Effects of continuous chelation on the instrumentation of curved canals with a martensitic NiTi file system: an ex vivo micro-CT evaluation.

This study aimed to evaluate the influence of continuous chelation on apical transportation and centrality in shaped curved canals prepared with a martensitic file system and evaluated by micro-CT. Twenty-four lower molar canals with a curvature of 25º-40º were scanned pre-operatively with micro-CT and divided into 2 groups according to two different irrigation regimens (n = 12). Group 1 was irrigated with NaOCl, group 2 with Dual Rinse. All canals were prepared with VDW.ROTATE system. The samples were scanned post-operatively and evaluated at 1, 3 and 5 mm from the apex to determine apical transportation and canal centrality using VG Studio software. Statistical analysis was performed with SPSS software using the non-parametric Mann-Whitney test. No statistically significant differences were found between the two groups for both apical transportation and canal centrality at any of the levels studied (p < 05). The use of continuous chelation during the instrumentation of the canals with martensitic alloy files does not produce greater transportation and does not generate changes in centralization compared to NaOCl-only irrigation. Combined chelation and disinfection while shaping with martensitic NiTi can simplify the irrigation regimen without inducing iatrogenic aberrations.

Clinical usefulness of serum angiotensin converting enzyme in silicosis.

INTRODUCTION: Silicosis is an irreversible and incurable disease. Preventive measures to eliminate exposure are the only effective way to reduce morbidity and mortality. In such situations, having a biomarker for early diagnosis or to predict evolution would be very useful in order to improve control of the disease. The elevation of serum angiotensin-converting enzyme (sACE) in silicosis has been described in previous studies, although its relationship with severity and prognosis is not clear. AIMS: To determine the levels of sACE in a cohort of patients with exposure to silica dust with and without silicosis, and to assess their impact on the prognosis of the aforementioned patients. METHOD: Prospective observational study on patients treated in a silicosis clinic from 2009 to 2018. sACE levels and pulmonary function tests were performed. Radiological progression was assessed in patients who had already had 2 X-rays of the thorax and / or two CT scans with at least a 1-year interval, from the time of inclusion in the study. RESULTS: A total of 413 cases of silicosis were confirmed, as well as 73 with exposure to silica dust but without silicosis. The mean sACE level for healthy subjects was 27.5±7.3U/L, for exposed patients without silicosis it was 49.6±24.2U/L, for simple silicosis it was 57.8±31,3U/L and for complicated silicosis it was 74.5±38.6U/L. Patients with a higher sACE generally progressed radiologically during follow-up (73.3±38.0 vs. 60.4±33.7; p<.001) and so the category of silicosis changed (73,9±38.1 vs. 62.5±34.6; p<.021). CONCLUSIONS: sACE was elevated in patients with silicosis, and the greater its severity, the higher it was, which is associated with disease progression measured radiologically or as a category change of silicosis.

Hospitalizations due to and with chronic obstructive pulmonary disease in Galicia: 20 years of evolution.

OBJECTIVE: This work aims to analyze the evolution of COPD-related hospitalizations in Galicia from 1996 to 2018 both as main cause of admission (DUE TO COPD) or when coded in any diagnostic order (WITH COPD), assessing the influence of age, sex, seasonality, and other main causes of the hospitalization. METHODS: An analysis was conducted of administrative healthcare database (CMBD) data on index COPD-related hospitalizations in Galicia from 1996 to 2018. Crude, specific, and standardized rates were calculated for the entire sample and according to age and sex groups. RESULTS: In the period from 1996 to 2018, there were 310,883 index admissions WITH COPD in Galicia, of which 29.6% were DUE TO COPD. Both WITH COPD and DUE TO COPD admission rates increased, mainly in men. There was a clear seasonality that was especially relevant in the DUE TO COPD group. The mean male-to-female ratio was approximately 4:1 in both groups, although it was lower in the extreme age groups, with no change over time. The mean age at admission increased three years in men during this period; there were no changes among women. The main causes of admission in those not hospitalized DUE TO COPD were heart failure and pneumonia. CONCLUSION: The combined evaluation of records of hospital admissions WITH COPD and DUE TO COPD offers additional information for a better understanding of the trends of this disease and allows for establishing hypotheses that explain the results described, providing information for better healthcare planning.

Active and sham transcranial direct current stimulation (tDCS) improved quality of life in female patients with fibromyalgia.

PURPOSE: Fibromyalgia (FM) is a chronic pain syndrome with a strong impact on quality of life (QoL). Treatment of this condition remains a challenge, due to the scarce evidence for the effectiveness of the therapeutic approaches available. Current attention is focused on transcranial direct current stimulation (tDCS), which has yielded promising results for pain treatment. Rather than focusing only on pain relief, in this study, we aimed to determine how active or sham tDCS (over three cortical targets -the primary motor cortex, the dorsolateral prefrontal cortex and the operculo-insular cortex-) affect QoL in patients with FM. METHODS: Using a double-blind, placebo-controlled design, we applied fifteen tDCS sessions of 20' to initial 130 participants (randomized to any of the four treatment groups). We evaluated the QoL (assessed by SF-36) and the symptoms' impact (assessed by FIQ-R) in baseline, after treatment and at 6 months follow-up. RESULTS: All groups were comparable as regards age, medication pattern and severity of symptoms before the treatment. We found that QoL and symptoms' impact improved in all treatment groups (including the sham) and this improvement lasted for up to 6 months. However, we did not observe any group effect nor group*treatment interaction. CONCLUSIONS: After the intervention, we observed a non-specific effect that may be due to placebo, favoured by the expectations of tDCS efficacy and psychosocial variables inherent to the intervention (daily relationship with therapists and other patients in the clinic). Therefore, active tDCS is not superior to sham stimulation in improving QoL in FM.

Correlative 3D cryo X-ray imaging reveals intracellular location and effect of designed antifibrotic protein-nanomaterial hybrids.

Revealing the intracellular location of novel therapeutic agents is paramount for the understanding of their effect at the cell ultrastructure level. Here, we apply a novel correlative cryo 3D imaging approach to determine the intracellular fate of a designed protein-nanomaterial hybrid with antifibrotic properties that shows great promise in mitigating myocardial fibrosis. Cryo 3D structured illumination microscopy (cryo-3D-SIM) pinpoints the location and cryo soft X-ray tomography (cryo-SXT) reveals the ultrastructural environment and subcellular localization of this nanomaterial with spatial correlation accuracy down to 70 nm in whole cells. This novel high resolution 3D cryo correlative approach unambiguously locates the nanomaterial after overnight treatment within multivesicular bodies which have been associated with endosomal trafficking events by confocal microscopy. Moreover, this approach allows assessing the cellular response towards the treatment by evaluating the morphological changes induced. This is especially relevant for the future usage of nanoformulations in clinical practices. This correlative super-resolution and X-ray imaging strategy joins high specificity, by the use of fluorescence, with high spatial resolution at 30 nm (half pitch) provided by cryo-SXT in whole cells, without the need of staining or fixation, and can be of particular benefit to locate specific molecules in the native cellular environment in bio-nanomedicine.

Screening of MRSA colonization in patients undergoing total joint arthroplasty.

BACKGROUND: Periprosthetic infection is commonly caused by Staphylococcus aureus and, if resistant to methicillin (MRSA), is associated with increase in severity and costs to patient and healthcare systems. MRSA colonizes 1-5% of the population, therefore using a screening and decolonisation protocol the risk of periprosthetic infection could be reduced. The objective of our study is to report the results of a preoperative MRSA screening and management protocol utilised at our hospital. METHODS: All patients undergoing a total joint arthroplasty at our hospital were preoperatively screened for MRSA colonization with swab samples of five different locations. Exposure to risk factors were investigated in colonised patients and they were treated for 5 days prior surgery with nasal mupirocin, chlorhexidine sponges and oral tablets. RESULTS: During the 48 months of the study, MRSA colonisation was identified in 22 (1.01%) of 2188 patients operated. The culture was positive only in the nasal swab in 55 patients. In five patients the nasal culture was negative, but they had another positive swab culture (three in the groin and two perianal). None of the patients reported a history of recent antibiotic treatment or hospitalization. CONCLUSION: At our institution, the prevalence of MRSA colonisation is 1.01% in patients undergoing hip and knee arthroplasty. Interestingly, our screening protocol included samples from five different anatomic locations, and it is important to highlight that we found patients with negative nares culture and positive cultures in other locations. Therefore, the number of carriers may be underdiagnosed if only nasal samples are obtained. LEVEL OF EVIDENCE: IV.

Validity of lung ultrasound to rule out iatrogenic pneumothorax performed by pulmonologists without experience in this procedure.

INTRODUCTION: Ultrasonography has been shown to be a useful tool for diagnosing pneumothorax in the hands of experts. After performing bronchopleural procedures, the recommendation is to perform chest radiography to rule out complications. Our objective was to determine the validity of lung ultrasound, conducted by pulmonologists without experience in this procedure, to tule out pneumothorax after invasive procedures. MATERIAL AND METHODS: Our prospective observational study consecutively included patients who underwent transbronchial lung biopsy (TBLB), therapeutic thoracentesis (TT) and/or transparietal pleural biopsies (PB) for whom subsequent chest radiography to rule out complications was indicated. In all cases, the same pulmonologist who performed the technique performed an ultrasound immediately after the procedure. A diagnosis of pneumothorax was considered in the presence of a lung point or the combination of the following signs: absence of pleural sliding, absence of B-lines and presence of the "barcode" sign. RESULTS: We included 275 procedures (149 TBLBs, 36 BPs, 90 TTs), which resulted in 14 (5.1%) iatrogenic pneumothoraxes. Ultrasonography presented a sensitivity of 78.5%, a specificity of 85% and positive and negative predictive value of 22% and 98.6%, respectively. Ultrasonography did not help detect the presence of 3 pneumothoraxes, one of which required chest drainage, but adequately diagnosed 2 pneumothoraxes that were not identified in the initial radiography. CONCLUSIONS: Lung ultrasound performed by pulmonologists at the start of their training helps rule out pneumothorax with a negative predictive value of 98.6%, thereby avoiding unnecessary radiographic control studies in a considerable number of cases.

Small-cell lung cancer in never-smokers.

BACKGROUND: Lung cancer is a public health problem worldwide. Small-cell lung cancer (SCLC) is the most aggressive histologic type, with a 5-year survival <10%. SCLC is closely associated with tobacco consumption and infrequent in never-smokers. We aim to describe SCLC characteristics in never-smokers recruited in a radon-prone area. PATIENTS AND METHODS: We designed a multicentric case series where SCLC cases were recruited consecutively following histologic confirmation. Detailed information was obtained for indoor radon exposure, occupation and environmental tobacco smoke. We also collected different clinical characteristics such as extended or limited disease at diagnosis. RESULTS: We recruited 32 never-smoking SCLC cases. Median age was 75 years and 87.5% were women; 47% had extended disease. Median radon concentration was 182 Bq/m3. There were no statistically significant differences in residential radon concentration neither regarding age at diagnosis nor regarding sex. The most frequent symptoms were constitutional syndrome (23.1%) and coughing (23.1%). As much as 63% of cases had an Eastern Cooperative Oncology Group Study (ECOG) status of 0-2. The 1- and 2-year survival rates were 34.4% and 21.9%, respectively. The 2-year survival rate with a localized tumor was 26.7%, compared with 18.8% for extended disease. CONCLUSIONS: These results show, for the first time, that indoor radon might not be associated with SCLC characteristics at diagnosis in never-smokers, and also confirms the low survival of this aggressive type of lung cancer also for never-smokers.

Effects of intensity, attention and medication on auditory-evoked potentials in patients with fibromyalgia.

Fibromyalgia (FM) has been associated to an increased processing of somatosensory stimuli, but its generalization to other sensory modalities is under discussion. To clarify this, we studied auditory event-related potentials (AEPs) to stimuli of different intensity in patients with FM and healthy controls (HCs), considering the effects of attention mechanisms and medication. We performed two experiments: In study 1 (n = 50 FM, 60 HCs), the stimuli were presented randomly within the sequence; in study 2 (n = 28 FM, 30 HCs), they were presented in blocks of the same intensity. We analyzed intensity and group effects on N1-P2 amplitude and, only for the FM group, the effect of medication and the correlation between AEPs and clinical variables. Contrary to the expectation, the patients showed a trend of reduced AEPs to the loudest tones (study 1) or no significant differences with the HCs (study 2). Medication with central effects significantly reduced AEPs, while no significant relationships between the N1-P2 amplitude/intensity function and patients' symptoms were observed. The findings do not provide evidence of augmented auditory processing in FM. Nevertheless, given the observed effect of medication, the role of sensory amplification as an underlying pathophysiological mechanism in fibromyalgia cannot be discarded.

Validity of thoracic ultrasonography to rule out iatrogenic pneumothorax performed by pulmonologists without experience in this procedure. / Validez de la ecografía torácica para descartar neumotórax iatrogénico realizada por neumólogos sin experiencia en este procedimiento.

INTRODUCTION: Ultrasonography has been shown to be a useful tool for diagnosing pneumothorax in the hands of experts. After performing bronchopleural procedures, the recommendation is to perform chest radiography to rule out complications. Our objective was to determine the validity of thoracic ultrasonography to rule out pneumothorax after invasive procedures, conducted by pulmonologists without experience in this procedure. MATERIAL AND METHODS: Our observational prospective study consecutively included patients who underwent transbronchial biopsy (TBB), evacuating thoracentesis (ECT) and/or transparietal pleural biopsies (TPB) who were indicated subsequent chest radiography to rule out complications. In all cases, the same pulmonologist who performed the technique performed an ultrasound immediately after the procedure. A diagnosis of pneumothorax was considered the presence of a lung point or the combination of the following signs: absence of pleural sliding, absence of B-lines and presence of the «barcode¼ sign. RESULTS: We included 275 procedures (149 TBBs, 36 TPBs, 90 ECTs), which resulted in 14 (5.1%) iatrogenic pneumothoraxes. Ultrasonography presented a sensitivity of 78.5%, a specificity of 85% and a positive and negative predictive value of 22% and 98.6%, respectively. Ultrasonography did not help detect the presence of 3 pneumothoraxes, one of which required chest drainage, but adequately diagnosed 2 pneumothoraxes that were not identified in the initial radiography. CONCLUSIONS: Thoracic ultrasonography performed by pulmonologists at the start of their training helps rule out pneumothorax with a negative predictive value of 98.6%, thereby avoiding unnecessary radiographic control studies in a considerable number of cases.

Social and clinical predictors associated with prolonged hospital stays for patients with severe exacerbation of chronic obstructive pulmonary disease. / Predictores sociales y clínicos asociados con estancia hospitalaria prolongada en pacientes con agudización grave de EPOC.

OBJECTIVE: To determine whether there are social factors that affect the prolonged hospital stay (PHS) of patients with severe chronic obstructive pulmonary disease exacerbation (COPDE), as well as clinical-demographic factors. METHODOLOGY: We conducted a prospective cohort study that consecutively included patients who were admitted to a Pneumology department for COPDE. We recorded demographic, clinical (tobacco use, exacerbations and infections, dyspnoea, impact according to CAT questionnaire, pulmonary function, comorbidities, oxygen therapy and noninvasive ventilation) and social (financial status, caregiver availability and overload, dependence for basic and instrumental activities, social risk and use of social services) variables, employing questionnaires and indices such as Barthel, Lawton-Brody, Zarit, Barber and Gijón. We performed a univariate and multivariate analysis using a logistic regression model. RESULTS: The study included 253 patients, with a mean age of 68.9±9.8years; 77.1% of whom were men. The logistic regression model included active tobacco use, FEV1 value, CAT score >10, dyspnoea 3-4 on the MMRC, the presence of bacteria in sputum cultures, cardiovascular comorbidity, anaemia, home oxygen therapy, living alone, rural residence, caregiver overload and detecting social-family risks/problems. The variables independently associated with the possibility of PHS were a CAT score >10 (OR, 8.9; P=.04) and detecting a social-family risk/problem (OR, 2.6; P=.04). Active smoking was a predictor of shorter stays (OR, 0.15; P=.002). CONCLUSIONS: Variables related to the social sphere play a relevant role in hospital stays, as do the impact of the disease and the persistent use of tobacco by patients with severe COPD exacerbation.

Immunomodulatory effect of pigeon serum in an acute and chronic murine model of bird fanciers lung.

INTRODUCTION: Since the immunopathological mechanisms of bird fancier's lung (BFL) are not well known, we created two models of the disease (acute and chronic BFL) to study and compare the pathways involved in its immunopathogenesis. MATERIALS AND METHODS: C57BL/6 mice were used. Two intraperitoneal injections of 100 µL of commercial pigeon serum (PS) or saline (SAL) were administered with an interval of 48 h in between. Subsequently, intranasal instillations of 40 µL of PS or SAL were performed three days a week, for three weeks in the acute model (AC/PS) and for twelve weeks in the chronic model (CR/PS). Total lung capacity (TLC) was assessed. Pulmonary inflammation was evaluated in bronchoalveolar lavage (BAL), and total serum immunoglobulin (Ig) G was measured in serum samples 24 h, 7 days and 14 days after the last exposure. Histological studies of lungs were assessed. RESULTS: A drop in TLC was observed in treated mice. This decrease was more marked in the CR/PS group (p < 0.001). Neutrophil and lymphocyte counts increased in both AC/PS and CR/PS groups (p < 0.01). The extent of airway inflammation was also examined in the histological analysis of the lungs, which showed predominant perivascular and peribronchiolar inflammation, with centrilobular oedema and subpleural inflammation in the AC/PS group. In the CR/PS group, the changes were greater, with increased levels of IL-5, IL-17F, IL-13 and IL-10 and decreased levels of IL-2. CONCLUSIONS: Bronchial inflammation is present in acute and chronic models of HP following exposure to PS. Our results support the role of neutrophils and IL-17 in the development of the disease and an evolution towards a Th-2 immune response in chronic HP. These models may serve as a tool for future studies of the pathogenesis of HP.

Neural correlates of cognitive dysfunction in fibromyalgia patients: Reduced brain electrical activity during the execution of a cognitive control task.

OBJECTIVES: Fibromyalgia (FM) is a generalized chronic pain syndrome of unknown aetiology. Although FM patients frequently complain of cognitive dysfunction, this is one of the least studied symptoms. Research on brain activity associated with the perceived cognitive impairment is particularly scarce. To address this gap, we recorded the brain electrical activity in participants during a cognitive control task. METHODS: Electroencephalograms (EEGs) were recorded in 19 FM patients and 22 healthy controls (all women) while they performed the Multi-Source Interference Task (MSIT). We analyzed the amplitude of the frontal N2 and parietal P3 components elicited in control and interference trials and their relation with reaction times. We also explored the relationship of perceived cognitive dysfunction, assessed using visual analogue scales (VAS) and the Memory Failures of Everyday (MFE-30) test, with N2 and P3 amplitudes. RESULTS: The N2 amplitudes were smaller in FM patients than in controls and were negatively associated with cognitive complaints. Unlike patients, healthy controls showed significant differences in the amplitude of P3 obtained from control vs. interference trials of the MSIT. Smaller N2 and P3 amplitudes were associated to longer reaction times. CONCLUSIONS: The findings suggest a reduction in frontal brain activity during performance of an interference task, which was associated with the patients' cognitive complaints. Findings on P3 suggest altered modulation of attention according to the task demands in FM patients. Deficits in flexibility in the allocation of attentional resources and cognitive control during complex tasks may explain the dyscognition reported by chronic pain patients.

Challenges in the diagnosis and control of Marek's disease virus in Colombia / Retos en el diagnóstico y control del virus de la enfermedad de Marek en Colombia

ABSTRACT Although the Colombian poultry industry has almost doubled its production in the last decade, our ability to diagnose and characterize avian pathogens is deficient, and there is little information of the circulating viral pathogens. One of these pathogens is Marek disease virus (MDV), which is an immunosuppressive agent that can cause high mortality rates and substantial production losses. Currently, there are few documented clinical cases due to the implementation of mass vaccination programs with GaHV-2 strains (serotype I) and HVT (serotype III). However, losses in production rates are likely occurring-due to immunosuppression and subclinical infections. The objective of this review is to describe MDV and the current status of the infection in Colombia.

RESUMEN Aunque la industria avícola colombiana ha crecido casi el doble en producción durante la última década, el diagnóstico de agentes infecciosos y caracterización de estos aún es escasa, y es poca la información acerca de las cepas virales circulantes en el país. Dentro de estos agentes se encuentra el Virus de la Enfermedad de Marek (VEM), el cual es un patógeno inmunosupresor que puede causar mortalidad elevada y graves pérdidas en la producción. Aunque es poco probable que ocurran casos clínicos de la enfermedad causada por el VEM, debido a los programas de vacunación generalizada con GaHV-2 (serotipo I) y HVT (serotipo III), la inmunosupresión que causan las infecciones subclínicas puede estar causando pérdidas considerables en la producción avícola nacional. El objetivo de esta revisión es describir brevemente la enfermedad de Marek y el estado actual del estudio de la infección en Colombia.

Effect of the stop-signal modality on brain electrical activity associated with suppression of ongoing actions.

To clarify how the modality of stop signals affects the ability to suppress ongoing actions, we compared behavioural indices and event-related potentials (ERPs) recorded in healthy volunteers performing visual and auditory stop-signal tasks. Auditory stop signals were associated with faster reaction times and shorter stop-N2 and stop-P3 latencies. Given that the tasks did not differ in attentional/arousal processes (go-P3 or stop-P3 amplitudes) or motor preparation (LRP amplitude, onset or latency), our results suggest that stop signal modality mainly affects bottom-up sensory processes (faster auditory processing). The ERP waveform obtained by subtracting successfully stopped from unsuccessfully stopped trials showed similar amplitude and topography in both tasks, indicating that the strength of top-down processes related to inhibition was independent of modality. The findings contribute further knowledge about the variables associated with efficient inhibition and have practical implications for the design of settings or interventions to improve reactive inhibition.

Hexapartite Entanglement in an above-Threshold Optical Parametric Oscillator.

We demonstrate, theoretically and experimentally, the generation of hexapartite modal entanglement by the optical parametric oscillator (OPO) operating above the oscillation threshold. We show that the OPO generates a rich structure of entanglement among sets of six optical sideband modes interacting through the nonlinear crystal. The class of quantum states thus produced can be controlled by a single parameter, the power of the external laser that pumps the system. Our platform allows for the generation of massive entanglement among many optical modes with well defined but vastly different frequencies, potentially bridging nodes of a multicolor quantum network.

Reduction of cardiac TGFß-mediated profibrotic events by inhibition of Hsp90 with engineered protein.

Myocardial fibroblast activation coupled with extracellular matrix production is a pathological signature of myocardial fibrosis and is governed mainly by transforming growth factor TGFß-Smad2/3 signaling. Targeting the ubiquitous TGFß leads to cellular homeostasis deregulation with adverse consequences. We previously showed the anti-fibrotic effects upon downregulation of 90-kDa heat shock protein (Hsp90), a chaperone that associates to the TGFß signaling cascade. In the present study, we use a fluorescent-labeled Hsp90 protein inhibitor (CTPR390-488) with specific Hsp90 binding properties to reduce myocardial pro-fibrotic events in vitro and in vivo. The mechanism of action involves the disruption of TGFßRI-Hsp90 complex, resulting in a decrease in TGFß signaling and reduction in extracellular matrix collagen. In vivo, decreased myocardial collagen deposition was observed upon CTPR390-488 treatment in a pro-fibrotic mouse model. This is the first study demonstrating the ability of an engineered Hsp90 protein inhibitor to block collagen expression, reduce the motility of myocardial TGFß-activated fibroblasts and ameliorate angiotensin-II induced cardiac myocardial fibrosis in vivo.