for decades. Simultaneously, both affected patients and the physicians who take care of them are increasingly frustrated that there is still no fully satisfactory treatment. Much of this frustration results from the fact that the pathobiology of AA remains unclear, and no single AA pathogenesis concept can claim to be universally accepted. In fact, some investigators still harbour doubts whether this even is an autoimmune disease, and the relative importance of CD8(+) T cells, CD4(+) T cells and NKGD2(+) NK or NKT cells and the exact role of genetic factors in AA pathogenesis remain bones of contention. Also, is AA one disease, a spectrum of distinct disease entities or only a response pattern of normal hair follicles to immunologically mediated damage? During the past decade, substantial progress has been made in basic AA-related research, in the development of new models for translationally relevant AA research and in the identification of new therapeutic agents and targets for future AA management. This calls for a re-evaluation and public debate of currently prevalent AA pathobiology concepts. The present Controversies feature takes on this challenge, hoping to attract more skin biologists, immunologists and professional autoimmunity experts to this biologically fascinating and clinically important model disease.

The precise determination of the window of implantation significantly improves ART outcomes.

The human endometrium is receptive to the embryo for a specific period of time known as the window of implantation (WOI). During this period, the endometrium shows a specific gene expression profile suitable for endometrial function evaluation. ER Map is a molecular tool able to accurately predict endometrial receptivity status by transcriptomic analysis. In this retrospective study, including 2256 subfertile patients undergoing ART treatment, the clinical value of precise WOI determination is studied in detail. Results obtained when single embryo transfers (sET) were scheduled either within the WOI timeframe as established by ER Map, or deviating from this WOI, are assessed and compared. Data obtained showed that 34.18% (771/2256) of patients had a displaced WOI. Analysis of ART outcomes showed significantly higher pregnancy rates in transfers scheduled within the WOI predicted compared to transfers that deviated more than 12h from this WOI (44.35% vs 23.08%, p < 0.001). The deviation from the WOI had also an impact on the progression of pregnancy, with a significant increase in pregnancy loss (~ twofold) observed in transfers that deviated more than 12h from the WOI predicted. These results indicate that the precise determination of the WOI and personalised embryo transfer can significantly improve clinical outcomes.

Hair loss in women.

Hair loss in women is a very common clinical complaint, and is usually associated with severe emotional distress. In this article, the authors review the most common clinical causes of hair loss in women, and emphasize the role of hormonal changes in the regulation of hair loss and hair growth.

Tay bridge and extracellular-regulated kinase activity are required for motoneuron function in the Drosophila neural system.

Extracellular regulated kinase (Erk) activity is required during neural development for the specification of cell fates in neuroblasts and neuronal lineages, and also regulates several aspects of the activity and survival of mature neurons. The activation of Erk is regulated at multiple levels by kinases and phosphatases that alter its phosphorylation state and by other proteins that regulate its subcellular localization. Here, we find that tay bridge (tay), a negative regulator of Erk in Drosophila imaginal discs, is required in the motoneurons to regulate the number and size of neuromuscular synapses in these cells. The expression of Tay is maximal in motoneurons with low levels of activated ERK, suggesting that Tay modulates the activity of Erk in these cells. We also found that loss of tay expression and increased Erk activity specifically in the motoneurons cause a reversible decrease in walking speed. Impaired motoneurons activity may be caused by alterations in the functionality and number of synaptic boutons developing at the neuromuscular junction in tay mutants.

Fruit development in Capsicum annuum: changes in capsaicin, lignin, free phenolics, and peroxidase patterns.

Pepper fruits, of Capsicum annuum cv. Padron, undergo changes in content of capsaicinoids, lignin, and free phenolics during the maturation process. Although capsaicinoids increase with development, the maximal levels of free phenolics and lignin are observed during the early stages of development. A decrease of peroxidase activity was observed during maturation, and this was related with a decrease in other physiological parameters studied, namely chlorophylls and pH. Subcellular fractionation studies reveal that most peroxidase activity is localized in the soluble fraction throughout development. The changes in the peroxidase activity were accompanied by changes in the different isoenzymes. Acidic isoenzymes increased whereas the basic isoenzymes decreased over the same period, and the changes in these isoenzymes were related with capsaicin metabolism.

A double-blind taste comparison of pediatric antibiotic suspensions.

This study examined the palatability of 22 antimicrobial suspensions by using five independent categories for scoring: appearance, smell, texture, taste, and aftertaste. The likely overall influence on patient compliance was also evaluated. Drugs were compared within their respective classes. The only antibiotics judged to be so unpalatable as to potentially jeopardize compliance were dicloxacillin, oxacillin, erythromycin/sulfisoxazole, and cefpodoxime. Among the penicillins, amoxicillin and ampicillin were preferred. Azithromycin was slightly superior to erythromycin and clarithromycin within the macrolide class. Many cephalosporins were ranked quite high, the best being loracarbef, cefadroxyl, cefprozil, and cefixime.

Prednisolone plus albuterol versus albuterol alone in mild to moderate bronchiolitis.

To evaluate combination therapy of mild to moderate bronchiolitis with bronchiodilators and corticosteroids, we treated 51 young children with first-time wheezing and symptoms of respiratory tract infection with albuterol plus either prednisolone or placebo for 5 days. Disease severity was scored on days 0, 2, 3, and 6. On day 2, prednisolone resulted in significantly lower scores (2.7 +/- 1.4 vs. 4.0 +/- 1.5 in all patients evaluated, p < 0.05) than placebo, whereas there was no detectable difference on day 6, suggesting that addition of prednisolone to albuterol transiently accelerates recovery from bronchiolitis. The clinical significance of this effect needs to be evaluated in further studies.

One-year clinical performance of a resin-modified glass ionomer and a resin composite restorative material in unprepared Class V restorations.

This study evaluated the clinical performance and appearance of a resin-modified glass ionomer and a resin composite over one year. Thirty-seven pairs of restorations of Fuji II LC and Z250/Single Bond were placed in caries-free cervical erosion/abfraction lesions without tooth preparation. Restorations were clinically evaluated at baseline and 6 and 12 months, using modified Ryge/USPHS criteria. No significant difference (p>0.05) was observed in performance of both materials, although retention of the Z250 restorations was below the minimum specified in the ADA Acceptance Program for Dentin and Enamel Adhesives. Little difference in the restorations' appearance was observed.

Penicillin and multiply antibiotic-resistant Streptococcus pneumoniae.

The emergence of multiply antibiotic-resistant pneumococci has become a worldwide problem. To document resistance among clinical or surveillance isolates, there are a number of excellent laboratory techniques and these can be used to guide clinical decisions. All pneumococci are currently susceptible to vancomycin, an important consideration in managing patients with serious, or life threatening infection.

[European immigration and social mobility in urban centers of Latin America (1880-1920)]. / Inmigracion europea y movilidad social en los centros urbanos de America Latina (1880-1920).

PIP: The authors provide a historical overview of the impact of European immigration on social structures in Latin America. The focus is on movements to Argentina and Brazil, with a lesser emphasis on Chile and Uruguay. Social mobility of foreigners is compared with that of natives. The relationship between migration and trends in urbanization and industrialization is analyzed, and factors such as economic conditions and political stability in the receiving countries, migrant access to land ownership, discrimination against migrants, length of stay, and reasons for leaving are examined.^ieng

Methicillin-resistant Staphylococcus aureus hepatic abscess in a patient with sickle-cell disease.

We report a case of a 16-year-old female patient with sickle-cell disease with a liver abscess secondary to methicillin-resistant Staphylococcus aureus (MRSA). She had initially presented with jaundice and abdominal pain and subsequently underwent endoscopic retrograde cholangio-pancreaticography followed by laparoscopic cholecystectomy for removal of gallstones. However, post-cholecystectomy she presented with generalized abdominal pain and computed tomography scan of the abdomen revealed a liver abscess. A pigtail catheter was inserted into the abscess and culture of the aspirate yielded MRSA (susceptibility pattern of the organism was compatible with community-acquired MRSA). She was treated with intravenous clindamycin for 6 weeks with complete resolution of the abscess.

The Hox gene Abdominal-B antagonizes appendage development in the genital disc of Drosophila.

In Drosophila, the Hox gene Abdominal-B is required to specify the posterior abdomen and the genitalia. Homologues of Abdominal-B in other species are also needed to determine the posterior part of the body. We have studied the function of Abdominal-B in the formation of Drosophila genitalia, and show here that absence of Abdominal-B in the genital disc of Drosophila transforms male and female genitalia into leg or, less frequently, into antenna. These transformations are accompanied by the ectopic expression of genes such as Distal-less or dachshund, which are normally required in these appendages. The extent of wild-type and ectopic Distal-less expression depends on the antagonistic activities of the Abdominal-B gene, as a repressor, and of the decapentaplegic and wingless genes as activators. Absence of Abdominal-B also changes the expression of Homothorax, a Hox gene co-factor. Our results suggest that Abdominal-B forms genitalia by modifying an underlying positional information and repressing appendage development. We propose that the genital primordia should be subdivided into two regions, one of them competent to be transformed into an appendage in the absence of Abdominal-B.

HIV drug and sex risk behaviors among American Indian and Alaska Native drug users: gender and site differences.

Little research has been conducted on HIV drug and sex risk behaviors of American Indians and Alaska Natives who use illicit drugs. Data from studies conducted with other ethnic groups indicates differences in HIV drug and sex risk behaviors of men and women and between drug users from different regions, cities, communities, and intervention sites. This study examines whether these differences in HIV drug and sex risk behaviors also exist for American Indians and Alaska Natives. Results indicate that risk behaviors of American Indians and Alaska Natives do differ like that of other ethnic groups. In particular American Indian and Alaska Native women reported engaging in significantly greater levels of some drug and many sex risk behaviors than men. Significant differences between intervention sites were also found for intensity of use of various drugs and for some HIV drug risk behaviors.

HIV sex and drug risk behavior and behavior change in a national sample of injection drug and crack cocaine using women.

This paper describes HIV sex and drug risk behavior and behavior change of injection drug and crack cocaine using women enrolled in a national multi-site Cooperative Agreement program. Baseline data on the 1,403 women who were randomly assigned to a two session intervention that was standardized across sites indicate that sex and drug risk behavior for becoming infected with HIV was considerable. Six-month post intervention follow-up data for the same sample of women show that significant reductions in sex and drug risk behavior were observed for the entire sample of women for the risk variables under study. Significant reductions were also demonstrated for various sub-groups of women enrolled in the study on most of the sex and drug risk variables. Given these findings, it appears that the standard intervention was effective in assisting drug using women reduce their behaviors that put them at risk of becoming infected with HIV. Further research in needed on the development and evaluation of HIV interventions that target specific risk behaviors and various HIV risk behavior profiles of women.