Fractional CO2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects

The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 70% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO2 laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects

ARTROPLASTIA ACETÁBULO-FEMORAL EM CÃES COM PERICÁRDIO BOVINO CONSERVADO

A articulação acetábulo-femoral é a mais acometida pela luxação traumática em cães e gatos, representando 50% de todas as luxações. Apesar da literatura médica veterinária descrever inúmeras técnicas para a redução da luxação, são freqüentes as recidivas pós-operatórias e as complicações como fibrose restritiva pós-ostectomia do colo femoral. Considerando-se o elevado número de cães com luxações acetábulo-femorais e as complicações pós-cirúrgicas em potencial, este experimento visa estabilizar a articulação acetábulo-femoral com a utilização de membrana biológica. Na primeira etapa do experimento, 10 cães sem raça definida, com peso médio de 10 kg foram submetidos à artrotomia e ressecção do ligamento redondo, iatrogenizando-se assim a luxação acetábulofemoral direita. Quinze dias após procedeu-se a artroplastia, reconstituindo-se o ligamento redondo com um segmento de pericárdio bovino conservado em glicerina 98%. Para estabilizar a articulação foram feitos dois orifícios, na posição de 10 e 1 horas, comunicando a epífise, colo e cabeça femorais ao acetábulo. Na seqüência dois segmentos de pericárdio medindo 10cm de comprimento por 1cm de largura foram inseridos nos trajetos, sendo que suas extremidades foram fixadas às fáscias musculares e periósteo através de suturas interrompidas simples com fio de polipropileno n º 2-0. No período pós-operatório além da administração de analgésicos, antibióticos e dos cuidados com a ferida cirúrgica, o membro pélvico direito foi imobilizado com bandagem de Ehmer durante 14 dias. Após a remoção da bandagem constatou-se atrofia por desuso temporária, pois o paciente deambulava normalmente após 2 semanas de fisioterapia. Nos exames radiográficos realizados nos 15º e 45º dias não observou-se luxação acetábulo-femoral, podendo-se concluir que a artroplastia com membrana biológica é uma técnica que pode ser indicada para reduzir luxação acetábulo-femoral, em cães. Coxofemoral arthroplasty in dogs with conserved bovine pericardium in glycerin 98% Abstract The coxofemoral is the more affected articulation by traumatic luxation in dogs and cats, representing about 50% of all the luxations cases in these species. In spite of de veterinary medical literature describe countless of techniques for the reduction of luxatio, are very frequent postoperative recurrence and complications as restrictive fibrosis after ostectomy of the femur head.Considering the high number of dogs with coxofemoral luxations and the potential post-surgical complications, this experiment aims to use a technique able to stabilize the coxofemural articulation with the use of biological membrane. In the first stage of the experiment, 10 dogs without defined race, with a medium weight of 10 kg were submitted to incision at the right joint followed by resection of the round ligament, promoting, this way, an acetabulo-femoral luxation. Fifteen days after, arthroplasty was performed by the reconstitution of the round ligament with a segment of bovine pericardium preserved in glycerin 98%. In order stabilize the articulation, two holes have been performed in the position of 10 and 1 hours, communicatiing the epiphysis, neck and head of the femur to the acetabulum. In the sequence, two pericardium segments, measuring 10 cm length by 1 cm width, were inserted in the stretch, and the extremities fastened to the muscuylar fascias and periosteum by means of simple interrupted sutures with n° 2 polypropilene thread. In the postoperative period, besides the administration of analgesic, antibiotics and the cares with the surgical wound, the right pelvic member was immobilized with Ehner´s bandage for 14 days. The occurrence of temporary unuse atrophies were observed after the removal of the bandage, the patient strolling back normally after 2 weeks of physiotherapy. Considering that no signal of residual luxation was observed in those patients at the radiographic control carried out at l5 and 45 days after the operation, it can be concluded that this technique can be indicated to reduce coxofemoral luxation in dogs

Pressure-and temperature induced phase transitions, piezochromism, NLC behaviour and pressure controlled Jahn–Teller switching in a Cu-based framework

In situ single-crystal diffraction and spectroscopic techniques have been used to study a previously unreported Cu-framework bis[1-(4-pyridyl)butane-1,3-dione]copper(II) (CuPyr-I). CuPyr-I was found to exhibit high-pressure and low-temperature phase transitions, piezochromism, negative linear compressibility, and a pressure induced Jahn?Teller switch, where the switching pressure was hydrostatic media dependent.The support by the Spanish Ministerio de Econom´ıa, Industria y Competitividad (PGC2018-101464-B-I00), and INNVAL 18/28 is also acknowledged

Introduction of Probiotic-Based Sanitation in the Emergency Ward of a Children's Hospital During the COVID-19 Pandemic

Background: Antimicrobial resistance (AMR) represents a major threat to public health, especially in the hospital environment, and the massive use of disinfectants to prevent COVID-19 transmission might intensify this risk, possibly leading to future AMR pandemics. However, the control of microbial contamination is crucial in hospitals, since hospital microbiomes can cause healthcare-associated infections (HAIs), which are particularly frequent and severe in pediatric wards due to children having high susceptibility. Aim: We have previously reported that probiotic-based sanitation (PCHS) could stably decrease pathogens and their AMR in the hospital environment, reduce associated HAIs in adult hospitals, and inactivate enveloped viruses. Here, we aimed to test the effect of PCHS in the emergency room (ER) of a children's hospital during the COVID-19 pandemic. Methods: Conventional chemical disinfection was replaced by PCHS for 2 months during routine ER sanitation; the level of environmental bioburden was characterized before and at 2, 4, and 9 weeks after the introduction of PCHS. Microbial contamination was monitored simultaneously by conventional culture-based CFU count and molecular assays, including 16S rRNA NGS for bacteriome characterization and microarrays for the assessment of the resistome of the contaminating population. The presence of SARS-CoV-2 was also monitored by PCR. Results and conclusions: PCHS usage was associated with a stable 80% decrease in surface pathogens compared to levels detected for chemical disinfection (P < 0.01), accompanied by an up to 2 log decrease in resistance genes (Pc < 0.01). The effects were reversed when reintroducing chemical disinfection, which counteracted the action of the PCHS. SARS-CoV-2 was not detectable in both the pre-PCHS and PCHS periods. As the control of microbial contamination is a major issue, especially during pandemic emergencies, collected data suggest that PCHS may be successfully used to control virus spread without simultaneous worsening of the AMR concern

Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers

Malignant pleural mesothelioma (MPM), a fatal cancer, is an occupational disease mostly affecting workers ex-exposed to asbestos fibers. The asbestos, a cancerogenic mineral of different chemical composition, was widely employed in western Countries in industrial manufactures of different types. MPM may arise after a long latency period, up to five decades. MPM is resistant to conventional chemo- and radio-therapies. Altogether, these data indicate that the identification of new and specific markers are of a paramount importance for an early diagnosis and treatment of MPM. In recent years, microRNAs expression was found dysregulated in patients, both in cancer cells and sera, affected by tumors of different histotypes, including MPM. Cell and circulanting microRNAs, found to be dysregulated in this neoplasia, were proposed as new biomarkers. It has been reported that circulating microRNAs are stable in biological fluids and could be employed as potential MPM biomarkers. In this investigation, circulating microRNAs (miR) from serum samples of MPM patients and workers ex-exposed to asbestos fibers (WEA) and healthy subjects (HS) were comparatively analyzed by microarray and RT-qPCR technologies. Our results allowed (i) to select MiR-3665, an endogenous stable microRNA, as the internal control to quantify in our analyses circulating miRNAs; to detect (ii) miR-197-3p, miR-1281 and miR 32-3p up-regulated in MPM compared to HS; (iii) miR-197-3p and miR-32-3p up-regulated in MPM compared to WEA; (iv) miR-1281 up-regulated in both MPM and WEA compared to HS. In conclusion, three circulating up-regulated microRNAs, i.e. miR-197-3p, miR-1281 and miR-32-3p are proposed as potential new MPM biomarker

A New Phenotype in Candida-Epithelial Cell Interaction Distinguishes Colonization- versus Vulvovaginal Candidiasis-Associated Strains

Vulvovaginal candidiasis (VVC) affects nearly 3/4 of women during their lifetime, and its symptoms seriously reduce quality of life. Although Candida albicans is a common commensal, it is unknown if VVC results from a switch from a commensal to pathogenic state, if only some strains can cause VVC, and/or if there is displacement of commensal strains with more pathogenic strains. We studied a set of VVC and colonizing C. albicans strains to identify consistent in vitro phenotypes associated with one group or the other. We find that the strains do not differ in overall genetic profile or behavior in culture media (i.e., multilocus sequence type [MLST] profile, rate of growth, and filamentation), but they show strikingly different behaviors during their interactions with vaginal epithelial cells. Epithelial infections with VVC-derived strains yielded stronger fungal proliferation and shedding of fungi and epithelial cells. Transcriptome sequencing (RNA-seq) analysis of representative epithelial cell infections with selected pathogenic or commensal isolates identified several differentially activated epithelial signaling pathways, including the integrin, ferroptosis, and type I interferon pathways; the latter has been implicated in damage protection. Strikingly, inhibition of type I interferon signaling selectively increases fungal shedding of strains in the colonizing cohort, suggesting that increased shedding correlates with lower interferon pathway activation. These data suggest that VVC strains may intrinsically have enhanced pathogenic potential via differential elicitation of epithelial responses, including the type I interferon pathway. Therefore, it may eventually be possible to evaluate pathogenic potential in vitro to refine VVC diagnosis. IMPORTANCE Despite a high incidence of VVC, we still have a poor understanding of this female-specific disease whose negative impact on women's quality of life has become a public health issue. It is not yet possible to determine by genotype or laboratory phenotype if a given Candida albicans strain is more or less likely to cause VVC. Here, we show that Candida strains causing VVC induce more fungal shedding from epithelial cells than strains from healthy women. This effect is also accompanied by increased epithelial cell detachment and differential activation of the type I interferon pathway. These distinguishing phenotypes suggest it may be possible to evaluate the VVC pathogenic potential of fungal isolates. This would permit more targeted antifungal treatments to spare commensals and could allow for displacement of pathogenic strains with nonpathogenic colonizers. We expect these new assays to provide a more targeted tool for identifying fungal virulence factors and epithelial responses that control fungal vaginitis

Zinc prevents vaginal candidiasis by inhibiting expression of an inflammatory fungal protein

This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via the DOI in this recordData and materials availability: All data associated with this study are present in the paper or the Supplementary Materials. Raw data from the figures are given in data file S1.Candida causes an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused by Candida albicans, which, in this setting, triggers nonprotective neutrophil infiltration, aggressive local inflammation, and symptomatic disease. Despite its prevalence, little is known about the molecular mechanisms underpinning the immunopathology of this fungal infection. In this study, we describe the molecular determinant of VVC immunopathology and a potentially straightforward way to prevent disease. In response to zinc limitation, C. albicans releases a trace mineral binding molecule called Pra1 (pH-regulated antigen). Here, we show that the PRA1 gene is strongly up-regulated during vaginal infections and that its expression positively correlated with proinflammatory cytokine concentrations in women. Genetic deletion of PRA1 prevented vaginal inflammation in mice, and application of a zinc solution down-regulated expression of the gene and also blocked immunopathology. We also show that treatment of women suffering from recurrent VVC with a zinc gel prevented reinfections. We have therefore identified a key mediator of symptomatic VVC, giving us an opportunity to develop a range of preventative measures for combatting this disease.Wellcome TrustMedical Research Council (MRC)National Institute for Health and Care Research (NIHR)Biotechnology and Biological Sciences Research Council (BBSRC

Principal variable selection to explain grain yield variation in winter wheat from features extracted from UAV imagery

Background: Automated phenotyping technologies are continually advancing the breeding process. However, collecting various secondary traits throughout the growing season and processing massive amounts of data still take great efforts and time. Selecting a minimum number of secondary traits that have the maximum predictive power has the potential to reduce phenotyping efforts. The objective of this study was to select principal features extracted from UAV imagery and critical growth stages that contributed the most in explaining winter wheat grain yield. Five dates of multispectral images and seven dates of RGB images were collected by a UAV system during the spring growing season in 2018. Two classes of features (variables), totaling to 172 variables, were extracted for each plot from the vegetation index and plant height maps, including pixel statistics and dynamic growth rates. A parametric algorithm, LASSO regression (the least angle and shrinkage selection operator), and a non-parametric algorithm, random forest, were applied for variable selection. The regression coefficients estimated by LASSO and the permutation importance scores provided by random forest were used to determine the ten most important variables influencing grain yield from each algorithm. Results: Both selection algorithms assigned the highest importance score to the variables related with plant height around the grain filling stage. Some vegetation indices related variables were also selected by the algorithms mainly at earlier to mid growth stages and during the senescence. Compared with the yield prediction using all 172 variables derived from measured phenotypes, using the selected variables performed comparable or even better. We also noticed that the prediction accuracy on the adapted NE lines (r = 0.58–0.81) was higher than the other lines (r = 0.21–0.59) included in this study with different genetic backgrounds. Conclusions: With the ultra-high resolution plot imagery obtained by the UAS-based phenotyping we are now able to derive more features, such as the variation of plant height or vegetation indices within a plot other than just an averaged number, that are potentially very useful for the breeding purpose. However, too many features or variables can be derived in this way. The promising results from this study suggests that the selected set from those variables can have comparable prediction accuracies on the grain yield prediction than the full set of them but possibly resulting in a better allocation of efforts and resources on phenotypic data collection and processing