Pattern of gonad maturation and the question of semelparity in the paedomorphic goby Aphia minuta

At variance with previous reports, the paedomorphic goby Aphia minuta does not show semelparity, but abbreviate iteroparity like other small Mediterranean gobiid species. In spring, the mature ovary contains several batches of eggs at different stages of vitellogenesis. This indicates that the breeding season of A. minuta is quite long and that spawning takes place at least twice during its short lifespan, involving in each ovulatory wave different batches of oocytes which undergo vitellogenesis at different times. These observations agree with the testicular cycle data. In males, which in spring exhibit active spermiation coinciding with deposition of the first batch of oocytes, spermatogonial mitosis also resumes, eventually resulting in the production of new sperm in summer.     

Biological traits of a sub-Antarctic nototheniid,Patagonotothen ramsayi,from the Burdwood Bank

The rock cod Patagonotothen ramsayi (Regan 1913) is the most abundant species of the genus Patagonotothen, occurring along the Patagonian shelf. It plays an important role in the demersal food web both as prey and predator, showing an increasing importance for the local finfish and squid trawl fisheries. Age structure and the reproductive traits were investigated from the population inhabiting the eastern shelf of Burdwood Bank, which represents the southernmost area of its geographical distribution. Adult specimens of P. ramsayi were collected during bottom trawling carried out in the austral summer. The specimens were aged by otolith readings, and their reproductive characteristics were assessed by macroscopical and histological analyses. Age was similar between sexes, ranging from 4 to 7 and from 4 to 8 years in males and females of comparable size, respectively. GSI was relatively low in females (<1.5 %), as fish were sampled far from the reported spawning season (June–August). Females were all in the early developing stage (III) on the macroscopic maturity scale, with the most advanced oocytes being in early vitellogenesis. The oocyte size distribution was bi-modal, with two partially overlapping modes consisting of oocytes of a maximum size of 0.66 mm. A few large atretic oocytes (diameter > 1 mm) were found in three females. Absolute fecundity ranged from approximately 30 to 120 thousands of eggs. No relationship was found between female size and fecundity, probably due to the relatively narrow range of the investigated fish sizes. Males were in the spent (VII) or resting (II) stages.     

Psoriasis verrugosa en un hombre con antecedentes de psoriasis en placa,reporte de caso y revisión de la literatura

Verrucous psoriasis is an atypical and rare variant of psoriasis with few cases reported in the literature. It is characterized by the presence of symmetric hypertrophic and verrucous plaques on the limbs and trunk.We present the case of a 63-year-old male patient with a history of vulgar psoriasis for 20 years who was receiving treatment with topical steroids and had developed a verrucous plaque in the distal third of the posterior aspect of the leg 10 years before. We conducted a biopsy of the lesion to confirm or discard the diagnostic impression of squamous cell carcinoma (verrucous). The histopathological study showed changes compatible with verrucous psoriasis ruling out the presence of malignancy.     

Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses

Background

Myelofibrosis (MF) is associated with a variety of burdensome symptoms and reduced survival compared with age-/sex-matched controls. This analysis evaluated the long-term survival benefit with ruxolitinib, a Janus kinase (JAK)1/JAK2 inhibitor, in patients with intermediate-2 (int-2) or high-risk MF.

Methods

This was an exploratory analysis of 5-year data pooled from the phase 3 COMFORT-I and -II trials. In both trials, patients could cross over to ruxolitinib from the control group (COMFORT-I, placebo; COMFORT-II, best available therapy). All continuing patients in the control groups crossed over to ruxolitinib by the 3-year follow-up. Overall survival (OS; a secondary endpoint in both trials) was evaluated using pooled intent-to-treat data from patients randomized to ruxolitinib or the control groups. OS was also evaluated in subgroups stratified by baseline anemia and transfusion status at week 24.

Results

A total of 528 patients were included in this analysis; 301 were originally randomized to ruxolitinib (COMFORT-I, n?=?155; COMFORT-II, n?=?146) and 227 to control (n?=?154 and n?=?73, respectively). The risk of death was reduced by 30% among patients randomized to ruxolitinib compared with patients in the control group (median OS, 5.3 vs 3.8 years, respectively; hazard ratio [HR], 0.70 [95% CI, 0.54–0.91]; P?=?0.0065). After correcting for crossover using a rank-preserving structural failure time (RPSFT) method, the OS advantage was more pronounced for patients who were originally randomized to ruxolitinib compared with patients who crossed over from control to ruxolitinib (median OS, 5.3 vs 2.3 years; HR [ruxolitinib vs RPSFT], 0.35 [95% CI, 0.23–0.59]). An analysis of OS censoring patients at the time of crossover also demonstrated that ruxolitinib prolonged OS compared with control (median OS, 5.3 vs 2.4 years; HR [ruxolitinib vs censored at crossover], 0.53 [95% CI, 0.36–0.78]; P?=?0.0013). The survival benefit with ruxolitinib was observed irrespective of baseline anemia status or transfusion requirements at week 24.

Conclusions

These findings support ruxolitinib treatment for patients with int-2 or high-risk MF, regardless of anemia or transfusion status. Further analyses will be important for exploring ruxolitinib earlier in the disease course to assess the effect on the natural history of MF.

Trial registration

ClinicalTrials.gov identifiers, NCT00952289 and NCT00934544.

     

Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

Background

Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease.

Aim

To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease.

Methods

We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces.

Results

We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium.

Conclusion

The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease.     

Childbirth Moderates the Genetic and Environmental Influences on BMI in Adult Twins

We report a study of the moderating role that the number of childbirths has on the genetic and environmental influences on BMI variation. We used a classical twin design with a sample of 704 adult female twins (334 monozygotic and 370 dizygotic). A gene–environment interaction (G × E) model was applied to estimate the moderating effects of childbearing. Results show that age and number of children exert a significant positive main effect on BMI. Furthermore, we found significant moderating effects of childbearing, with a larger number of children associated with an increased sensitivity to environmental factors.     

The diagnostic approach to early Alzheimer's disease. What are we talking about? Conceptual considerations

Progress in knowledge of the physiopathology of Alzheimer's disease over the last few decades has allowed much earlier diagnosis, even before the onset of clinical symptoms. Although the use of biomarkers is still far from being widespread and cannot be recommended outside research settings, their potential use has led to a review of the diagnostic criteria employed in the last few years. Among other criteria, asymptomatic and prodromal phases have been definitively incorporated into the spectrum of the disease and have been redefined. In future, the possibility of an earlier and more accurate diagnosis will allow the application of treatments acting in these phases, delaying progression to more advanced stages or even halting the disease before clinical manifestations develop. Currently, such treatments are still far from being a reality and interest in biomarkers centers on research since their detection could allow standardization of the samples used in clinical trials and exclusion of individuals showing signs of prodromal disease but who will never develop the disease.