The interplay between HPV, other Sexually Transmissible Infections and genital microbiome on cervical microenvironment (MicroCervixHPV study).

Background: The importance of Cervicovaginal Microbiota in protecting against infections (such as HPV) is already well established, namely through Lactobacillus spp., as well as the mechanism through which HPV leads to Cervical Neoplasia. However, it is not possible to classify HPV as a complete carcinogen. Thus, the importance of exploring Cervicovaginal dysbiosis with the intention of deciphering this interaction with HPV, takes on greater relevance. The main objectives of this study were: 1) Comparison of the MCV composition of women with or without HPV and women with ASCUS or LSIL; 2) Characterization of cytokines present in the vaginal microenvironment; 3) Evaluation of the blood count ratios as prognostic systemic inflammatory biomarkers; 4) Correlation between MCV, HPV serotypes and cytokines. Methods: This was a retrospective, observational, multicenter, cross-sectional study. CVM analysis was performed by isolation RNA and sequencing on a NGS platform. Cytokine concentrations of CVM were obtained through Multiplex platform. Statistical analysis was performed in SPSS v 26.0. An α of 0.05 was considered statistically significant. Results: Highlighting the core of the study, CVM types of CST I and CST IV were found to influence the emergence of cervical lesions. Neutrophil-to-Lymphocyte ratio was found to impact the prognosis of ASCUS. Within CVM, Lactobacillus prevent the growth of other CST IV species, while the latter express symbiotic relationships with each other and show affinity for specific HPV serotypes. At last, RANTES chemokine is significantly elevated in cervicovaginal infections. Conclusion: The importance of using vaginal cytokine profiles and CVM is highlighted in the hypothesis of prevention of Cervical Neoplasia development, as well as in its use as a prognostic biomarker. Taken together, these insights are one step closer to personalized medicine.

MANAGEMENT OF THE UPPER LIMB ARTERIOVENOUS MALFORMATIONS.

Arteriovenous malformations (AVMs) involving the upper limb constitute 10% of the total AVMs. In the upper limb, AVMs are more frequent in the hand than in the arm, being the hand one of the body's regions more frequently associated with AVMs, coming after the head and neck. The total prevalence of the upper limb AVMs remains unknown and there is currently no definitive consensus for the treatment of upper limb AVMs. The purpose of this study was to review the best evidence of the treatment for the upper limb AVMs and describe their clinical characteristics and diagnosis. The majority of patients with asymptomatic AVMs follows a conservative management. In the symptomatic patients, the treatment with surgery and or chemical embolization is beneficial. The amputation can be necessary in the case of life-threatening and massive AVMs, constituting the first step in patient's rehabilitation. Although the most common option for the management of symptomatic or functional AVMs is the embolo-sclerotherapy combined with surgery, different outcomes should be taken into account to plan the treatment, specially the presence of symptoms, bleeding and heart failure.

The Therapeutic Potential of Hematopoietic Stem Cells in Bone Regeneration.

The repair process of bone fractures is a complex biological mechanism requiring the recruitment and in situ functionality of stem/stromal cells from the bone marrow (BM). BM mesenchymal stem/stromal cells have been widely explored in multiple bone tissue engineering applications, whereas the use of hematopoietic stem cells (HSCs) has been poorly investigated in this context. A reasonable explanation is the fact that the role of HSCs and their combined effect with other elements of the hematopoietic niches in the bone-healing process is still elusive. Therefore, in this review we intend to highlight the influence of HSCs in the bone repair process, mainly through the promotion of osteogenesis and angiogenesis at the bone injury site. For that, we briefly describe the main biological characteristics of HSCs, as well as their hematopoietic niches, while reviewing the biomimetic engineered BM niche models. Moreover, we also highlighted the role of HSCs in translational in vivo transplantation or implantation as promoters of bone tissue repair. Impact statement The ability of bone to natural self-heal depends on the size and stabilization level of the tissue fracture, and it is impaired in several pathophysiological conditions. Considering that the available treatment options have demonstrated limited regenerative performance, the hematopoietic stem cells (HSCs) co-cultured in different tissue engineering strategies have emerged as a powerful tool to promote effective bone regeneration and healing. Here, we reviewed the most important biomimetic bone-marrow hematopoietic niches and showed the regenerative potential of these cells, both in vitro and in translational in vivo transplantation/implantation approaches. This knowledge encourages the development of new HSC-related bone regenerative therapies.

Management of The Carotid Artery Stenosis in Asymptomatic Patients.

BACKGROUND: An asymptomatic carotid stenosis (CS) is defined as a stable atherosclerotic luminal narrowing in patients with no history of ipsilateral cerebral or ocular ischemic events in the past six months. The bifurcation of the common carotid artery makes this area vulnerable to atherosclerosis due to the features of haemodynamic flow. The exact prevalence of asymptomatic patients with CS remains unknown and opinions on the treatment of these patients are controversial. OBJECTIVE: The authors aimed to review the evidence on the management of the asymptomatic CS and describe its clinical characteristics, diagnosis and treatment management. METHODS: A comprehensive review of the literature was carried out to collate data from relevant studies concerning patients with extracranial moderate to severe asymptomatic carotid stenosis. The data used was identified by a search using PubMed and Google Scholar with the keywords / MESH terms "carotid stenosis", in combination with the term "asymptomatic". For this study, the authors focused on publications in the past two decades, using English publications. RESULTS: A few studies have addressed the prevalence, natural course and/or prognostic impact of asymptomatic CS in patients under medical treatment or undergoing vascular surgery procedures. The prevalence of asymptomatic CS ranged from 0.3% to 4.5% in women and 0.5% to 5.7% in men - The risk of stroke/TIA in these patients was reported between 2% to 5% annually with a downward trend across time to 0.5% with current best medical therapy. CONCLUSION: A great proportion of patients with asymptomatic CS should be submitted to conservative management with best medical therapy. However, selective surgical management should be considered if high risk features are present.

Functionalizing the Mesoporous Silica Shell of Upconversion Nanoparticles To Enhance Bacterial Targeting and Killing via Photosensitizer-Induced Antimicrobial Photodynamic Therapy.

Core-shell nanoparticles operating by infrared-to-visible energy upconversion (UCNPs) have been proposed as theranostic carriers for photosensitizers to increase deep-tissue penetration of photodynamic therapy against tumors and bacterial infections. Herein we present a series of core-shell mesoporous silica-coated NaYF4:Yb:Er UCNPs (mSiO2@UCNP) with different surface functionalizations to enhance bacterial targeting and loaded with the hydrophobic photosensitizer SiPc (silicon 2,9,16,23-tetra-tert-butyl-29H,31H-phthalocyanine dihydroxide) to boost the bactericidal effect against Gram-positive and Gram-negative bacteria upon near-infrared irradiation. Förster resonance energy transfer (FRET) from the UCNP core to loaded SiPc was facilitated, while its efficiency depended on UCNP shell functionalization, which influences the SiPc penetration depth into the mesoporous silica, constituting a convenient tool to modify FRET intensity. Functionalized UCNPs displayed dark toxicity toward Gram-negative E. coli of up to 5 orders of magnitude, while Gram-positive S. aureus viability was not decreased in the dark, offering practical means for discriminating between the two bacterial strains. Directly exciting SiPc on the UNCP led to complete eradication of E. coli and a drastic decrease of colony-forming units of S. aureus of up to 7 orders of magnitude. With this study, we demonstrate strategies to potentiate antimicrobial photodynamic therapy on nanoparticular structures that can lead to next-generation photosensitizing systems based on UCNPs to help encounter and eradicate resistant bacteria, as well as for theranostics and future in vivo applications.

Could dysnatremias play a role as independent factors to predict mortality in surgical critically ill patients?

Several studies have demonstrated the impact of dysnatremias on mortality of intensive care unit (ICU) patients. The objective of this study was to assess whether dysnatremia is an independent factor to predict mortality in surgical critically ill patients admitted to ICU in postoperative phase.One thousand five hundred and ninety-nine surgical patients (58.8% males; mean age of 60.6 ±â€Š14.4 years) admitted to the ICU in the postoperative period were retrospectively studied. The patients were classified according to their serum sodium levels (mmol/L) at admission as normonatremia (135-145), hyponatremia (<135), and hypernatremia (>145). APACHE II, SAPS III, and SOFA were recorded. The capability of each index to predict mortality of ICU and hospital mortality of patients was analyzed by multiple logistic regression.Hyponatremia did not have an influence on mortality in the ICU with a relative risk (RR) = 0.95 (0.43-2.05) and hospital mortality of RR = 1.40 (0.75-2.59). However, this association was greater in patients with hypernatremia mortality in the ICU (RR = 3.33 [95% confidence interval, CI 1.58-7.0]) and also in hospital mortality (RR = 2.9 [ 95% CI = 1.51-5.55). The pairwise comparison of ROC curves among the different prognostic indexes (APACHE II, SAPS III, SOFA) did not show statistical significance. The comparison of these indexes with serum sodium levels for general population, hyponatremia, and normonatremia was statistically significant (P < .001). For hypernatremia, the AUC and 95% CI for APACHE II, SAPS III, SOFA, and serum sodium level were 0.815 (0.713-0.892), 0.805 (0.702-0.885), 0.885 (0.794-0.945), and 0.663 (0.549-0.764), respectively. The comparison among the prognostic indexes was not statistically significant. Only SOFA score had a statistic difference compared with hypernatremia (P < .02).The serum sodium levels at admission, especially hypernatremia, may be used as an independent predictor of outcome in the surgical critically ill patients.