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Background: Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract infection (LRTI) and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV) LRTI, and to identify biomarkers that can objectively assess RSV disease severity. Methods and Findings: This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135), HRV (n = 30), and influenza (n =16) LRTI, and healthy age- and sex-matched controls (n = 39). A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US) and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US) with high sensitivity (94% [95% CI 87%-98%]) and specificity (98% [95% CI 88%-99%]). It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes) persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants ( Conclusions: Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues for biomarker discovery and identification of potential therapeutic or preventive targets, and demonstrates that large microarray datasets can be translated into a biologically meaningful context and applied to the clinical setting. Please see later in the article for the Editors' Summary., Introduction Lower respiratory tract infections (LRTIs) are associated with significant morbidity and mortality in children worldwide [1]. The implementation of vaccination with conjugate vaccines against the most common causes of [...]

Following the performance of a superovulation protocol, multiple nodules were observed bilaterally in the uterine horns of 31 of 276 (11.2%) C57BL/6 J female mice aged 8.5 ± 0.6 (mean and standard error of mean) weeks. These lesions prevented embryo collection, and the uterine decidual reaction was suspected. Samples of pathological uteri (n = 20) and the normal genital tracts of donors treated with a similar superovulation protocol (control group, n = 10) were collected. Immunohistochemistry was performed to evaluate pancytokeratin, desmin, vimentin, progesterone receptor (PR), estrogen receptor α (ERα), Ki-67, cyclin D3 and c-Myc expression, as well as quantitative polymerase chain reaction to assess cyclin D3, Hoxa-10 and heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA expression. The uterine decidual reaction presented a high degree of structural organization and specifically affected the antimesometrial region of the endometrium. The abnormal decidual cells were large polygonal cells that were frequently polyploid or binucleated and strongly positive for desmin. Immunohistochemistry showed higher Ki-67 proliferation index and higher expression of PR and cyclin D3 in decidual cells in the antimesometrial aspect of the endometrium, compared to nondecidualized endometrial stromal cells in the mesometrial aspect of affected uteri, and compared to endometrial stromal cells in healthy uteri. High expression of cyclin D3 and Hoxa-10 mRNA was also observed in uteri affected by the decidual reaction. These results suggest that PR overexpression in endometrial stromal cells, likely due to high progesterone levels, triggers cyclin D3 and Hoxa-10 overexpression, which may be involved in the pathological mechanisms of the mouse uterine decidual reaction. [ABSTRACT FROM AUTHOR]

Rat bone marrow cells were cultured in vitro in a collagen-gel medium at 0.5% fetal bovine serum concentration for 10 days in the presence of recombinant human transforming growth factor-beta-1, genetically engineered to contain a collagen binding domain (rhTGF-β1-F2), or a commercial rhTGF-β1. To compare the effects of TGF-βs with other growth factors in which the osteogenic capacity has been widely documented, a recombinant human bone morphogenetic protein (rhBMP-2) was evaluated. Once serum conditions compatible with growth were re-established, the selected cells were cultured for 6 more days in the presence of the growth factor. In the last 2 days, dexamethasone (dex) and β-glycerophosphate (β-GP) were added to promote osteogenesis. After this 16-day period, cells were placed into diffusion chambers or demineralized bone matrix (DBM) implants, and implanted subdermally on the backs of rats for 28 days. Biochemical, histological, and immunohistochemistry analysis provided evidence of cartilage (commercial rhTGF-β1-treated cells), osteoid (rhTGF-β1-F2-treated cells), and bone tissues (rhBMP-2 treated cells), inside the diffusion chambers, whereas bone, cartilage, and osteoid were observed inside the DBM implants under any of the three growth factors effect. Our study advances the technology capable of selecting a cell population from bone marrow that, in the presence of rhTGF-β1 or rhBMP-2 in vitro, achieves chondro-osteogenic potential in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background: Periodontitis and erectile dysfunction (ED) have been linked with cardiovascular disease. The association of periodontitis and ED with the occurrence of major adverse cardiovascular events has not been previously assessed. The aim of this study was to determine if the presence of periodontitis and ED has any effect on the incidence of major adverse cardiovascular events., Methods: Male patients that attended the Urology service were enrolled in a prospective study. Erectile dysfunction was diagnosed according to the International Index of Erectile Function. Sociodemographic data and periodontal clinical parameters were gathered (pocket probing depth, clinical attachment loss, bleeding on probing (BoP), plaque index and number of teeth) at baseline. Major adverse cardiovascular events occurred both before and during the follow-up time were registered. Bivariate analyses, as well as a multivariate analysis were performed, adjusting for potential confounders., Results: A total of 158 patients were included, with a mean follow-up of 4.2 years. A greater number of major adverse cardiovascular events occurred in the group that presented periodontitis and ED (P = 0.038). After adjusting by age and previous cardiovascular disease in the multivariate analysis, the annual major adverse cardiovascular event rate was estimated to be 3.7 times higher in the same group (P = 0.049). Other periodontal clinical variables together with ED supported these results and were close to statistical significance., Conclusions: Patients with periodontitis and ED, adjusted by age and a cardiovascular disease, showed 3.7 times more risk of suffering major adverse cardiovascular events after mean follow-up of 4.2 years., (© 2021 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

The etiology of prostate cancer (PCa) remains uncertain, and the role of diet is unclear. We aimed to evaluate the role of diet, through dietary patterns, on PCa, considering tumor aggressiveness and extension. The CAPLIFE study is a population-based case-control study including a total of 428 incident PCa cases and 393 controls aged 40-80 years. Dietary information was collected through a validated food frequency questionnaire. Three dietary patterns were identified through principal component analysis: "Mediterranean," "Western," and "Unhealthy," which were categorized into tertiles according to the control group cutoff points. Tumor aggressiveness and extension was determined. Logistic regression models were used to assess the association between dietary patterns and PCa. High adherence to an unhealthy dietary pattern was associated with higher odds of PCa, OR T3vsT1 = 1.52 (95% CI 1.02-2.27), especially for cases with ISUP 1-2 and localized PCa tumors. This association was not observed with a Western or Mediterranean pattern. In conclusion, adherence to an unhealthy diet appears to be associated with higher odds of PCa, especially for cases with ISUP 1-2 and localized PCa tumors.

Aim: To determine the association between chronic periodontitis and erectile dysfunction adjusting for biochemical markers and other comorbidities., Methods: A case-control study was conducted on 158 male patients; 80 cases with erectile dysfunction according to the International Index of Erectile Function and 78 controls. Sociodemographic data were gathered, and a periodontal examination was performed. Testosterone, lipid profile, C-reactive protein and glycaemic parameters were assessed. All variables were compared between groups, and multivariate logistic regression analyses were performed., Results: 74% of the cases were diagnosed with chronic periodontitis. Number of sites with pocket probing depth 4-6 mm (p = 0.05) and number of sites with clinical attachment loss >3 mm (p < 0.01) were higher in the cases. Triglycerides (p < 0.01), C-reactive protein (p = 0.02) and glycosylated haemoglobin (p = 0.04) were also higher in the cases. Logistic regression showed that patients with chronic periodontitis were more likely to have erectile dysfunction (OR=2.17; 95% CI (1.06-4.43); p = 0.03) independently of other confounders., Conclusion: Patients with erectile dysfunction showed worse periodontal condition. Chronic periodontitis seems to play a key role as a risk factor in the pathogenesis of erectile dysfunction independently of other morbidities., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The shrinkage of surgical specimens (SS) is known in human skin (HS) but has not been studied in an artificial skin (AS) or mouse skin (MS)., Objectives: To quantify the degree of shrinkage of SS and establish its timing in HS and an in vitro and animal model to explore the possible causes of this phenomenon., Methodology: We collected 100 SS of HS, 50 SS of AS synthesized with fibrin-agarose biomaterials and 21 SS of MS. The width and length of specimens were measured before the surgical excision (pre-SE), at 5 minutes postsurgery (ex vivo), and after 24 hours of fixation in formalin (postfixation). Histological staining was performed to analyze the differences between HS, AS, and MS that may explain the differences in shrinkage., Results: Between pre-SE and postfixation, the width and length shrank by 16.1% and 17.1% in HS, 14.5% and 8.5% in AS, and 26.5% and 23.1% in MS (P < 0.01), respectively. Shrinkage largely occurred between pre-SE and ex vivo. Cells and interstitial fibers were scant in AS and abundant in MS., Conclusions: Almost all of the shrinkage occurred during the first 5 minutes postsurgery. According to the AS model findings, 53.6% of SS shrinkage would be explained by the action of dermal fibers and other cellular components of the dermis.

Objective: Renal stone formation is a multifactorial process depending in part on urine composition. Other parameters relate to structural or pathological features of the kidney. To date, routine laboratory estimation of urolithiasis risk has been based on determination of urinary composition. This process requires collection of at least two 24 h urine samples, which is tedious for patients. The most important feature of urinary lithogenic risk is the balance between various urinary parameters, although unknown factors may be involved. The objective of this study was to compare data obtained using a commercial kit with those of a laboratory prototype, using a multicentre approach, to validate the utility of these methods in routine clinical practice., Material and Methods: A simple new commercial test (NefroPlus®; Sarstedt AG & Co., Nümbrecht, Germany) evaluating the capacity of urine to crystallize calcium salts, and thus permitting detection of patients at risk for stone development, was compared with a prototype test previously described by this group. Urine of 64 volunteers produced during the night was used in these comparisons. The commercial test was also used to evaluate urine samples of 83 subjects in one of three hospitals., Results: Both methods were essentially in complete agreement (98%) with respect to test results. The multicentre data were: sensitivity 94.7%; specificity 76.9%; positive predictive value (lithogenic urine) 90.0%; negative predictive value (non-lithogenic urine) 87.0%; test efficacy 89.2%., Conclusion: The new commercial NefroPlus test offers fast and cheap evaluation of the overall risk of development of urinary calcium-containing calculi.

Rat bone marrow cells were cultured in vitro in a collagen-gel medium at 0.5% fetal bovine serum concentration for 10 days in the presence of recombinant human transforming growth factor-beta-1, genetically engineered to contain a collagen binding domain (rhTGF-beta1-F2), or a commercial rhTGF-beta1. To compare the effects of TGF-betas with other growth factors in which the osteogenic capacity has been widely documented, a recombinant human bone morphogenetic protein (rhBMP-2) was evaluated. Once serum conditions compatible with growth were re-established, the selected cells were cultured for 6 more days in the presence of the growth factor. In the last 2 days, dexamethasone (dex) and beta-glycerophosphate (beta-GP) were added to promote osteogenesis. After this 16-day period, cells were placed into diffusion chambers or demineralized bone matrix (DBM) implants, and implanted subdermally on the backs of rats for 28 days. Biochemical, histological, and immunohistochemistry analysis provided evidence of cartilage (commercial rhTGF-beta1-treated cells), osteoid (rhTGF-beta1-F2-treated cells), and bone tissues (rhBMP-2 treated cells), inside the diffusion chambers, whereas bone, cartilage, and osteoid were observed inside the DBM implants under any of the three growth factors effect. Our study advances the technology capable of selecting a cell population from bone marrow that, in the presence of rhTGF-beta1 or rhBMP-2 in vitro, achieves chondro-osteogenic potential in vitro and in vivo.

Two Spanish siblings, a boy and girl, with transcobalamin II (TCII) deficiency are described. Both have grown and developed mentally normally after 10 years of vitamin B12 therapy. Two other siblings died soon after birth and it is almost certain that they also suffered from TCII deficiency.