The Global Initiative for Asthma recommends as-needed inhaled corticosteroid (ICS)-formoterol as an alternative to maintenance ICS plus short-acting β
-agonist (SABA) reliever at step 2 of its stepwise treatment algorithm. Our aim was to assess the efficacy and safety of these two treatment regimens, with a focus on prevention of severe exacerbation.

We performed a systematic review and meta-analysis of all randomised controlled trials (RCTs) comparing as-needed ICS-formoterol with maintenance ICS plus SABA. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov were searched from database inception to 12 December 2019. The primary outcome was time to first severe exacerbation. RCTs were excluded if they used as-needed budesonide-formoterol as part of a maintenance and reliever regimen, or did not report on severe exacerbations. The review is registered with PROSPERO (identifier number CRD42020154680).

Four RCTs (n=8065 participants) were included in the analysis. As-needed ICS-formoterol was associated with a prolonged time to first severe exacerbation (hazard ratio 0.85, 95% CI 0.73-1.00; p=0.048) and reduced daily ICS dose (mean difference -177.3 μg, 95% CI -182.2--172.4 μg). Asthma symptom control was worse in the as-needed group (Asthma Control Questionnaire-5 mean difference 0.12, 95% CI 0.09-0.14), although this did not meet the minimal clinically important difference of 0.50 units. There was no significant difference in serious adverse events (OR 1.07, 95% CI 0.84-1.36).

As-needed ICS-formoterol offers a therapeutic alternative to maintenance low-dose ICS plus SABA in asthma and may be the preferred option when prevention of severe exacerbation is the primary aim of treatment.
As-needed ICS-formoterol offers a therapeutic alternative to maintenance low-dose ICS plus SABA in asthma and may be the preferred option when prevention of severe exacerbation is the primary aim of treatment.Higher body mass index (BMI) is associated with less severe airway obstruction in older asthma patients with fixed airflow obstruction. This is potentially mediated through BMI-related mechanisms that increase lung stiffness (i.e. reduce lung compliance). https//bit.ly/3jBwCNy.The aim was to determine whether losartan reduces cigarette smoke (CS)-induced airway inflammation and mucus hypersecretion in an in vitro model and a small clinical trial. Primary human bronchial epithelial cells (HBECs) were differentiated at the air-liquid interface (ALI) and exposed to CS. Expression of transforming growth factor (TGF)-β1 and the mucin MUC5AC, and expression or activity of matrix metalloproteinase (MMP)-9 were measured after CS exposure. Parameters of mucociliary clearance were evaluated by measuring airway surface liquid volumes, mucus concentrations, and conductance of cystic fibrosis transmembrane conductance regulator (CFTR) and large conductance, Ca2+-activated and voltage-dependent potassium (BK) channels. Nasal cells were collected from study participants and expression of MUC5AC, TGF-β1, and MMP-9 mRNAs was measured before and after losartan treatment. In vitro, CS exposure of HBECs caused a significant increase in mRNA expression of MUC5AC and TGF-β1 and MMP-9 activity and decreased CFTR and BK channel activities, thereby reducing airway surface liquid volumes and increasing mucus concentrations. Treatment of HBECs with losartan rescued CS-induced CFTR and BK dysfunction and caused a significant decrease in MUC5AC expression and mucus concentrations, partially by inhibiting TGF-β signalling. In a prospective clinical study, cigarette smokers showed significantly reduced mRNA expression levels of MUC5AC, TGF-β1, and MMP-9 in the upper airways after 2 months of losartan treatment. Our findings suggest that losartan may be an effective therapy to reduce inflammation and mucus hypersecretion in CS-induced chronic airway diseases.Standard bronchoscopy and EBUS-TBNA have good diagnostic yield and are relatively safe procedures in the setting of SVCS. However, complications may arise from the underlying malignancy and its proximity to central vital structures. https//bit.ly/37HXFUY.Multiple clinical conditions are combined with genetic mutations to contribute to the development of pulmonary vascular remodelling in hereditary haemorrhagic telangiectasia. A systematic aetiological evaluation is required for these patients. https//bit.ly/34V7HPy.
Probiotic treatments might contribute to the prevention of ventilator-associated pneumonia (VAP). Due to its unclear clinical effects, here we intend to assess the preventive effect and safety of probiotics on intensive care unit (ICU) patients.

Eligible randomised controlled trials were selected in databases until 30 September 2019. https://www.selleckchem.com/products/nvp-bgt226.html The characteristics of the studies were extracted, including study design, definition of VAP, probiotics intervention, category of included patients, incidence of VAP, mortality, duration of mechanical ventilation (MV) and ICU stay. Heterogeneity was evaluated by Chi-squared and I
tests.

15 studies involving 2039 patients were identified for analysis. The pooled analysis suggests significant reduction on VAP (risk ratio, 0.68; 95% Cl, 0.60 to 0.77; p<0.00001) in a fixed-effects model. Subgroup analyses performed on the category of clinical and microbiological criteria both support the above conclusion; however, there were no significant differences in duration of MV or length of ICU stay in a random-effects model. Also, no significant differences in total mortality, overall mortality, 28-day mortality or 90-day mortality were found in the fixed-effects model.

The probiotics helped to prevent VAP without impacting the duration of MV, length of ICU stay or mortality.
The probiotics helped to prevent VAP without impacting the duration of MV, length of ICU stay or mortality.This document constitutes a summary of the clinical practice guidelines (CPGs) prepared at the initiative of the Latin American Thoracic Society (ALAT). Due to new evidence in the treatment of severe asthma, it was agreed to select six clinical questions, and the corresponding recommendations are provided herein. After considering the quality of the evidence, the balance between desirable and undesirable impacts and the feasibility and acceptance of procedures, the following recommendations were established. 1) We do not recommend the use of an inhaled corticosteroid (ICS) plus formoterol as rescue medication in the treatment of severe asthma. 2) We suggest performing many more high-quality randomised studies to evaluate the efficacy and safety of tiotropium in patients with severe asthma. 3) Omalizumab is recommended in patients with severe uncontrolled allergic asthma with serum IgE levels above 30 IU. 4) Anti-interleukin (IL)-5 drugs are recommended in patients with severe uncontrolled eosinophilic asthma (cut-off values above 150 cells·µL-1 for mepolizumab and above 400 cells·µL-1 for reslizumab).

6%, 4.8-28.6%) less frequent, P=0.033) but not anti-native-CII. There was no impact of age/gender on AutoAbs associations with diseases either looking at positivity or levels. In SF, OA patients were often ACPA+ (45.9%) although less frequently than in RA (P=0.004). Anti-CarP were rarely observed (<5% all samples). All collagen AutoAbs were more frequent in RA compared to OA (all P<0.010) but only levels of anti-CII and anti-ROS-CII were significantly higher in they RA (P<0.050).

Although the frequency of AutoAbs for PTM proteins were lower in OA sera compared to RA, a higher proportion of OA SF were positive. The relative retention of AutoAbs in the OA joint requires further investigation.
Although the frequency of AutoAbs for PTM proteins were lower in OA sera compared to RA, a higher proportion of OA SF were positive. The relative retention of AutoAbs in the OA joint requires further investigation.
Osteoarthritis (OA) is a serious joint disease with no disease-modifying medical treatment. To develop treatments targeting synovium, we must improve our understanding of the effects of OA-related changes in synovial physiology on joint tissue outcomes. The aim of this study was to investigate the effects of synovial pathology due to post-traumatic OA (PTOA) on articular chondrocyte physiology.

We first developed and validated a novel joint tissue co-culture system to model the biological interactions between synovium and articular chondrocytes. Whole-joint synovial tissue from a surgical rat model of PTOA vs sham and surgical-naïve controls was placed into a co-culture system with adult primary articular chondrocytes (n=4-5). The effects of PTOA synovium on chondrocyte anabolic, inflammatory, and catabolic gene expression and sulfated glycosaminoglycan (sGAG) secretion and aggrecan synthesis were tested, and results from early and later stages of PTOA development were compared.

Synovial injury by arthrontribute to PTOA progression.
Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Saturated and n-6 fatty acids (FAs) increase, whereas n-3 FAs reduce inflammation. We examined whether FA levels affected the development of OA.

We studied participants from the Multicenter Osteoarthritis study (MOST) at risk of developing knee OA. After baseline, repeated knee x-rays and MRIs were obtained and knee symptoms queried through 60 month follow-up. Using baseline fasting samples, serum FAs were analyzed with standard assays. After excluding participants with baseline OA, we defined two sets of cases those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage loss and synovitis and of knee pain using WOMAC and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of saturated, n-3 and n-6 FAs adjusting for age, sex, BMI, education, race, baseline pain and depressive symptoms.

We studied 260 cases with incident symptomatic and 259 with incident radiographic OA. Mean age was 61 years (61% women). We found no signficant nor suggestive associations of FA levels with incident OA (e.g., for incident symptomatic OA, OR per s.d. increase in n-3 FA 1.00 (0.85, 1.18) nor with any OA outcome in knee or hand.

Despite previously described effects on systemic inflammation, blood levels of FAs were not associated with risk of later knee OA or other OA outcomes.
Despite previously described effects on systemic inflammation, blood levels of FAs were not associated with risk of later knee OA or other OA outcomes.
To compare ground reaction force patterns (GRF) during walking among legs defined by presence or absence of knee pain and/or radiographic knee osteoarthritis (ROA).

Principal component analysis extracted major modes of variation (PCs) in GRF data from the Multicenter Osteoarthritis Study during self-paced walking. Legs were categorized as pain+ROA (n=168), ROA only (n=303), pain only (n=476), or control (n=1877). Relationships between group and GRF PCs were examined using Generalized Estimating Equations, adjusted for age, sex, body mass index, race, and clinic site with and without additional adjustment for gait speed.

With or without speed adjustment, pain+ROA had flatter vertical GRF waveforms than control (speed adjusted PC2 difference [95%CI]-66 [-113,-20]), pain+ROA and ROA only had higher lateral GRF at impact and greater mid-stance medial GRF than control (speed adjusted PC3 difference 9 [3,16] and 6 [2,10], respectively), and ROA only had higher early vs late medial GRF than control (speed adjung.L-asparaginase (EC 3.5.1.1) showed great commercial value owing to its effective treatment of acute lymphoblastic leukemia (ALL), lymphoid system malignancies and Hodgkin disease, and also to its use in the prevention of acrylamide formation in fried and baked foods. In this study, a type I L-asparaginase gene from Bacillus licheniformis Z-1 (BlAase) was cloned and expressed in Bacillus subtilis RIK 1285. Results showed that even without the mediation of any N-terminal signal peptides, BlAase can efficiently secrete into the medium. Further investigation indicated that the secretion of the BlAase was via neither Sec- nor Tat-dependent secretion pathway, and both the N- and C-terminal regions of the BlAase were essential for its expression and secretion, implying that BlAase might be secreted via a non-classical secretion pathway. To explore its secretion ability, BlAase was used as a signal peptide to direct the secretion of various heterologous proteins, where two of five proteins were successfully secreted with the mediation of BlAase. To the best of our knowledge, this is the first time to achieve extracellular expression of L-asparaginase via non-classical protein secretion pathway in B. subtilis, and provide a potential tool for secretion of recombinant proteins expressed in B. subtilis using BlAase as a signal peptide.Natural gums and mucilages from plant-derived polysaccharides are potential candidates for a tissue-engineering scaffold by their ability of gelation and biocompatibility. Herein, we utilized Glucuronoxylan-based quince seed hydrogel (QSH) as a scaffold for tissue engineering applications. Optimization of QSH gelation was conducted by varying QSH and crosslinker glutaraldehyde (GTA) concentrations. Structural characterization of QSH was done by Fourier Transform Infrared Spectroscopy (FTIR). Furthermore, morphological and mechanical investigation of QSH was performed by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The protein adsorption test revealed the suitability of QSH for cell attachment. Biocompatibility of QSH was confirmed by culturing NIH-3T3 mouse fibroblast cells on it. Cell viability and proliferation results revealed that optimum parameters for cell viability were 2 mg mL-1 of QSH and 0.03 M GTA. SEM and DAPI staining results indicated the formation of spheroids with a diameter of approximately 300 μm. Furthermore, formation of extracellular matrix (ECM) microenvironment was confirmed with the Collagen Type-I staining. Here, it was demonstrated that the fabricated QSH is a promising scaffold for 3D cell culture and tissue engineering applications provided by its highly porous structure, remarkable swelling capacity and high biocompatibility.Kraft pulping, organosolv process and acid hydrolysis were applied on an elm clone. The solubilized lignins were recovered and analyzed. Kraft pulping and acid hydrolysis led to lignins with higher phenolic OH content as result of extensive cleavage of β-O-4' linkages, as revealed by 13C solid state and 13C-1H heteronuclear single quantum coherence nuclear magnetic resonance. This depolymerization also yielded lower molecular weight lignins inferred by size exclusion chromatography. Contrarily, organosolv process gave rise to a lignin with a more preserved structure, maintaining a large number of β-O-4' linkages. Consequently, organosolv lignin presented lower phenolic OH content and higher molecular weight. https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html Moreover, the high content of the labile native β-O-4' linkages in organosolv lignin resulted in a lower thermostability as compared to the kraft and acid lignins. On the other hand, the solubilized lignins from kraft and acid processes displayed an enrichment of S-units, whereas lignin from organosolv process was slightly enriched in G-units, containing all of them different native as well as pre-treatment derived units. These results could help to increase the inventory of lignin sources available for future lignin-based products, for which knowledge of the lignin properties versus application requirements is crucial.Fucoidan has received much attention in healthy food and biomedicine owing to their unique (bio)physicochemical properties, particularly antibacterial and antiviral. Pathogenic microorganisms and probiotics are coexisting in many tissues (e.g., gut, oral, and vagina). However, the effect of fucoidan on probiotics has not been examined. Herein, fucoidan sterilized by different methods (i.e., 0.22 μm filter and high-temperature autoclave) is applied to explore its effect on the responses of Lactobacillus rhamnosus. It is found that high-temperature autoclave treatment causes the depolymerization of fucoidan. Further, the proliferation, morphology, and metabolism of probiotics are greatly dependent on the concentrations of fucoidan. The formation of probiotic biofilm is reduced with an increased concentration of fucoidan. Moreover, the antibacterial ability of probiotics initially increases and then decreases with an increased concentration of fucoidan. Thus, fucoidan could serve as a new marine-origin prebiotic, offering new insight into probiotic modulation and its application in inhibiting bacterial infections.While Fusobacterium necrophorum historically has been considered normal tonsillar flora, recent studies from Europe and the US have suggested that carriage occur transiently in adolescence and young adulthood. However, no studies originating from Africa exist. In this cross-sectional study of tonsillar carriage of F. necrophorum, we aimed to investigate geographical differences in tonsillar carriage rates of F. necrophorum in healthy participants aged 15-25 years in Sweden and Zambia and further investigate the age distribution of tonsillar carriage in Zambia. Specimens were obtained by tonsillar swabs and analyzed with real-time PCR for F. necrophorum. In participants aged 15-25 years, tonsillar carriage was more common in Sweden 21/100 (21%) than in Zambia 6/192 (3%), p less then 0.001. In Zambian participants aged above 25 years tonsillar carriage was rare 1/76 (1%). In conclusion, the high rate of tonsillar carriage in participants aged 15-25 years in Sweden has implications on the interpretation of tonsillar findings in patients with pharyngotonsillitis. Interestingly, a geographical difference was found with tonsillar carriage rarely identified in Zambia.Cancer is the second leading cause of death worldwide being responsible for 9.6 million deaths in 2018. Epigenetic alterations are key in directing the aberrant expression of tumor-associated genes that drive cellular malignant transformation and cancer progression. Among epigenetic alterations, DNA methylation is the most deeply studied one in relation to environmental exposure. Tissue biopsies have traditionally been the main procedure by which a small sample of body tissue is excised to confirm cancer diagnosis or to indicate the primary site when cancer has spread. In contrast, the analysis of circulating tumor-derived material, or tumor circulome, by means of liquid biopsy of peripheral blood, urine, saliva or sputum is a noninvasive, fast and reproducible alternative to tissue biopsy. Recently, the assessment of epigenetic alterations such as DNA methylation and hydroxymethylation in circulating free DNA has been proved possible. These marks can be associated to prognosis and response to a variety of treatments including chemotherapy, hormonotherapy or immunotherapy.

A 24-year-old male came to our clinic for a volumetric increase of a suspected scrotal hemangioma with thrombosis episodes. The ultrasound rose the suspicion of hemangioma and the Magnetic Resonance (MR) of the scrotum confirmed the suspicion. The mass was surgically removed and histopathology described a hemangioma cavernous. The postoperative course was regular and no subsequent relapse was shown in 5 months follow-up.OBJECTIVE To compare the surgical results, complications, and satisfaction levels of patients who underwent malleable penile prosthesis implantation (M-PPI) and Ambicor penile prosthesis implantation (A-PPI). MATERIAL AND METHODS One hundred forty two patients who underwent penile prosthesis implantation [M-PPI (Promedon- Tube®, Cordoba, Argentina) 81, and A-PPI (American Medical Systems, Minnesota, USA) 61] between 2013-2018 were evaluated retrospectively. Patients' age, body mass index, smoking history, etiological factors, modified "Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) Questionnaire" scores, shortening of the penis, and complications were recorded. RESULTS The patients who performed A-PPI implantation were younger (56.27 ± 10.81 vs. 51.47 ± 11.79, p = 0.009). The EDITS scores of 31(38.2%) patients who underwent M-PPI and 44 (72.4%) patients who underwent A-PPI were available. It was observed that the scores on the following questions were statistical significantly higher in the A-PPI group "Overall, are you satisfied with your penile prosthesis?, How much of your expectations did penile prosthesis meet?, How often do you use your penile prosthesis?" (p = 0.05, p = 0.048, p = 0.038). No difference was observed between the groups in terms of the scores on the other three questions (p = 0.447, p = 0.326, p = 0.365). A 61.3% of patients in MPPI (19/31) group, and 56.8% of patients in A-PPI (25/44) group stated penile shortening (p = 0.417). Mean shortening was reported as 2.1 ± 0.45 cm, and 2.12 ± 0.52 cm, in M-PPI and A-PPI groups, respectively (p = 0.90). CONCLUSION It is remarkable that the patients who underwent A-PPI experienced higher satisfaction with their prosthesis. Even though it has not been evidenced in the current literature data, patients who have had either M-PPI or A-PPI should be informed about the risk of penile shortening.OBJECTIVE The most crucial steps of percutaneous nephrolithotomy (PCNL) are the percutaneous access and dilation of the access route. Recent literature suggests that papillary access to renal calyx is the accepted method. Despite this rule, we do not always make papillary puncture and we puncture wherever we can to achieve stone-free status and reduce unnecessary access. In this study, we present our results with papillary vs non-papillary access in patients with a kidney stone. MATERIAL AND METHODS Two hundred and seven patients with non-papillary access and 69 patients with papillary access who had similar demographics (age, body mass index (BMI), stone size) were selected with pair match analysis (31). Preoperative and postoperative data were collected from the patient's chart. Operative time (from starting surgery to nephrostomy tube), drop-in hematocrit level, transfusion rate, duration of hospital stay, perioperative and postoperative complications (Clavien-Dindo Classification) and stone-free status (no or less then 3 mm residual stone) were also evaluated in both groups. RESULTS The mean operative time was similar in between two groups. The mean hematocrit decreases not differ between the two groups (p = 0.56). In papillary group, only 2 patients (3.2%) required transfusion and only one patient (1.4%) in the non-papillary group had a transfusion with no statistically significant difference (p = 0.43). The overall complication rates were 7.1% in the papillary group and 7.2% in the non-papillary group (p = 0.89). Postoperative mean creatinine level was similar between the two groups.  Conclusions In this study, we found that non-papillary access is a feasible option for PCNL in the terms of stone-free status and complication rates.OBJECTIVE We aimed to retrospectively evaluate the effectiveness and safety of flexible ureteroscopy (f-URS), semirigid ureteroscopy (sr-URS), and shock wave lithotripsy (SWL) to treat single 11-20 mm stones in the proximal ureter. MATERIALS AND METHODS Patients treated at our clinic for 11-20 mm single stones in the proximal ureter who underwent f-URS, sr-URS or SWL as initial lithotripsy methods were compared in terms of their clinical characteristics and treatment outcomes. RESULTS A comparison among 201 patients who had undergone f-URS, 119 patients who had undergone sr-URS, and 162 patients who had undergone SWL showed no significant baseline differences in patients' demographic and stone characteristics. Stone-free rates on the 15th day and 3rd month were higher with f-URS (89.6% and 97%, respectively) than with sr-URS (67.2% and 94.1%, respectively) and SWL (41.4% and 79.0%, respectively; all p less then 0.001). Retreatment rates were significantly higher with SWL than with the other two modalities (p less then 0.001); auxiliary procedure rates were significantly lower with f-URS than with the other two modalities (p less then 0.001). Treatment-related complication rate at the end of the 3rd month was lower with f-URS than with SWL (p = 0.022). Furthermore, f-URS was more effective than sr-URS for treating impacted stones. CONCLUSIONS We found that f-URS was highly successful as an initial lithotripsy procedure for medium-sized proximal ureteral stones, and it helped achieve early stone-free outcomes with a lower need for retreatment and auxiliary procedures, lower complication rates, and higher effectiveness on the impacted stones compared with sr-URS and SWL.OBJECTIVE Urinary tract infections (UTIs) are defined as the symptomatic presence of pathogens in the urinary tract that are typically diagnosed by microscopy and culture of urine samples. Over the long-term antibiotic courses, alternative prophylactic methods as probiotics, cranberry juices and D-mannose have been introduced for recurrence prevention. The present study aimed to determine whether a new combination of D-Mannose, Pomegranate extract, Prebiotics and Probiotics is effective in modifying symptoms reported by women with acute uncomplicated acute cystitis. MATERIAL AND METHODS This is a pilot study, performed between September 2018 and November 2018 at the Department of Urology of Villa Stuart Private Hospital. A dose of a new combination of agents was administered twice daily for 5 days and then once a day for 10 days. Together with the compound, forced hydration (> 2 liters/day) has been strongly suggested. https://www.selleckchem.com/products/sn-011-gun35901.html Antibiotics were permitted only in case of clinical worsening. Changes in patients' symptoms, the therapeutic effects and changes in quality of life (QoL) were evaluated clinically and through a validated questionnaire, the Acute Cystitis Symptom Score (ACSS) at the first visit (T0), 15 (T1) and 30 (T2) days later.

OBJECTIVE To analyze and compare the expression of Toll-like receptors by regulatory T cells present in the peritoneal fluid of patients with and without endometriosis. METHODS Regulatory T cells were isolated from peritoneal fluid of women with and without endometriosis, collected during surgery, and mRNA was extracted for analysis of Toll-like receptors expression by reverse-transcriptase polymerase chain reaction. RESULTS Patients with endometriosis presented regulatory T cells expressing a larger number and variety of Toll-like receptors when compared to regulatory T cells from patients in the Control Group. Toll-like receptor-1 and Toll-like receptor-2 in regulatory T cells were expressed in both groups. All other expressed Toll-like receptors types were only found in regulatory T cells from the Endometriosis Group. CONCLUSION Patients with endometriosis had peritoneal regulatory T cells expressing various Toll-like receptors types.Probiotic therapy is a viable alternative to chlorhexidine, a widely used antiseptic in dentistry that produces significant adverse effects. This systematic review aimed to analyze the effects of probiotics on experimental gingivitis in humans. Two independent reviewers conducted a comprehensive literature search until March 2019. Randomized clinical trials and controlled clinical trials were selected. Outcome data were extracted and critically analyzed. A total of five articles were included in the qualitative synthesis. No meta-analysis could be conducted due to the heterogeneity of the selected studies. The use of probiotics showed a slight improvement in clinical parameters. Changes in gingival crevicular fluid volume were lower in the presence of the probiotic than in the placebo group. All the studies showed that the immediate, positive effects of probiotics during the period of discontinued mechanical oral hygiene were due to the modulation of the host response, not the anti-plaque effect. Investigators should conduct randomized clinical trials to elucidate the mechanisms of probiotic action and develop improved delivery systems.in English, Portuguese FUNDAMENTO A ablação da fibrilação atrial (FA) e do flutter atrial dependente de istmo cavo-tricuspídeo (FLA-ICT) pode ser realizada simultaneamente quando as duas arritmias tenham sido registradas antes do procedimento. Entretanto, a melhor abordagem não é clara quando pacientes com FLA-ICT são encaminhados para ablação sem o registro prévio de FA. OBJETIVOS Avaliar a prevalência e identificar os preditores de ocorrência do primeiro episódio de FA após ablação de FLA-ICT em pacientes sem o registro prévio de FA. MÉTODOS Coorte retrospectiva de pacientes submetidos exclusivamente a ablação por cateter para FLA-ICT, sem registro prévio de FA. As características clínicas foram comparadas entre os grupos em que houve ocorrência de FA pós-ablação de FLA-ICT vs. https://www.selleckchem.com/products/AG14361.html sem ocorrência de FA. O nível de significância estatística adotado foi de 5%. Na análise de preditores, o desfecho primário avaliado foi ocorrência de FA após ablação de FLA-ICT. RESULTADOS De um total de 227 pacientes submetidos a ablação de FLA-ICT (110 com registro de FA e 33 sem seguimento adequado), 84 pacientes foram incluídos, dos quais 45 (53,6%) apresentaram FA pós-ablação. Não houve variáveis preditoras de ocorrência de FA. Os escores HATCH e CHA2DS2-VASC foram semelhantes nos dois grupos. As taxas de recorrência de FLA-ICT e complicações após a ablação foram de 11,5% e 1,2%, respectivamente. CONCLUSÕES A ablação de FLA-ICT é eficaz e segura, mas 50% dos pacientes desenvolvem FA após ablação. Entretanto, ainda é incerto o papel da ablação combinada (FLA-ICT e FA) visando prevenção da ocorrência de FA. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).in English, Portuguese FUNDAMENTOS Afrodescendentes têm sido associados a uma maior gravidade da hipertensão arterial e maior incidência de complicações cardiovasculares. Características na apresentação da hipertensão resistente (HR) ou hipertensão refratária (HRf), especificamente nessa etnia, não têm sido devidamente estudadas. OBJETIVOS O estudo compara características clínicas e epidemiológicas e prevalência de eventos cardiovasculares em afrodescendentes com diagnóstico de HR ou de HRf. MÉTODOS Estudo transversal realizado em ambulatório de referência para pacientes com Hipertensão Grave. O nível de significância foi de 5%. RESULTADOS Avaliados 146 pacientes consecutivos, dos quais 68,7% eram do sexo feminino. A média de idade foi de 61,8 anos, sendo 88,4% afrodescendentes (pardos ou negros). 51% apresentavam HRf. Houve alta prevalência de fatores de risco cardiovascular 34,2% tinham diabetes, 69,4% dislipidemia, 36,1% obesidade e 38,3% história de tabagismo. Função renal reduzida foi observada em 34,2%. Eventos cardiovasculares prévios ocorreram em 21,8% para infarto do miocárdio e em 19,9% para acidente vascular cerebral. O escore de risco de Framingham foi moderado/alto em 61%. Os pacientes com HRf eram mais jovens (média de idade de 59,38±11,69 anos versus 64,10±12,23 anos, p=0,02), tinham mais dislipidemia (83,8 versus 66,7%, p=0,021) e acidente vascular cerebral (30,4 versus 12,3%, p=0,011) quando comparados aos com HR. O uso de combinação de ACEi/BRA+CCB+Diurético, clortalidona e espironolactona também foi mais frequente em indivíduos com HRf. CONCLUSÃO Afrodescendentes com HR apresentaram alto risco cardiovascular, alta prevalência de HRf, maior frequência de dislipidemia e de acidente vascular cerebral, compatível com alta incidência de lesão a órgãos-alvo. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).in English, Portuguese FUNDAMENTO A doença arterial coronariana (DAC) associada à quimioterapia está se tornando um tema emergente na prática clínica. Contudo, o mecanismo subjacente da quimioterapia associada à DAC permanence incerto. OBJETIVOS O estudo investigou a associação entre a quimioterapia e as anomalias anatômicas ateroscleróticas das artérias coronárias dentre pacientes com cancer de pulmão. MÉTODOS Foram incluídos pacientes submetidos à angiografia coronária (AGC), entre 2010 e 2017, com câncer de pulmão prévio. Os fatores de risco associados à DAC e os dados sobre o câncer de pulmão foram avaliados. Avaliamos as anomalias das artérias coronárias de acordo com o escore SYNTAX (SXescore) calculado à AGC. Na análise de regressão logística, o escore SYNTAX foi classificado como alto (SXescoreALTO) se ≥22. Os dados foram analisados através de estatística descritiva e análise de regressão. RESULTADOS Ao todo, 94 pacientes foram incluídos no estudo. O SXescore foi mais alto no grupo com quimioterapia quando comparado com o grupo sem quimioterapia (25,25, IIQ [4,50–30,00] versus 16,50, IIQ [5,00–22,00]; p = 0,0195).

Accumulation of senescent cells in the bone marrow leads to age-related bone degeneration. Identifying the key senescent cell types and the factors they release that are responsible for skeletal aging is of keen interest. In a new study by Li et al. (2021), it is shown that immune cells, including neutrophils and macrophages, are critical cell types in this aging process, and that they secrete grancalcin to promote such aging.In a new study, Zhu et al. (2021) show that mitigating dysbiosis by the probiotic L. casei Zhang reduces kidney inflammation via restoring short-chain fatty acid-producing gut microbiome and nicotinamide metabolism. These findings shed light on the underlying mechanisms of probiotics in treating human kidney diseases.In this issue, we showcase review and research articles from our scientific colleagues in China. But behind the detailed methods, figures, and datasets are the people who have made it their life's work to advance science. Here, we pause to listen to their own voices and learn about the stories and motivation driving their research.
This study aims to search for reliable serological biomarkers allowing the early prediction of cystic echinococcosis (CE) post-operative outcomes.

We applied immunoprecipitation (IP) of Echinococcus granulosus protoscolex antigens with pediatric CE patients' plasma collected at 1-month and 1-year post-surgery, followed by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS). We compared IP proteomic content from relapsed patients within the first-year post-surgery (RCE) to cases with no relapses until 3 post-operative years (NRCE). Selected proteins were recombinantly synthesized and assessed for their prognostic performance by Enzyme-linked immunosorbent assay (ELISA).

A total of 305 immunoreactive parasitic proteins were identified, 59 of which were significantly more abundant in RCE than NRCE for both time-points. Four proteins showed the most promising characteristics for predicting CE outcomes cytoplasmic malate dehydrogenase (Eg-cMDH), citrate synthase (Eg-CS), annexin A6 and severin. ELISA-IgG against the four markers were significantly lower at 1-year post-surgery than 1-month in NRCE, in contrast to RCE that displayed either stable or higher levels. The Eg-cMDH and Eg-CS showed the best prognostic performance, with respective probabilities of being "relapse-free" of 83% and 81%, if a decrease of IgG levels occurred between 1-month and 1-year post-surgery.

The Eg-cMDH and Eg-CS are promising biomarkers to predict early CE post-surgical outcomes.
The Eg-cMDH and Eg-CS are promising biomarkers to predict early CE post-surgical outcomes.
Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat infective endocarditis (IE) with documented success. This study aims to identify risk factors for treatment failure and poor outcomes in patients with IE treated through OPAT.

We conducted a retrospective analysis of all episodes of IE treated over 13 years (September 2006 - September 2019) at a large teaching hospital in Sheffield, UK. We defined OPAT failure as unplanned readmission or death within 30 days of discharge from the OPAT service. Major adverse cardiac events (MACE) were defined as a composite of IE-related death, cardiac surgery, and recurrence of IE within the first year of completion of OPAT.

Overall, 168 episodes of IE were reviewed. OPAT failure and MACE occurred in 44 episodes (26.2%) and 29 episodes (17.3%) respectively. On multivariable analysis, pre-existing renal failure (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.08-8.30; P=0.034) and Charlson comorbidity score (aOR, 1.29 per unical outcomes.
We aim to study the viral kinetics and host inflammatory response of RSV infection in older adults, and their correlation with disease severity.

We performed a prospective observational study in adults with RSV infection. We serially collected nasal-throat swabs for quantification of RSV-A and RSV-B viral load, and peripheral blood samples for measurement of cytokine/chemokine concentrations. The study endpoints were (i) requiring supplemental oxygen therapy, and (ii) non-invasive ventilation, intensive care, or died within 30 days of admission. We performed multivariable logistic regression models to identify independent variables for severe disease.

We enrolled 71 hospitalized patients and 10 outpatients treated for RSV infection (median age 75 years, 51% male, and 74% with comorbidities). Among hospitalized patients, 61% required supplemental oxygen therapy, and 18% had severe disease requiring non-invasive ventilation or intensive care, or died within 30 days. Inflammatory cytokine/chemokines IL-6, CXCL8/IL-8, CXCL9/MIG and CXCL10/IP-10 increased significantly during the acute phase of illness. IL-6 concentration was independently associated with severe disease after adjusting for confounding factors. RSV viral load was not associated with disease severity throughout the course of illness.

Host inflammatory response is a major marker of severe disease in older adults with RSV infection.
Host inflammatory response is a major marker of severe disease in older adults with RSV infection.
Despite the importance of prenatal care, quality measurement efforts have focused on the number of prenatal visits, or prenatal care adequacy, rather than the services received. It is unknown whether receiving more prenatal visits is associated with receiving more guideline-based prenatal care services. The relationship between guideline-based prenatal care and patients' clinical and sociodemographic characteristics has also not been studied.

To measure receipt of guideline-based prenatal care among pregnant patients and to describe the association of guideline-based prenatal care with the number of prenatal visits and other patient characteristics.

This is a retrospective descriptive cohort study of 176,092 pregnancy episodes between 2016-2019. We used de-identified administrative claims data on commercial enrollees across the United States from the OptumLabs® Data Warehouse. We identified eight components of prenatal care that are universally recommended by the American College of Obstetricians and Gyal care better than visit count or adequacy alone.At each cell division, the spindle self-organizes from microtubules and motors. In human spindles, the motors dynein and Eg5 generate contractile and extensile stress, respectively. Inhibiting dynein or its targeting factor NuMA leads to unfocused, turbulent spindles, and inhibiting Eg5 leads to monopoles; yet, bipolar spindles form when both are inhibited together. What, then, are the roles of these opposing motors? Here, we generate NuMA/dynein- and Eg5-doubly inhibited spindles that not only attain a typical metaphase shape and size but also undergo anaphase. However, these spindles have reduced microtubule dynamics and are mechanically fragile, fracturing under force. Furthermore, they exhibit lagging chromosomes and a dramatic left-handed twist at anaphase. Thus, although these opposing motors are not required for spindle shape, they are essential to its mechanical and functional robustness. This work suggests a design principle whereby opposing active stresses provide robustness to force-generating cellular structures.It is widely known that red blood cells (RBCs) are responsible for respiration and the transport of gas. However, recent reports have also described the immune properties of RBCs, therefore creating new understanding for the functionality of RBCs. However, little is known about the immunological role of RBCs in bony fish. In this study, we used RBCs from Clarias fuscus as a model and demonstrate that these cells exhibited phagocytic ability with both latex beads and bacteria. Scanning electron microscopy and transmission electron microscopy provided visual confirmation of the phagocytotic process in RBCs. In addition, we used flow cytometry and fluorescence microscopy to analyse the rate of phagocytosis in RBCs. We found that RBCs exhibited stable phagocytotic ability with latex beads ranging from 0.5 to 1.0 μm in size. In response to bacterial stimulation, RBCs produced reactive oxygen species (ROS) and nitric oxide synthase (NOS), which are harmful to bacteria. RBCs also have an antioxidant system. Under conditions of oxidative stress, the expression levels of antioxidant enzymes, and particularly those of superoxide dismutase（SOD） increased significantly. Our results show that the erythrocytes of bony fish are phagocytic and also produce ROS which are toxic to bacteria. In addition, RBCs have an antioxidant system that removes excess ROS production to protect cells from oxidative damage.Previous researches have reported significant levels of heavy metals in indoor air of smoking cafés. The current research aimed to evaluate the potential exposure of smoking cafés workers to heavy metals through quantifying amounts of these pollutants in urine samples. To this end, 35 waterpipe/cigarette cafés workers were selected as the exposed population, 35 employees from non-smoking cafe' as the control group 1 (CG1) and 25 cases of the normal citizens as the control group 2 (CG2); and their urine samples were taken. Samples were then prepared by acid digestion approach and measured by the ICP in order to determine amount of heavy metals in them. The findings of the current work show the significant difference among urinary levels of metals in the exposed and both CG1 and CG2 (P value less then 0.05). Furthermore, urinary metal levels in samples collected from smoking café workers after the exposure were considerably higher than those were collected before the exposure (P-value less then 0.05). According to the findings, "tobacco type" could be considered as a leading factor for heavy metal exposure in studied smokers. Additionally, a positive and significant association was found between urinary metals and urinary levels of 8-OHdG (a markers of DNA degradation through oxidative stress). Therefore, workers in waterpipe/cigarette café can be classified as high risk people in terms of DNA oxidative damage.The MANORAA platform uses structure-based approaches to provide information on drug design originally derived from mapping tens of thousands of amino acids on a grid. In-depth analyses of the pockets, frequently occurring atoms, influential distances, and active-site boundaries are used for the analysis of active sites. The algorithms derived provide model equations that can predict whether changes in distances, such as contraction or expansion, will result in improved binding affinity. The algorithm is confirmed using kinetic studies of dihydrofolate reductase (DHFR), together with two DHFR-TS crystal structures. Empirical analyses of 881 crystal structures involving 180 ligands are used to interpret protein-ligand binding affinities. MANORAA links to major biological databases for web-based analysis of drug design. The frequency of atoms inside the main protease structures, including those from SARS-CoV-2, shows how the rigid part of the ligand can be used as a probe for molecular design (http//manoraa.org).The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), B.1.617.2, emerged in India and has spread to over 80 countries. B.1.617.2 replaced B.1.1.7 as the dominant virus in the United Kingdom, resulting in a steep increase in new infections, and a similar development is expected for other countries. Effective countermeasures require information on susceptibility of B.1.617.2 to control by antibodies elicited by vaccines and used for coronavirus disease 2019 (COVID-19) therapy. We show, using pseudotyping, that B.1.617.2 evades control by antibodies induced upon infection and BNT162b2 vaccination, although to a lesser extent as compared to B.1.351. https://www.selleckchem.com/products/ca3.html We find that B.1.617.2 is resistant against bamlanivimab, a monoclonal antibody with emergency use authorization for COVID-19 therapy. Finally, we show increased Calu-3 lung cell entry and enhanced cell-to-cell fusion of B.1.617.2, which may contribute to augmented transmissibility and pathogenicity of this variant. These results identify B.