Masticatory function and mortality among older adults living in long-term care facilities in Brazil.

OBJECTIVE: To investigate the association between mortality and masticatory function in older adults living in long-term care facilities (LTCFs), controlling for demographic and health covariates. BACKGROUND: Poor oral health has been associated with mortality; however, no previous study investigated whether objective and self-reported poor masticatory function is a predictor of early mortality in LTCFs. MATERIALS AND METHODS: Baseline characteristics of 295 participants were collected, including age, sex, polypharmacy, mobility, activities of daily living, frailty, nutritional status, and objective (masticatory performance - chewing gum) and self-reported masticatory function. The participants were followed-up with for 4 years to record the mortality data. Cox regression models were run to analyse the data (α = .05). RESULTS: During the 4-year follow-up, 124 (42.0%) participants died. Older adults with poor masticatory performance (hazard ratio [HR] = 1.59, 95% confidence interval [95% CI] = 1.07-2.36) and those who self-reported masticatory dysfunction (HR = 1.48, 95% CI = 1.01-2.16) were at higher risk of early death than those with good mastication. However, in a multivariate model including both objective and self-reported masticatory function, only the objective measurement remained associated with early death (HR = 1.52, 95% CI = 1.02-2.27). CONCLUSION: Poor masticatory performance seems to be associated with early death in older adults living in LTCFs, but they may have shared risk factors accumulated throughout life that were not covered by the study period.

Proteomic analysis of chromophobe renal cell carcinoma and benign renal oncocytoma biopsies reveals shared metabolic dysregulation.

BACKGROUND: This study investigates the proteomic landscapes of chromophobe renal cell carcinoma (chRCC) and renal oncocytomas (RO), two subtypes of renal cell carcinoma that together account for approximately 10% of all renal tumors. Despite their histological similarities and shared origins, chRCC is a malignant tumor necessitating aggressive intervention, while RO, a benign growth, is often subject to overtreatment due to difficulties in accurate differentiation. METHODS: We conducted a label-free quantitative proteomic analysis on solid biopsies of chRCC (n = 5), RO (n = 5), and normal adjacent tissue (NAT, n = 5). The quantitative analysis was carried out by comparing protein abundances between tumor and NAT specimens. Our analysis identified a total of 1610 proteins across all samples, with 1379 (85.7%) of these proteins quantified in at least seven out of ten LC‒MS/MS runs for one renal tissue type (chRCC, RO, or NAT). RESULTS: Our findings revealed significant similarities in the dysregulation of key metabolic pathways, including carbohydrate, lipid, and amino acid metabolism, in both chRCC and RO. Compared to NAT, both chRCC and RO showed a marked downregulation in gluconeogenesis proteins, but a significant upregulation of proteins integral to the citrate cycle. Interestingly, we observed a distinct divergence in the oxidative phosphorylation pathway, with RO showing a significant increase in the number and degree of alterations in proteins, surpassing that observed in chRCC. CONCLUSIONS: This study underscores the value of integrating high-resolution mass spectrometry protein quantification to effectively characterize and differentiate the proteomic landscapes of solid tumor biopsies diagnosed as chRCC and RO. The insights gained from this research offer valuable information for enhancing our understanding of these conditions and may aid in the development of improved diagnostic and therapeutic strategies.

A foretaste for pediatric glioblastoma therapy: targeting the NF-kB pathway with DHMEQ.

PURPOSE: While pediatric glioblastomas are molecularly distinct from adult counterparts, the activation of NF-kB is partially shared by both subsets, playing key roles in tumor propagation and treatment response. RESULTS: We show that, in vitro, dehydroxymethylepoxyquinomicin (DHMEQ) impairs growth and invasiveness. Xenograft response to the drug alone varied according to the model, being more effective in KNS42-derived tumors. In combination, SF188-derived tumors were more sensitive to temozolomide while KNS42-derived tumors responded better to the combination with radiotherapy, with continued tumor regression. CONCLUSION: Taken together, our results strengthen the potential usefulness of NF-kB inhibition in future therapeutic strategies to overcome this incurable disease.

Effects of tongue lesions and palatal coverage on oral sensory functions.

STATEMENT OF PROBLEM: Oral stereognosis (OS) plays a significant role in the oral rehabilitation of patients with edentulism, as it influences their adaptation to new prostheses. Because of the essentially tactile characteristic of oral sensory perception, the tongue and palate appear to have a crucial function in OS. However, little is known about the influence of tongue lesions on OS and sensorial function. In addition, controversies remain regarding the role of the palate. PURPOSE: The purpose of this clinical study was to evaluate whether tongue lesions and palatal coverage are disruptive to OS and gustatory function. MATERIAL AND METHODS: Seventy participants (mean age=30.7 ±6.7 years) were divided into a tongue lesion group (experimental; n=35) and a control group (n=35). The tongue lesion group included participants with geographic, fissured, or hairy tongue. OS was evaluated with the oral stereognosis ability (OSA) test. Gustatory function was assessed with exposure to flavored solutions. After completing the above tests, the participants received a palate covering device, and then OS and gustatory function were immediately reevaluated. Data were analyzed with the Mann-Whitney and Wilcoxon tests (α=.05). RESULTS: OSA and gustatory function scores did not differ among the tongue lesion and control groups with and without palatal coverage (all P>.05). After palatal coverage, the tongue lesion group took more time to perform the OSA test than the control group (P<.05). CONCLUSIONS: Neither the presence of tongue lesions nor palatal coverage influenced OS or gustatory function. The OSA test response times were longer for the tongue lesion group after they had received palatal coverage.

Funding assistance and global productivity in the field of implant overdentures: A bibliometric analysis of 35 years.

STATEMENT OF PROBLEM: Implant overdentures have been widely used as a treatment option for edentulous patients. However, the development of implants, aside from commercial growth, requires funding assistance to determine scientific reliability and clinical applications. Nonetheless, bibliometric studies in the implant overdenture field are lacking. PURPOSE: The purpose of this bibliometric analysis was to evaluate the prevalence of funding and its bibliometric associated parameters according to the financial assistance granted and the implant overdenture documentation over time. MATERIAL AND METHODS: Six databases were assessed, and 12 bibliometric parameters related to the economy, geographical origin, publication details, and corresponding author metrics were recorded. An incidence rate ratio was applied by using a multiple Poisson regression model (α=.05) to assess the association between funding and each bibliometric parameter. RESULTS: In total, 1369 studies published between 1986 and 2021 were assessed bibliometrically. The prevalence of funded studies was 34.8% (n=477). The parameter associated with the presence of funding was country income (P<.01), with those having a high and upper-middle income being more funded than those with a lower-middle and low income. Oceania and South America were the continents more frequently funded (P<.05), with Africa being the least frequent. Randomized and nonrandomized controlled trials, in vitro studies, and in silico studies were more funded (P<.001) than case reports and series. Stud and ball attachment systems were more funded (P<.01) than studies with more than 1 retention system. Funding increased over time (P<.01), and corresponding authors with a higher h-index had more studies funded (P<.05). CONCLUSIONS: The number of funded studies on implant overdentures increased over the years. Other bibliometric parameters such as country income, continent, study design, retention system, and corresponding author h-index were associated with the frequency of funded studies published.

The multifaceted NF-kB: are there still prospects of its inhibition for clinical intervention in pediatric central nervous system tumors?

Despite advances in the understanding of the molecular mechanisms underlying the basic biology and pathogenesis of pediatric central nervous system (CNS) malignancies, patients still have an extremely unfavorable prognosis. Over the years, a plethora of natural and synthetic compounds has emerged for the pharmacologic intervention of the NF-kB pathway, one of the most frequently dysregulated signaling cascades in human cancer with key roles in cell growth, survival, and therapy resistance. Here, we provide a review about the state-of-the-art concerning the dysregulation of this hub transcription factor in the most prevalent pediatric CNS tumors: glioma, medulloblastoma, and ependymoma. Moreover, we compile the available literature on the anti-proliferative effects of varied NF-kB inhibitors acting alone or in combination with other therapies in vitro, in vivo, and clinical trials. As the wealth of basic research data continues to accumulate, recognizing NF-kB as a therapeutic target may provide important insights to treat these diseases, hopefully contributing to increase cure rates and lower side effects related to therapy.

Bibliometric assessment in implant-retained overdenture articles: Mapping citation and journal impact factor trends.

STATEMENT OF PROBLEM: Implant-retained overdentures are a recognized treatment option. However, a comprehensive assessment of all articles on implant-retained overdentures to identify publication standards such as mean citation and the Journal Citation Reports (JCR) impact factor is lacking. PURPOSE: The purpose of this bibliometric assessment was to evaluate the association of mean citation and JCR impact factor with bibliometric parameters in articles on implant-retained overdentures. MATERIAL AND METHODS: Articles reporting randomized controlled clinical trials (RCTs) and nonrandomized controlled clinical trials (N-RCTs); case reports and series; retrospective studies; and in silico, in vitro, or systematic reviews in 6 databases were included. Data were extracted, and 2 multiple Poisson regressions analyses were applied (α=.05). The dependent variables were mean citation and JCR impact factor, which were evaluated to identify their association with bibliometric parameters by using prevalence ratio (PR) values. RESULTS: A total of 1369 articles published from 1986 to 2021 were included. The data revealed a high mean citation and high JCR impact factor for RCT, N-RCT, retrospective, and in vitro studies (P<.05). In silico studies presented a high mean citation (P<.001). Senior researchers with a high h-index were more likely to have a high mean citation and publications with a high JCR impact factor (P<.001). Also, senior authors associated with an international network were more likely to have a high mean citation (P=.001). High-income countries had more studies with a high mean citation and JCR impact factor (P<.05). Higher JCR impact factors were associated with articles evaluating only the maxilla or mandible (P<.05). The topics "implant setting" and "macrodesign" were associated with a high mean citation (P<.05). CONCLUSIONS: The publication trends suggest a high mean citation and a high JCR impact factor for clinical designs (RCT, N-RCT, retrospective) and in vitro studies. The same pattern was also displayed for researchers with a high h-index and located in high-income countries.

Prosthetic rehabilitation status, dental prosthesis functionality and masticatory function in nursing home residents.

OBJECTIVE: To evaluate the association of masticatory function with prosthetic rehabilitation status and dental prosthesis functionality in nursing home residents. BACKGROUND: Prosthetic rehabilitation status and dental prosthesis functionality may adversely affect mastication of older people, and this relationship is underestimated in nursing home residents. MATERIALS AND METHODS: This cross-sectional study included 179 nursing home residents who used dental prostheses [mean (SD) age: 78.9 (9.0) years]. Masticatory function data were determined by assessing (a) masticatory performance using two-colour chewing gum, and (b) swallowing thresholds by counting the number of peanut chewing cycles. Older adults were categorised as: (1) using dental prostheses in both jaws (n = 100) and (2) partially dentate using removable partial dental prostheses (RPDPs) or complete dentures (CDs) in only one jaw (n = 41), or (3) edentulous using CD in only one jaw (n = 38). Stability, retention, occlusion, vertical dimension and defects were considered in assessing dental prosthesis functionality. RESULTS: Greater variance of hue (VOH) of the chewing gum and lower swallowing thresholds (worse masticatory function) was associated with edentulous using CD in only one jaw. Older adults wearing dental prostheses with poor occlusion and vertical dimensions presented worse masticatory function. Dental prosthesis stability was associated with lower VOH values. Higher number of chewing cycles while eating peanuts was associated with non-broken dental prosthesis use. CONCLUSION: Edentulous participants using CD in only one jaw and non-functional dental prosthesis use negatively affect the masticatory function of nursing home residents.

Does the institutionalization influence elderly's quality of life? A systematic review and meta-analysis.

BACKGROUND: Institutionalization is a global phenomenon and its impact on elderly's quality of life (QoL) is under discussion. This systematic review and meta-analysis evaluated the influence of the institutionalization on elderly's QoL. METHODS: Searches were performed in Medline, Scopus, Web of Science, Lilacs, Cochrane Library and SIGLE by two independent reviewers up to May 2019. The eligibility criteria were based on PECO strategy, considering observational studies in elderly (P), which were (E) or not (C) institutionalized to identify differences in their QoL (O). For qualitative synthesis, data were extracted and risk of bias was evaluated through a validated guideline. Meta-analysis was based on Mean Difference (MD) and Standard Mean Difference (SMD) calculation (p ≤ 0.05). The evidence was quality-tested using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: The initial search identified 3841 articles. Duplicates were removed, titles and abstracts were read and eligibility criteria were applied, remaining 16 sixteen cross-sectional studies that were included for data extraction and qualitative synthesis. Out of 16 articles, 14 evaluated the Health-Related Quality of Life, using Leipad (n = 2), WHOQOL-BREF and/or OLD (n = 8), SF-36 or RAND-36 (n = 4) questionnaires, and two assessed the Oral Health-Related Quality of Life, through GOHAI questionnaire. One eligible article was considered as low risk of bias. In the meta-analysis, 12 studies were included. Leipad questionnaire did not show differences on elderly's QoL (MD 0.11 [- 0.10, 0.32] I2 = 76%). Differences on elderly's QoL were detected through WHOQOL-BREF (SMD -0.70 [CI95%: - 0.94, - 0.47] I2 = 93%), WHOQOL-OLD (SMD -1.13 [- 1.47, - 0.80] I2 = 91%) and SF-36/RAND-36 (MD -5.97 [CI95%: - 11.29, - 0.64] I2 = 90%). All studies had very low or low certainty of evidence, since the study design influenced evidence classification, and show high heterogeneity. CONCLUSION: Although the institutionalization influences negatively the elderly's QoL, further well-designed studies are needed to confirm this evidence.

Masticatory function in nursing home residents: Correlation with the nutritional status and oral health-related quality of life.

BACKGROUND: Masticatory function of institutionalised elders and its relationship with nutrition and oral health-related quality of life (OHRQoL) are unknown. OBJECTIVES: This multicentre cross-sectional study evaluated the influence of the presence of teeth and dentures on masticatory function (masticatory performance and swallowing threshold) in institutionalised elders. Correlation of masticatory function with nutrition and OHRQoL was also verified. METHODS: Older adults (n = 344; mean age (SD) = 77.70 (9.10)), selected from nursing homes in two Brazilian cities, were classified as edentulous with or without complete dentures (CDs), and partially dentate with or without prosthesis. Masticatory performance was assessed using a two-colour chewing gum. Swallowing threshold was set by the number of chewing cycles performed until swallowing 3.7 g of peanuts. Nutrition was screened by Mini-Nutritional Assessment-Short Form and body composition. OHRQoL was evaluated through Geriatric Oral Health Assessment Index (GOHAI) and Oral Health Impact Profile (OHIP-14). The Kruskal-Wallis test and Spearman's correlation were used (α = 0.05). RESULTS: Edentulous elders without CDs had lower masticatory performance than those with CDs and partially dentate with or without prosthesis (P < .05). Swallowing threshold of edentulous elders with CDs and partially dentate with prosthesis was greater than edentulous elders without CDs and partially dentate without prosthesis (P < .05). Masticatory function was not correlated with nutrition. Masticatory performance was correlated (P < .05) with GOHAI (r2  = -.154) and swallowing threshold with GOHAI (r2  = .162) and OHIP-14 (r2  = -.146). CONCLUSION: The absence of teeth and dentures negatively affected the masticatory function. Although the masticatory function was not correlated with institutionalised elders' nutrition, their OHRQoL was negatively impacted.

Mimicking the tumor microenvironment: Fibroblasts reduce miR-29b expression and increase the motility of ovarian cancer cells in a co-culture model.

Ovarian cancer (OC) is a highly prevalent gynecological malignancy worldwide. Throughout ovarian carcinogenesis, the crosstalk between cellular components of the microenvironment, including tumor cells and fibroblasts, is proposed to play critical roles in cancer progression. The dysregulation of microRNA expression is also a pronounced feature of the OC. The screening of microRNAs, mainly those involved in OC microenvironment, could have diagnostic and/or therapeutic potential for this malignancy. Thus, we assessed the influence of fibroblasts on microRNA expression and the motility of OC cells. To achieve this goal, SKOV-3 cancer cells were co-cultured with human normal fibroblasts derived from primary culture (FP-96). Cell viability, expression of tumor suppressor microRNAs and oncomiRs by RT-qPCR, cell migration by wound healing assay and analysis of MMP-2 activity by zymography were performed in SKOV-3 cells. Moreover, α-smooth muscle actin (α-SMA) expression was evaluated by Western blot in FP-96 fibroblasts. Notably, the co-culture downregulated the tumor suppressor miR-29b and increased migration of SKOV-3 cells. In addition, co-culture increased the activity of MMP-2, which is a miR-29 target, and accounted for extracellular matrix remodeling and augmented cellular motility. Concomitantly, the co-culture system induced α-SMA expression in FP-96 fibroblasts, the commonly expressed marker in cancer-associated fibroblasts (CAFs). Our findings suggest that the potential crosstalk between OC cells and fibroblasts in tumor microenvironment may play a key role in the progression of OC.

Basement membrane extract attenuates the more malignant gene expression profile accentuated by fibronectin in prostate cancer cells.

Prostate cancer (PCa) has high mortality rates, with most of the deaths resulting from the development of metastasis. Fibronectin (FN) plays key roles in cell adhesion and affects the migratory behavior of cells. In the tumor microenvironment and also in the blood plasma during metastasis, FN displays increased expression, however its role in prostate cancer remains poorly understood. This study aimed to unveil the specific roles of FN as a soluble component, alone or in combination with a complex basement membrane. To investigate the impact of FN in neoplastic prostate cells, we evaluated the gene expression of LNCaP cells by RT-qPCR after exposure to soluble FN (25 µg/mL) either alone or in combination with a basement membrane. When FN was the predominant matrix element, such as in blood plasma, PCa tumor cells increased their expression of genes related to an invasive behavior and resistance to apoptosis, including CDH2, ITGA5, AKT1, and BCL2. However, the combined presence of FN and a complex basement membrane had the opposite effect on LNCaP cells, in which the expression levels of CDH2, ITGA5, AKT1, and BCL2 were reduced. Hierarchical clustering analysis with LNCaP and RWPE-1 cells showed that LNCaP cells exposed to an enriched extracellular matrix displayed an expression pattern more similar to that shown by RWPE-1 cells, a cell line that illustrates characteristics of the normal prostate epithelium. These findings provide the groundwork for future studies addressing the role of FN in tumor growth, particularly in the context of cancer evolution/progression from a solid primary tumor to a transitory circulating state.

Platelet hyperaggregability in obesity: is there a role for nitric oxide impairment and oxidative stress?

Epidemiological evidence has shown that platelet activation markers are consistently elevated in obesity, contributing to its prothrombotic state. In order to improve the understanding of the regulation of platelet function in obesity, the aim of this study was to investigate the l-arginine-nitric oxide (NO) pathway in obese adults without other cardiovascular risk factor. Seventeen obese (body mass index [BMI] 35.9±1.0 kg/m(2) ) and eighteen age-matched normal weight subjects (BMI 22.0±0.6 kg/m(2) ) were included in this study. l-arginine influx was measured with incubation of l-[(3) H]-arginine. NO synthase (NOS) and arginase activities were determined by the citrulline assay and the conversion of l-[(14) C]-arginine to [(14) C]-urea, respectively. Cyclic guanosine monophosphate (cGMP) content was evaluated by enzyme-linked immunosorbent assay. In addition, the study analyzed: platelet aggregation; intraplatelet antioxidant enzymes, via superoxide dismutase (SOD) and catalase activities; and systemic levels of l-arginine, fibrinogen, and C-reactive protein (CRP). Obese patients presented a significant decrease of platelet l-arginine influx, NOS activity, and cGMP levels, along with platelet hyperaggregability. On the presence of NO donor, platelet aggregation was similar between the groups. The fibrinogen and CRP systemic levels were significantly higher and SOD activity was reduced in obesity. No significant differences were observed in plasma levels of l-arginine and intraplatelet arginase and catalase activities between groups. The diminished NO bioavailability associated with inflammatory status and impaired enzymatic antioxidant defence may contribute to future cardiovascular complications in obesity.

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity.

Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the "omics" era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/ß-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, many commonalities have been described, among which the nuclear factor kappa B (NF-κB) stands out. Its altered activation is pervasive in cancer, with pleiotropic action on many disease-relevant traits. Thus, in the scope of this article, we highlight the evidence of NF-κB dysregulation in OS and its integration with other cancer-related pathways while we summarize the repertoire of compounds that have been described to interfere with its action. In silico strategies were used to demonstrate that NF-κB is closely coordinated with other commonly dysregulated signaling pathways not only by functionally interacting with several of their members but also by actively participating in the regulation of their transcription. While existing inhibitors lack selectivity or act indirectly, the therapeutic potential of targeting NF-κB is indisputable, first for its multifunctionality on most cancer hallmarks, and secondly, because, as a common downstream effector of the many dysregulated pathways influencing OS aggressiveness, it turns complex regulatory networks into a simpler picture underneath molecular heterogeneity.

Use of Electron Microscopy for the Detection of Contaminant Endophytic Bacteria In Vitro.

The success of in vitro cultivation, particularly for micropropagation purposes, depends on the efficient control of contaminants. In this context, the sterilization of plant material constitutes a fundamental step in initiating cultures. Microbial contaminants can be found either on the surface (epiphyte) or inside plant explants (endophyte). However, the latter is generally challenging to detect and may not always be eradicated through surface sterilization alone. Endophyte contaminants, such as bacteria, can persist within plant material over several cultivation cycles, potentially interfering with or inhibiting in vitro establishment, growth, or recovery of cryopreserved materials. Therefore, microscopy techniques, such as electron microscopy, can yield valuable insights into bacterial endophytes' localization, tissue colonization patterns, and functions in in vitro plant culture. This information is essential for adopting effective strategies for eliminating, preventing, or harmonious coexistence with contaminants.

Development and validation of a clinical nomogram to predict prostatic inflammation in men with lower urinary tract symptoms.

BACKGROUND: Prostatic inflammation is an important etiological component of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). The Prostatic Inflammation Nomogram Study (PINS) aimed to develop and validate a nomogram for predicting the presence of prostatic inflammation in men with LUTS. METHODS: This non-interventional, cross-sectional, prospective study was conducted in six secondary/tertiary centers across Cyprus, Greece, Italy, Portugal, and Spain. Men (≥40 years) with BPH/LUTS scheduled to undergo prostatic surgery or transrectal ultrasound-guided (TRUS) prostate biopsy were included. Fifteen demographic and clinical participant characteristics were selected as possible predictors of prostatic inflammation. The presence of inflammation (according to Irani score) in the prostatic tissue samples obtained from surgery/TRUS biopsy was determined. The effect of each characteristic on the likelihood a prostate specimen demonstrated inflammation (classified by Irani score into two categories, 0-2 [no/minimal inflammation] or 3-6 [moderate/severe inflammation]) was assessed using multiple logistic regression. A nomogram was developed and its discriminatory ability and validity were assessed. RESULTS: In total, 423 patients (mean age 68.9 years) were recruited. Prostate volume ultrasound (PVUS) > 50 mL, history of urinary tract infection (UTI) treatment, presence of diabetes, and International Prostate Symptom Score (IPPS) Storage score were statistically significant predictors of Irani classification. Logistic regression demonstrated a statistically significant effect for leucocytes detected via urine dipstick, presence of diabetes, PVUS > 50 mL, history of UTIs, and higher IPSS Storage score for the odds of an inflammatory score category of 3-6 versus 0-2. The nomogram had a concordance index of 0.71, and good internal validity. CONCLUSIONS: The nomogram developed from PINS had good predictive ability and identified various characteristics to be predictors of prostatic inflammation. Use of the nomogram may aid in individualizing treatment for LUTS, by identifying individuals who are candidates for therapies targeting prostatic inflammation.

Low Cubilin/Myeloperoxidase ratio as a promising biomarker for prognosis of high-grade T1 bladder cancer.

PURPOSE: T1 bladder cancer is known for its high progression and recurrence rates. Identifying aggressive tumours at the non-muscle-invasive stage is crucial to allow early interventions and subsequently increase patient survival. This study aimed to investigate the potential of the cubilin/myeloperoxidase (CUBN/MPO) ratio as a high-grade T1 bladder cancer biomarker. METHODS: Urine samples were collected from 30 patients who underwent transurethral resection of the tumour with high-grade T1 bladder cancer (June 2015 to December 2019) before surgery. The urinary proteome was analysed using high-resolution mass spectrometry and the CUBN/MPO ratio was calculated. The primary outcome was the recurrence during the follow-up (around 31.5 months after resection). Univariate Cox regression and Kaplan-Meier curves were used for data analysis. RESULTS: Patients with a low CUBN/MPO ratio exhibited upregulated MPO and/or downregulated CUBN. This group of patients had a higher incidence of disease recurrence and progression. Low CUBN/MPO ratio was significantly associated with a higher likelihood of recurrence, progression, and death. It is worth noting that this study was exploratory and conducted on a small sample size, so further research is needed to validate these findings in larger cohorts. CONCLUSION: This study highlights the potential of the CUBN/MPO ratio as a prognostic biomarker for high-grade T1 bladder cancer.

Richieri-costa and Pereira syndrome: severe phenotype.

Richieri-Costa and Pereira syndrome, described in 1992, comprises short stature, Robin sequence, cleft mandible, limb malformations, and short larynx, deformed or lack of epiglottis, and abnormal aryepiglottic folds. There are 32 reported cases, only one described outside Brazil. We describe a 4-month-old boy with the most severe phenotype yet reported.

An Overview on the Effect of Severe Plastic Deformation on the Performance of Magnesium for Biomedical Applications.

There has been a great interest in evaluating the potential of severe plastic deformation (SPD) to improve the performance of magnesium for biological applications. However, different properties and trends, including some contradictions, have been reported. The present study critically reviews the structural features, mechanical properties, corrosion behavior and biological response of magnesium and its alloys processed by SPD, with an emphasis on equal-channel angular pressing (ECAP) and high-pressure torsion (HPT). The unique mechanism of grain refinement in magnesium processed via ECAP causes a large scatter in the final structure, and these microstructural differences can affect the properties and produce difficulties in establishing trends. However, the recent advances in ECAP processing and the increased availability of data from samples produced via HPT clarify that grain refinement can indeed improve the mechanical properties and corrosion resistance without compromising the biological response. It is shown that processing via SPD has great potential for improving the performance of magnesium for biological applications.

Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.

Childhood cancer is considered rare, corresponding to ~3% of all malignant neoplasms in the human population. The World Health Organization (WHO) reports a universal occurrence of more than 15 cases per 100,000 inhabitants around the globe, and despite improvements in diagnosis, treatment and supportive care, one child dies of cancer every 3 min. Consequently, more efficient, selective and affordable therapeutics are still needed in order to improve outcomes and avoid long-term sequelae. Alterations in kinases' functionality is a trademark of cancer and the concept of exploiting them as drug targets has burgeoned in academia and in the pharmaceutical industry of the 21st century. Consequently, an increasing plethora of inhibitors has emerged. In the present study, the expression patterns of a selected group of kinases (including tyrosine receptors, members of the PI3K/AKT/mTOR and MAPK pathways, coordinators of cell cycle progression, and chromosome segregation) and their correlation with clinical outcomes in pediatric solid tumors were accessed through the R2: Genomics Analysis and Visualization Platform and by a thorough search of published literature. To further illustrate the importance of kinase dysregulation in the pathophysiology of pediatric cancer, we analyzed the vulnerability of different cancer cell lines against their inhibition through the Cancer Dependency Map portal, and performed a search for kinase-targeted compounds with approval and clinical applicability through the CanSAR knowledgebase. Finally, we provide a detailed literature review of a considerable set of small molecules that mitigate kinase activity under experimental testing and clinical trials for the treatment of pediatric tumors, while discuss critical challenges that must be overcome before translation into clinical options, including the absence of compounds designed specifically for childhood tumors which often show differential mutational burdens, intrinsic and acquired resistance, lack of selectivity and adverse effects on a growing organism.