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Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. FSGS is considered as a podocyte disease due to the fact that in the majority of patients with FSGS, the lesion results from defects in the podocyte structure. However, FSGS does not result exclusively from podocyte-associated genes. In this study, we used a genetic approach based on targeted next-generation sequencing (NGS) of 242 genes to identify the genetic cause of FSGS in seven Tunisian families. The sequencing results revealed the presence of eight distinct mutations including seven newly discovered ones: the c.538G>A (p.V180M) in NPHS2, c.5186G>A (p.R1729Q) in PLCE1 and c.232A>C (p.I78L) in PAX2 and five novel mutations in COL4A3 and COL4A4 genes. Four mutations (c.209G>A (p.G70D), c.725G>A (p.G242E), c.2225G>A (p.G742E), and c. 1681_1698del) were detected in COL4A3 gene and one mutation (c.1424G>A (p.G475D)) was found in COL4A4. In summary, NGS of a targeted gene panel is an ideal approach for the genetic testing of FSGS with multiple possible underlying etiologies. We have demonstrated that not only podocyte genes but also COL4A3/4 mutations should be considered in patients with FSGS.

Previous studies have reported that heparan sulfate proteoglycans (HSPGs) promote amyloid-beta peptide and tau fibrillization in Alzheimer disease (AD) and provide resistance against proteolytic breakdown. We compared the expression levels of 17 HSPG core proteins in 18 AD cases and 6 controls. RT-PCR was used to analyze transcription levels. Immunohistochemistry was performed to localize HSPGs in the brain tissue. We detected expression of all HSPG genes investigated. SDC1, GPC3, and CD44v3 showed the lowest levels of expression, while SDC3 and GPC1 showed the highest. Remarkably, SDC4 and SRGN were overexpressed in most of the areas analyzed. Immunohistochemistry revealed the presence of both SDC4 and SRGN mostly associated with tau and amyloid-β pathology throughout the AD brains. In conclusion, in view of the involvement of HSPGs in AD pathology, especially SDC4 and SRGN, there would seem to be a relationship between the regulation of core protein expression and the pathological features suggesting HSPGs are potential inducers of the disease.

MYH9 related diseases are caused by mutations in the MYH9 gene and constitute a rare group of genetic entities. Its inheritance follows an autosomal dominant pattern. The MYH9 gene, encodes the nonmuscle myosin heavy chain IIA, expressed in different tissues and especially in podocytes and mesangial cells. The disorder is characterized by the presence of macrothrombocytopenia, leukocyte inclusions and a variable risk of developing renal failure, hearing loss and early-onset cataracts. We describe the case of a 27-year-old Caucasian woman, diagnosed initially with idiopathic thrombocytopenic purpura. After a detailed family history and the appearance of renal involvement and hearing loss, genetic testing allowed to make the diagnosis of nephropathy associated with MYH9 mutation. This case is an example of the delayed diagnosis of uncommon diseases and highlights the usefulness genetic testing. A review of the disease is provided. Resumen: Las enfermedades relacionadas con mutaciones del gen MYH9 son un grupo de patologías genéticas raras. Su herencia sigue un patrón autosómico dominante en donde el gen MYH9, codifica la cadena pesada de la miosina IIA no muscular que se expresa en diferentes tejidos pero especialmente en los podocitos y en las células mesangiales. Este trastorno se caracteriza por la presencia de macrotrombocitopenia, inclusiones leucocitarias y un riesgo variable de desarrollar insuficiencia renal, hipoacusia y cataratas en edad juvenil o adulta. Describimos el caso de una mujer de 27 años, de raza caucásica, diagnosticada inicialmente de púrpura trombocitopénica idiopática. Tras una detallada historia familiar y el desarrollo de síntomas clínicos posteriores con afectación renal e hipoacusia, se le realizó un estudio genético que nos permitió el diagnóstico de nefropatía asociada a la mutación en el gen MYH9. Este caso destaca el retraso del diagnóstico y la utilidad del estudio genético en pacientes con enfermedades muy poco frecuentes. Se procede a la revisión de la enfermedad en este artículo. Keywords: MYH9 nephropathy, Hearing loss, Thrombocytopenia, Alport syndrome, Epstein syndrome, May-Hegglin anomaly, Palabras clave: Nefropatía MYH9, Hipoacusia, Trombocitopenia, Síndrome de Alport, Síndrome de Epstein, Anomalía de May-Hegglin, Sindrome de Sebastián

This study analyses the cross-sectional effect of sources of stress during the peak of COVID-19 pandemic on nurses´ psychological distress, focusing on the mediating role of coping strategies, both problem focused and emotion focused and resilience.Cross-sectional and quantitative analyses.Structural equation modelling was performed using survey data obtained during the period between 1 April-25 May 2020 in a sample of 421 nurses from 39 Spanish provinces.Results confirmed that: (a) All the stressors have a significant, direct, and negative relationship with nurses´ psychological distress; (b) Emotion-focused strategies is negatively related to nurses´ psychological distress directly and indirectly through resilience; and (c) Problem-focused strategies is positively related to nurses´ psychological distress and negatively and indirectly through emotion-focused strategies.This study identifies an important mediation sequence of stressors on psychological distress through the simultaneous concurrent effect of Problem-focused and Emotion-focused strategies and resilience. It shows that enacting the two coping mechanisms and resilience resources is important to achieve an adaptive effect on nurses´ mental health.Nurses with insufficient preparation and those with high levels of fear of contagion do not enact proper coping strategies. Thus, these nurses need special consideration due to their risk of higher vulnerability.目的: 本研究旨在分析新冠肺炎疫情高度蔓延期间压力源对护士心理困扰的横断面影响, 重点探讨以问题、情绪为中心的应对策略和弹性的中介作用。 设计: 横截面和定量分析。 方法: 利用2020年4月1日至5月25日期间获得的调查数据, 对西班牙39个省的421名护士进行结构方程建模。 结果: 结果证实: (a)压力源与护士的心理困扰呈显著、直接、负面相关; (b) 受弹性影响, 以情绪为中心的策略与护士的心理困扰直接或间接负相关; 以及 (c)以问题为中心的策略与护士的心理困扰正相关, 而以情绪为中心的策略与护士的心理困扰呈负相关或间接相关。 结论: 本研究过程中, 通过以问题为中心的策略、以情绪为中心的策略和心理弹性的并发效应, 确定压力源对心理困扰的重要中介序列。研究结果表明,上述两大机制和弹性资源对护士的心理健康有重要影响, 且此类影响可变更。 影响: 缺少准备的护士和对传染病高度恐惧的护士均未制定适当的应对策略。因此, 此类护士更易遭受影响,应特别考虑。.

The COVID-19 pandemic started at the end of 2019 and can be considered one of the most difficult health crises of the past century. It has had a devastating effect around the world, not only for public health, but also for the economy, labor market, and other facets of individual and societal life. Health systems have been put under high strain, and health professionals have experienced unusual and stressful work circumstances. With the aim of drawing lessons for nursing education, the present study analyzed, during the weeks of peak infection in Spain, the stress experience and coping strategies of a sample of 403 nurses from the Spanish health system. Specifically, we analyzed how tenure, stress appraisal, problem-focused coping, and support-seeking coping predicted nurses&rsquo, awareness of their education needs, both in terms of technical-professional knowledge and skills and transversal skills. Structural equation modeling analysis revealed that more tenure (years of experience) was related to lower stress appraisal (workload, &minus, 0.12, p &lt, 0.05, insufficient preparation, &minus, 0.33, p &lt, 0.001, and fear of contagion &minus, 0.36, p &lt, 0.001) and more problem focused coping (PFC) strategies were related to higher awareness of professional (0.18, p &lt, 0.01) and transversal educational needs (0.17, p &lt, 0.01) while support seeking strategies just related to transversal training needs (0.10, p &lt, 0.05). Moreover, the participants provided valuable input about specific contents to be considered in future nursing education programs. Implications for redesigning the nursing degree curriculum are analyzed in the discussion section.

Background Inherited kidney diseases are one of the leading causes of chronic kidney disease (CKD) that manifests before the age of 30 years. Precise clinical diagnosis of early-onset CKD is complicated due to the high phenotypic overlap, but genetic testing is a powerful diagnostic tool. We aimed to develop a genetic testing strategy to maximize the diagnostic yield for patients presenting with early-onset CKD and to determine the prevalence of the main causative genes. Methods We performed genetic testing of 460 patients with early-onset CKD of suspected monogenic cause using next-generation sequencing of a custom-designed kidney disease gene panel in addition to targeted screening for c.428dupC MUC1. Results We achieved a global diagnostic yield of 65% (300/460), which varied depending on the clinical diagnostic group: 77% in cystic kidney diseases, 76% in tubulopathies, 67% in autosomal dominant tubulointerstitial kidney disease, 61% in glomerulopathies and 38% in congenital anomalies of the kidney and urinary tract. Among the 300 genetically diagnosed patients, the clinical diagnosis was confirmed in 77%, a specific diagnosis within a clinical diagnostic group was identified in 15%, and 7% of cases were reclassified. Of the 64 causative genes identified in our cohort, 7 (COL4A3, COL4A4, COL4A5, HNF1B, PKD1, PKD2 and PKHD1) accounted for 66% (198/300) of the genetically diagnosed patients. Conclusions Two-thirds of patients with early-onset CKD in this cohort had a genetic cause. Just seven genes were responsible for the majority of diagnoses. Establishing a genetic diagnosis is crucial to define the precise aetiology of CKD, which allows accurate genetic counselling and improved patient management.

Rationale & Objective Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare underdiagnosed cause of end-stage renal disease (ESRD). ADTKD is caused by mutations in at least 4 different genes: MUC1, UMOD, HNF1B, and REN. Study Design Retrospective cohort study. Setting & Participants 56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing for UMOD, MUC1, REN, and HNF1B was performed. Predictors Hyperuricemia, ultrasound findings, renal histology, genetic mutations. Outcomes Age at ESRD, rate of decline in estimated glomerular filtration rate. Results ADTKD was diagnosed in 25 families (45%), 9 carried UMOD pathogenic variants (41 affected members), and 16 carried the MUC1 pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified in REN or HNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1 versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with the MUC1 duplication presented higher risk for developing ESRD (HR, 2.24; P=0.03). The slope of decline in estimated glomerular filtration rate showed no significant difference between groups (−3.0mL/min/1.73m2 per year in the ADTKD-UMOD group versus −3.9mL/min/1.73m2 per year in the ADTKD-MUC1 group; P=0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKD-UMOD (87% vs 54%; P=0.006). Although gout occurred more frequently in this group, the difference was not statistically significant (24% vs 7%; P=0.07). Limitations Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication. Conclusions The main genetic cause of ADTKD in our Spanish cohort is the MUC1 pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with the MUC1 mutation than in those with UMOD mutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals with ADTKD-UMOD.

Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.

Rationale & Objective: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS). Study Design: Retrospective cohort study. Setting & Participants: 82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected. Observations: A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P = 0.8), causative genes (P = 0.6), or type of variant (P = 0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was -1.46 (-1.66 to -1.26) mL/min/1.73 m(2) per year for the overall group, with no significant differences between ADAS genes (P = 0.2). Limitations: The relatively small size of this series from a single country, potentially limiting generalizability. Conclusions: Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.

Research in centers for people with intellectual and developmental disabilities has somewhat neglected the relationship between workers' burnout and users' service evaluations. Two independent survey studies tested this connection. In the first study (100 centers, 714 workers, and 612 family members), results confirmed that burnout has a negative relationship with workers' perceptions of service quality. In turn, these perceptions are associated with the service quality perceptions of family members and their satisfaction with the service. In a replication sample (86 centers, 601 workers, and 819 family members), we reproduced these results and added situational constraints in the model. Both social and technical constraints correlated positively and significantly with burnout. These studies offer a view of the relationships between burnout and service quality.

BACKGROUND Heparan sulfate proteoglycans (HSPGs) promote amyloid-β peptide and tau fibrillization in Alzheimer's disease (AD) and provide resistance against proteolytic breakdown. Heparanase (HPSE) is the only enzyme that cleaves heparan sulfate (HS). Heparanase 2 (HPSE2) lacks HS-degrading activity, although it is able to interact with HS with high affinity. OBJECTIVE To analyze HPSE and HPSE2 expressions at different stages of AD. METHODS RT-PCR was used to analyze transcription levels of both heparanases at different stages of AD, and immunohistochemistry was performed to localize each one in different parts of the brain. RESULTS Both proteins appeared overexpressed at different stages of AD. Immunohistochemistry indicated that the presence of the heparanases was related to AD pathology, with intracellular deposits found in degenerated neurons. At the extracellular level, HPSE was observed only in neuritic plaques with a fragmented core, while HPSE2 appeared in those with compact cores as well. CONCLUSION Given the involvement of HSPGs in AD pathology, there would seem to be a relationship between the regulation of heparanase expression, the features of the disease, and a possible therapeutic alternative.

Adalimumab (ADA) is a recombinant human monoclonal antibody indicated for the treatment of psoriasis that specifically inhibits tumor necrosis factor. Until recently we only had the presentation of 40 mg of ADA, being the standard dose in adults an initial administration of 80 mg, followed by 40 mg every 2 weeks. Newly the presentation of 80 mg of ADA has been commercialized, allowing the administration of the standard dose or a higher dose, with fewer injections. In this study, we retrospectively studied 11 patients with psoriasis who have received treatment with the presentation of 80 mg of ADA in two dermatology departments of two hospitals in Spain since its commercialization until June 2019. At the end of the study, an improvement in the mean final Psoriasis Area Severity Index (PASI) of all patients was observed, without any patient presenting any adverse effects. This study shows the efficacy and safety of 80 mg of ADA in a sample of 11 patients with psoriasis.

Understanding happiness and well-being has been one of the central issues for psychologists in recent decades. Happiness orientations have been identified as important pathways toward different types of well-being, and so the development and validation of scales for their measurement is an important step in their study. The present research aims to adapt and validate the Spanish Orientations to Happiness Scale (SOTH), a 6-item scale based on the Orientations to Happiness Questionnaire. This brief scale, which measures hedonic and eudemonic orientations, was administered to 1,647 Spanish workers. Scale structure was subjected to exploratory (EFA) and confirmatory (CFA) factor analysis to obtain evidence of factorial validity. Evidence for convergent validity was assessed by correlating the scale with two measures of hedonic and eudaimonic well-being, and discriminant validity was assessed with the average variance extracted (AVE). Results of EFA showed a two-factor solution, and CFA partially supported this structure, χ2(8,N= 793) = 36.61, p < .001; RMSEA = .06; SRMR = .05; CFI = .97; ACFI = .96. Results also demonstrated appropriate convergent and discriminant validity. The SOTH Scale has been shown to be reliable (CR indices > .72) and valid (AVE = .50), and so it is a valuable tool for assessing orientations to happiness in the Spanish context. Finally, the scientific value and practical utility of the scale are discussed.

Wine sensory sessions normally involve the tasting of several samples, to remove food residues from the mouth the use of palate cleansers (PC) is needed. Until now, there is no agreement on the best PC to use during wine tasting sessions. The aim of this work is to study the relationship between the components retained in saliva after wine tasting and the remnant sensory feeling (astringency, alcohol, and acidity). For that, different common PC (water, carbonated water, and milk) were tested and saliva samples (expectorated and scraped) from nine trained panelists were collected after wine with and without PC trials. Results showed that after palate cleansing and not cleansing, astringency, alcoholic and acidity perception were influenced by time, PC and panelist. Astringency perception showed the greatest intensity in comparison to alcoholic and acidity. Milk was the only PC which reduced quantifiable polyphenols in expectorated saliva, as well as reducing astringency feelings. Although compositions of expectorated and scraped saliva correlated between them, polyphenols accumulated in the expectorated saliva significantly more. Retained polyphenols were correlated with astringency perception, but no correlation was found with salivary proteins. These findings assessed the astringency build-up effect during wine tasting due to polyphenols accumulation in saliva, remarking the importance of an adequate PC selection. All things considered, the present work confirmed the relationship between after-swallow mouthfeel perception and mouth residues instrumentally quantified. Also, milk has proven to be the most effective of the three PC., [Practical applications] During tasting the accumulation of residues from previous wine samples tasted, could mislead the judgment of wine sensory qualities by oenologists. Therefore, between tasting samples it is highly important to choose the right PC. However, until now the selection of PC remains empirical, therefore in this work, we proposed to study the residues in saliva by using different PC and quantifying instrumentally, the wine residues. The methodology selected to quantify the wines residues in saliva was quick and easy to use. Furthermore, instrumental results were related with the sensory feeling of mouth cleanliness without considering individual panel member's preferences of PC. In this study, to remove astringency feeling, milk was shown to be the best cleanser in comparison with water, carbonated water or nothing, but oenologist/winemakers could use this instrumental methodology in saliva to select which one is the best among their current PC used., The authors of this work were funded by the projects AGL2015-64522-C2-R-01 and RTC-2016-4556-1. L.L. would like to thank the Spanish “Juan de la Cierva” program for her contract (ref FJCI-2014-19907).

This study aimed to analyze the mechanisms through which work characteristics are related to psychological well-being, exploring the mediational role of work meaningfulness and job satisfaction, and investigating differences in the patterns of relationships between two age groups. The sample was composed of 36,896 workers from the 5th European Working Conditions Survey. Structural equation modeling analyses and multiple group analyses were performed. The results revealed a parallel mediational model, in which work meaningfulness and general job satisfaction mediate the relationships between work characteristics and well-being. Additionally, job satisfaction partially mediates the relationship between meaningfulness and well-being. These results were confirmed in both age groups (under 55 years old and older workers), but age moderates the relationships between social support and the mediating variables and the relationships between the mediating variables and general well-being. The present study uncovers significant pathways through which time pressure, decision latitude, and social support are related to psychological well-being, depicting an important step in better understanding how and when work characteristics are related to positive outcomes. It provides important clues for promoting psychosocial health at work at the European level.

AimsTo investigate the expression of major proteins related to primary neurodegenerative diseases and their prognostic significance in brains with Creutzfeldt-Jakob disease (CJD).Materials and methodsThirty consecutive cases of confirmed CJD during the period 2010–2015 at Basque Brain bank were retrospectively reviewed. Moreover, major neurodegenerative-associated proteins (phosphorylated Tau, 4R tau, 3R tau, alpha-synuclein, TDP43, amyloid beta) were tested. Clinical data were reviewed. Cases were divided according to the presence or absence of copathology. Survival curves were also determined.ResultsCopathology was significantly associated with survival in brains with CJD (4.2±1.2 vs 9.2±1.9; P=0.019) and in brains with MM1/MV1 CJD (2.1±1.0 vs 6.7±2.8; P=0.012). Besides, the presence of more than one major neurodegenerative-associated protein was significantly associated with survival (4.2±1.2 vs 10.7±2.6; P=0.017). Thus, univariate analyses further pointed out variables significantly associated with better survival: copathology in CJD (HR=0.430; P=0.033); more than one neurodegenerative-associated protein in CJD (HR=0.369; P=0.036) and copathology in MM1/MV1 CJD (HR=0.525; P=0.032).ConclusionThe existence of copathology significantly prolongs survival in patients with rapidly progressive dementia due to CJD. The study of major neurodegenerative-associated proteins in brains with CJD could allow us to further understand the molecular mechanisms behind prion diseases.

Traditionally, research focussing on psychosocial factors in the construction industry has focused mainly on the negative aspects of health and on results such as occupational accidents. This study, however, focuses on the specific relationships among the different positive psychosocial factors shared by construction workers that could be responsible for occupational well-being and outcomes such as performance. The main objective of this study was to test whether personal resources predict self-rated job performance through job resources and work engagement. Following the predictions of Bandura's Social Cognitive Theory and the motivational process of the Job Demands-Resources Model, we expect that the relationship between personal resources and performance will be fully mediated by job resources and work engagement. The sample consists of 228 construction workers. Structural equation modelling supports the research model. Personal resources (i.e. self-efficacy, mental and emotional competences) play a predicting role in the perception of job resources (i.e. job control and supervisor social support), which in turn leads to work engagement and self-rated performance. This study emphasises the crucial role that personal resources play in determining how people perceive job resources by determining the levels of work engagement and, hence, their self-rated job performance. Theoretical and practical implications are discussed.

This paper is a report of a social cognitive theory-guided study about the link between supervisors' transformational leadership and staff nurses' extra-role performance as mediated by nurse self-efficacy and work engagement.Past research has acknowledged the positive influence that transformational leaders have on employee (extra-role) performance. However, less is known about the psychological mechanisms that may explain the links between transformational leaders and extra-role performance, which encompasses behaviours that are not considered formal job requirements, but which facilitate the smooth functioning of the organization as a social system.Seventeen supervisors evaluated nurses' extra-role performance, the data generating a sample consisting of 280 dyads. The nurses worked in different health services in a large Portuguese hospital and the participation rate was 76·9% for nurses and 100% for supervisors. Data were collected during 2009. A theory-driven model of the relationships between transformation leadership, self-efficacy, work engagement and nurses' extra-role performance was tested using Structural Equation Modelling.Data analysis revealed a full mediation model in which transformational leadership explained extra-role performance through self-efficacy and work engagement. A direct relationship between transformational leadership and work engagement was also found.Nurses' supervisors with a transformational leadership style enhance different 'extra-role' performance in nurses and this increases hospital efficacy. They do so by establishing a sense of self-efficacy but also by amplifying their levels of engagement in the workplace.

Our purpose was to extend the Job Demand-Resources Model (SchaufeliBakker, 2004) by including personal resources, job demands and job resources to predict burnout (exhaustion, cynicism, depersonalization) and work engagement (vigour and dedication). The sample comprised 274 teachers from 23 secondary schools of the Valencian Community (Spain). Hierarchical multiple regression analyses have revealed: (1) the predictor effect of quantitative overload on exhaustion and dedication at T2, (2) role conflict on cynicism and (3) role ambiguity on dedication. Lastly, the mediating role of burnout and engagement at T2. Practical implications and directions of future research are discussed.

Canavan disease is a rare autosomal recessive leukodystrophy characterized by abnormal accumulation of N-acetyl aspartate (NAA) in brain white matter. Currently, there is no cure for this disease, and management of patients consists mainly of treating symptoms. We describe a 3-month-old girl who was hospitalized for poor head control and decreased muscle tone. A battery of laboratory and genetic (homozygous mutation p.C218X) analysis revealed the presence of Canavan disease. Lithium citrate was initiated at a dosage of 45 mg/kg per day after diagnosis. Periodic controls of thyroid and liver function, and lithium levels in blood showed that this drug was sure and well tolerated. After 1 year of treatment, NAA levels decreased by approximately 20% in the brain region, urinary NAA levels showed a reduction of 80%, and patient improved alertness and visual tracking but continued with no heat support, axial hypotonia, and spastic diplegia. In our patient, the results obtained after drug administration are important with respect to the decrease in NAA and more discreet in clinical improvement. However, given the absence of adverse effects and limited treatment options, lithium citrate may be a good alternative to stop the progression of the disease and improve the quality of life of patients.