MVA-based vaccine candidates expressing SARS-CoV-2 prefusion-stabilized spike proteins of the Wuhan, Beta or Omicron BA.1 variants protect transgenic K18-hACE2 mice against Omicron infection and elicit robust and broad specific humoral and cellular immune responses.

Despite the decrease in mortality and morbidity due to SARS-CoV-2 infection, the incidence of infections due to Omicron subvariants of SARS-CoV-2 remains high. The mutations acquired by these subvariants, mainly concentrated in the receptor-binding domain (RBD), have caused a shift in infectivity and transmissibility, leading to a loss of effectiveness of the first authorized COVID-19 vaccines, among other reasons, by neutralizing antibody evasion. Hence, the generation of new vaccine candidates adapted to Omicron subvariants is of special interest in an effort to overcome this immune evasion. Here, an optimized COVID-19 vaccine candidate, termed MVA-S(3P_BA.1), was developed using a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein from the Omicron BA.1 variant. The immunogenicity and efficacy induced by MVA-S(3P_BA.1) were evaluated in mice in a head-to-head comparison with the previously generated vaccine candidates MVA-S(3P) and MVA-S(3Pbeta), which express prefusion-stabilized S proteins from Wuhan strain and Beta variant, respectively, and with a bivalent vaccine candidate composed of a combination of MVA-S(3P) and MVA-S(3P_BA.1). The results showed that all four vaccine candidates elicited, after a single intramuscular dose, protection of transgenic K18-hACE2 mice challenged with SARS-CoV-2 Omicron BA.1, reducing viral loads, histopathological lesions, and levels of proinflammatory cytokines in the lungs. They also elicited anti-S IgG and neutralizing antibodies against various Omicron subvariants, with MVA-S(3P_BA.1) and the bivalent vaccine candidate inducing higher titers. Additionally, an intranasal immunization in C57BL/6 mice with all four vaccine candidates induced systemic and mucosal S-specific CD4+ and CD8+ T-cell and humoral immune responses, and the bivalent vaccine candidate induced broader immune responses, eliciting antibodies against the ancestral Wuhan strain and different Omicron subvariants. These results highlight the use of MVA as a potent and adaptable vaccine vector against new emerging SARS-CoV-2 variants, as well as the promising feature of combining multivalent MVA vaccine candidates.

Related metacognitions, desire thinking and identity differentially predict compulsion and withdrawal symptoms in problematic Instagram use.

Work has identified that metacognitive thought results in desire-based thinking and perpetuates the magnitude and severity of maladaptive behaviour including problematic social media use, and also that one's ingroup identity is related to increasing problematic behaviour. No evidence has ascertained the relative contribution of these as related differential factors in the experience of problematic social media use. The current study explored the comparative importance of components of desire thinking, positive and negative metacognitions and dimensions of ingroup identity on degree of problematic use among 147 current Instagram users. Results showed that for predicting general problematic Instagram use negative metacognitive beliefs and the verbal perseverance component of desire-based thinking were significant. Importantly, however, different factors appeared to be important for predicting distinct aspects of problematic Instagram. For compulsivity indicators, negative metacognitions and verbal perseveration were essential, whereas for the withdrawal component identity centrality (and no other dimensions of identity) and imaginal prefiguration emerge as the sole independent predictors.

Psychological Aspects of Facial Palsy.

This article discusses the psychological effects of facial palsy (FP) in adults. FP is the abnormal functioning of facial muscles resulting from temporary or permanent damage of the facial nerves. Following facial paralysis, patients can develop motor and psychosocial functioning issues impacting quality of life. In addition, real or perceived judgment in social settings of those with FP increases the risk of low self-esteem, anxiety, and depression. Currently, most available research focuses on surgical patients and suggests a lack of psychological support throughout the affliction. A multidisciplinary approach when treating patients with FP can help improve the patient's quality of life.

Motivación Intrínseca y Perspectiva Temporal de Universitarios del Noroeste de México / Intrinsic Motivation and Temporal Perspective of University Students in Northwestern Mexico

Resumen Se buscó identificar el perfil de motivación intrínseca (MI) y su relación con la perspectiva temporal en estudiantes universitarios del noroeste de México. En una muestra no probabilística por conveniencia de 553 estudiantes, se puso a prueba un modelo de motivación intrínseca, autoeficacia, orientación al logro, percepción escolar, morosidad y orientaciones temporales (pasado, presente y futuro). Se conformó un modelo estructural de MI que posee bondad de ajuste práctica adecuada. El modelo explica 48% de la variabilidad de la motivación intrínseca; destaca el efecto positivo de la orientación al logro (peso estructural=.65*) y el efecto negativo e indirecto (a través de la autoeficacia) de la morosidad (peso estructural=-.53*) sobre la MI. Y un efecto positivo de las orientaciones temporales (pasado negativo, presente hedonista y presente fatalista) sobre la morosidad (peso estructural=.54*). El estudio ofrece información sobre los aspectos que deben ser desarrollados en los estudiantes universitarios en relación con la motivación intrínseca.

Abstract The purpose of this study was to identify the intrinsic motivation (IM) profile and its relationship with time perspective in a non-probabilistic convenience sample of 553 students university students from a northwestern region in Mexico. Structural equation models were fitted for intrinsic motivation, with self-efficacy, achievement orientation, school perception, procrastination and temporal orientations (past, present and future) as direct and indirect predictors. A structural model of IM was formed that has adequate practical goodness-of-fit. The overall model explained 48% of the variance for intrinsic motivation. Achievement orientation was positively associated (structural weight =.65*) with intrinsic motivation while procrastination was negatively and indirectly (through self-efficacy) related (structural weight =.53*) to IM. Temporal orientations (negative past, hedonistic present and fatalistic present) were positively related to procrastination (structural weight =.54*). This study provides information regarding important predictors of intrinsic motivation that can be targeted among university students.

IKK1 aggravates ischemia-reperfusion kidney injury by promoting the differentiation of effector T cells.

Ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI), and experimental work has revealed detailed insight into the inflammatory response in the kidney. T cells and NFκB pathway play an important role in IRI. Therefore, we examined the regulatory role and mechanisms of IkappaB kinase 1 (IKK1) in CD4+T lymphocytes in an experimental model of IRI. IRI was induced in CD4cre and CD4IKK1Δ mice. Compared to control mice, conditional deficiency of IKK1 in CD4+T lymphocyte significantly decreased serum creatinine, blood urea nitrogen (BUN) level, and renal tubular injury score. Mechanistically, lack in IKK1 in CD4+T lymphocytes reduced the ability of CD4 lymphocytes to differentiate into Th1/Th17 cells. Similar to IKK1 gene ablation, pharmacological inhibition of IKK also protected mice from IRI. Together, lymphocyte IKK1 plays a pivotal role in IRI by promoting T cells differentiation into Th1/Th17 and targeting lymphocyte IKK1 may be a novel therapeutic strategy for IRI.

Selection of phage-displayed antibodies with high affinity and specificity by electrophoresis in microfluidic devices.

A method development aimed for high-throughput and automated antibody screening holds great potential for areas ranging from fundamental molecular interactions to the discovery of novel disease markers, therapeutic targets, and monoclonal antibody engineering. Surface display techniques enable efficient manipulation of large molecular libraries in small volumes. Specifically, phage display appeared as a powerful technology for selecting peptides and proteins with enhanced, target-specific binding affinities. Here, we present a phage-selection microfluidic device wherein electrophoresis was performed under two orthogonal electric fields through an agarose gel functionalized with the respective antigen. This microdevice was capable of screening and sorting in a single round high-affinity phage-displayed antibodies against virus glycoproteins, including human immunodeficiency virus-1 glycoprotein 120 or the Ebola virus glycoprotein (EBOV-GP). Phages were differentially and laterally swept depending on their antigen affinity; the high-affinity phages were recovered at channels proximal to the application site, whereas low-affinity phages migrated distal after electrophoresis. These experiments proved that the microfluidic device specifically designed for phage-selection is rapid, sensitive, and effective. Therefore, this is an efficient and cost-effective method that allowed highly controlled assay conditions for isolating and sorting high-affinity ligands displayed in phages.

Kidney Biopsy Findings in Patients with SARS-CoV-2 Infection or After COVID-19 Vaccination.

BACKGROUND: Emerging case series described a temporal association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and de novo or relapsing kidney diseases. We aimed to further understand vaccination- and coronavirus disease 2019 (COVID-19)-associated kidney diseases. METHODS: We present findings from native kidney biopsies of patients recently vaccinated against SARS-CoV-2 ( n =27) and those with COVID-19 ( n =15), reviewed at a single German center. Diagnoses were compared among all native kidney biopsies ( n =10,206) obtained between the prepandemic (2019), pandemic (2020), and vaccination periods (2021) to determine whether there was an increase in kidney diseases in the observed periods. RESULTS: Biopsy indication was increased serum creatinine and/or new-onset proteinuria. Glomerulopathies (20/27, 74%) were more common than tubulointerstitial diseases in postvaccination patients, with necrotizing GN (8/27, 30%) and primary podocytopathies and other GN types (6/27, 22% each) the most common forms. Acute tubular injury was the most common kidney disease in patients with COVID-19, followed by thrombotic microangiopathy (TMA) and necrotizing GN. The postvaccination and COVID-19 infection groups had similar kidney function recovery rates (69% and 73%, respectively). Furthermore, the frequencies of necrotizing GN, pauci-immune GN, TMA, or primary podocytopathies at our center did not increase between 2019 and 2021. CONCLUSIONS: We observed differences in entity frequencies between the SARS-CoV-2 vaccination or COVID-19 groups, with glomerulopathies being more common in patients after vaccination and tubulointerstitial diseases in patients with COVID-19. Cases of TMA were observed only in the COVID-19 group. We detected no increase in the frequency of necrotizing GN, TMA, or podocytopathies between 2019 and 2021. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Kidney Histopathology After COVID-19 and SARS-CoV-2 Vaccination, NCT05043168.

European fitness landscape for children and adolescents: updated reference values, fitness maps and country rankings based on nearly 8 million test results from 34 countries gathered by the FitBack network.

OBJECTIVES: (1) To develop reference values for health-related fitness in European children and adolescents aged 6-18 years that are the foundation for the web-based, open-access and multilanguage fitness platform (FitBack); (2) to provide comparisons across European countries. METHODS: This study builds on a previous large fitness reference study in European youth by (1) widening the age demographic, (2) identifying the most recent and representative country-level data and (3) including national data from existing fitness surveillance and monitoring systems. We used the Assessing Levels of PHysical Activity and fitness at population level (ALPHA) test battery as it comprises tests with the highest test-retest reliability, criterion/construct validity and health-related predictive validity: the 20 m shuttle run (cardiorespiratory fitness); handgrip strength and standing long jump (muscular strength); and body height, body mass, body mass index and waist circumference (anthropometry). Percentile values were obtained using the generalised additive models for location, scale and shape method. RESULTS: A total of 7 966 693 test results from 34 countries (106 datasets) were used to develop sex-specific and age-specific percentile values. In addition, country-level rankings based on mean percentiles are provided for each fitness test, as well as an overall fitness ranking. Finally, an interactive fitness platform, including individual and group reporting and European fitness maps, is provided and freely available online (www.fitbackeurope.eu). CONCLUSION: This study discusses the major implications of fitness assessment in youth from health, educational and sport perspectives, and how the FitBack reference values and interactive web-based platform contribute to it. Fitness testing can be conducted in school and/or sport settings, and the interpreted results be integrated in the healthcare systems across Europe.

Mechanical Confinement and DDR1 Signaling Synergize to Regulate Collagen-Induced Apoptosis in Rhabdomyosarcoma Cells.

Fibrillar collagens promote cell proliferation, migration, and survival in various epithelial cancers and are generally associated with tumor aggressiveness. However, the impact of fibrillar collagens on soft tissue sarcoma behavior remains poorly understood. Unexpectedly, this study finds that fibrillar collagen-related gene expression is associated with favorable patient prognosis in rhabdomyosarcoma. By developing and using collagen matrices with distinct stiffness and in vivo-like microarchitectures, this study uncovers that the activation of DDR1 has pro-apoptotic and of integrin ß1 pro-survival function, specifically in 3D rhabdomyosarcoma cell cultures. It demonstrates that rhabdomyosarcoma cell-intrinsic or extrinsic matrix remodeling promotes cell survival. Mechanistically, the 3D-specific collagen-induced apoptosis results from a dual DDR1-independent and a synergistic DDR1-dependent TRPV4-mediated response to mechanical confinement. Altogether, these results indicate that dense microfibrillar collagen-rich microenvironments are detrimental to rhabdomyosarcoma cells through an apoptotic response orchestrated by the induction of DDR1 signaling and mechanical confinement. This mechanism helps to explain the preference of rhabdomyosarcoma cells to grow in and metastasize to low fibrillar collagen microenvironments such as the lung.

Nanobodies Protecting From Lethal SARS-CoV-2 Infection Target Receptor Binding Epitopes Preserved in Virus Variants Other Than Omicron.

The emergence of SARS-CoV-2 variants that escape from immune neutralization are challenging vaccines and antibodies developed to stop the COVID-19 pandemic. Thus, it is important to establish therapeutics directed toward multiple or specific SARS-CoV-2 variants. The envelope spike (S) glycoprotein of SARS-CoV-2 is the key target of neutralizing antibodies (Abs). We selected a panel of nine nanobodies (Nbs) from dromedary camels immunized with the receptor-binding domain (RBD) of the S, and engineered Nb fusions as humanized heavy chain Abs (hcAbs). Nbs and derived hcAbs bound with subnanomolar or picomolar affinities to the S and its RBD, and S-binding cross-competition clustered them in two different groups. Most of the hcAbs hindered RBD binding to its human ACE2 (hACE2) receptor, blocked cell entry of viruses pseudotyped with the S protein and neutralized SARS-CoV-2 infection in cell cultures. Four potent neutralizing hcAbs prevented the progression to lethal SARS-CoV-2 infection in hACE2-transgenic mice, demonstrating their therapeutic potential. Cryo-electron microscopy identified Nb binding epitopes in and out the receptor binding motif (RBM), and showed different ways to prevent virus binding to its cell entry receptor. The Nb binding modes were consistent with its recognition of SARS-CoV-2 RBD variants; mono and bispecific hcAbs efficiently bound all variants of concern except omicron, which emphasized the immune escape capacity of this latest variant.

Estructura Factorial de Agencia Personal en Estudiantes Colombianos y Mexicanos / Factor Structure of Personal Agency in Colombian and Mexican Students

Resumen En el presente estudio se busca analizar los predictores de la agencia personal de estudiantes universitarios, diferenciando entre estudiantes colombianos y mexicanos. Para lo cual se exploraron las estructuras factoriales de la Agencia Personal de ambos grupos de estudiantes, así como las interrelaciones que exhiben los factores en cada una de las muestras. Se trabajó con una muestra no probabilística de 243 estudiantes, 127 mexicanos y 116 colombianos quienes respondieron la Escala de Agencia Personal del IASE. Un AF-MM refleja universalidad a juzgar por los valores de chi cuadrado; sin embargo, sí se presentan diferencias entre los predictores de cada factor para ambas muestras. Se discute acerca de que estudios de este tipo permiten el uso de la escala de Agencia personal como predictor de dicho factor para estudiantes de ambas muestras dado que es un instrumento culturalmente sensible y relevante para la realidad cultural latinoamericana.

Abstract The present study seeks to analyze the predictors of the personal agency of university students, differentiating between Colombian and Mexican students. For which the factorial structures of the Personal Agency of both groups of students were explored, as well as the interrelationships exhibited by the factors in each of the samples. We worked with a non-probabilistic sample of 243 students, 127 Mexicans and 116 Colombians who answered the IASE Personal Agency Scale. An AF-MM reflects universality as judged by chi square values; however, there are differences between the predictors of each factor for both samples. It is discussed that studies of this allow the use of the Personal Agency scale as a predictor of said factor for students from both samples, given that it is a culturally sensitive and relevant instrument for the Latin American cultural reality.

Molecular consequences of SARS-CoV-2 liver tropism.

Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated2,3. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.

Plasticity and conditional essentiality of modification enzymes for domain V of Escherichia coli 23S ribosomal RNA.

Escherichia coli rRNAs are post-transcriptionally modified at 36 positions but their modification enzymes are dispensable individually for growth, bringing into question their significance. However, a major growth defect was reported for deletion of the RlmE enzyme, which abolished a 2'O methylation near the peptidyl transferase center (PTC) of the 23S rRNA. Additionally, an adjacent 80-nt "critical region" around the PTC had to be modified to yield significant peptidyl transferase activity in vitro. Surprisingly, we discovered that an absence of just two rRNA modification enzymes is conditionally lethal (at 20°C): RlmE and RluC. At a permissive temperature (37°C), this double knockout was shown to abolish four modifications and be defective in ribosome assembly, though not more so than the RlmE single knockout. However, the double knockout exhibited an even lower rate of tripeptide synthesis than did the single knockout, suggesting an even more defective ribosomal translocation. A combination knockout of the five critical-region-modifying enzymes RluC, RlmKL, RlmN, RlmM, and RluE (not RlmE), which synthesize five of the seven critical-region modifications and 14 rRNA and tRNA modifications altogether, was viable (minor growth defect at 37°C, major at 20°C). This was surprising based on prior in vitro studies. This five-knockout combination had minimal effects on ribosome assembly and frameshifting at 37°C, but greater effects on ribosome assembly and in vitro peptidyl transferase activity at cooler temperatures. These results establish the conditional essentiality of bacterial rRNA modification enzymes and also reveal unexpected plasticity of modification of the PTC region in vivo.

A new therapeutic approach with tocilizumab in a 39-year-old patient with recurrent diabetic myonecrosis.

We report the case of a 39-year-old female patient with acute painful swelling of the left thigh and symmetric muscle weakness in both upper legs. The patient had a history of long-standing, poorly controlled type 1 diabetes which required dialysis. Serum inflammatory markers were highly elevated. Magnetic resonance imaging (MRI) indicated necrotic or inflammatory colliquation. As antibiotic therapy did not lead to clinical improvement, a successful anti-inflammatory therapy with prednisolone was initiated. Three months later, the patient presented with a new onset of progressive and painful muscle swelling of the right thigh. MRI showed pronounced swelling of the right adductor muscles and inflammatory markers were massively elevated. In the absence of autoantibodies or any infectious agents and the recurrent symptomatology, relapsing diabetogenic myonecrosis was diagnosed. Initially, clinical improvement could only be achieved with high-dose glucocorticosteroids. Intravenous immunoglobulins did not show an effect, whereas serological and clinical remission was achieved after we administered tocilizumab intravenously. Diabetic myonecrosis is a rare complication of long-term, poorly controlled diabetes mellitus. Acute muscle pain and elevated inflammatory markers should prompt suspicion. Contralateral muscle involvement is also suggestive of the disease. The optimisation of diabetes treatment is crucial in order to prevent further disease complications.

[Transhumanism and law: from human nature to self-determination as the foundation of human rights]. / Transhumanismo y derecho: de la naturaleza humana a la autodeterminación como fundamento de los derechos humanos.

This article analyzes the general evolution of human rights due to the influence of transhumanist ideas, which were already present in 1948. Specifically, we will consider their denial of human nature, and self-determination as the new cornerstone of the legal order. We will see how nature is no longer considered the foundation of law, and instead how the focus is now on self-determination and the possibilities of technology. Although the 1948 Declaration of Rights has not changed, the anthropological conception has been modified, and new rights have been introduced, thanks to the interpretation made by the courts. The proposal is to recover the notion of human nature and natural law, which offers a universal terrain for dialogue and inspiring keys to find the true rights of the person and the good of society.

Safety and efficacy of different antibiotic regimens in patients with ocular toxoplasmosis: systematic review and meta-analysis.

BACKGROUND: Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis, which leads to visual impairment in a large proportion of patients. Antibiotics and corticosteroids lower the risk of permanent visual loss by controlling infection and inflammation. However, there remains disagreement regarding optimal antibiotic therapy for OT. Therefore, this systematic review and meta-analysis were performed to determine the effects and safety of existing antibiotic treatment regimens for OT. METHODS: MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, LILACS, WHO International Clinical Trials Registry Platform portal, ClinicalTrials.gov, and Gray Literature in Europe ("OpenGrey") were searched for relevant studies; manual searches of reference lists were performed for studies identified by other methods. All published and unpublished randomized controlled trials that compared antibiotic schemes known to be effective in OT at any dosage, duration, and administration route were included. Studies comparing antibiotics with placebo were excluded. This review followed standard methodological procedures recommended by the Cochrane group. RESULTS: Ten studies were included in the narrative summary, of which four were included for quantitative synthesis (meta-analysis). Interventions were organized into three groups: intravitreal clindamycin versus pyrimethamine + sulfadiazine, trimethoprim + sulfamethoxazole versus other antibiotics, and other interventions. The first comparison favored intravitreal clindamycin (Mean difference (MD) = 0.10 logMAR; 95% confidence interval = 0.01 to 0.22). However, this finding lacks clinical relevance. Other outcomes showed no statistically significant differences between the treatment groups. In general, the risk of performance bias was high in evaluated studies, and the quality of the evidence found was low to very low. CONCLUSIONS: No antibiotic scheme was superior to others, and the selection of a treatment regimen depends on multiple factors; therefore, treatment should be chosen based on safety, sulfa allergies, and availability.

Prevalence of hyperthyroidism, hypothyroidism, and euthyroidism in thyroid eye disease: a systematic review of the literature.

BACKGROUND: Thyroid eye disease is an autoimmune disorder of the orbital retrobulbar tissue commonly associated with dysthyroid status. The most frequent condition is hyperthyroidism, although it is also present in hypothyroid and euthyroid patients. The prevalence of thyroid conditions in patients with thyroid eye disease had been previously evaluated; however, there is no consensus on a global prevalence. The study aims to estimate the prevalence of hyperthyroidism, hypothyroidism, and euthyroidism in patients with TED, through a systematic review of literature. METHODS: We conducted a systematic review of the literature following the PRISMA guidelines, in MEDLINE, COCHRANE, EMBASE, Science Direct, and LILACS databases. Inclusion criteria were primary studies of patients with a diagnosis of thyroid eye disease made by an ophthalmologist or with diagnosis criteria, with measurement of thyroid function (TSH, T3, and free T4), and diagnosis of the primary thyroid condition. A quality assessment was made through the Joanna Briggs Institute Quality tools. Finally, we extracted relevant details about the design, the results, and the prevalence of thyroid disorders in thyroid eye disease. RESULTS: The initial search revealed 916 studies, of which finally thirteen met inclusion criteria. Six studies were performed in Europe (Germany, Wales, and Spain), five in Asia (Iran, South Korea, Japan, and Singapore), one in North America (USA), and one in Africa (Ghana). The global prevalence, in patients of thyroid eye disease, was 10.36% for hypothyroidism, 7.9% for euthyroidism, and 86.2% for hyperthyroidism. CONCLUSIONS: Professionals should be aware that thyroid eye disease can be present in patients with a normal thyroid function. The assessment for these patients is based on orbital images; serum TSH, T3, and free T4; antibody levels as thyrotropin receptor antibodies; and thyroperoxidase levels. Additionally, we want to encourage research in this field in other regions of the world such as Latin America. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42020107167.

Ophthalmological treatment of early-onset sarcoidosis/Blau syndrome in a Colombian child: A case report.

PURPOSE: To report the ophthalmological approach of a patient with Blau syndrome (BS) in Colombia. OBSERVATIONS: We describe a 9-year-old Colombian boy with sporadic BS due to a de novo nucleotide-binding oligomerization domain containing 2 (NOD2) mutation, who presented with joint and dermatologic symptoms. He was referred to the uveitis service with a single functional eye, due to retinal detachment in the other eye. Despite treatment with corticosteroids, methotrexate, and adalimumab, the patient continued to exhibit progressive disease. CONCLUSION: BS-related uveitis is characterized by severe ocular morbidity. Appropriate interdisciplinary treatment is necessary for the correct identification and management of the disease, considering the inherent difficulty in its diagnosis due to its diverse clinical manifestations. The severity of BS-related uveitis in this report highlights the need for more effective therapies.

Patients' preferences of cutaneous leishmaniasis treatment outcomes: Findings from an international qualitative study.

BACKGROUND: Cutaneous leishmaniasis (CL) is a disease that often affects exposed skin areas and may heal leaving lifelong scars. Patients' expectations from treatment are rarely considered in drug development for CL. An initiative aiming to address shortcomings in clinical trial design and conduct for CL treatments involving the researchers' community is on-going. This manuscript presents patient-preferred outcomes for CL and an assessment on how to consider these in the conduct of future trials. METHODOLOGY/PRINCIPAL FINDINGS: We report preferred treatment outcomes by 74 patients with confirmed CL in endemic regions of Brazil, Burkina Faso, Colombia, Iran, Morocco, Peru and Tunisia during individual in-depth interviews. Beyond outcomes customarily considered in trials (such as lesion appearance and adverse events), patients talked about a large number of outcomes related to quality of life, such as pain, scar formation, and others affecting their work and daily activities. They also reported fears around getting rid of the parasite, disease recurrence, and possible sequelae. CONCLUSIONS/SIGNIFICANCE: The study results provide a rich insight into important outcomes for CL treatments, as well as related topics, from the perspective of a diverse patient population. Among the outcomes identified, we argue that those related to quality of life as well as recurrence should be included to a greater extent for assessment in clinical trials, and discuss the suitability of measurement instruments such as the Dermatology Quality of Life Index (DLQI). Interviews also point out the potential need to address concerns related to parasitological cure or scar formation, such as social stigmatization and disability. In addition, patients should be given information in order to clarify reported misconceptions. This study therefore suggests a methodology for consulting CL patients on outcomes as elements of clinical trial design, and how to incorporate these outcomes in trials. It also discusses how reported outcomes could be addressed in clinical care.

Efecto de Mediación de la Agencia Humana en Escenarios Educativos / Mediation Effect to Human Agency in Educational Settings

Resumen La Agencia humana ha sido estudiada desde varias disciplinas de las ciencias sociales y aunque tienen similitudes en su conceptualización y características, existe un aislamiento en su estudio y ausencia de comunicación entre disciplinas. Se buscó probar el efecto de mediación de los tres modos de Agencia propuestos por Bandura en el contexto del aprendizaje en educación superior. Los análisis factoriales confirmatorios por modelamiento de ecuaciones estructurales de los resultados de la aplicación a estudiantes universitarios, del Inventario de Agencia en Situaciones Escolares (IASE), elaborado exprofeso para este estudio, permitió probar un efecto de mediación entre la agencia personal y la agencia colectiva a través de la agencia mediada. La relación tríadica de la agencia propuesta por la teoría, centrada en situaciones escolares, es un aporte a la etnopsicometría que permite asumir el papel de múltiples factores en el proceso de adquisición de aprendizajes complejos.

Abstract The Human Agency has been studied from various Social Science disciplines and although they exhibit similarities in their conceptualization and characteristics, a lack of communication between disciplines is detected. We sought to test the mediation effect of the three modes of Agency proposed by Bandura in the context of learning in higher education. A confirmatory factor analysis of the Inventory of Agency in School Situations, elaborated for this study, allowed to prove a mediation effect between the personal agency and the collective agency through the mediated agency. The triadic relationship of agency proposed by the theory, centered on school situations, is a contribution to ethnopsychometry that allows us to assume the role of multiple factors in the process of acquiring complex learning.