Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Molecular detection of Histoplasma capsulatum in organ samples from bats randomly captured in urban areas of Araraquara, São Paulo state, Brazil.

The mycosis histoplasmosis is also considered a zoonosis that affects humans and other mammalian species worldwide. Among the wild mammals predisposed to be infected with the etiologic agent of histoplasmosis, bats are relevant because they are reservoir of Histoplasma species, and they play a fundamental role in maintaining and spreading fungal propagules in the environments since the infective mycelial phase of Histoplasma grows in their accumulated guano. In this study, we detected the fungal presence in organ samples of bats randomly captured in urban areas of Araraquara City, São Paulo, Brazil. Fungal detection was performed using a nested polymerase chain reaction to amplify a molecular marker (Hcp100) unique to H. capsulatum, which revealed the pathogen presence in organ samples from 15 out of 37 captured bats, indicating 40.5% of infection. Out of 22 Hcp100-amplicons generated, 41% corresponded to lung and trachea samples and 59% to spleen, liver, and kidney samples. Data from these last three organs suggest that bats develop disseminated infections. Considering that infected bats create environments with a high risk of infection, it is important to register the percentage of infected bats living in urban areas to avoid risks of infection to humans, domestic animals, and wildlife.

LIFT procedure: postoperative outcomes, risk factors for fistula recurrence and continence impairment.

Ligation of the intersphincteric fistula tract has been recently employed as definitive treatment of anal fistulas. However, it carries a potential risk of continence impairment, fistula recurrence, and repeated operations. This study aimed to assess postoperative outcomes related to this procedure and evaluate the potential influence of preoperative and intraoperative features. Patients who underwent LIFT procedure between June 2012 and September 2021 were retrospectively analyzed. Patients were divided according to whether they developed fistula recurrence and on the history of a surgery prior to the LIFT. Preoperative features, postoperative outcomes, and risk factors adverse outcomes were analyzed. Forty-eight patients were included, of which 25 received primary LIFT, being the high transsphincteric fistula pattern the most frequent (62.5%). The median follow-up was 13.3 months, with a recurrence rate of 20.8%, of which the majority presented an intersphincteric fistula pattern (50%); and continence impairment rate of 16.7%. A higher prevalence of diabetes (p = 0.026) and a trend towards a higher prevalence of patients with a history of high transsphincteric fistula (0.052) were observed in the group with fistula recurrence. The history of diabetes and the operation time with a cut-off value ≥ 69 min showed a trend as a risk factors for developing fistula recurrence (0.06) and postoperative continence impairment (0.07), respectively. The LIFT procedure seems to be safe in terms of morbidity, with a reasonable incidence of recurrences, showing better results when it is primarily performed. Preoperative characteristics should be considered as they may impact outcomes.

Fish skin grafts versus standard of care on wound healing of chronic diabetic foot ulcers: A systematic review and meta-analysis.

INTRODUCTION: This study will explore the effectiveness of fish skin grafts (FSG) in ulcer healing in diabetic foot disease compared to standard of care (SOC). METHODS: The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases of PubMed, EMBASE, and Web of Science (WoS) internet were searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration. Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests. RESULTS: Five randomised controlled trials (RCTs) with a total of 411 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving fish skin grafts (OR = 3.34, 95% CI 2.14-5.20, p < 0.01, I2 = 0%) compared to control groups. CONCLUSION: Fish skin grafts have been shown to be more effective for achieving complete ulcer healing compared to current conventional treatments in diabetic foot disease.

Pseudomonas taetrolens ULE-PH5 and Pseudomonas sp. ULE-PH6 Isolated from the Hop Rhizosphere Increase Phosphate Assimilation by the Plant.

Most of the phosphorus incorporated into agricultural soils through the use of fertilizers precipitates in the form of insoluble salts that are incapable of being used by plants. This insoluble phosphorus present in large quantities in soil forms the well-known "phosphorus legacy". The solubilization of this "phosphorus legacy" has become a goal of great agronomic importance, and the use of phosphate-solubilizing bacteria would be a useful tool for this purpose. In this work, we have isolated and characterized phosphate-solubilizing bacteria from the rhizosphere of hop plants. Two particular strains, Pseudomonas taetrolens ULE-PH5 and Pseudomonas sp. ULE-PH6, were selected as plant growth-promoting rhizobacteria due to their high phosphate solubilization capability in both plate and liquid culture assays and other interesting traits, including auxin and siderophore production, phytate degradation, and acidic and alkaline phosphatase production. These strains were able to significantly increase phosphate uptake and accumulation of phosphorus in the aerial part (stems, petioles, and leaves) of hop plants, as determined by greenhouse trials. These strains are promising candidates to produce biofertilizers specifically to increase phosphate adsorption by hop plants.

Ludificación y neurorrehabilitación motora en niños y adolescentes: revisión sistemática / Gamification and neurological motor rehabilitation in children and adolescents: A systematic review

Introducción La ludificación consiste en emplear el juego en contextos no lúdicos. Su uso en la rehabilitación motora de patologías neurológicas está muy extendido, pero sobre todo en pacientes adultos. El objetivo de esta revisión fue describir el uso de la ludificación en los tratamientos de rehabilitación en niños y adolescentes con afectación neuromotora. Métodos Se realizó una revisión sistemática de ensayos clínicos en diferentes bases de datos: Medline (a través de Pubmed), Scielo, SCOPUS, Dialnet, Cinahl y PEDro de la literatura científica publicada hasta la fecha siguiendo el protocolo PRISMA. La calidad metodológica de los estudios identificados se evaluó a través de la escala PEDro. Resultados De un total de 469 estudios localizados se seleccionaron 10 ensayos clínicos que cumplieron los criterios de inclusión. Se analizaron los sistemas de ludificación utilizados como parte del tratamiento rehabilitador en distintas afecciones neuromotoras en niños y adolescentes. La parálisis cerebral fue la afección con mayor número de estudios (n = 6), seguida del trastorno del desarrollo de la coordinación (n = 3). También se estudió la alteración del equilibrio y coordinación por causa neurológica (n = 1). Conclusión El uso de la ludificación en rehabilitación aporta beneficios al tratamiento convencional de las alteraciones neuromotoras en niños y adolescentes, siendo el incremento de la motivación y de la adherencia terapéutica los que mayor consenso han alcanzado entre autores. Fuerza, equilibrio, funcionalidad y coordinación son otras variables analizadas que, si bien sugieren mejoras, necesitarían futuras investigaciones para determinar una óptima dosificación. (AU)

Introduction Gamification consists of the use of games in non-playful contexts. It is widely employed in the motor rehabilitation of neurological diseases, but mainly in adult patients. The objective of this review was to describe the use of gamification in the rehabilitation of children and adolescents with neuromotor impairment. Methods We performed a systematic review of clinical trials published to date on the MEDLINE (PubMed), Scielo, SCOPUS, Dialnet, CINAHL, and PEDro databases, following the PRISMA protocol. The methodological quality of the studies identified was assessed using the PEDro scale. Results From a total of 469 studies, 10 clinical trials met the inclusion criteria. We analysed the gamification systems used as part of the rehabilitation treatment of different neuromotor conditions in children and adolescents. Cerebral palsy was the most frequently studied condition (6 studies), followed by developmental coordination disorder (3), and neurological impairment of balance and coordination (1). Conclusion The use of gamification in rehabilitation is helpful in the conventional treatment of neuromotor disorders in children and adolescents, with increased motivation and therapeutic adherence being the benefits with the greatest consensus among authors. While strength, balance, functional status, and coordination also appear to improve, future research should aim to determine an optimal dosage. (AU)

Ludificación y neurorrehabilitación motora en niños y adolescentes: revisión sistemática / Gamification and neurological motor rehabilitation in children and adolescents: A systematic review

Introducción La ludificación consiste en emplear el juego en contextos no lúdicos. Su uso en la rehabilitación motora de patologías neurológicas está muy extendido, pero sobre todo en pacientes adultos. El objetivo de esta revisión fue describir el uso de la ludificación en los tratamientos de rehabilitación en niños y adolescentes con afectación neuromotora. Métodos Se realizó una revisión sistemática de ensayos clínicos en diferentes bases de datos: Medline (a través de Pubmed), Scielo, SCOPUS, Dialnet, Cinahl y PEDro de la literatura científica publicada hasta la fecha siguiendo el protocolo PRISMA. La calidad metodológica de los estudios identificados se evaluó a través de la escala PEDro. Resultados De un total de 469 estudios localizados se seleccionaron 10 ensayos clínicos que cumplieron los criterios de inclusión. Se analizaron los sistemas de ludificación utilizados como parte del tratamiento rehabilitador en distintas afecciones neuromotoras en niños y adolescentes. La parálisis cerebral fue la afección con mayor número de estudios (n = 6), seguida del trastorno del desarrollo de la coordinación (n = 3). También se estudió la alteración del equilibrio y coordinación por causa neurológica (n = 1). Conclusión El uso de la ludificación en rehabilitación aporta beneficios al tratamiento convencional de las alteraciones neuromotoras en niños y adolescentes, siendo el incremento de la motivación y de la adherencia terapéutica los que mayor consenso han alcanzado entre autores. Fuerza, equilibrio, funcionalidad y coordinación son otras variables analizadas que, si bien sugieren mejoras, necesitarían futuras investigaciones para determinar una óptima dosificación. (AU)

Introduction Gamification consists of the use of games in non-playful contexts. It is widely employed in the motor rehabilitation of neurological diseases, but mainly in adult patients. The objective of this review was to describe the use of gamification in the rehabilitation of children and adolescents with neuromotor impairment. Methods We performed a systematic review of clinical trials published to date on the MEDLINE (PubMed), Scielo, SCOPUS, Dialnet, CINAHL, and PEDro databases, following the PRISMA protocol. The methodological quality of the studies identified was assessed using the PEDro scale. Results From a total of 469 studies, 10 clinical trials met the inclusion criteria. We analysed the gamification systems used as part of the rehabilitation treatment of different neuromotor conditions in children and adolescents. Cerebral palsy was the most frequently studied condition (6 studies), followed by developmental coordination disorder (3), and neurological impairment of balance and coordination (1). Conclusion The use of gamification in rehabilitation is helpful in the conventional treatment of neuromotor disorders in children and adolescents, with increased motivation and therapeutic adherence being the benefits with the greatest consensus among authors. While strength, balance, functional status, and coordination also appear to improve, future research should aim to determine an optimal dosage. (AU)

False lumen hemodynamics and partial thrombosis in chronic aortic dissection of the descending aorta.

OBJECTIVES: Partial thrombosis of the false lumen (FL) in patients with chronic aortic dissection (AD) of the descending aorta has been associated with poor outcomes. Meanwhile, the fluid dynamic and biomechanical characteristics associated with partial thrombosis remain to be elucidated. This retrospective, single-center study tested the association between FL fluid dynamics and biomechanics and the presence and extent of FL thrombus. METHODS: Patients with chronic non-thrombosed or partially thrombosed FLs in the descending aorta after an aortic dissection underwent computed tomography angiography, cardiovascular magnetic resonance (CMR) angiography, and a 4D flow CMR study. A comprehensive quantitative analysis was performed to test the association between FL thrombus presence and extent (percentage of FL with thrombus) and FL anatomy (diameter, entry tear location and size), fluid dynamics (inflow, rotational flow, wall shear stress, kinetic energy, and flow acceleration and stasis), and biomechanics (pulse wave velocity). RESULTS: Sixty-eight patients were included. In multivariate logistic regression FL kinetic energy (p = 0.038) discriminated the 33 patients with partial FL thrombosis from the 35 patients with no thrombosis. Similarly, in separated multivariate linear correlations kinetic energy (p = 0.006) and FL inflow (p = 0.002) were independently related to the extent of the thrombus. FL vortexes, flow acceleration and stasis, wall shear stress, and pulse wave velocity showed limited associations with thrombus presence and extent. CONCLUSION: In patients with chronic descending aorta dissection, false lumen kinetic energy is related to the presence and extent of false lumen thrombus. CLINICAL RELEVANCE STATEMENT: In patients with chronic aortic dissection of the descending aorta, false lumen hemodynamic parameters are closely linked with the presence and extent of false lumen thrombosis, and these non-invasive measures might be important in patient management. KEY POINTS: • Partial false lumen thrombosis has been associated with aortic growth in patients with chronic descending aortic dissection; therefore, the identification of prothrombotic flow conditions is desirable. • The presence of partial false lumen thrombosis as well as its extent was related with false lumen kinetic energy. • The assessment of false lumen hemodynamics may be important in the management of patients with chronic aortic dissection of the descending aorta.

Autologous platelet-rich plasma (APRP) in diabetes foot disease: a meta-analysis.

INTRODUCTION: This study will explore the effectiveness of autologous platelet-rich plasma in the treatment of diabetic foot disease compared to conventional treatments, based on the ulcer healing rate. METHODS: The electronic databases of PubMed, EMBASE, and WOS internet were searched. Evaluated outcome rate of complete ulcer healing. Statistical analysis was performed with RevMan 5.0 software and SPSS 25.0. RESULTS: Eleven RCTs with 828 patients were included in this study. The meta-analysis showed a higher complete ulcer healing rate (OR = 3.69, 95 % CI 2.62 to 5.20, P < 0.01, I2 = 0 %) in growth factors based in autologous platelech-rich plasma (aPRP) group compared with control. Mixed evidence was seen for publication bias, but analyses by using the trim-and-fill method did not appreciably alter results. CONCLUSION: Autologous platelet-rich plasma can improve the complete healing rate of the ulcer compared to current conventional treatments in diabetic foot ulcer patients.

Three-dimensional aortic geometry mapping via registration of non-gated contrast-enhanced or gated and respiratory-navigated MR angiographies.

BACKGROUND: The measurement of aortic dimensions and their evolution are key in the management of patients with aortic diseases. Manual assessment, the current guideline-recommended method and clinical standard, is subjective, poorly reproducible, and time-consuming, limiting the capacity to track aortic growth in everyday practice. Aortic geometry mapping (AGM) via image registration of serial computed tomography angiograms outperforms manual assessment, providing accurate and reproducible 3D maps of aortic diameter and growth rate. This observational study aimed to evaluate the accuracy and reproducibility of AGM on non-gated contrast-enhanced (CE-) and cardiac- and respiratory-gated (GN-) magnetic resonance angiographies (MRA). METHODS: Patients with thoracic aortic disease followed with serial CE-MRA (n = 30) or GN-MRA (n = 15) acquired at least 1 year apart were retrospectively and consecutively identified. Two independent observers measured aortic diameters and growth rates (GR) manually at several thoracic aorta reference levels and with AGM. Agreement between manual and AGM measurements and their inter-observer reproducibility were compared. Reproducibility for aortic diameter and GR maps assessed with AGM was obtained. RESULTS: Mean follow-up was 3.8 ± 2.3 years for CE- and 2.7 ± 1.6 years for GN-MRA. AGM was feasible in the 93% of CE-MRA pairs and in the 100% of GN-MRA pairs. Manual and AGM diameters showed excellent agreement and inter-observer reproducibility (ICC>0.9) at all anatomical levels. Agreement between manual and AGM GR was more limited, both in the aortic root by GN-MRA (ICC=0.47) and in the thoracic aorta, where higher accuracy was obtained with GN- than with CE-MRA (ICC=0.55 vs 0.43). The inter-observer reproducibility of GR by AGM was superior compared to manual assessment, both with CE- (thoracic: ICC= 0.91 vs 0.51) and GN-MRA (root: ICC=0.84 vs 0.52; thoracic: ICC=0.93 vs 0.60). AGM-based 3D aortic size and growth maps were highly reproducible (median ICC >0.9 for diameters and >0.80 for GR). CONCLUSION: Mapping aortic diameter and growth on MRA via 3D image registration is feasible, accurate and outperforms the current manual clinical standard. This technique could broaden the possibilities of clinical and research evaluation of patients with aortic thoracic diseases.

Gamification and neurological motor rehabilitation in children and adolescents: a systematic review.

INTRODUCTION: Gamification consists of the use of games in non-playful contexts. It is widely employed in the motor rehabilitation of neurological diseases, but mainly in adult patients. The objective of this review was to describe the use of gamification in the rehabilitation of children and adolescents with neuromotor impairment. METHODS: We performed a systematic review of clinical trials published to date on the MEDLINE (PubMed), Scielo, SCOPUS, Dialnet, CINAHL, and PEDro databases, following the PRISMA protocol. The methodological quality of the studies identified was assessed using the PEDro scale. RESULTS: From a total of 469 studies, 11 clinical trials met the inclusion criteria. We analysed the gamification systems used as part of the rehabilitation treatment of different neuromotor conditions in children and adolescents. Cerebral palsy was the most frequently studied condition (6 studies), followed by developmental coordination disorder (3), neurological gait disorders (1), and neurological impairment of balance and coordination (1). CONCLUSION: The use of gamification in rehabilitation is helpful in the conventional treatment of neuromotor disorders in children and adolescents, with increased motivation and therapeutic adherence being the benefits with the greatest consensus among authors. While strength, balance, functional status, and coordination also appear to improve, future research should aim to determine an optimal dosage.

Pelvic Diameter is not Associated with Positive Circumferential Resection Margin in Rectal Cancer: Retrospective Analysis of 78 Cases

Abstract Objective To identify if there is an association between pelvic entry and pelvic outlet diameters with increased positive circumferential resection margin (CRM) in rectal cancer. Introduction Positive CRMin rectalcancerisa majorpredictor forlocal anddistant recurrence. Pelvic diameters may be related to the difficulty of dissection, as well as intrinsic tumor characteristics such as tumor size, location, distance from the anal margin, and T stage, which may compromise the integrity of the mesorectum and circumferential margin involvement. Methods A retrospective review of the patient's medical records who underwent surgical resection of rectal adenocarcinoma from January 2012 to June 2022 was performed. The patient's preoperative staging, operative characteristics, and histopathologic outcomes were gathered from the medical records. Preoperative MRI scanning was done in all patients. MRI pelvimetry was done by two observers. CRM involvement was recorded as stated in the pathology report. Pelvimetry variables were dichotomized according to their mean values for correlation analysis. The odds ratio (OR) was calculated from a binary logistics regression model to assess the relation between the positive CRM and the independent variables. Results A total of 78 patients were included in this study. A positive CRM was reported in 10 patients (12.8%). BMI >27.4 + 6.6 (p = 0.02), positive extramural vascular invasion (p = 0.027), positive CRM by MRI scanning (p = 0.004), and anal sphincter involvement (p = 0.03) were associated with positive CRM. Pelvimetry values were not associated with a positive CRM. Conclusion No association was found between the pelvic diameters measured by MRI pelvimetry with a positive CRM.

Evaluation of Anticancer and Anti-Inflammatory Activities of Some Synthetic Rearranged Abietanes.

Synthesis of the rearranged abietane diterpenes pygmaeocins C and D, viridoquinone, saprorthoquinone, and 1-deoxyviroxocine has been successfully achieved. The anticancer and anti-inflammatory activities of selected orthoquinonic compounds 5, 7, 13, and 19, as well as pygmaeocin C (17), were evaluated for the first time. The antitumor properties were assessed using three cancer cell lines: HT29 colon cancer cells, Hep G2 hepatocellular carcinoma cells, and B16-F10 murine melanoma cells. Compounds 5 and 13 showed the highest cytotoxicity in HT29 cells (IC50 = 6.69 ± 1.2 µg/mL and IC50 = 2.7 ± 0.8 µg/mL, respectively). Cytometric studies showed that this growth inhibition involved phase S cell cycle arrest and apoptosis induction, possibly through the activation of the intrinsic apoptotic pathway. Morphological apoptotic changes, including nuclear fragmentation and chromatin condensation, were also observed. Furthermore, the anti-inflammatory activity of these compounds was evaluated on the basis of their ability to inhibit nitric oxide production on the lipopolysaccharide activated RAW 264.7 macrophage cell line. Although all compounds showed high anti-inflammatory activity, with percentages between 40 and 100%, the highest anti-inflammatory potential was obtained by pygmaeocin B (5) (IC50NO = 33.0 ± 0.8 ng/mL). Our results suggest that due to their dual roles, this type of compound could represent a new strategy, contributing to the development of novel anticancer agents.

Nailfold videocapillaroscopy patterns in systemic sclerosis: implications for cutaneous subsets, disease features and prognostic value for survival.

OBJECTIVES: To assess the associations and prognostic value of scleroderma patterns by nailfold videocapillaroscopy (NVC) in patients with systemic sclerosis (SSc) and cutaneous subsets. METHODS: At baseline, 1356 SSc patients from the RESCLE registry were compared according to the scleroderma pattern as Late pattern and non-Late pattern, which included Early and Active patterns. Patient characteristics, disease features, survival time and causes of death were analysed. RESULTS: Late pattern was identified in 540 (39.8%), and non-Late pattern in 816 (60.2%) patients (88% women; 987 lcSSc/251 dcSSc). Late pattern was associated to dcSSc (OR=1.96; p<0.001), interstitial lung disease (ILD) (OR=1.29; p=0.031), and scleroderma renal crisis (OR=3.46; p<0.001). Once the cutaneous subset was disregarded in an alternative analysis, both digital ulcers (DU) (OR=1.29; p<0.037) and anti-topoisomerase I antibodies (OR=1.39; p< 0.036) emerged associated with the Late pattern. By cutaneous subsets, associations with Late pattern were: (1) in dcSSc, acro-osteolysis (OR=2.13; p=0.022), and systolic pulmonary artery pressure >40 mmHg by Doppler echocardiogram (OR=2.24; p<0.001); and (2) in lcSSc, ILD (OR=1.38; p=0.028). Survival was reduced in dcSSc with Late pattern compared to non-Late pattern (p=0.049). Risk factors for SSc mortality in multivariate regression Cox analysis were age at diagnosis (HR=1.03; p<0.001), dcSSc (HR=2.48; p<0.001), DU (HR=1.38; p=0.046), ILD (HR=2.81; p<0.001), and pulmonary arterial hypertension (HR=1.99; p<0.001). CONCLUSIONS: SSc patients with Late pattern more frequently present dcSSc and develop more fibrotic and vascular manifestations. Advanced microangiopathy by NVC identifies dcSSc patients at risk of reduced survival due to SSc-related causes.

Risk factors and associated factors for calcaneal apophysitis (Sever's disease): a systematic review.

OBJECTIVES: The aim of this review was to identify the potential intrinsic and extrinsic risk factors (RFs), associated factors (AFs) and consequences of developing calcaneal apophysitis (CA). DESIGN: Systematic review. DATA SOURCES: Cochrane Library, Embase, Medline Ovid, PubMed, Web of Science and Evidence, searched from inception to April 2021. ELIGIBILITY CRITERIA: We included cohort, case-control and cross-sectional studies that were conducted in patients younger than 18 years who were exposed to RFs or who presented with factors associated with developing CA. Studies in languages other than English or Spanish were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers worked independently to evaluate the risk of bias of included studies. The Newcastle-Ottawa Scale (adapted version) was used. RESULTS: A total of 736 studies were identified and 11 observational studies fully met the inclusion criteria, including 1265 participants with a mean age of 10.72 years. Four studies identified extrinsic factors, 10 identified intrinsic factors and three identified both. The extrinsic and intrinsic RFs, AFs and consequences of CA include limitation of ankle dorsiflexion, foot alignment, stiffness and mobility of the midfoot, plantar pressures and ground reaction force, body mass index, age, gender, presence of other osteochondroses and practice of sport. The risk of bias varied, being either moderate or low. CONCLUSIONS: Regarding the factors and consequences associated with CA (Sever's disease), ankle dorsiflexion limitation is the most frequent intrinsic factor studied, followed by peak plantar pressures and foot malalignment. However, disagreements between the investigators of the included studies were found; in some cases, there is a lack of unanimity between different studies as to which factors are considered to be RFs, AFs and consequences. PROSPERO REGISTRATION NUMBER: CRD42021246366.

Effectiveness of a gamified digital intervention based on lifestyle modification (iGAME) in secondary prevention: a protocol for a randomised controlled trial.

INTRODUCTION: Combating physical inactivity and reducing sitting time are one of the principal challenges proposed by public health systems. Gamification has been seen as an innovative, functional and motivating strategy to encourage patients to increase their physical activity (PA) and reduce sedentary lifestyles through behaviour change techniques (BCT). However, the effectiveness of these interventions is not usually studied before their use. The main objective of this study will be to analyse the effectiveness of a gamified mobile application (iGAME) developed in the context of promoting PA and reducing sitting time with the BCT approach, as an intervention of secondary prevention in sedentary patients. METHODS AND ANALYSIS: A randomised clinical trial will be conducted among sedentary patients with one of these conditions: non-specific low back pain, cancer survivors and mild depression. The experimental group will receive a 12-week intervention based on a gamified mobile health application using BCT to promote PA and reduce sedentarism. Participants in the control group will be educated about the benefits of PA. The International Physical Activity Questionnaire will be considered the primary outcome. International Sedentary Assessment Tool, EuroQoL-5D, MEDRISK Instruments and consumption of Health System resources will be evaluated as secondary outcomes. Specific questionnaires will be administered depending on the clinical population. Outcomes will be assessed at baseline, at 6 weeks, at the end of the intervention (12 weeks), at 26 weeks and at 52 weeks. ETHICS AND DISSEMINATION: The study has been approved by the Portal de Ética de la Investigación Biomédica de Andalucía Ethics Committee (RCT-iGAME 24092020). All participants will be informed about the purpose and content of the study and written informed consent will be completed. The results of this study will be published in a peer-reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION NUMBER: NCT04019119.

Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis.

AIMS: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. METHODS AND RESULTS: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. CONCLUSION: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.

Population-based evaluation of the impact of socioeconomic status on clinical outcomes in patients with heart failure in integrated care settings.

INTRODUCTION AND OBJECTIVES: Low socioeconomic status (SES) is associated with poor outcomes in patients with heart failure (HF). We aimed to examine the influence of SES on health outcomes after a quality of care improvement intervention for the management of HF integrating hospital and primary care resources in a health care area of 209 255 inhabitants. METHODS: We conducted a population-based pragmatic evaluation of the implementation of an integrated HF program by conducting a natural experiment using health care data. We included all individuals consecutively admitted to hospital with at least one ICD-9-CM code for HF as the primary diagnosis and discharged alive in Catalonia between January 1, 2015 and December 31, 2019. We compared outcomes between patients exposed to the new HF program and those in the remaining health care areas, globally and stratified by SES. RESULTS: A total of 77 554 patients were included in the study. Death occurred in 37 469 (48.3%), clinically-related hospitalization in 41 709 (53.8%) and HF readmission in 29 755 (38.4%). On multivariate analysis, low or very low SES was associated with an increased risk of all-cause death and clinically-related hospitalization (all Ps <.05). The multivariate models showed a significant reduction in the risk of all-cause death (HR, 0.812; 95%CI, 0.723-0.912), clinically-related hospitalization (HR, 0.886; 95%CI, 0.805-0.976) and HF hospitalization (HR, 0.838; 95%CI, 0.745-0.944) in patients exposed to the new HF program compared with patients exposed to the remaining health care areas and this effect was independent of SES. CONCLUSIONS: An intensive transitional HF management program improved clinical outcomes, both overall and across SES strata.

Whipple's Disease: A Systematic Review of the Literature

Introduction: Whipple's disease is a chronic systemic disease with a predilection for the digestive system, especially the small intestine. It was first described in 1907 by George H. Whipple, who named it intestinal lipodystrophy. It is caused by a gram-positive bacterium belonging to the Actinomycetaceae family called Tropheryma whipplei. Objective: To characterize patients with Whipple's disease. Materials and methods: A systematic literature review was carried out using the DeCS terms enfermedad de Whipple (Whipple's disease) or (Tropheryma whipplei) in the Pubmed/Medline, Scopus, Scielo, Science Direct, Embase, Cochrane Library, BIREME, Proquest, and Redalyc databases; 123 articles were analyzed. Results: 123 published articles corresponding to case reports and series were examined, noting a higher prevalence in males (70.6%). The most frequent manifestations were joint symptoms (61%), followed by weight loss (47.1%) and diarrhea (43.4%). The most used diagnostic method was polymerase chain reaction (PCR) (63.2%), followed by biopsy (50.7%) and pathological examination with PAS (periodic acid Schiff) granules (47.8%). The management most used was antibiotic therapy with a predominance of trimethoprim/sulfamethoxazole and ceftriaxone. Conclusions: Whipple's disease has a low prevalence, occurs more frequently in white people, mainly affects the elderly, has a predilection for the male sex, and is characterized as a chronic systemic disease with a predilection for the digestive system, especially the small intestine.

Introducción: la enfermedad de Whipple es una enfermedad crónica sistémica con predilección por el aparato digestivo, especialmente el intestino delgado. Fue descrita por vez primera en 1907 por George H. Whipple, quien la denominó lipodistrofia intestinal. Es causada por una bacteria grampositiva perteneciente a la familia de los Actinomycetaceae denominada Tropheryma whipplei. Objetivo: caracterizar a los pacientes con enfermedad de Whipple. Materiales y métodos: se realizó una revisión sistemática de la literatura, de los términos DeCS enfermedad de Whipple (whipple Disease) o (Tropheryma whipplei) en las bases de datos Pubmed/Medline, Scopus, Scielo y Science Direct, Embase, Cochrane Library, BIREME, Proquest y Redalyc; se analizaron 123 artículos. Resultados: se analizaron 123 artículos publicados que correspondían a reportes y series de casos en los cuales se evidenció una mayor prevalencia en varones (70,6%). Las manifestaciones más frecuentes fueron los síntomas articulares (61%), seguidos de pérdida de peso (47,1%) y diarrea (43,4%). El método diagnóstico más usado fue la reacción en cadena de la polimerasa (PCR) (63,2%), seguido por la biopsia (50,7%) y, por último, examen anatomopatológico con gránulos PAS (ácido peryódico de Schiff) (47,8%). El manejo más empleado fue la antibioticoterapia con predominio de trimetoprima/sulfametoxazol y ceftriaxona. Conclusiones: la enfermedad de Whipple tiene una baja prevalencia, se presenta con mayor frecuencia en personas de raza blanca, afecta principalmente a los adultos mayores, tiene predilección por el sexo masculino y se caracteriza por ser una enfermedad crónica sistémica con predilección por el aparato digestivo, especialmente el intestino delgado.

Wine yeast selection in the Iberian Peninsula: Saccharomyces and non-Saccharomyces as drivers of innovation in Spanish and Portuguese wine industries.

Yeast selection for the wine industry in Spain started in 1950 for the understanding of the microbial ecology, and for the selection of optimal strains to improve the performance of alcoholic fermentation and the overall wine quality. This process has been strongly developed over the last 30 years, firstly on Saccharomyces cerevisiae, and, lately, with intense activity on non-Saccharomyces. Several thousand yeast strains have been isolated, identified and tested to select those with better performance and/or specific technological properties. The present review proposes a global survey of this massive ex-situ preservation of eukaryotic microorganisms, a reservoir of biotechnological solutions for the wine sector, overviewing relevant screenings that led to the selection of strains from 12 genera and 22 species of oenological significance. In the first part, the attention goes to the selection programmes related to relevant wine-producing areas (i.e. Douro, Extremadura, Galicia, La Mancha and Uclés, Ribera del Duero, Rioja, Sherry area, and Valencia). In the second part, the focus shifted on specific non-Saccharomyces genera/species selected from different Spanish and Portuguese regions, exploited to enhance particular attributes of the wines. A fil rouge of the dissertation is the design of tailored biotechnological solutions for wines typical of given geographic areas.