Androgenic alopecia; the risk–benefit ratio of Finasteride

Finasteride is currently approved and largely used as a therapeutic option for androgenetic alopecia. Apparently a safe drug and effective at the onset of its application, several concerns have since appeared over the years regarding the frequency and magnitude of finasteride adverse effects, which in some cases appear irreversible even after drug termination. This paper discusses the use of finasteride for androgenic alopecia from two distinct perspectives. On the one hand, androgenic alopecia is a condition that especially affects a person’s self-image and esteem, aspects that are subjectively-constructed and thus relative and changeable. On the other hand, this condition involves a multifactorial etiology, with androgens being only partly responsible. Because androgens have important and unique physiological roles within the body, any procedure that results in androgenic suppression should be advised with caution. Furthermore, adverse effects induced by finasteride are neither fully documented nor easily treated. Finally, as alternative therapeutic approaches (such as topical finasteride) become available, the oral administration of finasteride for androgenic alopecia should, in our opinion, be reevaluated. Due to such concerns, a detailed and informed discussion should take place with patients considering therapy with finasteride for androgenic alopecia

Astrophysical S factor for the radiative capture 12N(p,gamma)13O determined from the 14N(12N,13O)13C proton transfer reaction

The cross section of the radiative proton capture reaction on the drip line nucleus 12N was investigated using the Asymptotic Normalization Coefficient (ANC) method. We have used the 14N(12N,13O)13C proton transfer reaction at 12 MeV/nucleon to extract the ANC for 13O -> 12N + p and calculate from it the direct component of the astrophysical S factor of the 12N(p,gamma)13O reaction. The optical potentials used and the DWBA analysis of the proton transfer reaction are discussed. For the entrance channel, the optical potential was inferred from an elastic scattering measurement carried out at the same time with the transfer measurement. From the transfer, we determined the square of the ANC, C^2(13Og.s.) = 2.53 +/- 0.30 fm-1, and hence a value of 0.33(4) keVb was obtained for the direct astrophysical S factor at zero energy. Constructive interference at low energies between the direct and resonant captures leads to an enhancement of Stotal(0) = 0.42(5) keVb. The 12N(p,gamma)13O reaction was investigated in relation to the evolution of hydrogen-rich massive Population III stars, for the role that it may play in the hot pp-chain nuclear burning processes, possibly occurring in such objects.Comment: 15 pages, 10 figures, 3 tables submitted to Phys. Rev.

Androgenic alopecia; the risk–benefit ratio of Finasteride

Finasteride is currently approved and largely used as a therapeutic option for androgenetic alopecia. Apparently a safe drug and effective at the onset of its application, several concerns have since appeared over the years regarding the frequency and magnitude of finasteride adverse effects, which in some cases appear irreversible even after drug termination. This paper discusses the use of finasteride for androgenic alopecia from two distinct perspectives. On the one hand, androgenic alopecia is a condition that especially affects a person’s self-image and esteem, aspects that are subjectively-constructed and thus relative and changeable. On the other hand, this condition involves a multifactorial etiology, with androgens being only partly responsible. Because androgens have important and unique physiological roles within the body, any procedure that results in androgenic suppression should be advised with caution. Furthermore, adverse effects induced by finasteride are neither fully documented nor easily treated. Finally, as alternative therapeutic approaches (such as topical finasteride) become available, the oral administration of finasteride for androgenic alopecia should, in our opinion, be reevaluated. Due to such concerns, a detailed and informed discussion should take place with patients considering therapy with finasteride for androgenic alopecia

Mechanical Stress Induces Biotic and Abiotic Stress Responses via a Novel cis-Element

Plants are continuously exposed to a myriad of abiotic and biotic stresses. However, the molecular mechanisms by which these stress signals are perceived and transduced are poorly understood. To begin to identify primary stress signal transduction components, we have focused on genes that respond rapidly (within 5 min) to stress signals. Because it has been hypothesized that detection of physical stress is a mechanism common to mounting a response against a broad range of environmental stresses, we have utilized mechanical wounding as the stress stimulus and performed whole genome microarray analysis of Arabidopsis thaliana leaf tissue. This led to the identification of a number of rapid wound responsive (RWR) genes. Comparison of RWR genes with published abiotic and biotic stress microarray datasets demonstrates a large overlap across a wide range of environmental stresses. Interestingly, RWR genes also exhibit a striking level and pattern of circadian regulation, with induced and repressed genes displaying antiphasic rhythms. Using bioinformatic analysis, we identified a novel motif overrepresented in the promoters of RWR genes, herein designated as the Rapid Stress Response Element (RSRE). We demonstrate in transgenic plants that multimerized RSREs are sufficient to confer a rapid response to both biotic and abiotic stresses in vivo, thereby establishing the functional involvement of this motif in primary transcriptional stress responses. Collectively, our data provide evidence for a novel cis-element that is distributed across the promoters of an array of diverse stress-responsive genes, poised to respond immediately and coordinately to stress signals. This structure suggests that plants may have a transcriptional network resembling the general stress signaling pathway in yeast and that the RSRE element may provide the key to this coordinate regulation

Multicenter analysis of sputum microbiota in tuberculosis patients.

The impact of tuberculosis and of anti-tuberculosis therapy on composition and modification of human lung microbiota has been the object of several investigations. However, no clear outcome has been presented so far and the relationship between M. tuberculosis pulmonary infection and the resident lung microbiota remains vague. In this work we describe the results obtained from a multicenter study of the microbiota of sputum samples from patients with tuberculosis or unrelated lung diseases and healthy donors recruited in Switzerland, Italy and Bangladesh, with the ultimate goal of discovering a microbiota-based biomarker associated with tuberculosis. Bacterial 16S rDNA amplification, high-throughput sequencing and extensive bioinformatic analyses revealed patient-specific flora and high variability in taxon abundance. No common signature could be identified among the individuals enrolled except for minor differences which were not consistent among the different geographical settings. Moreover, anti-tuberculosis therapy did not cause any important variation in microbiota diversity, thus precluding its exploitation as a biomarker for the follow up of tuberculosis patients undergoing treatment

Structure around the island of inversion with single-neutron knockout reactions at GANIL

CERN-Proceedings-2010-001 available at http://www.fluka.org/Varenna2009/procmat.htmInternational audienceThe nuclear structure of the 31Mg nucleus has been studied with the singleneutron knockout reaction. We report on the preliminary results of an experiment performed with the EXOGAM array coupled, for the first time, to the SPEG spectrometer at GANIL.We present a provisional result for the inclusive single-neutron knockout cross section of σinc= 90(5) mb. Preliminary exclusive cross sections for the measured bound states, including the ground state, are also presented. Finally, preliminary longitudinal momentum distributions for the ground state and first excited state are also shown. These results are compared to Monte Carlo Shell-Model calculations in the sd-pf region

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification