胆囊炎并发胆结石保守疗法与护理配合

老年胆囊疾病患者多数为慢性结石性胆囊炎,该病临床表现无特异性,起病缓慢,大多由急性胆囊炎反复发作迁延而至。由于年岁所限患者多采取保守疗法。如消炎利胆片、舒胆通、等口服药,起到了缓解病情的作用,但难根治。我院内科在治疗上加用了中药制剂,起到了疏肝理气、利胆通腑的药物疗效。同时护理人员注意调节好患者情志,使患者气血调和、气体通畅,加上规律饮食,确保患者及早康复。     

Biopolymer-Based Films from Sodium Alginate and Citrus Pectin Reinforced with SiO2

Blend films based on sodium alginate (SA) and citrus pectin (P) reinforced with different concentrations of SiO₂ (0–10% w/w) were developed in this study. From the morphological (SEM) and structural (FT-IR) evaluation, it was verified that the incorporation of the reinforcing agent did not drastically modify the microstructure of the films, nor did new chemical bonds form. However, the XRD results suggested a slight reduction in the crystallinities of the blends by the incorporation of SiO₂. Among the formulations prepared, the addition of a 5% reinforcing agent was responsible for the simultaneous improvement of mechanical and barrier properties. Comparing the control sample (SA/P) with the SA/P/5.0%SiO₂ film, the tensile strength increased from 27.7 ± 3.7 to 40.6 ± 4.5 MPa, and the water-vapor transmission rate decreased from 319.8 ± 38.7 to 288.9 ± 23.5 g m⁻² day⁻¹. Therefore, SiO_2, as a reinforcing agent in SA/P blends, represents a simple and effective strategy for improving the properties of biopolymer-based films in applications, such as packaging.     

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.     

La participación ciudadana en la investigación desde la perspectiva de investigadores de atención primaria

ObjectiveExplore the strengths, weaknesses, opportunities and threats (SWOT) for development of public involvement in research by Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAPJGol) according to primary health care researchers in Catalonia (Spain).MethodsCross-sectional study carried out in 2017 with 36 primary health care research teams accredited by IDIAPJGol and its management staff. An open questionnaire (paper and online) was designed and piloted to develop a SWOT technique, and 65 answers were obtained (14 in paper and 51 online). A thematic content analysis was carried out.ResultsMost informants consider public involvement in research a useful, innovative, viable and essential strategy, but it requires a change of mentality and a move away from the hierarchical paradigm. It can be difficult to execute and can complicate studies. They are concerned about which citizens should be involve, how to select them, possible conflicts of interest and training needs. The main proposals for its implementation are to disseminate previous strategies, encourage motivation and synergies among citizens, researchers and institutions, and to clarify the roles of the actors involved. IDIAPJGol should develop recommendations for the public involvement in research, encourage their inclusion, have a mentor and advise the research teams.ConclusionsDespite the challenges, developing public involvement in research in primary health care is essential and feasible, what it is more should be based on a participatory strategy with all actors. The citizens can participate in any kind of design and phase of the research, adapting each project, being the primary health care a privileged area to develop the public involvement in research.     

High S100B Levels Predict Antidepressant Response in Patients With Major Depression Even When Considering Inflammatory and Metabolic Markers

BackgroundThe relationship between antidepressant response and glial, inflammatory, and metabolic markers is poorly understood in depression. This study assessed the ability of biological markers to predict antidepressant response in major depressive disorder (MDD).MethodsWe included 31 MDD outpatients treated with escitalopram or sertraline for 8 consecutive weeks. The Montgomery-Åsberg Depression Rating Scale (MADRS) was administered at baseline and at week 4 and 8 of treatment. Concomitantly, blood samples were collected for the determination of serum S100B, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL)-C levels. Treatment response was defined as ≥50% improvement in the MADRS score from baseline to either week 4 or 8. Variables associated with treatment response were included in a linear regression model as predictors of treatment response.ResultsTwenty-seven patients (87%) completed 8 weeks of treatment; 74% and 63% were responders at week 4 and 8, respectively. High S100B and low HDL-C levels at baseline were associated with better treatment response at both time points. Low CRP levels were correlated with better response at week 4. Multivariate analysis showed that high baseline S100B levels and low baseline HDL-C levels were good predictors of treatment response at week 4 (R^2 =0.457, P = .001), while S100B was at week 8 (R² = 0.239, P = .011). Importantly, baseline S100B and HDL-C levels were not associated with depression severity and did not change over time with clinical improvement.ConclusionsSerum S100B levels appear to be a useful biomarker of antidepressant response in MDD even when considering inflammatory and metabolic markers.     

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.     

SARS-CoV-2 Accessory Protein ORF8 Decreases Antibody-Dependent Cellular Cytotoxicity

Viruses use many different strategies to evade host immune responses. In the case of SARS-CoV-2, its Spike mutates rapidly to escape from neutralizing antibodies. In addition to this strategy, ORF8, a small accessory protein encoded by SARS-CoV-2, helps immune evasion by reducing the susceptibility of SARS-CoV-2-infected cells to the cytotoxic CD8+ T cell response. Interestingly, among all accessory proteins, ORF8 is rapidly evolving and a deletion in this protein has been linked to milder disease. Here, we studied the effect of ORF8 on peripheral blood mononuclear cells (PBMC). Specifically, we found that ORF8 can bind monocytes as well as NK cells. Strikingly, ORF8 binds CD16a (FcγRIIIA) with nanomolar affinity and decreases the overall level of CD16 at the surface of monocytes and, to a lesser extent, NK cells. This decrease significantly reduces the capacity of PBMCs and particularly monocytes to mediate antibody-dependent cellular cytotoxicity (ADCC). Overall, our data identifies a new immune-evasion activity used by SARS-CoV-2 to escape humoral responses.     

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.     

One Health surveillance of West Nile and Usutu viruses: a repeated cross-sectional study exploring seroprevalence and endemicity in Southern France, 2016 to 2020

BackgroundWest Nile virus (WNV) and Usutu virus (USUV), two closely related flaviviruses, mainly follow an enzootic cycle involving mosquitoes and birds, but also infect humans and other mammals. Since 2010, their epidemiological situation may have shifted from irregular epidemics to endemicity in several European regions; this requires confirmation, as it could have implications for risk assessment and surveillance strategies.AimTo explore the seroprevalence in animals and humans and potential endemicity of WNV and USUV in Southern France, given a long history of WNV outbreaks and the only severe human USUV case in France in this region.MethodsWe evaluated the prevalence of WNV and USUV in a repeated cross-sectional study by serological and molecular analyses of human, dog, horse, bird and mosquito samples in the Camargue area, including the city of Montpellier, between 2016 and 2020.ResultsWe observed the active transmission of both viruses and higher USUV prevalence in humans, dogs, birds and mosquitoes, while WNV prevalence was higher in horses. In 500 human samples, 15 were positive for USUV and 6 for WNV. Genetic data showed that the same lineages, WNV lineage 1a and USUV lineage Africa 3, were found in mosquitoes in 2015, 2018 and 2020.ConclusionThese findings support existing literature suggesting endemisation in the study region and contribute to a better understanding of USUV and WNV circulation in Southern France. Our study underlines the importance of a One Health approach for the surveillance of these viruses.