Lymphatic vessel density and epithelial D2-40 immunoreactivity in pre-invasive and invasive lesions of the uterine cervix

OBJECTIVE: We sought to determine the significance of lymphatic vessel density (LVD) in pre-malignant lesions and carcinomas of the uterine cervix and to evaluate the prognostic value of lymphatic invasion and D2-40 positivity in tumor cells in the three histological types of invasive lesions. The correlation of LVD, lymphatic invasion and D2-40 positivity in tumor cells with EGFR and COX-2 expressions was also evaluated. METHODS: We studied 50 cervicitis, 50 low-grade squamous intraepithelial lesions (LSIL) (CIN1), 51 high-grade squamous intraepithelial lesions (HSIL) (CIN2/CIN3), 49 invasive squamous cells carcinomas (SCC), 43 adenocarcinomas (AC) and 30 adenosquamous cells carcinomas (ASC). The immunoreaction assay was performed using the monoclonal antibody D2-40. RESULTS: Significant differences in LVD were found among all categories of pre-invasive and invasive lesions (p=0.001 and p<0.001, respectively). LVD in invasive lesions was significantly greater than in pre-invasive lesions (p<0.001) and no significant association was found between LVD in invasive lesions and both lymph node invasion and/or metastasis. D2-40 positivity in tumor cells was associated with a better prognosis in ASC cases. EGFR and COX-2 expressions in invasive lesions were not associated with LVD; however, they correlated with both lymphatic invasion and D2-40 positivity in tumor cells. CONCLUSIONS: Lymphatic neovascularization begins early in intraepithelial lesions and continues to increase towards malignancy. Both lymphatic invasion and decrease in D2-40 expression in tumor cells appear to have a prognostic value.     

Umbilical cord rupture and vasa previa: a report of a case

Vasa previa is a rare condition, frequently lethal, in which fetal blood vessels coming from the placenta or the umbilical cord cross the entrance of the childbirth channel before presentation. The abnormal blood vessels are result of a velamentous cord insertion or a placental alteration. It happens in 1:3000 births, with a high perinatal mortality. A 16 years-old primigest patient, at 34.6 week of gestation, was admitted to the labor, which has a good evolution, without any complication. A male new born was obtained without hearth rate or vitality, Apgar scale 0-0, weight 2800 grams, who presented an umbilical cord rupture 3 centimeters from its abdominal insertion, no where the fetal blood vessels are unprotected. It is necessary an adequate prenatal care, diagnosis and accurate management, to avoid the mortality by this rare clinical entity.     

Randomised Clinical Trial to Analyse the Efficacy of Eggshell Membrane to Improve Joint Functionality in Knee Osteoarthritis

Osteoarthritis is a source of chronic pain and disability. Dietary supplements have been shown to be a more secure option than NSAIDS. Particularly, the eggshell membrane has demonstrated efficacy in relieving joint pain and stiffness. A clinical trial was designed in which three groups were assigned to two different doses of this supplement and compared to a placebo control group. The primary outcome variable was knee pain, which was assessed using a visual analogue scale. Secondary outcome variables were knee functional ability, quadriceps muscle strength (assessed by isometric and isokinetic trials), and quality of sleep. All groups showed a significant decrease in pain perception, although maximum values were obtained in the high-dose group. Isokinetic and isometric trials showed a significant increase in strength in the high-dose group. Eggshell membrane showed the potential to reduce pain and stiffness symptomatology. Here, for the first time, two quantitative variables (mobility and strength of knee joint) were used to accurately evaluate changes in the quality of life of subjects affected by knee joint pain. The results of this study indicate a dose-dependent response, which should be taken into account for later use in therapeutics to establish the correct dosage.     

Corrosion Behavior of Al Modified with Zn in Chloride Solution

Aluminum-based alloys have been considered candidate materials for cathodic protection anodes. However, the Al-based alloys can form a layer of alumina, which is a drawback in a sacrificial anode. The anodes must exhibit uniform corrosion to achieve better performance. Aluminum can be alloyed with Zn to improve their performance. In this sense, in the present research, the electrochemical corrosion performance of Al-xZn alloys (x = 1.5, 3.5, and 5 at.% Zn) exposed to 3.5 wt.% NaCl for 24 h was evaluated. Polarization curves, linear polarization resistance (LPR), and electrochemical impedance spectroscopy (EIS) were used to identify the electrochemical behavior. The microstructure of the samples before the corrosion assessment was characterized by means of X-ray diffraction analyses (XRD) and scanning electron microscopy (SEM). In addition, microstructures of the corroded surfaces were characterized using X-ray mappings via SEM. Polarization curves indicated that Zn additions changed the pseudo-passivation behavior from what pure Al exhibited in a uniform dissolution regime. Furthermore, the addition of Zn shifted the corrosion potential to the active side and increased the corrosion rate. This behavior was consistent with the proportional decrease in polarization resistance (R_p) and charge transfer resistance (R_ct) in the EIS. The analysis of EIS was done using a mathematical model related to an adsorption electrochemical mechanism. The adsorption of chloride at the Al-Zn alloy surface formed aluminum chloride intermediates, which controlled the rate of the process. The rate constants of the reactions of a proposed chemical mechanism were evaluated.     

Mechanism of voltage sensing in Ca2+- and voltage-activated K+ (BK) channels

In neurosecretion, allosteric communication between voltage sensors and Ca²⁺ binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4.

Excitable tissues accomplish their signaling functions thanks in part to the interplay of several voltage-sensitive ion channels (1–6). Hence, to understand these processes, it is crucial to establish how voltage-sensitive ion channels sense changes in the electric field across the membrane, an issue that has been a matter of extensive study and intense debate for decades. The most widely accepted mechanism proposes the existence of voltage-sensor domains (VSDs), modules that undergo two or more discrete conformational states in response to changes in the membrane voltage. The simplest model considers two states: active (A), which promotes pore opening, and resting (R), which promotes channel closing. To accomplish its function, VSDs contain voltage-sensitive particles, which move in response to changes in the electric field. This movement triggers the interconversion between the two discrete conformational states. These voltage-sensing particles are typically the guanidine groups of arginine residues within the S4 transmembrane segment, which undergo a combination of rotational, translational, and tilting movement in response to changes in membrane voltage (7–14).The large-conductance Ca²⁺- and voltage-activated K⁺ (BK) channels have a wide distribution in mammalian tissues (15–18), where they participate in a diversity of physiological processes. Their malfunction is often related to diverse pathological conditions (19, 20). BK channel open probability is independently regulated by membrane depolarization and intracellular Ca²⁺ concentration (21, 22), each stimulus being detected by specialized modules. Like other voltage-sensitive K⁺ (Kv) channels, BK is an homotetramer in which each of its α subunits consists of a pore domain (PD; S5-S6 transmembrane segments), a voltage-sensing domain (VSD; S1–S4 transmembrane segments) containing a positively charged S4, and a cytosolic C-terminal regulatory domain, which contains the Ca²⁺-binding sites (23, 24). Also, like some members of other K⁺ channel families (25, 26), the VSD and PD of BK are non–domain swapped (23, 24). BK channels display some distinctive structural and functional features: Despite sharing the selectivity filter sequence with Kv channels, BK unitary conductance and selectivity are exquisitely high (27–30). The BK α subunit has an additional transmembrane segment S0 [therefore, its N terminus faces the extracellular medium (31)], and the voltage sensitivity in BK channels is significantly lower than that of Kv channels, presumably because of their lower number of gating charges (32).Although thoroughly studied, research into BK VSD and its voltage dependence has faced several technical obstacles. The relatively small gating charge per channel (32) and the large conductance of the BK pore makes isolating of the gating currents from the ionic currents a tough experimental challenge. In addition, because mutations of VSD residues can produce very large shifts in both the gating charge-voltage (Q(V)) and the conductance-voltage G(V)) relationships (33), it is necessary to use extreme voltages to accurately measure the voltage dependence of some mutants. Consequently, the identification of BK gating charges has been addressed by using indirect approaches (33, 34). The combination of electrophysiology measurements and kinetic modeling suggests a decentralized VSD in the BK channel, where four charged residues (D153 and R167 in S2, D186 in S3, and R213 in S4) act as voltage sensor particles (33). A recent report of the atomistic cryo-electron microscopy (cryo-EM) structures of the human BK channel and its homolog in Aplysia californica (AcSlo) revealed minor structural differences between the VSD in both the Ca²⁺-bound (open pore) and the Ca²⁺-unbound (closed pore) conformations (23, 24, 35). This result can be explained if the conformational changes of the BK VSD upon activation are small compared to those that occur during the activation of other channels, such as HCN channels (12–14).In this study, we identified voltage-sensing particles in the BK channel by using a direct functional approach, involving gating of current measurements and analysis of the Q(V) curves spanning 800 mV in the voltage axis. Systematic neutralization of the individual charged residues in the VSD (S1–S4) revealed that only the neutralization of two arginines in S4 (R210 and R213) changed the voltage dependence of the Q(V) curves. Neutralization of other VSD charges point to roles in tuning of the half-activation voltage of the VSD and its allosteric coupling with the PD. Molecular dynamics (MD) simulations based on the cryo-EM structures of the human BK channel (35) as templates suggested that R210 and R213 lie in a very narrow septum separating intra- and extracellular water-filled vestibules. This interpretation is consistent with the robust hyperpolarization-activated proton currents generated when R210 is mutated to the protonable amino acid histidine. Overall, our results point to a unique and distinctive mode of activation in BK: In contrast to Kv channels, where positive charges move one by one through a charge transfer center (absent in BK channels) that spans the entire electric field (36, 37), charge movement in BK channels is limited to the small displacement of R210 and R213, which itself constitutes a narrow septum where the electric field drops.     

Effectiveness of influenza vaccination in preventing influenza in primary care,Navarre, Spain, 2021/22

Compared with individuals unvaccinated in the current and three previous influenza seasons, in 2021/22, influenza vaccine effectiveness at primary care level was 37% (95% CI: 16 to 52) for current season vaccination, regardless of previous doses, and 35% (95% CI: −3 to 45) for only previous seasons vaccination. Against influenza A(H3N2), estimates were 39% (95% CI: 16 to 55) and 24% (95% CI: −8 to 47) suggesting moderate effectiveness of current season vaccination and possible remaining effect of prior vaccinations.     

Troponina I por Percentil 99 da Definição Universal de Infarto do Miocárdio versus Ponto de Corte de Melhor Acurácia em Síndromes Coronárias Agudas

Background Contemporary diagnosis of ACS and risk stratification are essential for appropriate management and reduction of mortality and recurrent ischemic events, in the acute phase of disease and after hospitalization. The Universal Definition of Myocardial Infarction recommends the detection of troponin levels above the 99^th percentile.Objectives To evaluate the occurrence of early death and acute myocardial infarction (AMI) in patients without elevation of troponin (<0.034 ng/mL), patients with mild elevation (above the 99^th percentile [>0.034 ng/mL and <0.12 ng/mL)], and patients with significant elevation of troponin (above the diagnostic cutoff for AMI defined by the troponin kit (≥0.12 ng/mL)]; and to analyze the impact of troponin on the indication for invasive strategy and myocardial revascularization.Methods Cross-sectional cohort study of patients with ACS with assessment of peak troponin I, risk score, prospective analysis of 30-day clinical outcomes and two-sided statistical tests, with statistical significance set at p<0.05.Results A total of 494 patients with ACS were evaluated. Troponin > 99^th percentile and below the cutoff point, as well as values above the cutoff, were associated with higher incidence of composite endpoint (p<0.01) and higher rates of percutaneous or surgical revascularization procedures (p<0.01), without significative difference in 30-day mortality.Conclusions Troponin levels above the 99^th percentile defined by the universal definition of AMI play a prognostic role and add useful information to the clinical diagnosis and risk scores by identifying those patients who would most benefit from invasive risk stratification and coronary revascularization procedures.     

Evolução e Estado Atual das Práticas de Implante Transcateter de Válvula Aórtica na América Latina – Estudo WRITTEN LATAM

Background:Transcatheter aortic valve replacement (TAVR) is a worldwide adopted procedure with rapidly evolving practices. Regional and temporal variations are expected to be found.Objective:To compare TAVR practice in Latin America with that around the world and to assess its changes in Latin America from 2015 to 2020.Methods:A survey was applied to global TAVR centers between March and September 2015, and again to Latin-American centers between July 2019 and January 2020. The survey consisted of questions addressing: i) center’s general information; ii) pre-TAVR evaluation; iii) procedural techniques; iv) post-TAVR management; v) follow-up. Answers from the 2015 survey of Latin-American centers (LATAM15) were compared with those of other centers around the world (WORLD15) and with the 2020 updated Latin-American survey (LATAM20). A 5% level of significance was adopted for statistical analysis.Results:250 centers participated in the 2015 survey (LATAM15=29; WORLD15=221) and 46 in the LATAM20. Combined centers experience accounted for 73 707 procedures, with WORLD15 centers performing, on average, 6- and 3-times more procedures than LATAM15 and LATAM20 centers, respectively. LATAM centers performed less minimalistic TAVR than WORLD15 centers, but there was a significant increase in less invasive procedures after 5 years in Latin-American centers. For postprocedural care, a lower period of telemetry and maintenance of temporary pacing wire, along with less utilization of dual antiplatelet therapy was observed in LATAM20 centers.Conclusion:Despite still having a much lower number of procedures, many aspects of TAVR practice in Latin-American centers have evolved in recent years, followingthe trend observed in developed country centers.