MARK1 regulates dendritic spine morphogenesis and cognitive functions in vivo.

Dendritic spines play a pivotal role in synaptic communication and are crucial for learning and memory processes. Abnormalities in spine morphology and plasticity are observed in neurodevelopmental and neuropsychiatric disorders, yet the underlying signaling mechanisms remain poorly understood. The microtubule affinity regulating kinase 1 (MARK1) has been implicated in neurodevelopmental disorders, and the MARK1 gene shows accelerated evolution in the human lineage suggesting a role in cognition. However, the in vivo role of MARK1 in synaptogenesis and cognitive functions remains unknown. Here we show that forebrain-specific conditional knockout (cKO) of Mark1 in mice causes defects in dendritic spine morphogenesis in hippocampal CA1 pyramidal neurons with a significant reduction in spine density. In addition, we found loss of MARK1 causes synaptic accumulation of GKAP and GluA2. Furthermore, we found that MARK1 cKO mice show defects in spatial learning in the Morris water maze and reduced anxiety-like behaviors in the elevated plus maze. Taken together, our data show a novel role for MARK1 in regulating dendritic spine morphogenesis and cognitive functions in vivo.

MARK1 regulates dendritic spine morphogenesis and cognitive functions in vivo.

Dendritic spines play a pivotal role in synaptic communication and are crucial for learning and memory processes. Abnormalities in spine morphology and plasticity are observed in neurodevelopmental and neuropsychiatric disorders, yet the underlying signaling mechanisms remain poorly understood. The microtubule affinity regulating kinase 1 (MARK1) has been implicated in neurodevelopmental disorders, and the MARK1 gene shows accelerated evolution in the human lineage suggesting a role in cognition. However, the in vivo role of MARK1 in synaptogenesis and cognitive functions remains unknown. Here we show that forebrain-specific conditional knockout (cKO) of Mark1 causes defects in dendritic spine morphogenesis in hippocampal CA1 pyramidal neurons with a significant reduction in spine density. In addition, we found that MARK1 cKO mice show defects in spatial learning in the Morris Water Maze and reduced anxiety-like behaviors in the Elevated Plus Maze. Furthermore, we found loss of MARK1 causes synaptic accumulation of GKAP and GluR2. Taken together, our data show a novel role for MARK1 in regulating dendritic spine morphogenesis and cognitive functions in vivo .

Nicotine on the developing brain.

Developmental periods such as gestation and adolescence have enhanced plasticity leaving the brain vulnerable to harmful effects from nicotine use. Proper brain maturation and circuit organization is critical for normal physiological and behavioral outcomes. Although cigarette smoking has declined in popularity, noncombustible nicotine products are readily used. The misperceived safety of these alternatives lead to widespread use among vulnerable populations such as pregnant women and adolescents. Nicotine exposure during these sensitive developmental windows is detrimental to cardiorespiratory function, learning and memory, executive function, and reward related circuitry. In this review, we will discuss clinical and preclinical evidence of the adverse alterations in the brain and behavior following nicotine exposure. Time-dependent nicotine-induced changes in reward related brain regions and drug reward behaviors will be discussed and highlight unique sensitivities within a developmental period. We will also review long lasting effects of developmental exposure persisting into adulthood, along with permanent epigenetic changes in the genome which can be passed to future generations. Taken together, it is critical to evaluate the consequences of nicotine exposure during these vulnerable developmental windows due to its direct impact on cognition, potential trajectories for other substance use, and implicated mechanisms for the neurobiology of substance use disorders.

Ethnicity and Parkinson's Disease: Motor and Nonmotor Features and Disease Progression in Latino Patients Living in Rural California.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder among older adults worldwide. Currently, studies of PD progression rely primarily on White non-Latino (WNL) patients. Here, we compare clinical profiles and PD progression in Latino and WNL patients enrolled in a community-based study in rural Central California. METHOD: PD patients within 5 years of diagnosis were identified from 3 counties between 2001 and 2015. During up to 3 visits, participants were examined by movement disorders specialists and interviewed. We analyzed cross-sectional differences in PD clinical features severity at each study visit and used linear mixed models and Cox proportional hazards models to compare motor, nonmotor, and disability progression longitudinally and to assess time to death in Latinos compared to WNL patients. RESULTS: Of 775 patients included, 138 (18%) self-identified as Latino and presented with earlier age at diagnosis (63.6 vs 68.9) and death (78.6 vs 81.5) than WNL. Motor (hazard ratio [HR] = 1.17 [0.71, 1.94]) and nonmotor symptoms did not progress faster in Latino versus WNL patients after accounting for differences in baseline symptom severity. However, Latino patients progressed to disability stages according to Hoehn and Yahr faster than WNL (HR = 1.81 [1.11, 2.96]). Motor and nonmotor symptoms in Latino patients were also medically managed less well than in WNL. CONCLUSIONS: Our PD study with a large proportion of Latino enrollees and progression data reveals disparities in clinical features and progression by ethnicity that may reflect healthcare access and structural socioeconomic disadvantages in Latino patients with PD.

Proximity to residential and workplace pesticides application and the risk of progression of Parkinson's diseases in Central California.

BACKGROUND: Pesticide exposure has consistently been associated with Parkinson's disease (PD) onset. Yet, fewer epidemiologic studies have examined whether pesticides influence PD motor and non-motor symptom progression. OBJECTIVES: Using a geographic information system tool that integrates agricultural pesticide use reports and land use records to derive ambient exposures at residences and workplaces, we assessed associations between specific pesticides previously related to PD onset with PD symptom progression in two PD patient cohorts living in agricultural regions of California. METHODS: We calculated the pounds of pesticide applied agriculturally near each participant's residential or occupational addresses from 1974 to the year of PD diagnosis, using a geographic information system tool that links the California Pesticide Use Reports database to land use data. We examined 53 pesticides selected a priori as they have previously been associated with PD onset. We longitudinally followed two PD patient cohorts (PEG1 N = 242, PEG2 N = 259) for an average of 5.0 years (SD ± 3.5) and 2.7 years (SD ± 1.6) respectively and assessed PD symptoms using the movement disorder specialist-administered Unified Parkinson's disease Rating Scale part III (UPDRS), Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS). Weighted time-to-event regression models were implemented to estimate effects. RESULTS: Ten agricultural pesticides, including copper sulfate (pentahydrate), 2-methyl-4-chlorophenoxyacetic acid (MCPA) dimethylamine salt, tribufos, sodium cacodylate, methamidophos, ethephon, propargite, bromoxynil octanoate, monosodium methanearsonate (MSMA), and dicamba, were associated with faster symptom progression. Among these pesticides, residential or workplace proximity to higher amounts of copper sulfate (pentahydrate) and MCPA (dimethylamine salt) was associated with all three progression endpoints (copper sulfate: HRs = 1.22-1.36, 95 % CIs = 1.03-1.73; MCPA: HRs = 1.27-1.35, 95 % CIs = 1.02-1.70). CONCLUSIONS: Our findings suggest that pesticide exposure may not only be relevant for PD onset but also PD progression phenotypes. We have implicated ten specific pesticide active ingredients in faster PD motor and non-motor decline.

CX3CR1 mutation alters synaptic and astrocytic protein expression, topographic gradients, and response latencies in the auditory brainstem.

The precise and specialized circuitry in the auditory brainstem develops through adaptations of cellular and molecular signaling. We previously showed that elimination of microglia during development impairs synaptic pruning that leads to maturation of the calyx of Held, a large encapsulating synapse that terminates on neurons of the medial nucleus of the trapezoid body (MNTB). Microglia depletion also led to a decrease in glial fibrillary acidic protein (GFAP), a marker for mature astrocytes. Here, we investigated the role of signaling through the fractalkine receptor (CX3CR1), which is expressed by microglia and mediates communication with neurons. CX3CR1-/- and wild-type mice were studied before and after hearing onset and at 9 weeks of age. Levels of GFAP were significantly increased in the MNTB in mutants at 9 weeks. Pruning was unaffected at the calyx of Held, but we found an increase in expression of glycinergic synaptic marker in mutant mice at P14, suggesting an effect on maturation of inhibitory inputs. We observed disrupted tonotopic gradients of neuron and calyx size in MNTB in mutant mice. Auditory brainstem recording (ABR) revealed that CX3CR1-/- mice had normal thresholds and amplitudes but decreased latencies and interpeak latencies, particularly for the highest frequencies. These results demonstrate that disruption of fractalkine signaling has a significant effect on auditory brainstem development. Our findings highlight the importance of neuron-microglia-astrocyte communication in pruning of inhibitory synapses and establishment of tonotopic gradients early in postnatal development.

The Professionalism of Critical Care Nurse Fellows After Completion of the Critical Care Nurse Fellowship Program.

Professionalism is paramount to the formation and functioning of new graduate critical care nurses. In this project, a sample of 110 new graduate nurses used a descriptive self-report electronic survey with Hall's Professionalism Inventory Scale. A great percentage of these new graduate critical care nurse fellows with high professionalism scores may be related to their participation in the Critical Care Nurse Fellowship orientation program. Perhaps, Nursing Professional Development specialists should incorporate classes on professional advancement planning for new graduate nurses.

Early Mobilization: Changing the Mindset.

BACKGROUND: Staff in the surgical intensive care unit (SICU) had several concerns about mobilizing patients receiving mechanical ventilation. OBJECTIVE: To assess and improve the mindset of SICU staff toward early mobilization of patients receiving mechanical ventilation before, 6 months after, and 1 year after implementation of early mobilization. METHODS: The Plan-Do-Study-Act model was used to guide the planning, implementation, evaluation, and interventions to change the mindset and practice of SICU staff in mobilizing patients receiving mechanical ventilation. Interventions to overcome barriers to early mobilization included interdisciplinary collaboration, multimodal education, and operational changes. The mindset of the SICU staff toward early mobilization of patients receiving mechanical ventilation was assessed by using a survey questionnaire distributed 2 weeks before, 6 months after, and 1 year after implementation of early mobilization. RESULTS: The median score on 6 of 7 survey questions changed significantly from before, to 6 months after, to 1 year after implementation, indicating a change in the mindset of SICU staff toward early mobilization of patients receiving mechanical ventilation. The SICU staff agreed that most patients receiving mechanical ventilation are able to get out of bed safely with coordination among personnel and that early mobilization of intubated patients decreases length of stay and decreases occurrence of ventilator-associated pneumonia, deep vein thrombosis, and skin breakdown. CONCLUSIONS: SICU interdisciplinary team collaboration, multimodal education, and operational support contribute to removing staff bias against mobilizing patients receiving mechanical ventilation.

A nursing education strategic plan for conquering catheter-associated urinary tract infections.

Catheter-associated urinary tract infections (CAUTIs) intercept opportunities for hospitals to achieve quality patient care outcomes, maintain sound financial performance, and ensure a positive health care experience. Nurse educators play a key role in designing effective strategies and establishing important partnerships aimed at reducing CAUTIs in hospitalized patients.

A inserção do psicólogo na residência multiprofissional em saúde: um relato de experiência em oncologia / The inclusion of psychologists in multidisciplinary home health: a report of experience in oncology / La inserción del psicólogo en la residencia multiprofesional en salud: un relato de experiencia en oncología

Este trabalho tem como objetivo relatar a experiência de duas psicólogas e sua inserção no programa da Residência Multiprofissional em Saúde na área de Oncologia do Hospital Universitário João de Barros Barreto. Pioneira no Estado do Pará, a Residência Multiprofissional, baseando-se nos princípios da universalidade, integralidade e equidade, disponibiliza à população um atendimento integral à saúde por meio da atuação direta de profissionais de Psicologia, Nutrição, Fisioterapia, Biomedicina, Enfermagem, Farmácia, Terapia Ocupacional e Odontologia, nos três níveis de atenção à saúde. Nessa experiência salientamos a importância do psicólogo inserido em equipe multiprofissional de saúde, apontando para a especificidade do seu papel com o paciente e com essa equipe. Por fim, destacamos a oportunidade de compartilhar percepções, sentimentos e condutas clínicas nos grupos desenvolvidos no ambiente hospitalar, centrados na tarefa de abordar o processo de morte e o morrer.(AU)

This paper aims to report the experience of two psychologists and their insertion in the Multidisciplinary Residency Program in Health in Oncology, University Hospital João de Barros Barreto. A pioneer in the State of Pará, the Multidisciplinary Residency, based on the principles of universality, comprehensiveness, and equity, the population provides a comprehensive healthcare through the direct intervention of psychologists, nutrition, physiotherapy, bio-medicine, nursing, pharmacy, therapy occupational and dentistry, the three levels of health care. In this experiment to emphasize the importance of the psychologist inserted in multi-professional health team, pointing to the specificity of its role with the patient and with this team. Finally, we highlight the opportunity to share perceptions, feelings and conduct in clinical groups developed in the hospital environment focused on the task of approaching the process of death and dying.(AU)

El objetivo de este trabajo es relatar la experiencia de dos psicólogas y su inserción en el Programa de Residencia Multiprofesional en Salud, en el área de Oncología del Hospital Universitario João de Barros Barreto. El Programa de Residencia Multiprofesional, es pionero en el Estado de Pará - Brasil, y basándose en los principios de la universalidad, integralidad e equidad, ofrece a la población una atención integral en lo que se refiere a la salud, a través de la intervención directa de profesionales de psicología, nutrición, fisioterapia, biomedicina, enfermería, farmacia, terapia ocupacional y odontología, en los tres niveles de atención a la salud. En esta experiencia resaltamos la importancia del psicólogo inserido en un equipo multiprofesional de salud, destacando la especificidad de su papel en relación al paciente y al equipo. Y para terminar, destacamos la oportunidad de compartir percepciones, sentimientos y conductas clínicas en los grupos desarrollados en el ambiente del hospital, concentrados en la tarea de abordar el proceso de muerte y el morir.(AU)

A inserção do psicólogo na residência multiprofissional em saúde: um relato de experiência em oncologia / The inclusion of psychologists in multidisciplinary home health: a report of experience in oncology / La inserción del psicólogo en la residencia multiprofesional en salud: un relato de experiencia en oncología

Este trabalho tem como objetivo relatar a experiência de duas psicólogas e sua inserção no programa da Residência Multiprofissional em Saúde na área de Oncologia do Hospital Universitário João de Barros Barreto. Pioneira no Estado do Pará, a Residência Multiprofissional, baseando-se nos princípios da universalidade, integralidade e equidade, disponibiliza à população um atendimento integral à saúde por meio da atuação direta de profissionais de Psicologia, Nutrição, Fisioterapia, Biomedicina, Enfermagem, Farmácia, Terapia Ocupacional e Odontologia, nos três níveis de atenção à saúde. Nessa experiência salientamos a importância do psicólogo inserido em equipe multiprofissional de saúde, apontando para a especificidade do seu papel com o paciente e com essa equipe. Por fim, destacamos a oportunidade de compartilhar percepções, sentimentos e condutas clínicas nos grupos desenvolvidos no ambiente hospitalar, centrados na tarefa de abordar o processo de morte e o morrer.

This paper aims to report the experience of two psychologists and their insertion in the Multidisciplinary Residency Program in Health in Oncology, University Hospital João de Barros Barreto. A pioneer in the State of Pará, the Multidisciplinary Residency, based on the principles of universality, comprehensiveness, and equity, the population provides a comprehensive healthcare through the direct intervention of psychologists, nutrition, physiotherapy, bio-medicine, nursing, pharmacy, therapy occupational and dentistry, the three levels of health care. In this experiment to emphasize the importance of the psychologist inserted in multi-professional health team, pointing to the specificity of its role with the patient and with this team. Finally, we highlight the opportunity to share perceptions, feelings and conduct in clinical groups developed in the hospital environment focused on the task of approaching the process of death and dying.

El objetivo de este trabajo es relatar la experiencia de dos psicólogas y su inserción en el Programa de Residencia Multiprofesional en Salud, en el área de Oncología del Hospital Universitario João de Barros Barreto. El Programa de Residencia Multiprofesional, es pionero en el Estado de Pará - Brasil, y basándose en los principios de la universalidad, integralidad e equidad, ofrece a la población una atención integral en lo que se refiere a la salud, a través de la intervención directa de profesionales de psicología, nutrición, fisioterapia, biomedicina, enfermería, farmacia, terapia ocupacional y odontología, en los tres niveles de atención a la salud. En esta experiencia resaltamos la importancia del psicólogo inserido en un equipo multiprofesional de salud, destacando la especificidad de su papel en relación al paciente y al equipo. Y para terminar, destacamos la oportunidad de compartir percepciones, sentimientos y conductas clínicas en los grupos desarrollados en el ambiente del hospital, concentrados en la tarea de abordar el proceso de muerte y el morir.