Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Encoding the Object Position for Assessment of Short Term Spatial Memory in Horses (Equus caballus)

In this study, the detour problem was combined with the classic delayed-response task to investigate equine short-term spatial memory. Test subjects were eight female horses, divided into two groups (A and B) of four subjects each. The motivating object was made to move and disappear behind one oftwo identical obstacles in a two-point-choice apparatus. After a 10 s (Group A) or 30 s (Group B) delay the animal was released to seek the object. Both groups made more correct (14.8 ± 1.3 forGroup A and 13.5 ± 3.1 for Group B, mean ± SD) than incorrect choices (5.3 ± 1.3 for Group A and6.5 ± 3.1 for Group B, mean ± SD) and the performance of each group was significantly above chance level (z = 4.14,  p = 0.000, for Group A and z = 3.02, p = 0.002, for Group B). Therefore, tested animals were able to recover the object by approaching the correct obstacle after 10 s or 30 s delays, showing that they had encoded and recovered from memory the existence of the target object and its location

The analysis of mutant alleles of different strength reveals multiple functions of Topoisomerase 2 in regulation of Drosophila chromosome structure

Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males are poorly condensed and exhibit dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome condensation is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on slight differences in Topo II concentration and/or activity

Distribution of human papillomavirus types in the anogenital tract of females and males.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection in both men and women, but there are limited data comparing the prevalence of HPV infection between genders and in different anogenital sites. This cross-sectional analysis describes the distribution of HPV types in the genital tract of 3,410 consecutive females and 1,033 males undergoing voluntary screening for HPV and referred to a single institution. The relationship between specific HPV types and the presence of anogenital lesions was examined. In both females and males, the overall prevalence of HPV infection was about 40%. A wide variety of HPV types was identified, but the prevalence of different types was remarkably similar in the two genders, even when considering different anatomical sites. HPV-6 was the most frequent (prevalence 13%) type in all anogenital sites in men followed by HPV-16 (7%), while HPV-16 was the most common type in women (about 6%), either in the cervix, vagina, or vulva, followed by HPV-6. In addition to HPV-16, HPV-58, HPV-33, HPV-31, and HPV-56 were the carcinogenic types detected most commonly and were significantly associated with high-grade squamous intraepithelial cervical lesions, while HPV-53 and HPV-66 were the most common among possibly carcinogenic types. In both genders, anogenital warts were associated with HPV-6 and HPV-11 infection, and, less frequently, with other types, like HPV-54, HPV-62, and HPV-66. These results show that genital HPV infection involves numerous HPV types, which have similar distribution patterns in females and males and in different anogenital anatomical sites

The site-specific CABs observed in <i>Top2^suo1/Top2^suo3</i> mutant brains are generated by bridge severing during anaphase.

<p>(A) Examples of wild type and <i>Top2</i> mutant anaphase figures with bridges and lagging acentric fragments. Scale Bar, 5 µm. (B) Examples of aberrations generated by chromosome breaks that occurred during the anaphase of the previous cells cycle. Panels 1–3 show metaphases carrying a broken third chromosome without the corresponding acentric fragment (1), a complete chromosome complement with an extra acentric fragment (2), and a complete isochromatid deletion with a breakpoint in region h47 of 3L heterochromatin; note that at one of the ends of the acentric fragments shown in panels 2 and 3 the sister chromatids are closely apposed as occurs in the heterochromatic regions. The aberrant metaphases shown in panels 1–3 are likely to be generated by anaphase events leading to the G1 configurations depicted in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004739#pgen-1004739-g005" target="_blank">Figure 5</a>. Panels 4–6 show Y chromosome aberrations resulting from duplication of the broken G1 Ys depicted in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004739#pgen-1004739-g005" target="_blank">Figure 5</a>. The remaining panels show chromosome exchanges between the Y chromosome and the 3L heterochromatin generated by interactions between broken G1 chromosomes, as illustrated in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004739#pgen-1004739-g005" target="_blank">Figure 5</a>. For example the Y-3 dicentric chromosome shown in panel (1–4) is generated by fusion of the broken ends of the G1 chromosomes in the 1 and 4 “cells” of <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004739#pgen-1004739-g004" target="_blank">Figure 4</a>. In all panels, arrowheads and arrows point to centric and acentric chromosome fragments, respectively; the asterisks indicate dicentric and translocation chromosomes involving the Y and 3L heterochromatin. The small arrows in panels (2–6) and (3–5) point to an additional break in 3L heterochromatin and an extra Y fragment, respectively. Scale Bar, 5 µm. (C) Distribution of 77 Y chromosome breakpoints and 23 third chromosome breakpoints of selected dicentrics and translocations. The heterochromatin maps are from Gatti and Pimpinelli <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004739#pgen.1004739-Gatti2" target="_blank">[60]</a>. The numbers above and below the maps indicate the different heterochromatin regions and the numbers of breakpoints found in these regions, respectively.</p

Top2 localization in wild type and <i>Top2</i> mutant larval brain cells.

<p>(A) Western blotting of brain extracts showing that the anti-Top2 antibody recognizes a 170 kDa band in control cells; this band is reduced in <i>Top2^suo1/Top2^suo1, Top2^suo1/Df</i> and <i>Top2^suo1/Top2^suo3</i> mutants and undetectable in <i>Top2^suo3/Df</i>. Tubulin was used as loading control. (B) Quantification of the relative intensities of the bands (± SD) from 4 different Western blotting experiments; the columns represent the relative ratios between the Top2 and the tubulin band intensities determined by densitometric analysis, with the wild type ratio set to 1. (C–E) Wild type male late prophase (C/C′), and female (D/D′) and male (E/E′) metaphases stained with the anti-Top2 antibody; note the discontinuous staining and the absence of Top2 accumulation at the kinetochores in D′ (arrowheads) and C′. In E′, the discontinuous staining is not visible but the centromeric regions of the major autosomes are clearly less stained than the other chromosomal regions. In <i>Top2^suo1/Df</i> mutant brains (F/F′) and <i>Top2^suo1/Top2^suo3</i> (G/G′) chromosome immunostaining is reduced compared to wild type. Scale Bar, 5 µm.</p

The X chromosome of polytene nuclei from <i>Top2</i> mutant males binds Mof.

<p>Note that Mof specifically decorates the X chromosome of both wild type and <i>Top2^suo1/Top2^suo3</i> males; wt, wild type.</p