Cortical origin of theta error signals.

A multi-scale approach elucidated the origin of the error-related-negativity (ERN), with its associated theta-rhythm, and the post-error-positivity (Pe) in macaque supplementary eye field (SEF). Using biophysical modeling, synaptic inputs to a subpopulation of layer-3 (L3) and layer-5 (L5) pyramidal cells (PCs) were optimized to reproduce error-related spiking modulation and inter-spike intervals. The intrinsic dynamics of dendrites in L5 but not L3 error PCs generate theta rhythmicity with random phases. Saccades synchronized the phases of the theta-rhythm, which was magnified on errors. Contributions from error PCs to the laminar current source density (CSD) observed in SEF were negligible and could not explain the observed association between error-related spiking modulation in L3 PCs and scalp-EEG. CSD from recorded laminar field potentials in SEF was comprised of multipolar components, with monopoles indicating strong electro-diffusion, dendritic/axonal electrotonic current leakage outside SEF, or violations of the model assumptions. Our results also demonstrate the involvement of secondary cortical regions, in addition to SEF, particularly for the later Pe component. The dipolar component from the observed CSD paralleled the ERN dynamics, while the quadrupolar component paralleled the Pe. These results provide the most advanced explanation to date of the cellular mechanisms generating the ERN.

Resolving the mesoscopic missing link: Biophysical modeling of EEG from cortical columns in primates.

Event-related potentials (ERP) are among the most widely measured indices for studying human cognition. While their timing and magnitude provide valuable insights, their usefulness is limited by our understanding of their neural generators at the circuit level. Inverse source localization offers insights into such generators, but their solutions are not unique. To address this problem, scientists have assumed the source space generating such signals comprises a set of discrete equivalent current dipoles, representing the activity of small cortical regions. Based on this notion, theoretical studies have employed forward modeling of scalp potentials to understand how changes in circuit-level dynamics translate into macroscopic ERPs. However, experimental validation is lacking because it requires in vivo measurements of intracranial brain sources. Laminar local field potentials (LFP) offer a mechanism for estimating intracranial current sources. Yet, a theoretical link between LFPs and intracranial brain sources is missing. Here, we present a forward modeling approach for estimating mesoscopic intracranial brain sources from LFPs and predict their contribution to macroscopic ERPs. We evaluate the accuracy of this LFP-based representation of brain sources utilizing synthetic laminar neurophysiological measurements and then demonstrate the power of the approach in vivo to clarify the source of a representative cognitive ERP component. To that end, LFP was measured across the cortical layers of visual area V4 in macaque monkeys performing an attention demanding task. We show that area V4 generates dipoles through layer-specific transsynaptic currents that biophysically recapitulate the ERP component through the detailed forward modeling. The constraints imposed on EEG production by this method also revealed an important dissociation between computational and biophysical contributors. As such, this approach represents an important bridge between laminar microcircuitry, through the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp.

Rapid Population-Based Surveillance of Prenatal and Postpartum Experiences During Public Health Emergencies, Puerto Rico, 2016‒2018.

The Pregnancy Risk Assessment Monitoring System-Zika Postpartum Emergency Response study, implemented in Puerto Rico during the Zika virus outbreak (2016-2017) and after Hurricanes Irma and María (2017-2018), collected pregnancy-related data using postpartum hospital-based surveys and telephone follow-up surveys. Response rates of 75% or more were observed across five study surveys. The study informed programs, increased the Puerto Rico Department of Health's capacity to conduct maternal‒infant health surveillance, and demonstrated the effectiveness of this methodology for collecting data during public health emergencies. (Am J Public Health. 2022;112(4):574-578. https://doi.org/10.2105/AJPH.2021.306687).

A Minimal Biophysical Model of Neocortical Pyramidal Cells: Implications for Frontal Cortex Microcircuitry and Field Potential Generation.

Ca2+ spikes initiated in the distal trunk of layer 5 pyramidal cells (PCs) underlie nonlinear dynamic changes in the gain of cellular response, critical for top-down control of cortical processing. Detailed models with many compartments and dozens of ionic channels can account for this Ca2+ spike-dependent gain and associated critical frequency. However, current models do not account for all known Ca2+-dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We overcome these limitations in a minimal two-compartment biophysical model. In our model, a basal-dendrites/somatic compartment included fast-inactivating Na+ and delayed-rectifier K+ conductances, while an apical-dendrites/trunk compartment included persistent Na+, hyperpolarization-activated cation (I h ), slow-inactivating K+, muscarinic K+, and Ca2+ L-type. The model replicated the Ca2+ spike morphology and its critical frequency plus three other defining features of layer 5 PC synaptic integration: linear frequency-current relationships, back-propagation-activated Ca2+ spike firing, and a shift in the critical frequency by blocking I h Simulating 1000 synchronized layer 5 PCs, we reproduced the current source density patterns evoked by Ca2+ spikes and describe resulting medial-frontal EEG on a male macaque monkey. We reproduced changes in the current source density when I h was blocked. Thus, a two-compartment model with five crucial ionic currents in the apical dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials, such as the error-related negativity.SIGNIFICANCE STATEMENT A minimal model of layer 5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. By redistributing voltage-gated and returning transmembrane currents in the model, we establish a theoretical framework for the investigation of cortical microcircuit contribution to intracranial local field potentials and EEG. This tractable model will enable biophysical evaluation of multiscale electrophysiological signatures and computational investigation of cortical processing.

Analytics and Lean Health Care to Address Nurse Care Management Challenges for Inpatients in Emerging Economies.

PURPOSE: Prescriptive and predictive analytics and artificial intelligence (AI) provide tools to analyze data with objectivity. In this paper, we provide an overview of how these techniques can improve nursing care, and we detail a quantitative model to afford managerial insights about care management in a Hospital in Colombia. Our main purpose is to provide tools to improve key performance indicators for the care management of inpatients which includes the nurse workload. METHODS: The optimal nurse-to-patient assignment problem is addressed using analytics, lean health care, and AI. Also, we propose a new mathematical model to optimize the nurse-to-patient assignment decisions considering several variables about the patient state such as the Barthel index, their risks, the complexity of the care, and the mental state. FINDINGS: Our results show that there are several processes inherent to compassionate nursing care that can be improved using technology. By using data analytics, we can also provide insights about the high variability of the care requirements and, by using models, find nurse-to-patient assignments that are nearly perfectly balanced. CONCLUSIONS: We illustrated this improvement with a pilot test that makes the equitable distribution of nursing workload the functionality of this strategy. The findings can be useful in highly complex hospitals in Latin America. CLINICAL RELEVANCE: The proposed model presents an opportunity to make near perfectly balanced nurse-to-patient assignments according to the number of patients and their health conditions using technology.

Preventing Vector-Borne Transmission of Zika Virus Infection During Pregnancy, Puerto Rico, USA, 2016-20171.

We examined pregnant women's use of personal protective measures to prevent mosquito bites during the 2016-2017 Zika outbreak in Puerto Rico. Healthcare provider counseling on recommended measures was associated with increased use of insect repellent among pregnant women but not with wearing protective clothing.

High Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous ß-Lactams.

Multidrug-resistant Enterobacteriaceae (MRE) colonize the intestine asymptomatically from where they can breach into the bloodstream and cause life-threatening infections, especially in heavily colonized patients. Despite the clinical relevance of MRE colonization levels, we know little about how they vary in hospitalized patients and the clinical factors that determine those levels. Here, we conducted one of the largest studies of MRE fecal levels by tracking longitudinally 133 acute leukemia patients and monitoring their MRE levels over time through extensive culturing. MRE were defined as Enterobacteriaceae species that acquired nonsusceptibility to ≥1 agent in ≥3 antimicrobial categories. In addition, due to the selective media used, the MRE had to be resistant to third-generation cephalosporins. MRE were detected in 60% of the patients, but their fecal levels varied considerably among patients and within the same patient (>6 and 4 orders of magnitude, respectively). Multivariate analysis of clinical metadata revealed an impact of intravenous beta-lactams (i.e., meropenem and piperacillin-tazobactam), which significantly diminished the fecal MRE levels in hospitalized patients. Consistent with a direct action of beta-lactams, we found an effect only when the patient was colonized with strains sensitive to the administered beta-lactam (P < 0.001) but not with nonsusceptible strains. We report previously unobserved inter- and intraindividual heterogeneity in MRE fecal levels, suggesting that quantitative surveillance is more informative than qualitative surveillance of hospitalized patients. In addition, our study highlights the relevance of incorporating antibiotic treatment and susceptibility data of gut-colonizing pathogens for future clinical studies and in clinical decision-making.

Preventing Sexual Transmission of Zika Virus Infection during Pregnancy, Puerto Rico, USA, 20161.

We examined condom use throughout pregnancy during the Zika outbreak in Puerto Rico during 2016. Overall, <25% of women reported consistent condom use during pregnancy. However, healthcare provider counseling was associated with a 3-fold increase in consistent use, reinforcing the value of provider counseling in Zika prevention efforts.

Overweight and obesity as predictors of early mortality in Mexican children with acute lymphoblastic leukemia: a multicenter cohort study.

BACKGROUND: Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL. METHODS: A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes. RESULTS: A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0-2.0; CDC: HR = 1.6, 95%CI:1.1-2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9-2.5; CDC: HR = 1.0; 95% CI:0.6-1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7-3.2; CDC: HR = 1.4; 95%CI:0.9-2.3) with early relapse were observed. CONCLUSIONS: Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment.

Identification and Characterization of Novel Fusion Genes with Potential Clinical Applications in Mexican Children with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia is the most common type of childhood cancer worldwide. Mexico City has one of the highest incidences and mortality rates of this cancer. It has previously been recognized that chromosomal translocations are important in cancer etiology. Specific fusion genes have been considered as important treatment targets in childhood acute lymphoblastic leukemia (ALL). The present research aimed at the identification and characterization of novel fusion genes with potential clinical implications in Mexican children with acute lymphoblastic leukemia. The RNA-sequencing approach was used. Four fusion genes not previously reported were identified: CREBBP-SRGAP2B, DNAH14-IKZF1, ETV6-SNUPN, ETV6-NUFIP1. Although a fusion gene is not sufficient to cause leukemia, it could be involved in the pathogenesis of the disease. Notably, these new translocations were found in genes encoding for hematopoietic transcription factors which are known to play an important role in leukemogenesis and disease prognosis such as IKZF1, CREBBP, and ETV6. In addition, they may have an impact on the prognosis of Mexican pediatric patients with ALL, with the potential to be included in the current risk stratification schemes or used as therapeutic targets.

Commitment and a sense of humanity for the adaptation of patients during hospital care.

OBJECTIVE: To develop a nursing practice model for the Clinic of the University of the La Sabana that supports the adaptive process of patients during and after their hospital experience. METHODOLOGY: This is a descriptive, methodological study implemented in different phases: (1) characterization of the context, (2) identification of the need for a nursing practice model for strengthening care, (3) literature review, (4) description of the model, and (5) validation. RESULTS: The context of a university hospital and international trends in the development of a professional nursing discipline require theoretical guidance for the ongoing improvement of the practice of nursing. The decision to apply Roy's conceptual model of adaptation clarifies the need for a complementary nursing practice model that brings this macro theory closer to the assistance reality. It is also necessary to make the vocation of service, knowledge and leadership of nursing visible whenever the human adaptive process is a priority. CONCLUSION: The University of La Sabana nursing practice model is a model focused on the commitment and humane treatment for the adaptation of patients during hospital care. It represents a consensus on the essentials of the nursing practice, which seek to support the adaptive process in order to have more comprehensive welfare and consequent improvement of the patient.

Agranular frontal cortical microcircuit underlying cognitive control in macaques.

The error-related negativity and an N2-component recorded over medial frontal cortex index core functions of cognitive control. While they are known to originate from agranular frontal areas, the underlying microcircuit mechanisms remain elusive. Most insights about microcircuit function have been derived from variations of the so-called canonical microcircuit model. These microcircuit architectures are based extensively on studies from granular sensory cortical areas in monkeys, cats, and rodents. However, evidence has shown striking cytoarchitectonic differences across species and differences in the functional relationships across cortical layers in agranular compared to granular sensory areas. In this minireview, we outline a tentative microcircuit model underlying cognitive control in the agranular frontal cortex of primates. The model incorporates the main GABAergic interneuron subclasses with specific laminar arrangements and target regions on pyramidal cells. We emphasize the role of layer 5 pyramidal cells in error and conflict detection. We offer several specific questions necessary for creating a specific intrinsic microcircuit model of the agranular frontal cortex.

The Nursing Inter Shift Handover: A Moment of Care for Patients and Their Family Caregivers.

Precedents: The transfer between nursing shifts must guarantee the quality of care for patients and their families in the hospital. This study aimed to transform the handover between nursing shifts to strengthen the care capacity of patients and their family caregivers, and improve the care capacity of nursing staff, in a Latin American university hospital. Methods: This is a Nursing Methodology Research developed in the following phases: (a) identification of the best handover practices between nursing shifts to apply them within the institutional culture; (2) diagnosis of the transfer between shifts in the hospital; (3) design and validation of the transformation proposal; (4) measurement of transfer indicators; and (5) definition of a path to improve this transfer. Results: The proposal developed focuses on the patient and their family caregiver. The proposed protocol considered the perspective of the care recipients, the nursing staff, and the best available evidence. The overall transfer rating over 10 months went from 65% to 84%. Conclusions: The adjustment to the transfer process made it possible to strengthen the care capacity of patients and their family caregivers and improve the care capacity of the nursing staff.

The S-REAL study: Spanish real-world data on unresectable stage III NSCLC patients treated with durvalumab after chemoradiotherapy.

OBJECTIVES: The S-REAL study aimed to assess the effectiveness of durvalumab as consolidation therapy after definitive chemoradiotherapy (CRT) in a real-world cohort of patients with locally advanced, unresectable stage III non-small cell lung cancer (LA-NSCLC) included in a Spanish early access program (EAP). METHODS: In this multicentre, observational, retrospective study we analysed data from patients treated in 39 Spanish hospitals, who started intravenous durvalumab (10 mg/kg every 2 weeks) between September 2017 and December 2018. The primary endpoint was progression-free survival (PFS). Secondary endpoints included patient characterization and adverse events of special interest (AESI). RESULTS: A total of 244 patients were followed up for a median of 21.9 months [range 1.2-34.7]. Median duration of durvalumab was 45.5 weeks (11.4 months) [0-145]. Median PFS was 16.7 months (95% CI 12.2-25). No remarkable differences in PFS were observed between patients with programmed cell death-ligand 1 (PD-L1) expression ≥ 1% or < 1% (16.7 versus 15.6 months, respectively). However, PFS was higher in patients who had received prior concurrent CRT (cCRT) versus sequential CRT (sCRT) (20.6 versus 9.4 months). AESIs leading to durvalumab discontinuation were registered in 11.1% of patients. CONCLUSIONS: These results are in line with prior published evidence and confirm the benefits of durvalumab in the treatment of LA-NSCLC patients in a real-world setting. We also observed a lower incidence of important treatment-associated toxicities, such as pneumonitis, compared with the pivotal phase III PACIFIC clinical study.

Development of a Professional Practice Nursing Model for a University Nursing School and Teaching Hospital: A nursing methodology research.

AIM: The aim of the study was to describe the process of developing a Professional Practice Model by a Nursing School and Nursing Department of University Hospital. DESIGN AND METHOD (S): This is a descriptive nursing methodology research, developed along three stages: preliminary, empirical and validation. The empirical phase used qualitative and quantitative methodology. 28 teachers from the nursing school and nurses from the hospital participated. We defined the elements of the nursing meta-paradigm from narratives and focus group. Then, we extracted propositions regarding the nature of nursing from the relationship between the meta-paradigm elements, which concluded in the core elements. RESULTS: The core elements of this nursing professional practice model are nursing seeks the well-being of the person, family or group; nursing is total and global, person-centred; nursing is compassionate; nursing entails up-to-date, quality scientific, technical and human competencies; nursing is delivered in a teaching hospital environment, with a Christian ethical perspective.

Effects of the discharge plan on the caregiving load of people with chronic disease: Quasi-experimental study.

OBJECTIVE: To determine the effect of an anticipated care plan, structured around hospital discharge (PC-AH-US), regarding the caregiving load of people with NTCD residing in Colombia, 2019-2021. METHOD: This is a quasi-experimental study with pre- and post-intervention measurements. It includes 1170 participants who represented 585 chronic disease patient-caregiver pairs. We compared the PC-AH-US intervention, to the regular intervention. RESULTS: The PC-AH-US intervention group showed better results in all dimensions when compared to the regular intervention group: Awareness 8.7 (SD: 0.7) and 6.8 (SD: 1.7); Acknowledgement of their unique conditions 11.3 (SD: 1.0) and 9.4 (SD: 1.8); Capacity to fulfill care tasks 8.8 (SD: 0.7) and 7.5 (SD: 1.5); Wellbeing 11.4 (SD: 0.90) and 8.87 (SD: 2.3); Anticipation 5.88 (SD: 0.4) and 4.7 (SD: 1.1) and Support Network 11.4 (SD: 0.8) and 9.9 (SD: 2.5). CONCLUSION: The PC-AH-US intervention group showed a statistically significant decrease in the caregiving load for people with NTCD (p < 00). There were no significant institutional differences in readmissions or deaths. The PC-AH-US intervention backs institutional policies meant to care for people with NTCD.

Nutritional Care for Institutionalized Persons with Dementia: An Integrative Review.

BACKGROUND: Older people are at risk of malnutrition, especially when they suffer from cognitive impairment. Guidelines that orient nursing care in this regard need to be updated. The aim of this review is to address the best available evidence on interventions that can benefit nutritional nursing care for institutionalized older adults with dementia. METHODS: Integrative review using the Dimensions and Eureka search engines, and the PubMed, Embase, Scielo, CINAHL, and ScienceDirect databases. We searched from the year 2015 through to 2021. We employed the MMAT guidelines for mixed, qualitative, and quantitative studies, and the PRISMA, CASP, and JBI guidelines to value the reviews. RESULTS: A total of 55 studies met the inclusion criteria. The best available evidence to support nutritional nursing care for institutionalized older adults with dementia highlights several aspects related to the assessment and caring interventions that are focused on people with dementia, their caregivers, and their context. CONCLUSIONS: Both the assessment and nutritional care interventions for older people with dementia should consider the patient-caregiver dyad as the subject of care and understand the context as a fundamental part of it. The analysis of the context should look further than the immediate environment.

Optimization and In Vitro Digestion of a Guava (Psidium guajava), Mamey (Pouteria sapota) and Stevia (Stevia rebaudiana) Functional Beverage.

Guava and mamey are phenolic- and carotenoid-rich fruits with potential health benefits, but are minimally used as ingredients in functional beverages. The objectives of the present work are to optimize the content of guava and mamey pulps and a stevia solution in the formulation of a functional beverage with high content of bioactive compounds and sensory acceptability using a mixture design analysis, and to analyze its composition after in vitro digestion. The optimized formulation (17.77 and 19.23 g of guava and mamey pulps, respectively; 1% stevia solution) yielded a beverage with 418.21 mg gallic acid equivalents (GAE)/100 mL and 0.20 mg ß-carotene/100 mL, and an antioxidant capacity of 213.58, 78.90 and 234.03 mg Trolox equivalents (TE)/100 mL using three methodologies. The mathematical model developed was significant (p < 0.05), according to R2 values between 0.70 and 0.75. α- and ß-carotene were quantified during the oral phase of in vitro digestion. Gallic, p-coumaric, ferulic and chlorogenic acids were also identified. The beverage had a general acceptability of 6.72. We conclude that the mathematical model developed was a good predictor of the experimental data and that the optimized beverage contained high bioactive concentrations (phenolics and carotenoids) and was well-accepted by potential consumers.

Maternal diet in pregnancy and acute leukemia in infants: a case-control study in Mexico City.

Introduction: Epidemiological studies around the world on acute leukemia (AL) and risk factors in infants are scarce. Infant AL has been proposed to originate in utero, which facilitates its study by establishing a short exposure time in pregnant women to environmental and dietary factors that could contribute to the risk of or protection against leukemia. We hypothesized that maternal diet during pregnancy may be an important factor involved in AL in offspring. Methods: We conducted a hospital-based case-control study from 2010 to 2019 on maternal diet during pregnancy in nine high-specialty public hospitals of different health institutions that diagnose and offer treatment to children with AL in Mexico City. Cases (n=109) were children ≤24 months of age with de novo diagnosis of AL, and controls (n=252) were children obtained in hospitals from second-level medical care matched for age, sex, and health institution. Maternal diet during pregnancy was obtained by a semiquantitative food frequency questionnaire. Unconditional logistic regression models were used to assess the association between food groups and infant AL. Potential confounders were assessed by constructing directed acyclic graphs (DAGs) with Dagitty software in which adjusted options were identified for the construction of unconditional logistic regression models. Results: Cases were slightly predominantly female (52.3%). The years of education of the mother in cases and controls was 0-9 on average, and those who reported smoking cigarettes and consuming alcohol during pregnancy did so at a low frequency. Regarding the mother's diet, the main findings were that the consumption of allium vegetables during pregnancy was inversely associated with AL for medium and high consumption (OR=0.26, 95% CI 0.14-0.46; P-trend< 0.001). In contrast, the high consumption of high-fat dairy products had a positive association with AL (OR=2.37, 95% CI 1.30-4.34; P-trend<0.001). No association was found between consumption of topoisomerase II inhibitor foods during pregnancy and AL. Conclusion: The results suggest that maternal intake during pregnancy of allium vegetables, specifically garlic, is inversely associated with the development of AL in children ≤24 months old. On the other hand, consumption of high-fat dairy products is positively associated with AL in children ≤24 months old.

Preliminary Effectiveness of a Strategy to Promote Healthy Lifestyle Habits in Schoolchildren.

PURPOSE: To measure the preliminary effectiveness of a strategy to promote healthy lifestyle habits in schoolchildren, aged 6 to 12 years, living in the Andean region of Colombia, 2018-2021. DESIGN AND METHODS: This is a Nursing Methodological Research, developed in phases: (1) Context and schoolchildren characterization; (2) Strategy design guided by the Whittemore and Grey criteria and the Bronfenbrenner ecological conceptual model; (3) Strategy validation with 11 experts; (4) Trial to evaluate preliminary effectiveness. We applied the strategy in seven different schools with the educational community including 955 schoolchildren between 6 and 12 years of age, 551 parents, 130 teachers and 7 members of the food staff. RESULTS: Our health promotion strategy "Prosalud" has five components: citizenship feeding and nutrition, physical activity, and rest; environment protection, and directing one's own life. It includes all the participants of the educational community. CONCLUSIONS: According to experts, the health promotion strategy "Prosalud" is valid to help promoting healthy lifestyle habits among schoolchildren. This strategy demonstrates its preliminary effectiveness in a group of school children from 6 to 12 years of age, their parents, teachers, and school food staff, in the Andean region of Colombia.