Diagnosis of Alzheimer's disease and behavioural variant frontotemporal dementia with machine learning-aided neuropsychological assessment using feature engineering and genetic algorithms.

BACKGROUND: Neuropsychological assessment is considered a valid tool in the diagnosis of neurodegenerative disorders. However, there is an important overlap in cognitive profiles between Alzheimer's disease (AD) and behavioural variant frontotemporal dementia (bvFTD), and the usefulness in diagnosis is uncertain. We aimed to develop machine learning-based models for the diagnosis using cognitive tests. METHODS: Three hundred and twenty-nine participants (170 AD, 72 bvFTD, 87 healthy control [HC]) were enrolled. Evolutionary algorithms, inspired by the process of natural selection, were applied for both mono-objective and multi-objective classification and feature selection. Classical algorithms (NativeBayes, Support Vector Machines, among others) were also used, and a meta-model strategy. RESULTS: Accuracies for the diagnosis of AD, bvFTD and the differential diagnosis between them were higher than 84%. Algorithms were able to significantly reduce the number of tests and scores needed. Free and Cued Selective Reminding Test, verbal fluency and Addenbrooke's Cognitive Examination were amongst the most meaningful tests. CONCLUSIONS: Our study found high levels of accuracy for diagnosis using exclusively neuropsychological tests, which supports the usefulness of cognitive assessment in diagnosis. Machine learning may have a role in improving the interpretation and test selection.

Argyrophilic grain disease presenting as behavioral frontotemporal dementia.

Argyrophilic grain disease (AgD) is a frequent late-onset 4R tauopathy of old age characterized by the presence of profuse spindle-shaped argyrophilic grains (AGs). It is a neurodegenerative disorder that is clinically characterized by a slow progressive amnestic mild cognitive impairment similar to Alzheimer's disease. In rare instances, it is characterized as a behavioral-variant frontotemporal dementia (bv-FTD). In this study, we report a case with typical clinical and neuroimaging features of bv-FTD, who had autopsy findings consistent with a definitive diagnosis of AgD. We suggest that AgD might be included in the differential diagnosis of patients presenting with bv-FTD.
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A 2'-O-Methyltransferase Responsible for Transfer RNA Anticodon Modification Is Pivotal for Resistance to Pseudomonas syringae DC3000 in Arabidopsis.

Transfer RNA (tRNA) is the most highly modified class of RNA species in all living organisms. Recent discoveries have revealed unprecedented complexity in the tRNA chemical structures, modification patterns, regulation, and function, suggesting that each modified nucleoside in tRNA may have its own specific function. However, in plants, our knowledge of the role of individual tRNA modifications and how they are regulated is very limited. In a genetic screen designed to identify factors regulating disease resistance in Arabidopsis, we identified SUPPRESSOR OF CSB3 9 (SCS9). Our results reveal SCS9 encodes a tRNA methyltransferase that mediates the 2'-O-ribose methylation of selected tRNA species in the anticodon loop. These SCS9-mediated tRNA modifications enhance susceptibility during infection with the virulent bacterial pathogen Pseudomonas syringae DC3000. Lack of such tRNA modification, as observed in scs9 mutants, specifically dampens plant resistance against DC3000 without compromising the activation of the salicylic acid signaling pathway or the resistance to other biotrophic pathogens. Our results support a model that gives importance to the control of certain tRNA modifications for mounting an effective disease resistance in Arabidopsis toward DC3000 and, therefore, expands the repertoire of molecular components essential for an efficient disease resistance response.

Validity of the CR-POSSUM model in surgery for colorectal cancer in Spain (CCR-CARESS study) and comparison with other models to predict operative mortality.

BACKGROUND: To validate and recalibrate the CR- POSSUM model and compared its discriminatory capacity with other European models such as POSSUM, P-POSSUM, AFC or IRCS to predict operative mortality in surgery for colorectal cancer. METHODS: Prospective multicenter cohort study from 22 hospitals in Spain. We included patients undergoing planned or urgent surgery for primary invasive colorectal cancers between June 2010 and December 2012 (N = 2749). Clinical data were gathered through medical chart review. We validated and recalibrated the predictive models using logistic regression techniques. To calculate the discriminatory power of each model, we estimated the areas under the curve - AUC (95% CI). We also assessed the calibration of the models by applying the Hosmer-Lemeshow test. RESULTS: In-hospital mortality was 1.5% and 30-day mortality, 1.7%. In the validation process, the discriminatory power of the CR-POSSUM for predicting in-hospital mortality was 73.6%. However, in the recalibration process, the AUCs improved slightly: the CR-POSSUM reached 75.5% (95% CI: 67.3-83.7). The discriminatory power of the CR-POSSUM for predicting 30-day mortality was 74.2% (95% CI: 67.1-81.2) after recalibration; among the other models the POSSUM had the greatest discriminatory power, with an AUC of 77.0% (95% CI: 68.9-85.2). The Hosmer-Lemeshow test showed good fit for all the recalibrated models. CONCLUSION: The CR-POSSUM and the other models showed moderate capacity to discriminate the risk of operative mortality in our context, where the actual operative mortality is low. Nevertheless the IRCS might better predict in-hospital mortality, with fewer variables, while the CR-POSSUM could be slightly better for predicting 30-day mortality. TRAIL REGISTRATION: Registered at: ClinicalTrials.gov Identifier: NCT02488161.

Loss of a Conserved tRNA Anticodon Modification Perturbs Plant Immunity.

tRNA is the most highly modified class of RNA species, and modifications are found in tRNAs from all organisms that have been examined. Despite their vastly different chemical structures and their presence in different tRNAs, occurring in different locations in tRNA, the biosynthetic pathways of the majority of tRNA modifications include a methylation step(s). Recent discoveries have revealed unprecedented complexity in the modification patterns of tRNA, their regulation and function, suggesting that each modified nucleoside in tRNA may have its own specific function. However, in plants, our knowledge on the role of individual tRNA modifications and how they are regulated is very limited. In a genetic screen designed to identify factors regulating disease resistance and activation of defenses in Arabidopsis, we identified SUPPRESSOR OF CSB3 9 (SCS9). Our results reveal SCS9 encodes a tRNA methyltransferase that mediates the 2´-O-ribose methylation of selected tRNA species in the anticodon loop. These SCS9-mediated tRNA modifications enhance during the course of infection with the bacterial pathogen Pseudomonas syringae DC3000, and lack of such tRNA modification, as observed in scs9 mutants, severely compromise plant immunity against the same pathogen without affecting the salicylic acid (SA) signaling pathway which regulates plant immune responses. Our results support a model that gives importance to the control of certain tRNA modifications for mounting an effective immune response in Arabidopsis, and therefore expands the repertoire of molecular components essential for an efficient disease resistance response.

[Urethral stricture in women]. / Estenosis uretral en la mujer.

UNLABELLED: To perform a bibliographic review on female urethra stenosis, following the criteria for evidence based medicine. METHODS: We performed a PubMed Search with the following keywords; "female urethral stricture ","women urethral stricture","female urethral reconstruction "and " female urethral stricture treatment ",without time limits, both in English and Spanish languages. RESULTS: Female urethra stenosis is a rare pathology, in which the working diagnosis is essential, as much as detailed physical examination, urodynamic study and radiological tests. We found in the literature a total of 73 cases treated with dilation with or without maintenance self catheterization, 120 cases treated with meatotomy, 65 cases treated by flap urethroplasty (46 with vaginal flap, 17 with vestibular flap and 12 with labia minora graft and 28 with oral mucosa grafts). There are not comparative studies between the various techniques, making it difficult to set up a therapeutic algorithm. CONCLUSIONS: The surgical treatment with flaps/grafts has the highest success rate; whereas less invasive procedures such as urethrotomy/meatotomy/dilations/self-catheterization should be reserved for short female urethra stenosis or women with high comorbidity.

Primary Healthcare Case Management Nurses and Assistance Provided to Chronic Patients: A Narrative Review.

Population aging is causing increases in the numbers of chronic diseases, with the consequent need for changes in health systems to better assist patients with chronic conditions. A narrative review was conducted in this study with the objective of analysing the scientific evidence on the care and assistance provided by Case Management Nurses (CMNs) to chronic patients in primary healthcare. A total of 15 articles published in English, Spanish, and Portuguese were selected in the following databases: PubMed, Embase, Cochrane Library, Scopus, Dialnet, Cinahl, and Web of Science. In total, 46.6% of the studies showed the assistance provided by CMNs for chronic pathologies. Most of the articles selected (80%) considered that the assistance offered by case management nurses in relation to chronic diseases is effective, enabling cost reductions, which supposes benefits at the economic and political levels. It was concluded that CMNs have proven to be efficient in caring for people with chronic diseases, improving the quality of life of these people and their caregivers; therefore, they have a fundamental role in the PHC.

Primary Health Care Case-Management Nurses during the COVID-19 Pandemic: A Qualitative Study.

The COVID-19 has caused high morbidity and mortality in vulnerable people, such as those affected by chronic diseases, and case-management nurses (CMNs) are reference professionals for their health care and management. The objective of this study is to better understand the discourse, experiences, and feelings about the professional performance of CMNs during the pandemic. A qualitative study was conducted by conducting semi-structured interviews with CMNs (n = 31) from the province of Seville (Spain) and performing a narrative discourse analysis. The Atlas Ti 6.2 software program was used. Two categories were defined: 1. CMNs' competencies (76 verbatim testimonies); and 2. Consequences of the COVID-19 pandemic (61 verbatim testimonies). This study was granted due permission by the Research Ethics Committee belonging to the University of Seville, under protocol code: 1139-N-22. The pandemic caused an increase in CMNs' workload, and they had to assume their usual care tasks for vulnerable populations in addition to simultaneously prioritizing assistance in nursing homes. We can highlight CMNs' adaptation to the pandemic situation and to these new requirements in the context of their significant social commitment to the advanced practice of the profession, a commitment that is closely related to leadership. We should also indicate that interpersonal relationships were improved, and that there was technological progress. Some CMNs mentioned an increase in their workload and reported experiencing burnout syndrome. We conclude that CMNs' management of health care during the pandemic has been extraordinary, especially in regard to the most vulnerable populations of patients, including individuals with chronic diseases and institutionalized older adults, a fact that has been valued by the institutions and by society in general.

[Management of prostate cancer biochemical recurrence in the clinical guidelines]. / Manejo de la recidiva bioquímica en el cáncer de próstata según las guías de práctica clínica.

OBJECTIVE: Review of the Guidelines which have major impact on the urological field, in order to compare and to know their recommendations in the diagnosis and management of biochemical relapse after a healing treatment of prostate cancer (radical prostatectomy or radiotherapy). METHODS: We review the Guidelines of the European Urological Association (EAU), the American Urological Association (AUA), of the National Comprehensive Cancer Network (NCCN) and those of the National Institute for Health and Clinical Excellence (NICE), as well as the scientific evidence on which they are based. RESULTS: In this paper we state the complexity of the subject being dealt with and coincidences and differences among them. The definition of relapse varies depending on whether the patient has undergone either radical prostatectomy or radiotherapy. Regarding treatment, in the first case early radiotherapy is the treatment of choice, but recommendations after radiotherapy are not so specific. CONCLUSION: Clinical Guidelines represent a great aid in decision making for the professional. Guidelines give recommendations with a higher o lower degree of scientific evidence and must be evaluated regularly to include new evidences which are coming through.

Lipid biomarkers and metal pollution in the Holocene record of Cartagena Bay (SE Spain): Coupled natural and human induced environmental history in Punic and Roman times.

We reconstructed the palaeoenvironmental conditions of Cartagena Bay during the Holocene after a multidisciplinary study to identify natural variations and the anthropic processes of this coastal area. A total of 119 samples were recovered for amino acid racemization dating, 3 for radiocarbon dating (14C), and four sets of 80 samples for sedimentological and palaeontological determination, mineralogical content, biomarker and trace elements quantification. Two natural scenarios were identified from the variations of n-alkane indices and palaeobiological content. The first period (6650-5750 yr cal BP) was marked by the development of euhaline marine conditions with strong inputs from aquatic macrophytes and high biodiversity. After a hiatus, the area underwent a profound change, becoming a paucispecific brackish marsh environment with increasing inputs from land plants, with possible episodes of emersion with a greater presence from terrestrial gastropods (3600-300 cal yr BP). By combining trace element abundance and stanol distributions, our study also provides a novel approach to identify the predominant influence of anthropogenic factors in the last three millennia in the coastal record of Cartagena Bay. Findings confirmed that Pb mining and metallurgy began during the Bronze Age, with considerable inputs of this heavy metal into the atmosphere during Phoenician, Punic and particularly Roman times compared to the Middle Ages. Pollution by Cu and Zn was also observed during Punic and Roman times, and was first documented in the Middle Ages. In addition, faecal stanols, such as coprostanol, derived mainly from humans, and 24-ethylcoprostanol from herbivores were present, thereby indicating for the first time a continuous presence of human populations and significant pollution input since 3600 yr cal BP, this being greater in the late Bronze Age and Phoenician, Punic and Roman times than during Late Antiquity and the Middle Ages, when the city was in decline.

Validation of a brief cross-cultural cognitive screening test in Multiple Sclerosis.

BACKGROUND: Several batteries have been developed for the cognitive assessment of people with multiple sclerosis (MS). However, all these tests have some limitations in general clinical practice and from a cross-cultural perspective. In this study, we aimed to validate a novel cognitive screening test, the Cross-Cultural Dementia screening test (CCD), in pwMS. METHODS: Seventy-five participants with relapsing-remitting MS and 75 healthy controls were enrolled and completed a comprehensive neuropsychological battery and the CCD. Intergroup comparisons, effect sizes, and correlations with previously validated tests were calculated for a majority and a pilot study of a minority sample. ROC curves were estimated, and random forest classification models were developed. RESULTS: There were statistically significant differences between cognitively impaired MS (MS-CI) group and healthy controls, and between MS-CI and non-cognitively impaired MS group in all subtests of CCD with medium to large effect sizes. Correlations with standardized neuropsychological tests were moderate to high, supporting concurrent validity. These results were replicated in the minority sample. The random forest models showed a very accurate classification using the CCD. This test showed good psychometric properties compared with SDMT. CONCLUSIONS: Our study validates the CCD for cognitive impairment screening in MS, showing advantages over other routinely used cognitive tests.

Neural basis of visuospatial tests in behavioral variant frontotemporal dementia.

Background: Recent models of visuospatial functioning suggest the existence of three main circuits emerging from the dorsal ("where") route: parieto-prefrontal pathway, parieto-premotor, and parieto-medial temporal. Neural underpinnings of visuospatial task performance and the sparing of visuospatial functioning in bvFTD are unclear. We hypothesized different neural and cognitive mechanisms in visuospatial tasks performance in bvFTD and AD. Methods: Two hundred and sixteen participants were enrolled for this study: 72 patients with bvFTD dementia and 144 patients with AD. Visual Object and Space Perception Battery Position Discrimination and Number Location (VOSP-PD and VOSP-NL) and Rey-Osterrieth Complex Figure (ROCF) were administered to examine visuospatial functioning, together with a comprehensive neuropsychological battery. FDG-PET was acquired to evaluate brain metabolism. Voxel-based brain mapping analyses were conducted to evaluate the brain regions associated with visuospatial function in bvFTD and AD. Results: Patients with AD performed worst in visuospatial tasks in mild dementia, but not at prodromal stage. Attention and executive functioning tests showed higher correlations in bvFTD than AD with ROCF, but not VOSP subtests. Visuospatial performance in patients with bvFTD was associated with bilateral frontal regions, including the superior and medial frontal gyri, supplementary motor area, insula and middle cingulate gyrus. Conclusion: These findings support the role of prefrontal and premotor regions in visuospatial processing through the connection with the posterior parietal cortex and other posterior cortical regions. Visuospatial deficits should be interpreted with caution in patients with bvFTD, and should not be regarded as hallmarks of posterior cortical dysfunction.

Cognitive dysfunction associated with COVID-19: A comprehensive neuropsychological study.

OBJECTIVE: Recent evidence suggests that patients suffering post-acute COVID syndrome frequently report cognitive complaints, but their characteristics and pathophysiology are unknown. This study aims to determine the characteristics of cognitive dysfunction in patients reporting cognitive complaints after COVID-19 and to evaluate the correlation between cognitive function and anxiety, depression, sleep, and olfactory function. METHODS: Cross-sectional study involving 50 patients with COVID-19 reporting cognitive complaints 9.12 ± 3.46 months after the acute infection. Patients were evaluated with a comprehensive neuropsychological protocol, and scales of fatigue, depression, anxiety, sleep and an olfactory test. Normative data and an age- and education matched healthy control group were used for comparison. RESULTS: COVID-19 patients showed a diminished performance on several tests evaluating attention and executive function, with alterations in processing speed, divided attention, selective attention, visual vigilance, intrinsic alertness, working memory, and inhibition; episodic memory; and visuospatial processing. Cognitive performance was correlated with olfactory dysfunction, and sleep quality and anxiety to a lesser extent, but not depression. CONCLUSIONS: Patients with COVID-19 reporting cognitive symptoms showed a reduced cognitive performance, especially in the attention-concentration and executive functioning, episodic memory, and visuospatial processing domains. Future studies are necessary to disentangle the specific mechanisms associated with COVID-19 cognitive dysfunction.

Examining Association of Personality Characteristics and Neuropsychiatric Symptoms in Post-COVID Syndrome.

BACKGROUND: We aimed to evaluate personality traits in patients with post-COVID syndrome, as well as the association with neuropsychiatric symptoms present in this disorder. METHODS: The Big Five Structure Inventory was administered to 93 consecutive patients with a diagnosis of post-COVID syndrome as defined by the WHO and to demographically matched controls. We also performed a comprehensive evaluation of depression, anxiety, fatigue, sleep quality, cognitive function, and olfactory function. RESULTS: Patients with post-COVID syndrome scored lower for emotional stability, equanimity, positive mood, and self-control. Extraversion, emotional stability, and openness correlated negatively with anxiety and depression levels. Conscientiousness correlated negatively with anxiety. No statistically significant correlations were observed between personality traits and cognitive function, sleep quality, olfactory function, or fatigue. Personality scores explained 36.3% and 41% of the variance in scores on the anxiety and depression scales, respectively. Two personality profiles with lower levels of emotional stability were associated with depression and anxiety. CONCLUSIONS: Our study shows higher levels of neuroticism in patients with post-COVID syndrome. Personality traits were predictive of the presence of depression and anxiety, but not cognitive function, sleep quality, or fatigue, in the context of post-COVID syndrome. These findings may have implications for the detection of patients at risk of depression and anxiety in post-COVID syndrome, and for the development of preventive and therapeutic interventions.

Neuropsychological Predictors of Fatigue in Post-COVID Syndrome.

Fatigue is one of the most disabling symptoms in several neurological disorders and has an important cognitive component. However, the relationship between self-reported cognitive fatigue and objective cognitive assessment results remains elusive. Patients with post-COVID syndrome often report fatigue and cognitive issues several months after the acute infection. We aimed to develop predictive models of fatigue using neuropsychological assessments to evaluate the relationship between cognitive fatigue and objective neuropsychological assessment results. We conducted a cross-sectional study of 113 patients with post-COVID syndrome, assessing them with the Modified Fatigue Impact Scale (MFIS) and a comprehensive neuropsychological battery including standardized and computerized cognitive tests. Several machine learning algorithms were developed to predict MFIS scores (total score and cognitive fatigue score) based on neuropsychological test scores. MFIS showed moderate correlations only with the Stroop Color-Word Interference Test. Classification models obtained modest F1-scores for classification between fatigue and non-fatigued or between 3 or 4 degrees of fatigue severity. Regression models to estimate the MFIS score did not achieve adequate R2 metrics. Our study did not find reliable neuropsychological predictors of cognitive fatigue in the post-COVID syndrome. This has important implications for the interpretation of fatigue and cognitive assessment. Specifically, MFIS cognitive domain could not properly capture actual cognitive fatigue. In addition, our findings suggest different pathophysiological mechanisms of fatigue and cognitive dysfunction in post-COVID syndrome.

Point-of-care manufacturing: a single university hospital's initial experience.

BACKGROUND: The integration of 3D printing technology in hospitals is evolving toward production models such as point-of-care manufacturing. This study aims to present the results of the integration of 3D printing technology in a manufacturing university hospital. METHODS: Observational, descriptive, retrospective, and monocentric study of 907 instances of 3D printing from November 2015 to March 2020. Variables such as product type, utility, time, or manufacturing materials were analyzed. RESULTS: Orthopedic Surgery and Traumatology, Oral and Maxillofacial Surgery, and Gynecology and Obstetrics are the medical specialties that have manufactured the largest number of processes. Working and printing time, as well as the amount of printing material, is different for different types of products and input data. The most common printing material was polylactic acid, although biocompatible resin was introduced to produce surgical guides. In addition, the hospital has worked on the co-design of custom-made implants with manufacturing companies and has also participated in tissue bio-printing projects. CONCLUSIONS: The integration of 3D printing in a university hospital allows identifying the conceptual evolution to "point-of-care manufacturing."

Effectiveness of two ultrasound-guided transrectal biopsy schemes in the diagnosis of prostate cancer. A randomized study.

OBJECTIVE: To determine whether a 10-core prostate biopsy scheme is superior to the sextant scheme in diagnosing prostate cancer in patients programmed for a first biopsy, with negative rectal digital examination and PSA between 3.5-20 ng/ml. METHODS: A randomized prospective study was performed comparing two prostate biopsy schemes, with randomization stratification according to prostate volume (< or = 50 ml and > 50 ml). Sample size predetermination yielded a minimum of 304 patients in order to achieve the primary objective. Statistical analysis was carried out on an intent-to-treat basis, using the chi-squared test and uni- and multivariate analysis via logistic regression. RESULTS: Cancer was detected in 27.3% of the cases. A significant association was observed between cancer diagnosis and age (p=0.03), prostate volume (p=0.0001) and ultrasound nodule identification (p=0.0001). No correlation was observed with the total number of cores in the series (p=0.37) or with prostate volume < or = 50 ml (p=0.87) or > 50 ml (p=0.09). In the multivariate analysis, age > 70 years (p=0.005), prostate volume < or = 50 ml (p=0.001), and ultrasound nodule identification (p=0.003) were identified as independent variables associated to cancer diagnosis. CONCLUSION: No statistically significant differences were found between the two prostate biopsy schemes. In glands over 50 ml in size, the sextant scheme may prove to be insufficient.

[Clinical results of loop ileostomy closures in rectal cancer surgical patients. Effect of chemotherapy in the waiting period]. / Resultados clínicos del cierre de ileostomías en asa en pacientes intervenidos de cáncer de recto. Efecto de la quimioterapia en el tiempo de espera.

INTRODUCTION: The introduction of sphincter preservation surgery in rectal cancer has led to an increase in the number of low resections protected with a loop ileostomy. This requires subsequent closure of the stoma, a surgical procedure which is not devoid of morbidity or mortality. The aims of the study were to analyse the clinical results of the passage reconstruction surgery and to find out the interval between both surgeries, as well as the role chemotherapy plays in this. PATIENTS AND METHOD: The prospective data of patients previously operated on for rectal cancer were used retrospectively with those whose ileostomy was closed between May 2004 and September 2008. Data associated to chemotherapy indication, interval between surgeries and complications were collected and analysed. RESULTS: A total of 54 consecutive patients with a mean age of 66 years were analysed. The mean interval between surgeries was 178 days, being significantly less in the patient group that did not receive chemotherapy (p=0.008). The post-operative stay was 6.3 days (SD=4.1). Mortality due to respiratory failure was 1.8% and the morbidity was 22.2%, with 7.4% requiring further surgery. CONCLUSIONS: The mortality and morbidity of ileostomy closures are not inconsiderable, although its advantages in the protection of the stoma justify its use. The ileostomy construction interval appears to be significantly affected by post-operative chemotherapy.