Validez y fiabilidad del inventario polidiagnóstico para trastornos psicóticos OPCRIT 4.0 adaptado al español.

OBJETIVO: Adaptar y validar al español el Inventario de Criterios Operativos Diagnósticos (OPCRIT 4.0) para tras-tornos psicóticos. Se trata de una herramienta que permite diagnosticar a un paciente mediante las principales clasifica-ciones diagnósticas. Material y métodos. Se realizó la traducción y retrotraducción del inventario original en inglés al español y se comprobó la validez de criterio, la validez concurrente y la fiabilidad interevaluador del mismo, a partir de una muestra de 106 historias clínicas de usuarios adultos de un centro de salud mental comunitario. RESULTADOS: Los datos obtenidos demostraron la validez y fiabilidad de la adaptación del OPCRIT 4.0 en la evaluación de la muestra de historias clínicas. CONCLUSIONES: La adaptación y validación al español del instrumento OPCRIT 4.0 permite disponer de un sistema rápido, fiable y útil para obtener el diagnóstico del trastorno psicótico en un paciente a través de diferentes sistemas de clasificación.

Genetic and clinical evidence of mitochondrial dysfunction in autism spectrum disorder and intellectual disability.

Clinical conditions commonly associated with mitochondrial disorders (CAMDs) are often present in autism spectrum disorders (ASD) and intellectual disability (ID). Therefore, the mitochondrial dysfunction hypothesis has been proposed as a transversal mechanism that may function in both disorders. Here, we investigated the presence of conditions associated with mitochondrial disorders and mitochondrial DNA (mtDNA) alterations in 122 subjects who presented ASD with ID (ASD group), 115 subjects who presented ID but not ASD (ID group) and 112 healthy controls (HC group). We assessed in the three study groups the presence of the clinical conditions through a questionnaire and the mtDNA content of two mitochondrial genes, MT-ND1 and MT-ND4, by qPCR. The mtDNA sequences of 98 ASD and 95 ID subjects were obtained by mtDNA-targeted next generation sequencing and analysed through the MToolBox pipeline to identify mtDNA mutations. Subjects with ASD and ID showed higher frequencies of constipation, edema, seizures, vision alterations, strabismus and sphincter incontinence than HCs subjects. ASD and ID subjects showed significantly lower mtDNA content than HCs in both MT-ND1 and MT-ND4 genes. In addition, we identified 49 putative pathogenic variants with a heteroplasmy level higher than 60%: 8 missense, 29 rRNA and 12 tRNA variants. A total of 28.6% of ASD and 30.5% of ID subjects carried at least one putative pathogenic mtDNA mutation. The high frequency of CAMDs, the low mtDNA content and the presence of putative pathogenic mtDNA mutations observed in both ASD and ID subjects are evidence of mitochondrial dysfunction in ASD and ID.

Evaluation of 2 Low-cost High-definition Video Systems for Venous Anastomosis.

Background. A literature review of the use of video systems for magnification has suggested that so far, this novel magnification system has only been used to perform arterial anastomoses. The aim of this study was to evaluate the use of 2 low-cost methods of video-assisted magnification in microvascular venous anastomosis in rats. Methods. Thirty rats were randomly divided into 3 matched groups according to the magnification system used: the microscope group, with venous anastomosis performed under a microscope; the camcorder system group, with the procedures performed under a high-definition Handycam HDR-XR160; and the Photographic camera group, for which procedures were performed with an EOS Rebel T3i photographic camera. In both video system groups, a magnification system was connected to a 42-in. television by an HDMI cable. We analyzed weight, venous caliber, total surgery and anastomosis time, patency immediately and 14 days postoperatively, number of stitches, and histological analyses. Results. There were no significant differences between the groups in weight, venous caliber, or number of stitches. Anastomosis under the video systems took longer. Patency rates were similar between the groups, except for the photographic system group that has a lower patency rate at 14 days. The histological analyses were similar in all groups. Conclusion. It is possible to perform a venous anastomosis in rats through video system magnification, with a satisfactory success rate comparable with that for procedures performed under microscopes; however, the kind of video system has a great influence on the final patency.

Association of Borderline Intellectual Functioning and Adverse Childhood Experience with adult psychiatric morbidity. Findings from a British birth cohort.

BACKGROUND: To examine whether Borderline Intellectual Functioning (BIF) and Adverse Childhood Experiences independently predict adult psychiatric morbidity. METHODS: We performed a secondary analysis of longitudinal data derived from the 1970 British Birth Cohort Study to examine whether BIF and Adverse Childhood Experiences independently predict adult mental distress as measured by the Malaise Inventory. Factor analysis was used to derive a proxy measure of IQ from cognitive testing at age 10 or 5. Variables that could be indicators of exposure to Adverse Childhood Experiences were identified and grouped into health related and socio-economic related adversity. RESULTS: Children with BIF were significantly more likely than their peers to have been exposed to Adverse Childhood Experiences (BIF mean 5.90, non-BIF mean 3.19; Mann-Whitney z = 31.74, p < 0.001). As adults, participants with BIF were significantly more likely to score above the cut-off on the Malaise Inventory. We found statistically significant relationships between the number of socio-economic Adverse Childhood Experiences and poorer adult psychiatric morbidity (r range 0.104-0.141, all p < 001). At all ages the indirect mediating effects of Adverse Childhood Experiences were significantly related to adult psychiatric morbidity. CONCLUSIONS: The relationship between BIF and adult psychiatric morbidity appears to be partially mediated by exposure to Adverse Childhood Experiences. Where possible, targeting Adverse Childhood Experiences through early detection, prevention and interventions may improve psychiatric morbidity in this population group.

Universal fluorescence module for intraoperative fluorescein angiography-a technical report.

BACKGROUND: Even in specialized centers, suboptimal aneurysm clipping can be as high as 12%. Intraoperative fluorescence angiography with indocyanine green and, more recently, fluorescein sodium have been shown to be a good method for intraoperative flow assessment. However, the cost with the apparatus it entails limits its widespread use. We have developed a low-cost universal fluorescence module (FM) designed to visualize fluorescein and perform intraoperative angiography. The purpose of this paper is to describe this device as well as to present our early experience with its use in the treatment of cerebral aneurysms. METHOD: A FM was designed and built using a cyan-blue narrow bandpass (460 to 490 nm) excitation filter and a yellow-orange longpass (blocking wavelengths under 520 nm) barrier filter mounted on a 3D-printed holding tray in a specific disposition to perfectly match the light source and the objective lens of the surgical microscope. It allowed switching from white light to fluorescence mode in a simple and sterile fashion. Its perfect attachment to the microscope was possible by reusing the lens fittings extracted from used original drape sets that would otherwise be discarded. Four patients underwent aneurysm clipping using the FM at two institutions from April to September 2018. RESULTS: A bright green fluorescence against a dark background was observed after intravenous bolus of fluorescein. Blood vessels became obviously distinct from non-contrast-filled structures such as clipped aneurysms and the brain. Vascular anatomy could be appreciated without any distortion, including perforating arteries. CONCLUSIONS: Intraoperative fluorescence angiography was successfully performed with the use of this universal FM after intravenous injection of fluorescein sodium. This simple and low-cost device may be useful in resource-limited centers, where other sorts of intraoperative angiography are not available.

The POMONA-ESP project methodology: Collecting data on health indicators for people with intellectual developmental disorders.

BACKGROUND: People with intellectual developmental disorders have significant health disparities and a lack of proper attention to their health needs. They have been underrepresented in scientific research, and very few studies have been carried out using a representative randomized sample. The aim of this study was to describe the methods used in the POMONA-ESP project to recruit a representative and randomized sample of participants with intellectual developmental disorders. METHODS: The POMONA-ESP project is an observational cross-sectional study. It aims to explore the health status of people with intellectual developmental disorders across Spain and the use they make of health services. RESULTS AND CONCLUSIONS: The results of the POMONA-ESP project may have a major impact on people with intellectual developmental disorders and society in general. It is the first study to obtain geographically representative epidemiological data from a large sample, information that is fundamental to improving care and healthcare planning for people with intellectual developmental disorders.

Health indicators in intellectual developmental disorders: The key findings of the POMONA-ESP project.

BACKGROUND: The aim of this paper was to summarize the main results of the POMONA-ESP project, the first study to explore health status in a large representative, randomized and stratified sample of people with intellectual developmental disorders in Spain. METHODS: The POMONA-ESP project collected information about the health of 953 individuals with intellectual developmental disorders. RESULTS: Diseases such as urinary incontinence, oral problems, epilepsy, constipation or obesity were highly prevalent among the participants; with gender-differentiated prevalences for certain conditions, and age and intellectual disability level as risk factors for disease. Overmedication was common in the sample, and drugs were often prescribed without any clinical indication or follow-up. The present authors also found a lack of important relevant information about the participant's health and a lack of adequate genetic counselling. CONCLUSIONS: Our findings may contribute to a better understanding of health status and needs of people with intellectual developmental disorders and suggest several courses of action to improve their health care.

A Psychopathological Comparison between Delusional Disorder and Schizophrenia.

OBJECTIVE: To contribute to a better differential clinical categorisation of delusional disorder (DD) versus schizophrenia (SZ) and to add and complete evidence from previous clinical studies of DD compared to schizophrenia. METHODS: A cross-sectional study using a clinical sample of 275 patients (132 patients with DD) was studied. Patients were consecutively attending public clinics located in urban and rural areas in both Andalusia and Catalonia (Spain). All participants met DSM-IV diagnostic criteria for either DD or SZ. Data were gathered on sociodemographics, illness duration, Barona-Index estimation of intelligence quotient (IQ), and global functioning, along with a thorough psychopathological assessment using the Positive and Negative Syndrome Scale (PANSS). Comparisons between both groups were calculated using χ2, Student t, and multivariate analysis of covariance tests. RESULTS: Patients with DD were older (mean [SD], 50.3 [14.6] years vs. 36.6 [11.1] years; t = 8.597; P ≤ 0.0001), were more frequently married (45.4% vs. 10.8%; χ2 = 38.569; P ≤ 0.0001), and had a higher mean estimated premorbid IQ (111.4 vs. 105.4; t = 2.609; P ≤ 0.01). On the other hand, SZ patients were predominantly male (71.4% vs. 48.9%; χ2 = 14.433; P ≤ 0.0001) and had greater work-related disability than DD patients (20.5% vs. 50.3%; χ2 = 19.564; P ≤ 0.001). Overall, the DD group showed a less severe PANSS psychopathology than SZ group. Thus, total mean (SD) PANSS scores for schizophrenia and delusional disorder, respectively, were 76.2 (22.4) versus 54.1 (18.4) ( t = -8.762; P ≤ 0.0001). Moreover, patients with DD showed a better global functioning than those with SZ (62.7 [13.2] vs. 51.9 [16.9]; F = 44.114; P ≤ 0.0001). CONCLUSIONS: DD is a milder and distinct disorder compared to SZ in terms of psychopathology and global functionality.

Awake craniotomy for right inferior lobule glioma.

Awake craniotomy is a method usually used for brain tumors near or within language and/or sensorimotor areas. Preservation of these important neurological functions, however, may not be enough for a normal life. The authors present a case of a 45-year-old woman with an inferior parietal lobule low-grade glioma who underwent an awake craniotomy with sensorimotor and spatial cognition mapping. The video can be found here: https://youtu.be/HMA_pZYg3Ms .

Patients' perspective on awake craniotomy for brain tumors-single center experience in Brazil.

BACKGROUND: Awake craniotomy with brain mapping is the gold standard for eloquent tissue localization. Patients' tolerability and satisfaction have been shown to be high; however, it is a matter of debate whether these findings could be generalized, since patients across the globe have their own cultural backgrounds and may perceive and accept this procedure differently. METHODS: We conducted a prospective qualitative study about the perception and tolerability of awake craniotomy in a population of consecutive brain tumor patients in Brazil between January 2013 and April 2015. Seventeen patients were interviewed using a semi-structured model with open-ended questions. RESULTS: Patients' thoughts were grouped into five categories: (1) overall perception: no patient considered awake craniotomy a bad experience, and most understood the rationale behind it. They were positively surprised with the surgery; (2) memory: varied from nothing to the entire surgery; (3) negative sensations: in general, it was painless and comfortable. Remarks concerning discomfort on the operating table were made; (4) postoperative recovery: perception of the postoperative period was positive; (5) previous surgical experiences versus awake craniotomy: patients often preferred awake surgery over other surgery under general anesthesia, including craniotomies. CONCLUSIONS: Awake craniotomy for brain tumors was well tolerated and yielded high levels of satisfaction in a population of patients in Brazil. This technique should not be avoided under the pretext of compromising patients' well-being.

[Hospital admissions and morbidity in people with intellectual developmental disorders]. / Acceso y morbilidad hospitalaria en personas con trastornos del desarrollo intelectual.

OBJECTIVE: People with intellectual developmental disorders (IDD) have worse health statuses in comparison with general population. The objective of this paper is to compare access and hospital morbimortality in people with IDD and general population. MATERIAL AND METHODS: We conducted a retrospective cross-sectional analytical study and analyzed data on admissions and discharges between IDD patients and the rest of them, in Ciudad Real, España. RESULTS: Out of 51 325 hospital admissions, 441 (0.9%) belonged to the group of persons with IDD. The IDD group had fewer programmed hospitalization than the general population and fewer surgical interventions. They presented more admissions for mental disorders and respiratory system diseases. CONCLUSIONS: The data presented confirm TDI population have different patterns of disease. Furthermore, this study reveal potential difficulties in access to health care in this population.

OBJETIVO: Las personas con trastornos del desarrollo intelectual (TDI) suelen presentar peor estado de salud que la población general. El objetivo de este estudio es evaluar el acceso y la morbimortalidad hospitalaria en los pacientes con TDI y compararla con la población general. MATERIAL Y MÉTODOS: Se realizó un estudio transversal retrospectivo y se compararon los datos de los ingresos y altas hospitalarias entre pacientes con TDI y sin dichos transtornos, en Ciudad Real, España. RESULTADOS: De un total de 51 325 altas, 441 (0.9%) correspondían a personas con TDI. Estas personas presentaban significativamente menos ingresos programados que la población general y menos intervenciones quirúrgicas y, a su vez, más ingresos debidos a enfermedades mentales y del sistema respiratorio. CONCLUSIONES: Las personas con TDI tienen patrones de morbilidad diferentes a los del resto de la población. Además este estudio revela posibles dificultades en el acceso a la atención sanitaria en estas personas.

Health profiles in people with intellectual developmental disorders.

OBJECTIVE: To better understand the health profiles of people with intellectual disability (ID), focusing on the variables that are associated with a poorer health status. MATERIALS AND METHODS: Data were collected from the Survey on Disability, Personal Autonomy and Dependency (EDAD 2008) of the Spanish National Statistics Institute (INE). The health data of 2840 subjects with IDD were analyzed in order to verify the impact of different variables on their health profiles. RESULTS: People with severe and profound levels of IDD presented a higher number of medical diagnoses. At residence centers there was a larger proportion of individuals with a higher prevalence of chronic diseases and more severe conditions; age also was an important factor. CONCLUSION: The health profiles of individuals with IDD differ depending on the severity level of their IDD and their degree of institutionalization. Further research is needed to provide better health care for people with IDD.

[New considerations on the health of the persons with intellectual developmental disorders]. / Nuevas consideraciones sobre la salud de las personas con trastornos del desarrollo intelectual.

Recent literature indicates that people with Disorders of Intellectual Development (DID) experience health disparities in the pathologies that they present, and a worst access to health care. However, current evidence-based knowledge is still sparse outside the Anglo-Saxon countries. The POMONA-I and POMONA-II European projects aimed to collect information on the health status of people with DID in Europe. The POMONA-ESP project in Spain is meant to collect health information in a wide and representative sample of persons with DID. Also, there are studies that claim for the need of specialized services for people with DID at the public health system. There are also studies about the current state of the education and training about DID for students within the health sector. In this paper we review the latest evidences about the health of the persons with DID and we present the main research activities and care initiatives about this issue.

Resumen: La literatura reciente indica que las personas con trastornos del desarrollo intelectual (TDI) presentan diferencias respecto de la población general en cuanto a la prevalencia de determinadas enfermedades y a la atención sanitaria que reciben. El conocimiento actual con base en la evidencia es aún muy escaso en países no anglosajones. Los proyectos europeos POMONA-I y POMONA-II tenían el objetivo de recoger información sobre el estado de salud de las personas con TDI en Europa. Actualmente, el proyecto POMONA-ESP en España pretende recoger dicha información en una muestra amplia y representativa de personas con TDI. También se están llevando a cabo otros estudios sobre la necesidad de contar con servicios especializados y sobre la formación que reciben los profesionales sanitarios sobre TDI. En este artículo se revisan las últimas evidencias sobre la salud de las personas con TDI y se exponen las principales actividades de investigación y asistencia sanitaria sobre este tema.

A Low-Cost High-Definition Video System for Microsurgical Hindlimb Replantation in Rats.

Background The surgical microscope is still essential for microsurgery, but several alternatives that show promising results are currently under development, such as endoscopes and laparoscopes with video systems; however, as yet, these have only been used for arterial anastomoses. The aim of this study was to evaluate the use of a low-cost video-assisted magnification system in replantation of the hindlimbs of rats. Methods Thirty Wistar rats were randomly divided into two matched groups according to the magnification system used: the microscope group, with hindlimb replantation performed under a microscope with an image magnification of 40× and the video group, with the procedures performed under a video system composed of a high-definition camcorder, macrolenses, a 42-in television, and a digital HDMI cable. The camera was set to 50× magnification. We analyzed weight, arterial and venous caliber, total surgery time, arterial and venous anastomosis time, patency immediately and 7 days postoperatively, the number of stitches, and survival rate. Results There were no significant differences between the groups in weight, arterial or venous caliber, or the number of stitches. Replantation under the video system took longer (p < 0.05). Patency rates were similar between groups, both immediately and 7 days postoperatively. Conclusion It is possible to perform a hindlimb replantation in rats through video system magnification, with a satisfactory success rate comparable with that for procedures performed under surgical microscopes.

Molecular characterization and descriptive analysis of carbapenemase-producing Gram-negative rod infections in Bogota, Colombia.

In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was blaKPC, specifically blaKPC-2 [38.6% (88/228)] and blaKPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with blaVIM-2 and blaNDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was blaKPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which Pseudomonas aeruginosa ST111 was mainly related to blaKPC-3. Klebsiella pneumoniae ST512, ST258, ST14, and ST1082 were exclusively associated with blaKPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were blaKPC-2 and blaKPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.IMPORTANCEAntimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel Pseudomonas aeruginosa, which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries.

Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial.

Background: Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. Methods: A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. Discussion: The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials. Trial registration: Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

Perspectives: the mental health care gap in intellectual disabilities in Spain: impact analysis and knowledge-to-action plan.

BACKGROUND: Intellectual developmental disorder or Intellectual disability (ID) is a prevalent condition with a high impact along the life-span particularly when associated to other mental disorders (MD). SPECIFIC AIM: To estimate the unmet needs and to design a knowledge to action plan to reduce the care gap in ID-MD in Spain. METHOD: We followed a 5-step `maxi' impact assessment and a mixed qualitative/quantitative design including expert panels, secondary analysis of databases and a prospective survey in the 17 regions in Spain. Schizophrenia was used as comparator due to similar prevalence rates and burden. RESULTS: Persons with ID-MD had ten times less outpatient contacts and hospital admissions than patients with schizophrenia. The outpatient case load was 2.31% in ID and 14.6% in schizophrenia. ID had the lowest hospitalization rate amongst all mental disorders but the highest length of stay. The expert panel estimated that half of persons with ID-MD are not adequately assessed and 95% do not receive the required care in Spain. Basic care needs include 6.5 beds and an ID-MD outpatient service per 1 million population. At least 134 specialized psychiatrists and psychologists and 277 beds are needed to reach the minimum standards in Spain. CONCLUSION: This study quantifies the ID-MD care gap in Spain and the basic specialized services needed. In spite of the societal and health implications of ID-MD the knowledge-to-action plan had a modest impact limited at the regions where ID-MD programmes were already implemented. IMPLICATIONS FOR HEALTH POLICY: Specific priority setting on ID-MH should be incorporated to mental health strategy at the Ministry of Health within a broader health and ID plan. National and regional policies should incorporate an integrative care approach through the life cycle. The development of excellence centers on ID-MD and a national observatory on this topic should be encouraged.

Mutations affecting synaptic levels of neurexin-1ß in autism and mental retardation.

The identification of mutations in genes encoding proteins of the synaptic neurexin-neuroligin pathway in different neurodevelopmental disorders, including autism and mental retardation, has suggested the presence of a shared underlying mechanism. A few mutations have been described so far and for most of them the biological consequences are unknown. To further explore the role of the NRXN1ß gene in neurodevelopmental disorders, we have sequenced the coding exons of the gene in 86 cases with autism and mental retardation and 200 controls and performed expression analysis of DNA variants identified in patients. We report the identification of four novel independent mutations that affect nearby positions in two regions of the gene/protein: i) sequences important for protein translation initiation, c.-3G>T within the Kozak sequence, and c.3G>T (p.Met1), at the initiation codon; and ii) the juxtamembrane region of the extracellular domain, p.Arg375Gln and p.Gly378Ser. These mutations cosegregate with different psychiatric disorders other than autism and mental retardation, such as psychosis and attention-deficit/hyperactivity disorder. We provide experimental evidence for the use of an alternative translation initiation codon for c.-3G>T and p.Met1 mutations and reduced synaptic levels of neurexin-1ß protein resulting from p.Met1 and p.Arg375Gln. The data reported here support a role for synaptic defects of neurexin-1ß in neurodevelopmental disorders.

Comparative Evaluation of Phenotypic Synergy Tests versus RESIST-4 O.K.N.V. and NG Test Carba 5 Lateral Flow Immunoassays for the Detection and Differentiation of Carbapenemases in Enterobacterales and Pseudomonas aeruginosa.

The spread of carbapenem-resistant Pseudomonas aeruginosa and carbapenemase-producing Enterobacterales (CPE) has dramatically impacted morbidity and mortality. COVID-19 pandemic has favored the selection of these microorganisms because of the excessive and prolonged use of broad-spectrum antibiotics and the outbreaks related to patient transfer between hospitals and inadequate personal protective equipment. Therefore, early CPE detection is considered essential for their control. We aimed to compare conventional phenotypic synergy tests and two lateral flow immunoassays for detecting carbapenemases in Enterobacterales and P. aeruginosa. We analyzed 100 carbapenem-resistant Gram-negative bacilli isolates, 80 Enterobacterales, and 20 P. aeruginosa (86 isolates producing KPC, NDM, OXA-48, IMP, and VIM carbapenemases and 14 non-carbapenemase-producing isolates). We performed a modified Hodge test, boronic acid and ethylenediaminetetraacetic acid (EDTA) synergy tests, and two lateral flow immunoassays: RESIST-4 O.K.N.V. (Coris Bioconcept) and NG Test Carba 5 (NG Biotech). In total, 76 KPC, seven VIM, one NDM, one OXA-48, and one isolate coproducing KPC + NDM enzymes were included. The concordance of different methods estimated by the Kappa index was 0.432 (standard error: 0.117), thus showing a high variability with the synergy tests with boronic acid and EDTA and reporting 16 false negatives that were detected by the two immunochromatographic methods. Co-production was only detected using immunoassays. Conventional phenotypic synergy tests with boronic acid and EDTA for detecting carbapenemases are suboptimal, and their routine use should be reconsidered. These tests depend on the degree of enzyme expression and the distance between disks. Lateral flow immunoassay tests are a rapid and cost-effective tool to detect and differentiate carbapenemases, improving clinical outcomes through targeted therapy and promoting infection prevention measures. IMPORTANCE Infections due to multidrug-resistant pathogens are a growing problem worldwide. The production of carbapenemases in Pseudomonas aeruginosa and Enterobacterales cause a high impact on the mortality of infected patients. Therefore, it is of great importance to have methods that allow the early detection of these multi-resistant microorganisms, achieving the confirmation of the type of carbapenemase present, with high sensitivity and specificity, with the aim of improving epidemiological control, dissemination, the clinical course to through targeted antibiotic therapy and promoting infection control in hospitals.