Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation.

Activation of the mechanistic target of rapamycin (mTOR) is a key metabolic checkpoint of pro-inflammatory T-cell development that contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), however, the underlying mechanisms remain poorly understood. Here, we identify a functional role for Rab4A-directed endosome traffic in CD98 receptor recycling, mTOR activation, and accumulation of mitochondria that connect metabolic pathways with immune cell lineage development and lupus pathogenesis. Based on integrated analyses of gene expression, receptor traffic, and stable isotope tracing of metabolic pathways, constitutively active Rab4AQ72L exerts cell type-specific control over metabolic networks, dominantly impacting CD98-dependent kynurenine production, mTOR activation, mitochondrial electron transport and flux through the tricarboxylic acid cycle and thus expands CD4+ and CD3+CD4-CD8- double-negative T cells over CD8+ T cells, enhancing B cell activation, plasma cell development, antinuclear and antiphospholipid autoantibody production, and glomerulonephritis in lupus-prone mice. Rab4A deletion in T cells and pharmacological mTOR blockade restrain CD98 expression, mitochondrial metabolism and lineage skewing and attenuate glomerulonephritis. This study identifies Rab4A-directed endosome traffic as a multilevel regulator of T cell lineage specification during lupus pathogenesis.

Two-dimensional hysterosalpingo-contrast-sonography compared to three/four-dimensional hysterosalpingo-contrast-sonography for the assessment of tubal occlusion in women with infertility/subfertility: a systematic review with meta-analysis.

In this meta-analysis, we aimed to compare the diagnostic accuracy of 2D- and 3D/4D-HyCoSy for the assessment of tubal occlusion in women with infertility, using a laparoscopic tubal chromoperturbation dye test as the reference standard. Studies assessing 2D- and 3D/4D-HyCoSy for the assessment of tubal occlusion in women with infertility were searched from January 1990 to April 2019 using Medline and Web of Science databases by three of the authors, using the terms: 'hysterosalpingo-contrast-sonography', 'sonohysterosalpingography', 'HyCoSy', 'HyFoSy', 'three-dimensional', 'four-dimensional', 'ultrasound', 'tubal patency' and 'tubal occlusion'. Data quality was determined using the QUADAS-2 tool. Thirty articles were included; twenty-one studies used 2D-HyCoSy to assess tubal occlusion, six used 3D/4D-HyCoSy, one study used both techniques but in a different set of patients and two used both techniques in the same patients. The risk of bias for most studies was low as determined by QUADAS-2, except for the patient selection domain. Overall, pooled estimated sensitivity and specificity of 2D-HyCoSy were 86% (95% CI = 80%-91%) and 94% (95% CI = 90%-96%), respectively. The corresponding figures for 3D/4D HyCoSy were 95% (95% CI = 89%-98%) and 89% (95% CI = 82%-94%). High heterogeneity was found for both sensitivity and specificity. No statistically significant differences were found between the methods (p = 0.13). We concluded that 2D-HyCoSy has a similar diagnostic performance to 3D/4D-HyCoSy.

Consequences of COVID-19 pandemic on myocardial infarction reperfusion therapy and prognosis.

Background The coronavirus disease (COVID-19) pandemic affected the prompt diagnosis and treatment of Acute myocardial infarction (AMI). AIM: To characterize the clinical profile of patients with AMI during the COVID-19 pandemic, comparing them with a historical cohort. MATERIAL AND METHODS: A case-control study of 96 patients with AMI transferred to a high-volume percutaneous coronary intervention (PCI) hospital between March and July 2020, and a historical cohort of 269 patients transferred during the same period in 2019. RESULTS: When comparing patients transferred during the pandemic with those of the historical cohort, the former were younger (63 ± 12 vs 68 ± 12 years, p < 0.01), had a higher frequency of hypertension (66 vs 45%, p < 0.01) and of smoking (40% vs 25%, p < 0.01). Also, during COVID-19 outbreak a higher proportion of patients had ST-elevation AMI consulting > 12 hours from the onset of symptoms (44 vs 0%, p < 0.01), a higher median door-to-device time (4 vs 3 hours, p < 0.01), a higher use of primary percutaneous coronary intervention (97 vs 71%, p < 0.01), and higher frequencies of cardiogenic shock (20 vs 4%, p < 0.01) and mechanical complications (10% vs 2%, p < 0.01). Patients during COVID pandemic had a higher thirty-day overall (20 vs 1.4%, p < 0.01) and cardiovascular mortality (13 vs 1%, p < 0.01). During the outbreak, 40% of patients had positive COVID-19 status, which was a predictor for thirty-day overall mortality (Risk ratio 2.90; 95% confidence intervals 1.14-7.36). CONCLUSIONS: During the pandemic patients with AMI exhibited delays in consultations and treatment, higher morbidity, and increased mortality. COVID-19 positivity was associated to worse thirty-day overall survival.

Consequences of COVID-19 pandemic on myocardial infarction reperfusion therapy and prognosis / Consecuencias de la pandemia COVID-19 en la reperfusión y pronóstico del infarto de miocardio

ABSTRACT Background The coronavirus disease (COVID-19) pandemic affected the prompt diagnosis and treatment of Acute myocardial infarction (AMI). Aim: To characterize the clinical profile of patients with AMI during the COVID-19 pandemic, comparing them with a historical cohort. Material and Methods: A case-control study of 96 patients with AMI transferred to a high-volume percutaneous coronary intervention (PCI) hospital between March and July 2020, and a historical cohort of 269 patients transferred during the same period in 2019. Results: When comparing patients transferred during the pandemic with those of the historical cohort, the former were younger (63 ± 12 vs 68 ± 12 years, p 12 hours from the onset of symptoms (44 vs 0%, p < 0.01), a higher median door-to-device time (4 vs 3 hours, p < 0.01), a higher use of primary percutaneous coronary intervention (97 vs 71%, p < 0.01), and higher frequencies of cardiogenic shock (20 vs 4%, p < 0.01) and mechanical complications (10% vs 2%, p < 0.01). Patients during COVID pandemic had a higher thirty-day overall (20 vs 1.4%, p < 0.01) and cardiovascular mortality (13 vs 1%, p < 0.01). During the outbreak, 40% of patients had positive COVID-19 status, which was a predictor for thirty-day overall mortality (Risk ratio 2.90; 95% confidence intervals 1.14-7.36). Conclusions: During the pandemic patients with AMI exhibited delays in consultations and treatment, higher morbidity, and increased mortality. COVID-19 positivity was associated to worse thirty-day overall survival.

Antecedentes: La pandemia COVID-19 afectó el tratamiento oportuno del infarto agudo de miocardio (IAM). Objetivo: Caracterizar el perfil clínico de pacientes con IAM durante la pandemia COVID-19 y compararlos con una cohorte histórica. Pacientes y Métodos: Estudio caso-control de 96 pacientes con IAM transferidos a un hospital de alto volumen de intervención coronaria percutánea (ICP) entre marzo julio de 2020 y una cohorte histórica de 269 pacientes transferidos en el mismo período de 2019 (n = 269). Resultados: Al comparar los pacientes transferidos durante pandemia y la cohorte histórica, los primeros eran más jóvenes (63 ± 12 y 68 ± 12 años respectivamente, p 12 h desde iniciados síntomas de IAM con elevación ST (44,4 y 0% respectivamente, p < 0,01), una mediana de tiempo puerta-guía mayor (4 y 3 horas respectivamente, p < 0,01), un mayor uso de ICP primaria (97 y 71% respectivamente, p < 0,01), mayor frecuencia de shock cardiogénico (19,8 y 4,1% respectivamente, p < 0.01) y complicaciones mecánicas (10,4 y 1,7% respectivamente, p < 0,01). A treinta días, los primeros tuvieron mayor mortalidad general (19,8 y 1,4% respectivamente p < 0.01) y cardiovascular (12,5 y 1,4% respectivamente, p < 0,01). Durante la pandemia, 40% de los pacientes presentó positividad para COVID-19, siendo un factor predictivo de mortalidad general (razón de riesgo 2,90; intervalos de confianza 95% 1,14-7,36). Conclusiones: Durante la pandemia, hubo retrasos en tiempos de consulta y tratamiento y mayor morbimortalidad del IAM. La positividad de COVID-19 se asoció a peor sobrevida general a treinta días.

Peripheral venoarterial extracorporeal membrane oxygenation for periprocedural Cardiogenic shock during interventional cardiology

ABSTRACT Background: Cardiogenic shock (CS) is uncommon in the cardiac catheterization laboratory (CCL) among patients undergoing coronary angiography. Periprocedural CS is more frequent in high-risk patients and in technically demanding procedures. Aim: To describe the clinical outcomes of patients who underwent peripheral venoarterial extracorporeal membrane oxygenation (pVA-ECMO) for CS associated with interventional cardiology procedures. Material and Methods: Review of clinical records of seven patients treated between January 2014 and October 2018. Results: pVA-ECMO was implanted within 6 hours of the interventional cardiology procedure. All patients had coronary artery disease and one of them also had symptomatic severe aortic stenosis. One patient entered the CCL in cardiac arrest. Percutaneous coronary intervention (PCI) was performed in all patients; four patients underwent an emergency procedure and five patients experienced PCI complications. One patient undergoing transcatheter aortic valve replacement suffered acute severe aortic regurgitation. An intra-aortic balloon pump was inserted at the CCL in five patients. Six patients experienced cardiac arrest. Mean SAVE score was -4.3 and baseline lactate 55 mg/dl. pVA-ECMO mean duration was 5 ± 4 days. Survival after both hospital discharge and 12 months of follow-up was 85.7% Regarding vascular access complications, we observed one access site hematoma and one episode of cannulation site bleeding requiring surgical repair. Conclusions: pVA-ECMO should be considered in patients with periprocedural CS as a bridge to recovery. Its use was associated with improved clinical outcomes in this series.

Antecedentes: El shock cardiogénico (SC) es infrecuente en el laboratorio de cateterismo cardíaco (LCC) entre pacientes que son sometidos a coronariografía. El SC peri-procedimiento es más frecuente en pacientes de alto riesgo y en procedimientos técnicamente complejos. Objetivos: Describir los resultados clínicos de pacientes que fueron conectados a oxigenación con membrana extracorpórea veno-arterial periférica (ECMO-VAp) por SC peri-procedimiento de cardiología intervencional. Material y Métodos: Revisión de fichas clínicas de siete pacientes tratados en nuestro centro desde enero de 2014 a octubre de 2018. Resultados: ECMO-VAp fue utilizado dentro de las primeras 6 horas del procedimiento. Todos los pacientes tenían enfermedad coronaria y uno de ellos tenía además estenosis aórtica severa. Un paciente ingresó al LCC en paro cardíaco. Una intervención coronaria percutánea (ICP) fue realizada en todos los pacientes; 4 se realizaron procedimientos de emergencia y 5 pacientes tuvieron complicaciones de la ICP. A un paciente se le realizó un reemplazo valvular aórtico percutáneo y desarrolló una insuficiencia valvular aórtica aguda severa. Se instaló un balón de contrapulsación en el LCC en 5 pacientes. Seis pacientes tuvieron un paro cardiorrespiratorio. El valor del score de SAVE fue de -4,3 y el lactato basal 55 mg/dL. La duración media del ECMO-VAp fue 5 ± 4 días. La sobrevida al alta y a los 12 meses fue 85,7%. Como complicaciones del sitio de acceso vascular se observaron 1 hematoma y un episodio de sangrado que requirió reparación quirúrgica. Conclusiones: ECMO-VAp debería ser considerado en pacientes con SC peri-procedimiento como un puente a recuperación; su utilización estuvo asociada con mejoría de resultados clínicos en esta serie.

Injury to the Superior Gluteal Artery during Intramedullary Fixation of a Proximal Femoral Fracture - A Case Report.

INTRODUCTION: Proximal femoral fractures represent a health problem of global proportions. Iatrogenic vascular lesion in the treatment of these fractures is an unusual potentially lethal complication, reported in only 0.2% of trochanteric fractures treated with intramedullary implants. Superior gluteal artery injury is extremely rare, with only two cases reported in literature. CASE REPORT: A 66-year-old Caucasian woman, with metastatic disease, was admitted with a right pertrochanteric fracture. She underwent closed reduction and long intramedullary nail fixation. Five days post-operatively, a sudden hemoglobin drop occurred. A computed tomography demonstrated an extensive hematoma. Angiography confirmed an arterial bleeding from the superior gluteal artery and subsequent selective embolization was successfully performed. CONCLUSION: The presence of anemia and thigh hematoma that progressively worsens post-operatively should raise the diagnostic suspicion of an iatrogenic vascular injury. To the best of our knowledge, this is only the third case reported of superior gluteal artery injury after intramedullary fixation of a proximal femoral fracture. We describe the post-operative course and management strategy and hope this will contribute to the global knowledge and increase awareness of these rare injuries.

Peripheral venoarterial extracorporeal membrane oxygenation for periprocedural Cardiogenic shock during interventional cardiology.

BACKGROUND: Cardiogenic shock (CS) is uncommon in the cardiac catheterization laboratory (CCL) among patients undergoing coronary angiography. Periprocedural CS is more frequent in high-risk patients and in technically demanding procedures. AIM: To describe the clinical outcomes of patients who underwent peripheral venoarterial extracorporeal membrane oxygenation (pVA-ECMO) for CS associated with interventional cardiology procedures. MATERIAL AND METHODS: Review of clinical records of seven patients treated between January 2014 and October 2018. RESULTS: pVA-ECMO was implanted within 6 hours of the interventional cardiology procedure. All patients had coronary artery disease and one of them also had symptomatic severe aortic stenosis. One patient entered the CCL in cardiac arrest. Percutaneous coronary intervention (PCI) was performed in all patients; four patients underwent an emergency procedure and five patients experienced PCI complications. One patient undergoing transcatheter aortic valve replacement suffered acute severe aortic regurgitation. An intra-aortic balloon pump was inserted at the CCL in five patients. Six patients experienced cardiac arrest. Mean SAVE score was -4.3 and baseline lactate 55 mg/dl. pVA-ECMO mean duration was 5 ± 4 days. Survival after both hospital discharge and 12 months of follow-up was 85.7% Regarding vascular access complications, we observed one access site hematoma and one episode of cannulation site bleeding requiring surgical repair. CONCLUSIONS: pVA-ECMO should be considered in patients with periprocedural CS as a bridge to recovery. Its use was associated with improved clinical outcomes in this series.

Lupus-associated endogenous retroviral LTR polymorphism and epigenetic imprinting promote HRES-1/RAB4 expression and mTOR activation.

Overexpression and long terminal repeat (LTR) polymorphism of the HRES­1/Rab4 human endogenous retrovirus locus have been associated with T cell activation and disease manifestations in systemic lupus erythematosus (SLE). Although genomic DNA methylation is diminished overall in SLE, its role in HRES-1/Rab4 expression is unknown. Therefore, we determined how lupus-associated polymorphic rs451401 alleles of the LTR regulate transcription from the HRES-1/Rab4 promoter and thus affect T cell activation. The results showed that cytosine-119 is hypermethylated while cytosine-51 of the promoter and the LTR enhancer are hypomethylated in SLE. Pharmacologic or genetic inactivation of DNA methyltransferase 1 augmented the expression of HRES-1/Rab4. The minimal promoter was selectively recognized by metabolic stress sensor NRF1 when cytosine-119 but not cytosine-51 was methylated, and NRF1 stimulated HRES-1/Rab4 expression in human T cells. In turn, IRF2 and PSIP1 bound to the LTR enhancer and exerted control over HRES-1/Rab4 expression in rs451401 genotype- and methylation-dependent manners. The LTR enhancer conferred markedly greater expression of HRES-1/Rab4 in subjects with rs451401CC over rs451401GG alleles that in turn promoted mechanistic target of rapamycin (mTOR) activation upon T cell receptor stimulation. HRES-1/Rab4 alone robustly activated mTOR in human T cells. These findings identify HRES-1/Rab4 as a methylation- and rs451401 allele-dependent transducer of environmental stress and controller of T cell activation.

[Proportion of patients with heart failure in a specialized clinic eligible for novel therapies]. / Pacientes elegibles para las nuevas terapias de la insuficiencia cardíaca en un policlínico especializado.

BACKGROUND: Pharmacological treatment improves survival in patients with heart failure with reduced ejection fraction. The use of sacubutril/valsartan and ivabradine has been recently approved and incorporated in the latest guidelines. AIM: To identify candidates eligible for these therapies among patients treated in a heart failure clinic, considering the inclusion criteria for the PARADIGM-HF and SHIFT trials. MATERIAL AND METHODS: Cross-sectional study on 158 patients aged 62 ± 11 years (67% male) with heart failure and reduced ejection fraction, with at least three months of follow-up and without decompensation. The percentage of patients complying for the inclusion criteria for the PARADIGM-HF y SHIFT trials was determined. RESULTS: In 37%, the etiology of heart failure was ischemic, 49% were in functional class I, their ejection fraction was 33 ± 11% and their median Pro-brain natriuretic peptide was 800 pg/mL. Ninety five percent were treated with vasodilators, 97% with beta-blockers and 82% with aldosterone antagonists. Using PARADIGM-HF and SHIFT criteria, 11 patients (7%) were eligible for sacubitril / valsartan and 21 patients (13.3%) for ivabradine. Among the main causes of non-eligibility for sacubitril / valsartan were being functional class I (48.7%) and not achieving a stable dose of enalapril ≥ 20 mg / day or losartan ≥ 100 mg / day (24.7%). In the case of ivabradine, apart from those in functional class I, the absence of sinus rhythm and a heart rate < 70 / min when receiving a maximal tolerated dose of beta-blockers, were present in 22%. CONCLUSIONS: A low percentage of our patients were eligible for these therapies. Among the causes that explain these results were clinical stability, a high percentage of patients in functional class I and being in a disease modifying treatment.

Pacientes elegibles para las nuevas terapias de la insuficiencia cardíaca en un policlínico especializado / Proportion of patients with heart failure in a specialized clinic eligible for novel therapies

Background: Pharmacological treatment improves survival in patients with heart failure with reduced ejection fraction. The use of sacubutril/valsartan and ivabradine has been recently approved and incorporated in the latest guidelines. Aim: To identify candidates eligible for these therapies among patients treated in a heart failure clinic, considering the inclusion criteria for the PARADIGM-HF and SHIFT trials. Material and Methods: Cross-sectional study on 158 patients aged 62 ± 11 years (67% male) with heart failure and reduced ejection fraction, with at least three months of follow-up and without decompensation. The percentage of patients complying for the inclusion criteria for the PARADIGM-HF y SHIFT trials was determined. Results: In 37%, the etiology of heart failure was ischemic, 49% were in functional class I, their ejection fraction was 33 ± 11% and their median Pro-brain natriuretic peptide was 800 pg/mL. Ninety five percent were treated with vasodilators, 97% with beta-blockers and 82% with aldosterone antagonists. Using PARADIGM-HF and SHIFT criteria, 11 patients (7%) were eligible for sacubitril / valsartan and 21 patients (13.3%) for ivabradine. Among the main causes of non-eligibility for sacubitril / valsartan were being functional class I (48.7%) and not achieving a stable dose of enalapril ≥ 20 mg / day or losartan ≥ 100 mg / day (24.7%). In the case of ivabradine, apart from those in functional class I, the absence of sinus rhythm and a heart rate < 70 / min when receiving a maximal tolerated dose of beta-blockers, were present in 22%. Conclusions: A low percentage of our patients were eligible for these therapies. Among the causes that explain these results were clinical stability, a high percentage of patients in functional class I and being in a disease modifying treatment.

Confronting a Paradox: A New Perspective of the Impact of Uncertainty in Suspense.

Suspense is a key narrative issue in terms of emotional gratifications. Reactions in response to this type of entertainment are positively related to enjoyment, having a significant impact on the audience's immersion and suspension of disbelief. Related to computational modeling of this feature, some automatic storytelling systems include limited implementations of suspense management system in their core. In this way, the interest of this subject in the area of creativity has resorted to different definitions from fields as narratology and the film industry, as much as several proposals of its constituent features. Among their characteristics, uncertainty is one of the most discussed in terms of impact and need: while many authors affirm that uncertainty is essential to evoke suspense, others limit or reject its influence. Furthermore, the paradox of suspense reflects the problem of including uncertainty as a component required in suspense creation systems. Due to this need to contrast the effects of the uncertainty in order to compute a general model for automatic storytelling systems, we conducted an experiment measuring suspense experienced by a group of subjects that read a story. While a group of them were told the ending of the story in advance, the members of the other group experimented the same story in chronological order. Both the subjects' reported suspense and their physiological responses are gathered and analyzed. Results provide evidence to conclude that uncertainty affects the emotional response of readers, but independently and in a different form than suspense does. It will help to propose a model in which uncertainty is processed separately as management of the amount of knowledge about the outcome available to the spectator, which acts as a control signal to modulate the input features, but not directly in suspense computing.

Study of the influence of physical, chemical and biological conditions that influence the deterioration and protection of Underwater Cultural Heritage.

Two wrecks related to the Battle of Trafalgar (1805) were studied. Following the guidelines of the UNESCO-2001 Convention for the Protection of the Underwater Cultural Heritage, a holistic and interdisciplinary approach based on the development of four of the thirty-six Rules of this international agreement was applied. A non-destructive survey technique was developed to obtain information from the scattered cannons and anchors without altering their condition (Rule 4). The work performed provided information about the origin of both wrecks, the Fougueux and the Bucentaure, two ships of the line of the French Navy, and allowed to characterize the state of conservation at each site without jeopardizing their future conservation in the marine environment. In addition, measurements of the main physical, chemical and biological variables allowed correlating the conservation status at each site with the marine environmental conditions (Rule 15). Thus, in Fougueux shipwreck large iron objects are corroding at a higher rate (between 0.180 and 0.246mmpy) due to high sediment remobilization and transport induced by waves at this site, causing damage by direct mechanical effect on metallic material and by removing the layer of corrosion products developed on the artefacts. Meanwhile artillery on Bucentaure site, covered with thick layers of biological concretion, is well preserved, with lower corrosion rates (0.073 to 0.126mmpy), and archaeological information is guaranteed. Finally, the effectiveness of the cathodic protection as a temporary measure for in situ conservation (Rule 1) was evaluated on a cannon. The use of a sacrificial anode after 9months reduced the average corrosion rate (from 0.103 to 0.064mmpy) and the percent of corrosion rate in 37.9%. These results are very useful for developing a decision making system of the Site Management Program, based on predictive models of artefacts permanence and risk factors in the marine environment (Rule 25).

Shoe Orthotics for the Treatment of Chronic Low Back Pain: A Randomized Controlled Trial.

OBJECTIVES: To investigate the efficacy of shoe orthotics with and without chiropractic treatment for chronic low back pain compared with no treatment. DESIGN: Randomized controlled trial. SETTING: Integrative medicine teaching clinic at a university. PARTICIPANTS: Adult subjects (N=225) with symptomatic low back pain of ≥3 months were recruited from a volunteer sample. INTERVENTIONS: Subjects were randomized into 1 of 3 treatment groups (shoe orthotic, plus, and waitlist groups). The shoe orthotic group received custom-made shoe orthotics. The plus group received custom-made orthotics plus chiropractic manipulation, hot or cold packs, and manual soft tissue massage. The waitlist group received no care. MAIN OUTCOME MEASURES: The primary outcome measures were change in perceived back pain (numerical pain rating scale) and functional health status (Oswestry Disability Index) after 6 weeks of study participation. Outcomes were also assessed after 12 weeks and then after an additional 3, 6, and 12 months. RESULTS: After 6 weeks, all 3 groups demonstrated significant within-group improvement in average back pain, but only the shoe orthotic and plus groups had significant within-group improvement in function. When compared with the waitlist group, the shoe orthotic group demonstrated significantly greater improvements in pain (P<.0001) and function (P=.0068). The addition of chiropractic to orthotics treatment demonstrated significantly greater improvements in function (P=.0278) when compared with orthotics alone, but no significant difference in pain (P=.3431). Group differences at 12 weeks and later were not significant. CONCLUSIONS: Six weeks of prescription shoe orthotics significantly improved back pain and dysfunction compared with no treatment. The addition of chiropractic care led to higher improvements in function.

Motivation, students' needs and learning outcomes: a hybrid game-based app for enhanced language learning.

In the context of European Higher Education students face an increasing focus on independent, individual learning-at the expense of face-to-face interaction. Hence learners are, all too often, not provided with enough opportunities to negotiate in the target language. The current case study aims to address this reality by going beyond conventional approaches to provide students with a hybrid game-based app, combining individual and collaborative learning opportunities. The 4-week study was carried out with 104 German language students (A1.2 CEFR) who had previously been enrolled in a first-semester A1.1 level course at a Spanish university. The VocabTrainerA1 app-designed specifically for this study-harnesses the synergy of combining individual learning tasks and a collaborative murder mystery game in a hybrid level-based architecture. By doing so, the app provides learners with opportunities to apply their language skills to real-life-like communication. The purpose of the study was twofold: on one hand we aimed to measure learner motivation, perceived usefulness and added value of hybrid game-based apps; on the other, we sought to determine their impact on language learning. To this end, we conducted focus group interviews and an anonymous Technology Acceptance Model survey (TAM). In addition, students took a pre-test and a post-test. Scores from both tests were compared with the results obtained in first-semester conventional writing tasks, with a view to measure learning outcomes. The study provides qualitative and quantitative data supporting our initial hypotheses. Our findings suggest that hybrid game-based apps like VocabTrainerA1-which seamlessly combine individual and collaborative learning tasks-motivate learners, stimulate perceived usefulness and added value, and better meet the language learning needs of today's digital natives. In terms of acceptance, outcomes and sustainability, the data indicate that hybrid game-based apps significantly improve proficiency, hence are indeed, effective tools for enhanced language learning.

Chronic Exertional Compartment Syndrome in a Healthy Young Man.

OBJECTIVE: The purpose of this case report is to describe a patient who presented with symptoms of exercise-induced compartment syndrome and was later referred for bilateral fasciotomy surgery. CLINICAL FEATURES: A 21-year-old patient presented for chiropractic care with the inability to run due to foot paresthesia and weakness. An exertion test and compartment pressure test diagnosed exercise-induced compartment syndrome. Exertion test and compartment pressure test were used to identify and diagnose exercise-induced compartment syndrome. INTERVENTION AND OUTCOME: The patient was diagnosed with exercise-induced compartment syndrome. He was treated conservatively and referred for additional testing. The orthopedic surgeon requested that 12 weeks of conservative care be provided prior to testing; treatment consisted of chiropractic care and rehabilitation exercises. Following the 12 weeks of treatment, the patient did not significantly respond to conservative care. A compartment pressure test confirmed the initial diagnosis of exercise-induced compartment syndrome. The patient underwent a unilateral fasciotomy surgery and recovered fully. Following the surgery, the patient returned to the chiropractic clinic with the same presentation in the contralateral leg. The same protocol of management resulted in the same outcome. Two years after surgical intervention, the patient continues to maintain an active lifestyle, able to run 2 to 3 miles per day without any exacerbations or symptomatology. CONCLUSION: Clinical awareness, a detailed history, and thorough examination with reproduction of symptomatology are necessary to form a proper diagnosis and treatment plan for these patients. Therefore, multidisciplinary medical communication would prove to be the most beneficial approach for the patient.

Cellulitis of the Knee in a 16-Month-Old Boy: A Case Report.

OBJECTIVE: The purpose of this case report is to describe the presentation of cellulitis in a 16-month-old boy to a chiropractic clinic. CLINICAL FEATURES: The patient presented with nontraumatic, sudden onset of nonpurulent erythema on the right knee. A plain film radiograph of the knee showed a 40-mm thickening of the anterior knee. A diagnosis of cellulitis was rendered based on the presentation of the rapidly spreading erythema and radiographically confirmed findings. INTERVENTION AND OUTCOME: The patient was immediately referred to the local emergency room. The patient was hospitalized, treated with clindamycin and amoxicillin for 3 days, and then discharged. The patient's pediatrician discontinued clindamycin treatment at the posthospitalization follow-up. Two weeks after treatment was discontinued, the patient was diagnosed with recurrent cellulitis. CONCLUSION: This case demonstrated that for this young patient with cellulitis of the knee, timely recognition and referral, together with patient or parent education and immediate treatment, were essential to a successful outcome.

Benthic assemblages, biodiversity and invasiveness in marinas and commercial harbours: an investigation using a bioindicator group.

Fouling communities on artificial marine structures are generally different from benthic communities in natural rocky habitats. However, they may also differ among different types of artificial structures. Two artificial structures in direct contact with arriving vessels were compared: floating pontoons within recreational marinas, and sea-walls within commercial harbours. Natural rocky habitats were used as a reference, and the genus Eudendrium (Cnidaria, Hydrozoa) was chosen as a bioindicator. The assemblages were different among the three types of habitat studied, with different species characterising each habitat. The probability of finding an invasive Eudendrium species was significantly higher on pontoons. Diversity was the lowest on pontoons, but it was not significantly different between sea-walls and natural rocks. In general, a barrier to the spread of exotic species exists between harbours and natural rocky habitats. Floating pontoons seem to be a less suitable habitat for native fauna and a key element in marine biological invasions.

Shoe orthotics for the treatment of chronic low back pain: a randomized controlled pilot study.

OBJECTIVES: The purpose of this pilot study was to investigate the feasibility of a randomized clinical trial of shoe orthotics for chronic low back pain. METHODS: The study recruited 50 patients with chronic low back pain through media advertising in a midwestern suburban area. Medical history and a low back examination were completed at a chiropractic clinic. Subjects were randomized to either a treatment group receiving custom-made shoe orthotics or a wait-list control group. After 6 weeks, the wait-list control group also received custom-made orthotics. This study measured change in perceived pain levels (Visual Analog Scale) and functional health status (Oswestry Disability Index) in patients with chronic low back pain at the end of 6 weeks of orthotic treatment compared with no treatment and at the end of 12 weeks of orthotic treatment. RESULTS: This study showed changes in back pain and disability with the use of shoe orthotics for 6 weeks compared with a wait-list control group. It appears that improvement was maintained through the 12-week visit, but the subjects did not continue to improve during this time. CONCLUSIONS: This pilot study showed that the measurement of shoe orthotics to reduce low back pain and discomfort after 6 weeks of use is feasible. A larger clinical trial is needed to verify these results.