DISC1 and reelin interact to alter cognition, inhibition, and neurogenesis in a novel mouse model of schizophrenia.

The etiology of schizophrenia (SCZ) is multifactorial, and depending on a host of genetic and environmental factors. Two putative SCZ susceptibility genes, Disrupted-in-Schizophrenia-1 (DISC1) and reelin (RELN), interact at a molecular level, suggesting that combined disruption of both may lead to an intensified SCZ phenotype. To examine this gene-gene interaction, we produced a double mutant mouse line. Mice with heterozygous RELN haploinsufficiency were crossed with mice expressing dominant-negative c-terminal truncated human DISC1 to produce offspring with both mutations (HRM/DISC1 mice). We used an array of behavioral tests to generate a behavioral phenotype for these mice, then examined the prefrontal cortex and hippocampus using western blotting and immunohistochemistry to probe for SCZ-relevant molecular and cellular alterations. Compared to wild-type controls, HRM/DISC1 mice demonstrated impaired pre-pulse inhibition, altered cognition, and decreased activity. Diazepam failed to rescue anxiety-like behaviors, paradoxically increasing activity in HRM/DISC1 mice. At a cellular level, we found increased α1-subunit containing GABA receptors in the prefrontal cortex, and a reduction in fast-spiking parvalbumin positive neurons. Maturation of adult-born neurons in the hippocampus was also altered in HRM/DISC1 mice. While there was no difference in the total number proliferating cells, more of these cells were in immature stages of development. Homozygous DISC1 mutation combined with RELN haploinsufficiency produces a complex phenotype with neuropsychiatric characteristics relevant to SCZ and related disorders, expanding our understanding of how multiple genetic susceptibility factors might interact to influence the variable presentation of these disorders.

Implementation of malnutrition quality improvement reveals opportunities for better nutrition care delivery for hospitalized patients.

BACKGROUND: Gaps in hospital-based nutrition care practices and opportunities to improve care of patients at risk of malnutrition or malnourished have been demonstrated by several US hospitals implementing quality improvement (QI) projects. This study examined the impact of nutrition care process improvements focused on better documentation of identification and diagnosis of malnutrition in 5 hospital services and differences between nutritionally targeted vs nontargeted services. METHODS: Data on malnutrition risk screening, nutrition assessment, malnutrition diagnosis, and nutrition care plan delivery were collected from 32,723 hospital encounters for patients admitted to the intensive care unit, pulmonology, oncology, urology, and general medicine services (targeted) as well as the rest of the nontargeted hospital services between 2017 and 2019. RESULTS: Higher rates of morbidity in targeted service patients compared with those in the patient population admitted in the nontargeted services were observed, including higher rates of malnutrition risk (37.43% vs 19.16%, P < .001), higher rates of moderate and severe malnutrition first identified by a registered dietitian nutritionist (20.27% vs 9.67%, P < .001), and malnutrition diagnosis confirmed by an admitting physician (16.72% vs 6.74%, P < .001). CONCLUSIONS: The findings suggest sustained improvements in confirmed rates of malnutrition identification and diagnosis are achievable. Targeting malnutrition QI efforts to hospital services with higher patient morbidity is an effective method for improving malnutrition diagnosis, in particular in hospitals with limited resources, which in turn can result in improved nutrition care delivery.

Identifying patients with malnutrition and improving use of nutrition interventions: A quality study in four US hospitals.

OBJECTIVE: This study investigated how specific nutrition interventions were implemented at four US hospitals, compared rates of malnutrition diagnosis and assessment between physicians and registered dietitian nutritionists (RDNs), and examined how these differences affected the nutrition intervention received during patients' hospital stay. METHODS: Data on patients' nutrition status and nutrition interventions were collected from 16 669 hospital inpatient records. Data on intervention utilization for patients with differing nutrition assessments and diagnoses from different health care practitioners were compared using descriptive statistics and χ2 tests. RESULTS: The study found high levels of agreement between physician diagnosis and RDN assessment of malnutrition (88%). Much of this agreement related to patients identified as not malnourished. Of patients identified as malnourished by either physician diagnosis or RDN assessment, agreement was reached in 55.5% of patients. Less than half (46.3%) of patients identified as malnourished had a documented nutrition intervention. Oral nutritional supplements (ONS) were the most commonly used intervention, with 5.1% of patients receiving them. Patients identified as malnourished by physician diagnosis, but not by RDN assessment, were more likely to receive enteral and parenteral nutrition. Patients identified as malnourished by RDN assessment, but not by physician diagnosis, were more likely to have received ONS, meals and snacks, counseling, and food/nutrition-related medication management. CONCLUSION: The high level of agreement on assessment and malnutrition diagnosis suggests positive levels of malnutrition care coordination at the study hospitals. However, significant room for improvement exists in providing interventions to inpatients diagnosed with malnourishment. Differences in interventions may reflect dissimilar approaches commonly used by different practitioners and should be a topic of future study.

How a Malnutrition Quality Improvement Initiative Furthers Malnutrition Measurement and Care: Results From a Hospital Learning Collaborative.

BACKGROUND: Malnutrition in hospitalized patients can adversely affect health outcomes and increase the cost of care. Real-world strategies are needed for prompt identification and treatment of patients at risk of malnutrition. OBJECTIVES: The aim of this quality improvement (QI) study was to measure the impact of a nutrition-focused program on the malnutrition care processes of participating hospitals. Secondary objectives were to determine whether improvements in these nutrition-related processes reduced hospital readmissions and length of stay (LOS) in patients ≥65 years. METHODS: A group of 27 US hospitals ("The Collaborative") implemented the Malnutrition Quality Improvement Initiative (MQii), as guided by a Malnutrition QI Toolkit and 4 electronic clinical quality measures (eCQMs), including (1) nutrition screening; (2) nutrition assessment following detection of malnutrition risk; (3) nutrition care plan for patients identified as malnourished after completed nutrition assessment; and (4) documentation of malnutrition diagnoses. Multivariate analyses identified the variables best correlated with patient outcomes. RESULTS: Improvements were observed for all 4 eCQMs. The greatest improvements were achieved as a result of timely nutrition assessment (P = .06) and malnutrition diagnosis (P = .02). Patients ≥65 years with a malnutrition diagnosis and nutrition care plan had a 24% lower likelihood of 30-day readmission but a longer mean LOS than did those without a care plan. CONCLUSIONS: In this study, the implementation of MQii practices significantly improved the identification of malnutrition. The prompt identification and treatment of patients at malnutrition risk can improve patient care and health, as well as reduce costly readmissions.

Value of Nutrition Support Therapy: Impact on Clinical and Economic Outcomes in the United States.

OBJECTIVE: Healthcare leaders seek guidance on prudent investment in programs that improve patient outcomes and reduce costs, which includes the value of nutrition therapy. The purpose of this project was to conduct an evidence review and evaluate claims analyses to understand the financial and quality impact of nutrition support therapy on high-priority therapeutic conditions. METHODS: Task 1 included a review of existing literature from 2013 to 2018 to identify evidence that demonstrated the clinical and economic impact of nutrition intervention on patient outcomes across 13 therapeutic areas (TAs). In Task 2, analytic claims modeling was performed using the Medicare Parts A and B claims 5% sample dataset. Beneficiaries diagnosed in 5 selected TAs (sepsis, gastrointestinal [GI] cancer, hospital-acquired infections, surgical complications, and pancreatitis) were identified in the studies from Task 1, and their care costs were modeled based on nutrition intervention. RESULTS: Beginning with 1099 identified articles, 43 articles met the criteria, with a final 8 articles used for the Medicare claims modeling. As examples of the modeling demonstrated, the use of advanced enteral nutrition formula could save at least $52 million annually in a sepsis population. The total projected annual cost savings from the 5 TAs was $580 million. CONCLUSION: Overall, optimization of nutrition support therapy for specific patient populations is estimated to reduce Medicare spending by millions of dollars per year across key TAs. These findings demonstrate the evidence-based value proposition of timely nutrition support to improve clinical outcomes and yield substantial cost savings.

Enhancing Identification and Management of Hospitalized Patients Who Are Malnourished: A Pilot Evaluation of Electronic Quality Improvement Measures.

Malnutrition in hospitalized patients has long been recognized as a contributor to poor patient outcomes; malnutrition often leads to higher costs of care. Thus, it is important to improve the identification of patients who are at risk for malnutrition or already malnourished and to initiate treatment to optimize outcomes. The Malnutrition Quality Improvement Initiative (MQii) is based on a dual-pronged approach consisting of a set of four electronic clinical quality measures and a Quality Improvement Toolkit that support delivery of high-quality malnutrition care by clinicians including nurses, registered dietitian nutritionists, and physicians. A large pilot hospital validated the four malnutrition electronic clinical quality measures (screening for nutrition risk, assessment, care plan, diagnosis), demonstrating their value in support of continuous quality improvement for hospital-based malnutrition care with the ultimate goal of better patient outcomes while reducing health care costs. FUNDING/SUPPORT: Publication of this supplement was supported by Abbott. The Academy of Nutrition and Dietetics does not receive funding for the MQii. Avalere Health's work to support the MQii was funded by Abbott.

Identifying and Managing Malnourished Hospitalized Patients Utilizing the Malnutrition Quality Improvement Initiative: The UPMC Experience.

Registered dietitian nutritionists at University of Pittsburgh Medical Center, a group of 40 academic, community, and specialty hospitals in Pittsburgh, PA, recognized the need to improve the identification and management of malnourished adult patients at their institutions. It was decided to pilot the Malnutrition Quality Improvement Initiative (MQii) at two institutions within their health care system. The MQii is based on the dual-pronged approach of malnutrition-focused electronic clinical quality measures and a quality improvement toolkit (MQii Toolkit), to help identify and manage malnourished adult patients. The quality improvement implementation focused on hospital-wide adoption of the Nutrition Focused Physical Examination (NFPE). The MQii team was guided by the malnutrition electronic clinical quality measures focused on completing a nutrition assessment (the NFPE) within 24 hours of identification of malnutrition risk and ensuring documentation of a malnutrition diagnosis when it was identified. Performance on both measures improved significantly (P<0.01). Performance on appropriate timing of nutrition risk screening improved slightly, and there was almost perfect compliance for completion of nutrition care plans in the presence of malnutrition. Overall, the performance data demonstrated the effectiveness of using the MQii to improve the nutrition processes and the ability to implement NFPE into the process of malnutrition identification. FUNDING/SUPPORT: Publication of this supplement was supported by Abbott. The Academy of Nutrition and Dietetics does not receive funding for the MQii. Avalere Health's work to support the MQii was funded by Abbott.

Resultados falsos negativos transoperatorios en los ganglios centinelas de cáncer de mama, asociación con las características histológicas del tumor en el Departamento de Patología del Hospital México / Intraoperative false negative results in sentinel nodes of breast cancer, association with the histological characteristics of the tumor in the Department of Pathology of Hospital México

Resumen:El carcinoma de mama representó el tumor en mujeres más frecuente en Costa Rica para el año 2013. La disección axilar en el cáncer de mama es una de las causas de mayor comorbilidad en las pacientes. La realización de un ganglio centinela para determinar si es necesario la disección axilar, ha resultado de gran ayuda, reduciendo las comorbilidades en las pacientes con cáncer de mama. La experiencia del cirujano en la realización de procedimiento y del patólogo, han reducido los falsos negativos en los ganglios centinelas por congelación hasta en un 4.5%.En este estudio se analizaron los ganglios centinelas por congelación que contaban con biopsia definitiva y se determinó que los falsos negativos para nuestro hospital eran del 1.2%, además en estos casos, se determinó la media de tipo histológico, el grado histológico y el tamaño del cáncer de mama. En conclusión, se determinó que una de las casusas principales asociadas a los falsos negativos es la presencia de tejido adiposo en el ganglio centinela.

AbstractBreast carcinoma represented de most frequent tumor in Costa Rica during 2013. The axillary dissection in pacients with breast cancer is one of the causes of the most frecuent comorbidity. Studying sentinel ganglion to decide if it is necesary to make an axillary dissection has become very useful in reducing comorbidity in pacients with breast cancer. The surgeon´s and de pathologist´s work experience with this procedure has reduced false positive results in the sentinel ganglion´s biopsies by frezzing method in 4,5%. During the current report the sentinel ganglions by freezing method that had a definite biopsy were studied and we arrived to the conclusion that for our hospital falsepositives were less than 1,2%. As well in this cases it was determined the histologic type, the histologic grade and the size of the breast cancer. In conclusion it was determined that one of the most frecuent causes associated with false positives is the presence of adipose tissue in the sentinel ganglion.

Using a Virtual Environment to Deliver Evidence-Based Interventions: The Facilitator's Experience.

BACKGROUND: Evidence-based interventions (EBIs) have the potential to maximize positive impact on communities. However, despite the quantity and quality of EBIs for prevention, the need for formalized training and associated training-related expenses, such as travel costs, program materials, and input of personnel hours, pose implementation challenges for many community-based organizations. In this study, the community of inquiry (CoI) framework was used to develop the virtual learning environment to support the adaptation of the ¡Cuídate! (Take Care of Yourself!) Training of Facilitators curriculum (an EBI) to train facilitators from community-based organizations. OBJECTIVE: The purpose of this study was to examine the feasibility of adapting a traditional face-to-face facilitator training program for ¡Cuídate!, a sexual risk reduction EBI for Latino youth, for use in a multi-user virtual environment (MUVE). Additionally, two aims of the study were explored: the acceptability of the facilitator training and the level of the facilitators' knowledge and self-efficacy to implement the training. METHODS: A total of 35 facilitators were trained in the virtual environment. We evaluated the facilitators' experience in the virtual training environment and determined if the learning environment was acceptable and supported the acquisition of learning outcomes. To this end, the facilitators were surveyed using a modified community of inquiry survey, with questions specific to the Second Life environment and an open-ended questionnaire. In addition, a comparison to face-to-face training was conducted using survey methods. RESULTS: Results of the community of inquiry survey demonstrated a subscale mean of 23.11 (SD 4.12) out of a possible 30 on social presence, a subscale mean of 8.74 (SD 1.01) out of a possible 10 on teaching presence, and a subscale mean of 16.69 (SD 1.97) out of a possible 20 on cognitive presence. The comparison to face-to-face training showed no significant differences in participants' ability to respond to challenging or sensitive questions (P=.50) or their ability to help participants recognize how Latino culture supports safer sex (P=.32). There was a significant difference in their knowledge of core elements and modules (P<.001). A total of 74% (26/35) of the Second Life participants did agree/strongly agree that they had the skills to deliver the ¡Cuídate! CONCLUSIONS: The results showed that participants found the Second Life environment to be acceptable to the learners and supported an experience in which learners were able to acquire the knowledge and skills needed to deliver the curriculum.

Avatars travel for free: virtual access to evidence-based intervention training and capacity building.

Virtual facilitator trainings have the potential to accelerate the dissemination of evidence-based interventions by increasing accessibility and affordability. We explore the feasibility and acceptability of translating facilitator trainings of ¡Cuídate!, an evidence-based sexual risk intervention for Latino youth, to a multi-user virtual environment (Second Life). We describe the adaptation process and compare participant ratings of face-to-face (n = 35) and Second Life trainings (n = 26). Second Life participants reported that training resources, activities, and demonstrations were good/very good (97%, 88.5%, 94%). While face-to-face participants rated training process outcomes significantly higher than those in Second Life (p < 0.05), these differences may not be practically significant given high ratings overall. Results suggest that virtual trainings are an acceptable and feasible option for training community facilitators on evidence-based interventions. This study contributes to the development of trainings necessary to disseminate and implement evidence-based interventions and is an important effort in providing end-users with access to trainings in order to provide needed community services.

Preparing facilitators from community-based organizations for evidence-based intervention training in Second Life.

BACKGROUND: A major barrier to the use and scale-up of evidence-based interventions are challenges related to training and capacity building. A cost-effective and highly interactive multi-user virtual environment, Second Life (SL) is a promising alternative for comprehensive face-to-face facilitator training. OBJECTIVE: The purpose of this study was to examine the feasibility of using SL to train facilitators from community-based organizations to use ¡Cuídate! (Take Care of Yourself), one of the few evidence-based interventions developed and tested with Latino youth to reduce sexual risk behaviors. METHODS: We recruited 35 participants from community-based organizations throughout the United States to participate in the SL ¡Cuídate! Training of Facilitators. Preparation to use SL consisted of four phases: (1) recruitment and computer capacity screening, (2) enrollment, (3) orientation to the SL program, and (4) technical support throughout the synchronous training sessions. Technical difficulties, the associated cause, and the mitigation strategy implemented were recorded during each session. Participants completed evaluations including perceptions of self-efficacy and confidence to complete the necessary skills to participate in SL training. RESULTS: Overall, participants reported high levels of self-efficacy for all skills necessary to participate in SL training. Based on an 11-point scale (0-10), self-efficacy to download and access the software was rated the highest: mean 8.29 (SD 2.19). Interacting with items in SL had the lowest mean score: mean 7.49 (SD 2.89). The majority of technical difficulties experienced by participants were related to inadequate Internet connections or computer malfunctions. CONCLUSIONS: Our findings support the feasibility of using SL for the ¡Cuídate! Training of Facilitators. The process used in this study to prepare participants to use SL can be used as a basis for other evidence-based intervention training in SL. This study is an important contribution to developing cost-effective and accessible training options for evidence-based interventions.

Lesión nodular de mama de crecimiento rápido / A nodular and fast growing breast mass

La hiperplasia estromal seudoangiomatosa es un hallazgo histológico benigno, relativamente infrecuente, caracterizada por aumento de la densidad mamaria, proliferación de fibras colágeno y del estroma que forma pseudoespacios capilares vacíos anastomosados entre sí. La etiología no es clara, pero tiene una marcada influencia hormonal. Tanto clínica como radiológicamente puede semejar lesiones benignas y malignas. La histología es fundamental para hacer el diagnóstico definitivo. Se reporta el caso clínico de una mujer herediana de 40 años con una masa mamaria derecha, deformante, asimétrica, de crecimiento rápido, dolorosa y multirecidivante, que finalmente resolvió con una mastectomía subcutánea.

Carcinoma metaplásico de mama: revisión de 6 casos diagnosticados en el Hospital México, durante el período 2000-2006 / Metaplasico breast carcinoma: revision 6 of cases diagnosed at the Hospital Mexico, during the period 2000-2006

El carcinoma metaplásico de mama es un tipo de carcinoma invasor sumamente raro, menos del 1 por ciento de todos los casos, y de alto grado histológico. Incluye un grupo heterogéneo de entidades malignas infrecuentes caracterizadas por mezclar un componente epitelial ductal invasor de alto grado con un componente escamoso o sarcomatoide que puede adoptar un fenotipo variable, con producción de matriz ósea, condroide o de células fusiformes. Estos tumores se caracterizan además por presentar parámetros de comportamiento agresivo, como ser grandes, de alto grado histológico, sin expresión de receptores hormonales ni de Her2/neu, pero que clínicamente presentan un pronóstico semejante al del carcinoma ductal usual, si se estratifica por estadios. En este estudio se revisaron 6 casos de carcinomas metaplásicos diagnosticados en el Hospital México entre 2000 y 2006, con el fin de establecer las variables clínicas y morfológicas de estos tumores y de determinar en la medida de lo posible su comportamiento biológico. En resumen, se encontraron hallazgos semejantes a los reportados en la bibliografía, con predominio de tumores grandes, de alto grado y con componente metaplásico de tipo escamoso, metástasis axilares en la tercera parte de la serie, receptores hormonales y Her2/neu negativos.

Carcinoma mucoepidermoide central de la mandíbula, en un paciente con displasia fibrosa quística mandibular / Central mucoepidermoid carcinoma of the mandible, in a patient with dysplasia fibrosis cystic to mandible

El carcinoma mucoepidermoide de glándula salival es un tumor frecuente; constituye el 15 por ciento de los tumores de dicha estructura. Sin embargo, en la madíbula son mucho menos frecuentes (menos de 200 casos reportados) y se le conoce como carcinoma mucoepidermoide central. La patogenia de este tumor intraóseo sigue siendo controversial. Al igual que otros carcinomas intaóseos primarios, puede tener varios orígenes: 1) atropamiento de glándulas mucosas retromolares en la mandíbula, 2) epitelio del seno maxila, 3) atropamiento iatrogéncio de glándula salivar menor (ej. en una osteomielitis o sinusitis crónica), 4) remanentes de lámina dental, 5) remanentes de tejido de glándula salival en la mandíbula, 6) transformación neoplásica de células mucosecretoras en el epitelio de revestimiento de quistes odontogénicos. Se presenta el caso de un hombre con un carcinoma mucoepidermoide central de la mandíbula y se hace una revisión del tema.

Carcinoma ameloblástico de la mandíbula / Ameloblastic carcinoma of the jaw

En el concepto de carcinoma intraóseo primario es exclusivo de la mandíbula y maxila, ya que se origina de componentes ondontogénicos. El carcinoma ameloblástico es una lesión sumamente infrecuente, que puede aparecer de novo o asociado a una lesión previa, como un quiste odontogénico o un ameloblastoma. El diagnóstico se establece cuando se encuentran elementos histológicos de ameloblastoma, que alternan con áreas de epitelio histológicamente malignas, con independencia de que existan metástasis. Esto lo diferencia del también infrecuente ameloblastoma metastatico, en el cual se encuentra un ameloblastoma con histología benigna, que inesperadamente mestatiza. La importancia de esta diferenciación radica en el pronóstico, ya que el carcinoma ameloblástico es una lesión muy agresiva, de crecimiento rápido, que tiende a provocar un gran efecto de masa que tiene alta tasa de recidiva y mortalidad, contrario al ameloblastoma metastásico, caso en que el paciente puede sobrevivir muchos años tras la aparición de la metástasis. Con el presente caso se ilustran algunos aspectos importantes sobre el comportamiento biológico del ameloblastoma, como su elevado potencial de recurrencia, el daño que puede provocar por extensión directa y ciertas complicaciones metabólicas que, aunque infrecuentes, puede asociar. Además, permite diferenciar clínica e histológicamente la rara transformación maligna que este puede presentar, lo mismo que la importancia de la clasificación adecuada de los carcinomas odontogénicos. Descriptores: Carcinoma ameloblástico, caso clínico.