Incidence of anastomotic leakage using powered circular staplers versus manual circular staplers for left colorectal anastomosis: a cost-effectiveness analysis.

BACKGROUND: Colorectal anastomotic leakage causes severe consequences for patients and healthcare system as it will lead to increased consumption of hospital resources and costs. Technological improvements in anastomotic devices could reduce the incidence of leakage and its economic impact. The aim of the present study was to assess if the use of a new powered circular stapler is cost-effective. METHOD: This observational study included patients undergoing left-sided circular stapled colorectal anastomosis between January 2018 and December 2021. Propensity score matching was carried out to create two comparable groups depending on whether the anastomosis was performed using a manual or powered circular device. The rate of anastomotic leakage, its severity, the consumption of hospital resources, and its cost were the main outcome measures. A cost-effectiveness analysis comparing the powered circular stapler versus manual circular staplers was performed. RESULTS: A total of 330 patients were included in the study, 165 in each group. Anastomotic leakage rates were significantly different (p = 0.012): 22 patients (13.3%) in the manual group versus 8 patients (4.8%) in the powered group. The effectiveness of the powered stapler and manual stapler was 98.27% and 93.69%, respectively. The average cost per patient in the powered group was €6238.38, compared with €9700.12 in the manual group. The incremental cost-effectiveness ratio was - €74,915.28 per patient without anastomotic complications. CONCLUSION: The incremental cost of powered circular stapler compared with manual devices was offset by the savings from lowered incidence and cost of management of anastomotic leaks.

Retrospective comparison between low-volume high-concentration and high-volume low-concentration levobupivacaine for bilateral erector spinae plane block in dogs undergoing hemilaminectomy.

OBJECTIVE: To compare the analgesic effect of a bilateral ultrasound-guided erector spinae plane block (ESPB) in dogs undergoing hemilaminectomy using either a low-volume high-concentration (LV-HC) or a high-volume low-concentration (HV-LC) local anaesthetic solution. STUDY DESIGN: Retrospective observational equivalence trial. ANIMALS: A total of 391 client-owned dogs undergoing hemilaminectomy. METHODS: Dogs were assigned to group LV-HC or HV-LC depending on whether 0.2-0.25% levobupivacaine (0.4-0.5 mL kg-1) or 0.125-0.15% levobupivacaine (0.8-1 mL kg-1) was used to perform the ESPB, respectively. The number of dogs in which intraoperative rescue fentanyl boluses were administered, the total dose of fentanyl administered, the overall methadone consumption during the first 24 hours postoperatively and anaesthetic complications were recorded. Univariate and multivariate statistical analyses were performed considering p < 0.05 significant. RESULTS: A total of 248 and 143 dogs were assigned to groups LV-HC and HV-LC, respectively. In group HV-LC, the number of dogs requiring fentanyl intraoperatively (64.3%) was higher (p = 0.0001) than that in group LV-HC (43.5%). The overall intraoperative fentanyl consumption was higher in group HV-LC between the first skin incision and the end of the lamina drilling (p = 0.028). According to the regression analysis, the group allocation was the best variable to predict the intraoperative fentanyl consumption (p < 0.001). Antimuscarinic drugs were administered more frequently in group LV-HC (p < 0.02). However, the prevalence of hypotension and other pharmacological cardiovascular interventions did not differ between groups. No differences in methadone consumption during the first 24 hours postoperatively were found between the groups. CONCLUSIONSAND CLINICAL RELEVANCE: When performing a bilateral ESPB in dogs undergoing hemilaminectomy, compared with HV-LC, the use of LV-HC local anaesthetic solution reduces the intraoperative fentanyl consumption without affecting the postoperative methadone requirement.

The importance of thyroid hormone signaling during early development: Lessons from the zebrafish model.

The zebrafish is an optimal experimental model to study thyroid hormone (TH) involvement in vertebrate development. The use of state-of-the-art zebrafish genetic tools available for the study of the effect of gene silencing, cell fate decisions and cell lineage differentiation have contributed to a more insightful comprehension of molecular, cellular, and tissue-specific TH actions. In contrast to intrauterine development, extrauterine embryogenesis observed in zebrafish has facilitated a more detailed study of the development of the hypothalamic-pituitary-thyroid axis. This model has also enabled a more insightful analysis of TH molecular actions upon the organization and function of the brain, the retina, the heart, and the immune system. Consequently, zebrafish has become a trendy model to address paradigms of TH-related functional and biomedical importance. We here compilate the available knowledge regarding zebrafish developmental events for which specific components of TH signaling are essential.

Effect of intravenous fentanyl on cough reflex and quality of endotracheal intubation in cats.

OBJECTIVE: To assess the effects of intravenous (IV) fentanyl on cough reflex and quality of endotracheal intubation (ETI) in cats. STUDY DESIGN: Randomized, blinded, negative controlled clinical trial. ANIMALS: A total of 30 client-owned cats undergoing general anaesthesia for diagnostic or surgical procedures. METHODS: Cats were sedated with dexmedetomidine (2 µg kg-1 IV), and 5 minutes later either fentanyl (3 µg kg-1, group F) or saline (group C) was administered IV. After alfaxalone (1.5 mg kg-1 IV) administration and 2% lidocaine application to the larynx, ETI was attempted. If unsuccessful, alfaxalone (1 mg kg-1 IV) was administered and ETI re-attempted. This process was repeated until successful ETI. Sedation scores, total number of ETI attempts, cough reflex, laryngeal response and quality of ETI were scored. Postinduction apnoea was recorded. Heart rate (HR) was continuously recorded and oscillometric arterial blood pressure (ABP) was measured every minute. Changes (Δ) in HR and ABP between pre-intubation and intubation were calculated. Groups were compared using univariate analysis. Statistical significance was set as p < 0.05. RESULTS: The median and 95% confidence interval of alfaxalone dose was 1.5 (1.5-1.5) and 2.5 (1.5-2.5) mg kg-1 in groups F and C, respectively (p = 0.001). The cough reflex was 2.10 (1.10-4.41) times more likely to occur in group C. The overall quality of ETI was superior in group F (p = 0.001), with lower laryngeal response to ETI (p < 0.0001) and ETI attempts (p = 0.045). No differences in HR, ABP and postinduction apnoea were found. CONCLUSIONS AND CLINICAL RELEVANCE: In cats sedated with dexmedetomidine, fentanyl could be considered to reduce the alfaxalone induction dose, cough reflex and laryngeal response to ETI and to improve the overall quality of ETI.

[Nosocomial outbreak of COVID-19 in an internal medicine ward: Probable airborne transmission]. / Brote nosocomial de COVID-19 en una planta de medicina interna: probable transmisión aérea.

Background and objectives: Despite the increasing evidence supporting the importance of airborne transmission in SARS-CoV-2 infection, it has not been considered relevant in the vast majority of reported nosocomial outbreaks of COVID-19. The aim of this study is to describe a nosocomial outbreak of SARS-CoV-2 infection whose features suggest that aerosol transmission had an important role. Methods: This is a descriptive analysis of a nosocomial outbreak of SARS-CoV-2 infection in an internal medicine ward that occurred in December 2020. All cases were confirmed by a positive PCR test for SARS-CoV-2. Results: From December 5 to December 17, 21 patients and 44 healthcare workers developed a nosocomial SARS-CoV-2 infection. Fifty-one of the 65 cases (78.5%) were diagnosed between December 6 and 9. The attack rate in patients was 80.8%. Among workers, the attack rate was higher in those who had worked at least one full working day in the ward (56.3%) than in those who had occasionally been in the ward (25.8%, p = 0.005). Three days before the first positive case was detected, 2 extractor fans were found to be defective, affecting the ventilation of 3 rooms. Sixteen cases were asymptomatic, 48 cases had non-severe symptoms, and 2 cases required admission to the intensive care unit. All patients eventually recovered. Conclusion: The high attack rate, the explosive nature of the outbreak, and the coincidence in time with the breakdown in air extractors in some rooms of the ward suggest that airborne transmission played a key role in the development of the outbreak.

Topical finasteride dose evaluation for treatment of androgenetic alopecia using computer simulations.

OBJECTIVE: Our objective was to evaluate the absorption of finasteride administered by oral and topical routes for treatment of androgenetic alopecia, by means of computer simulations using the GastroPlus ® software. MATERIAL AND METHODS: In vivo plasma concentration profile of oral administration of finasteride 1 mg tablets from the literature was used in the software to build a compartmental pharmacokinetic model that was extrapolated to simulate topical administration of finasteride 0.25% solution in the scalp. Results were compared to literature and other drug concentrations (0.1% and 1%) were also predicted. RESULTS: Compared to literature data, predictive plasma curve from oral administration of finasteride 1 mg showed good correlation, R2=0.992, and Cmax=4.6769 ng/mL. Simulations of topical administration in the scalp for finasteride 0.25% solution showed good correlation, R2=0.908, and Cmax=0.04325 ng/mL when compared to literature data. Topical administration was also simulated at concentrations 0.1% and 1%, both with low plasma concentrations. CONCLUSION: The results obtained in this study suggest that topical finasteride is a potential treatment for androgenetic alopecia in the concentrations analyzed using computer simulations in GastroPlus ®.

Safety and outcomes of routine endovascular thrombectomy in large artery occlusion recorded in the SITS Register: An observational study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate the safety and outcomes of thrombectomy in anterior circulation acute ischaemic stroke recorded in the SITS-International Stroke Thrombectomy Register (SITS-ISTR) and compare them with pooled randomized controlled trials (RCTs) and two national registry studies. METHODS: We identified centres recording ≥10 consecutive patients in the SITS-ISTR with at least 70% of available modified Rankin Scale (mRS) at 3 months during 2014-2019. We defined large artery occlusion as intracranial internal carotid artery, first and second segment of middle cerebral artery and first segment of anterior cerebral artery. Outcome measures were functional independence (mRS score 0-2) and death at 3 months and symptomatic intracranial haemorrhage (SICH) per modified SITS-MOST. RESULTS: Results are presented in the following order: SITS-ISTR, RCTs, MR CLEAN Registry and German Stroke Registry (GSR). Median age was 73, 68, 71 and 75 years; baseline NIHSS score was 16, 17, 16 and 15; prior intravenous thrombolysis was 62%, 83%, 78% and 56%; onset to reperfusion time was 289, 285, 267 and 249 min; successful recanalization (mTICI score 2b or 3) was 86%, 71%, 59% and 83%; functional independence at 3 months was 45.5% (95% CI: 44-47), 46.0% (42-50), 38% (35-41) and 37% (35-41), respectively; death was 19.2% (19-21), 15.3% (12.7-18.4), 29.2% (27-32) and 28.6% (27-31); and SICH was 3.6% (3-4), 4.4% (3.0-6.4), 5.8% (4.7-7.1) and not available. CONCLUSION: Thrombectomy in routine clinical use registered in the SITS-ISTR showed safety and outcomes comparable to RCTs, and better functional outcomes and lower mortality than previous national registry studies.

Combined hyperosmolarity and inflammatory conditions in stressed human corneal epithelial cells and macrophages to evaluate osmoprotective agents as potential DED treatments.

PURPOSE: To develop an easy-to-perform combined model in human corneal epithelial cells (HCECs) and Balb/c mice macrophages J774.A1 (MP) for preliminary screening of potential ophthalmic therapeutic substances. METHODS: HCECs were exposed to different osmolarities (350-500 mOsm/L) and MTT assay was employed for cell survival and flow cytometry to assess apoptosis-necrosis and relative cell size (RCS) distribution. Effectiveness of Betaine, L-Carnitine, Taurine at different concentrations (ranging from 20 mM to 200 mM) was studied. Also, mucoadhesive polymers such as Hyaluronic acid (HA) and Hydroxypropylmethylcellulose (HPMC) (0.4 and 0.8%) were evaluated. Cells were pre-incubated with the compounds (8h) and then exposed to hyperosmotic stress (470 mOsm/L) for 16h. Moreover, anti-inflammatory activity was performed in LPS-stimulated MP. RESULTS: Exposure to hyperosmotic solutions between 450 and 500 mOsm/L promoted the highest cell death after 16h exposures (p < 0.0001) with a drop in viability to 34.96% ± 11.77 for 470 mOsm/L. Pre-incubation with Betaine at 150 mM and 200 mM provided the highest cell survival against hyperosmolarity (66.01% ± 3.65 and 65.90% ± 0.78 respectively) while HA 0.4% was the most effective polymer in preventing cell death (42.2% ± 3.60). Flow cytometry showed that Betaine and Taurine at concentrations between 150-200 mM and 20-80 mM respectively presented the highest anti-apoptotic activity. Also, HA and HPMC polymers reduced apoptotic-induced cell death. All osmoprotectants modified RCS, and polymers increased their value over 100%. L-Carnitine 50 mM, Taurine 40 mM and HA 0.4% presented the highest TNF-α inhibition activity (60%) albeit all of them showed anti-inflammatory inhibition percentages higher than 20% CONCLUSIONS: HCECs hyperosmolar model combined with inflammatory conditions in macrophages allows the screening of osmoprotectants by simulating chronic hyperosmolarity (16h) and inflammation (24h).

Anesthetic Management of Successful Extracorporeal Resuscitation After Six Hours of Cardiac Arrest Due to Severe Accidental Hypothermia.

Accidental hypothermia (AH) in Mediterranean countries often is underestimated. AH should be suspected in patients also in moderate climates throughout all seasons. Compared with other countries, the mortality rate due to AH in Spain is low, and hypothermia rarely is recognized and treated. The case of a patient who experienced cardiac arrest due to severe AH and was resuscitated for more than six hours using extracorporeal life support recently was published. Herein that case is reviewed, with the anesthetic management during cannulation detailed. In addition, the authors highlight how the application of extracorporeal cardiopulmonary resuscitation guidelines is different in AH patients, how in-hospital (HOPE score) triage criteria should be applied, and how the establishment of clear standard operating procedures and education strategies should be promoted.

Disentangling functional trait variation and covariation in epiphytic lichens along a continent-wide latitudinal gradient.

Characterizing functional trait variation and covariation, and its drivers, is critical to understand the response of species to changing environmental conditions. Evolutionary and environmental factors determine how traits vary among and within species at multiple scales. However, disentangling their relative contribution is challenging and a comprehensive trait-environment framework addressing such questions is missing in lichens. We investigated the variation in nine traits related to photosynthetic performance, water use and nutrient acquisition applying phylogenetic comparative analyses in lichen epiphytic communities on beech across Europe. These poikilohydric organisms offer a valuable model owing to their inherent limitations to buffer contrasting environmental conditions. Photobiont type and growth form captured differences in certain physiological traits whose variation was largely determined by evolutionary processes (i.e. phylogenetic history), although the intraspecific component was non-negligible. Seasonal temperature fluctuations also had an impact on trait variation, while nitrogen content depended on photobiont type rather than nitrogen deposition. The inconsistency of trait covariation among and within species prevented establishing major resource use strategies in lichens. However, we did identify a general pattern related to the water-use strategy. Thus, to robustly unveil lichen responses under different climatic scenarios, it is necessary to incorporate both among and within-species trait variation and covariation.

Survival outcome in severe left-sided congenital diaphragmatic hernia with and without fetal endoscopic tracheal occlusion in a country with suboptimal neonatal management.

OBJECTIVE: To evaluate the impact of fetal endoscopic tracheal occlusion (FETO) on improving survival of fetuses with severe left-sided congenital diaphragmatic hernia (CDH), as compared with contemporaneous cases managed expectantly during pregnancy, in a country with suboptimal neonatal management. METHODS: In this prospective cohort study, consecutive fetuses with isolated left-sided CDH, normal karyotype and severe pulmonary hypoplasia (defined as liver herniation and observed/expected lung-to-head circumference ratio below 26%) were selected for FETO at less than 32 weeks of gestation in a single tertiary referral center in Queretaro, Mexico. Postnatal outcome (survival up to 28 days after birth) was compared between fetuses treated with FETO and contemporaneous cases with similar lung size managed expectantly during pregnancy. RESULTS: Twenty-five fetuses with isolated severe left-sided CDH treated with FETO were matched individually with 25 cases managed expectantly during pregnancy. Endotracheal placement of the balloon was performed successfully on the first attempt in all cases. The median gestational age (GA) at balloon placement was 29.1 (range, 25.6-31.8) weeks and 34.1 (range, 30.0-36.1) weeks at balloon removal. There were no technical problems with the introduction or removal of the balloon in any cases. The median GA at delivery was significantly lower in the group treated with FETO than in those managed expectantly (35.3 vs 37.7 weeks; P = 0.04). The survival rate was significantly higher in the group treated with FETO than in those without fetal intervention (32% vs 0%; P < 0.001). CONCLUSION: In settings with suboptimal neonatal management, FETO was associated with improved neonatal survival in fetuses with isolated left-sided CDH and severe pulmonary hypoplasia. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Resultado de supervivencia en una hernia diafragmática congénita grave del lado izquierdo, con y sin oclusión traqueal endoscópica fetal en un país con un tratamiento neonatal subóptimo OBJETIVO: Evaluar el impacto de la oclusión traqueal endoscópica fetal (OTEF) en la mejora de la supervivencia de los fetos con hernia diafragmática congénita (HDC) grave del lado izquierdo, en comparación con los casos actuales tratados como embarazo gestante, en un país con un tratamiento neonatal subóptimo. MÉTODOS: En este estudio prospectivo de cohortes, se seleccionaron fetos consecutivos con HDC aislada del lado izquierdo, cariotipo normal e hipoplasia pulmonar grave (definida como hernia hepática y una proporción observada/esperada de la circunferencia pulmonar-cabeza inferior al 26%) para una OTEF antes de las 32 semanas de gestación, en un único centro de medicina especializada terciaria en Querétaro (México). El resultado postnatal (supervivencia hasta los 28 días después del nacimiento) se comparó entre fetos tratados con OTEF y los casos contemporáneos con tamaño pulmonar similar, tratados como embarazo gestante. RESULTADOS: Veinticinco fetos con HDC grave aislada del lado izquierdo que habían sido tratados con OTEF fueron emparejados individualmente con 25 casos tratados como embarazo gestante. La colocación endotraqueal del globo se realizó con éxito en el primer intento en todos los casos. La mediana de la edad gestacional (EG) en el momento de la colocación del globo fue de 29,1 (rango, 25,6-31,8) semanas y 34,1 (rango, 30,0-36,1) semanas cuando se retiró el globo. En ningún caso hubo problemas técnicos con la introducción o la retirada del globo. La mediana de la EG en el momento del parto fue significativamente menor en el grupo tratado con OTEF que en el grupo tratado como gestante (35,3 vs 37,7 semanas; P=0,04). La tasa de supervivencia fue significativamente más alta en el grupo tratado con OTEF que en los casos sin intervención fetal (32% vs 0%; P<0,001). CONCLUSIÓN: En los entornos con un tratamiento neonatal subóptimo, la OTEF se asoció con una mejora de la supervivencia neonatal en los fetos con HDC aislada del lado izquierdo y con hipoplasia pulmonar grave. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Rowell syndrome complicated with macrophage activation syndrome in a child.

Rowell syndrome (RS) is a rare disease characterized by the association of systemic lupus erythematosus (SLE) or cutaneous lupus with lesions similar to erythema multiforme and the presence of autoantibodies including ANA, SSA, SSB, or rheumatoid factor. Due to the low incidence of this disease, the epidemiology of RS is not clear. So far there are 95 cases reported in the literature; of these, only seven cases are pediatric patients. Macrophage activation syndrome (MAS) is an increasingly recognized complication of SLE, although its true prevalence in childhood is still unknown. We describe a unique pediatric patient with RS who developed MAS.

A case study on the re-establishment of the cyanolichen symbiosis: where do the compatible photobionts come from?

BACKGROUND AND AIMS: In order to re-establish lichen symbiosis, fungal spores must first germinate and then associate with a compatible photobiont. To detect possible establishment limitations in a sexually reproducing cyanolichen species, we studied ascospore germination, photobiont growth and photobiont association patterns in Pectenia plumbea. METHODS: Germination tests were made with ascospores from 500 apothecia under different treatments, and photobiont growth was analysed in 192 isolates obtained from 24 thalli. We determined the genotype identity [tRNALeu (UAA) intron] of the Nostoc cyanobionts from 30 P. plumbea thalli from one population. We also sequenced cyanobionts of 41 specimens of other cyanolichen species and 58 Nostoc free-living colonies cultured from the bark substrate. KEY RESULTS: Not a single fungal ascospore germinated and none of the photobiont isolates produced motile hormogonia. Genetic analyses revealed that P. plumbea shares Nostoc genotypes with two other cyanolichen species of the same habitat, but these photobionts were hardly present in the bark substrate. CONCLUSIONS: Due to the inability of both symbionts to thrive independently, the establishment of P. plumbea seems to depend on Dendriscocaulon umhausense, the only cyanolichen species in the same habitat that reproduces asexually and acts as a source of appropriate cyanobionts. This provides support to the hypothesis about facilitation among lichens.

Tuning the size, composition and structure of Au and Co50Au50 nanoparticles by high-power impulse magnetron sputtering in gas-phase synthesis.

Gas-phase synthesis of nanoparticles with different structural and chemical distribution is reported using a circular magnetron sputtering in an ion cluster source by applying high-power impulses. The influence of the pulse characteristics on the final deposit was evaluated on Au nanoparticles. The results have been compared with the more common direct current approach. In addition, it is shown for the first time that high-power impulses in magnetron based gas aggregation sources allows the growth of binary nanoparticles, CoAu in this case, with a variety of crystalline and chemical arrangements which are analyzed at the atomic level.

Micro ad-hoc Health Social Networks (uHSN). Design and evaluation of a social-based solution for patient support.

OBJECTIVE: To contribute the design, development, and assessment of a new concept: Micro ad hoc Health Social Networks (uHSN), to create a social-based solution for supporting patients with chronic disease. DESIGN: After in-depth fieldwork and intensive co-design over a 4-year project following Community-Based Participatory Research (CBPR), this paper contributes a new paradigm of uHSN, defining two interaction areas (the "backstage", the sphere invisible to the final user, where processes that build services take place; and the "onstage", the visible part that includes the patients and relatives), and describes a new transversal concept, i.e., "network spaces segments," to provide timely interaction among all involved profiles and guaranteeing qualitative relationships. This proposal is applicable to any service design project and to all types of work areas; in the present work, it served as a social-based solution for supporting patients with chronic disease in two real-life health scenarios: a Parkinson disease patient association and a Stroke rehabilitation service in a hospital. These two scenarios included the following main features: thematic (related to the specific disease), private, and secure (only for the patient, relatives, healthcare professional, therapist, carer), with defined specific objectives (around patient support), small size (from tens to hundreds of users), ability to integrate innovative services (e.g., connection to hospital information service or to health sensors), supported by local therapeutic associations, and clustered with preconfigured relationships among users based in network groups. MEASUREMENTS: Using a mixed qualitative and quantitative approach for 6 months, the performance of the uHSN was assessed in the two environments: a hospital rehabilitation unit working with Stroke patients, and a Parkinson disease association providing physiotherapy, occupational therapy, psychological support, speech therapy, and social services. We describe the proposed methods for evaluating the uHSN quantitatively and qualitatively, and how the scientific community can replicate and/or integrate this contribution in its research. RESULTS: The uHSN overcomes the main limitations of traditional HSNs in the main areas recommended in the literature: privacy, security, transparency, system ecology, Quality of Service (QoS), and technology enhancement. The qualitative and quantitative research demonstrated its viability and replicability in four key points: user acceptance, productivity improvement, QoS enhancement, and fostering of social relations. It also meets the expectation of connecting health and social worlds, supporting distance rehabilitation, improving professionals' efficiency, expanding users' social capital, improving information quality and immediacy, and enhancing perceived peer/social/emotional support. The scientific contributions of the present paper are the first step not only in customizing health solutions that empower patients, their families, and healthcare professionals, but also in transferring this new paradigm to other scientific, professional, and social environments to create new opportunities.

Graphitization of Glassy Carbon after Compression at Room Temperature.

Glassy carbon is a technologically important material with isotropic properties that is nongraphitizing up to ∼3000 °C and displays complete or "superelastic" recovery from large compression. The pressure limit of these properties is not yet known. Here we use experiments and modeling to show permanent densification, and preferred orientation occurs in glassy carbon loaded to 45 GPa and above, where 45 GPa represents the limit to the superelastic and nongraphitizing properties of the material. The changes are explained by a transformation from its sp^{2} rich starting structure to a sp^{3} rich phase that reverts to fully sp^{2} bonded oriented graphite during pressure release.

Naegleria fowleri immunization modifies lymphocytes and APC of nasal mucosa.

We investigated whether intranasal immunization with amoebic lysates plus cholera toxin modified the populations of T and B lymphocytes, macrophages and dendritic cells by flow cytometry from nose-associated lymphoid tissue (NALT), cervical lymph nodes (CN), nasal passages (NP) and spleen (SP). In all immunized groups, the percentage of CD4 was higher than CD8 cells. CD45 was increased in B cells from mice immunized. We observed IgA antibody-forming cell (IgA-AFC) response, mainly in NALT and NP. Macrophages from NP and CN expressed the highest levels of CD80 and CD86 in N. fowleri lysates with either CT or CT alone immunized mice, whereas dendritic cells expressed high levels of CD80 and CD86 in all compartment from immunized mice. These were lower than those expressed by macrophages. Only in SP from CT-immunized mice, these costimulatory molecules were increased. These results suggest that N. fowleri and CT antigens are taking by APCs, and therefore, protective immunity depends on interactions between APCs and T cells from NP and CN. Consequently, CD4 cells stimulate the differentiation from B lymphocytes to AFC IgA-positive; antibody that we previously found interacting with trophozoites in the nasal lumen avoiding the N. fowleri attachment to nasal epithelium.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Pharmacogenetics of methylphenidate response and tolerability in attention-deficit/hyperactivity disorder.

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder. However, a considerable interindividual variability exists in clinical outcome, which may reflect underlying genetic influences. We analyzed 57 single-nucleotide polymorphisms in 9 dopamine-related candidate genes (TH, DBH, COMT, DAT1 and DRD1-5) as potential predictors of MPH efficacy and tolerability, and we considered prenatal and perinatal risk factors as environmental hazards that may influence treatment effects in a gene-by-environment analysis. Our results provide evidence for the contribution of DRD3 (P=0.041; odds ratio (OR)=4.00), DBH (P=0.032; OR=2.85), TH (P=5.5e-03; OR=4.34) and prenatal smoking (P=1.7e-03; OR=5.10) to the clinical efficacy of MPH, with a higher risk for treatment failure in genetically susceptible subjects whose mother smoked during pregnancy. Adverse events after MPH treatment were significantly associated with variation in DBH (P=6.4e-03; OR=0.28) and DRD2 (P=0.047; OR=3.76). This study suggests that the dopaminergic system together with prenatal smoking exposure may moderate MPH treatment effects.

European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch.

BACKGROUND AND PURPOSE: To support clinical decision-making in central neurological disorders, a physical examination is used to assess responses to passive muscle stretch. However, what exactly is being assessed is expressed and interpreted in different ways. A clear diagnostic framework is lacking. Therefore, the aim was to arrive at unambiguous terminology about the concepts and measurement around pathophysiological neuromuscular response to passive muscle stretch. METHODS: During two consensus meetings, 37 experts from 12 European countries filled online questionnaires based on a Delphi approach, followed by plenary discussion after rounds. Consensus was reached for agreement ≥75%. RESULTS: The term hyper-resistance should be used to describe the phenomenon of impaired neuromuscular response during passive stretch, instead of for example 'spasticity' or 'hypertonia'. From there, it is essential to distinguish non-neural (tissue-related) from neural (central nervous system related) contributions to hyper-resistance. Tissue contributions are elasticity, viscosity and muscle shortening. Neural contributions are velocity dependent stretch hyperreflexia and non-velocity dependent involuntary background activation. The term 'spasticity' should only be used next to stretch hyperreflexia, and 'stiffness' next to passive tissue contributions. When joint angle, moment and electromyography are recorded, components of hyper-resistance within the framework can be quantitatively assessed. CONCLUSIONS: A conceptual framework of pathophysiological responses to passive muscle stretch is defined. This framework can be used in clinical assessment of hyper-resistance and will improve communication between clinicians. Components within the framework are defined by objective parameters from instrumented assessment. These parameters need experimental validation in order to develop treatment algorithms based on the aetiology of the clinical phenomena.