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Importance: Although many hospitals universally screen their patients for functional mobility and activity impairment, there is no common method to do this for cognitive impairment. Establishing an interdisciplinary and standardized process to screen for cognitive impairment is essential for early identification of impairments, optimization of patients' function, and safe discharge planning. Previously, the reliability and validity of the Activity Measure for Post-Acute Care Applied Cognitive Inpatient Short Form "6-Clicks" (AM-PAC ACISF) were measured among occupational therapy practitioners and speech-language pathologists; however, its reliability among other team members, specifically nurses, is unknown. This study reports the interprofessional interrater reliability of the AM-PAC ACISF in the acute care hospital setting., Objective: To examine the nursing-therapist interrater reliability of the AM-PAC ACISF in the acute care hospital setting., Design: A prospective study using a convenience sample., Setting: Acute care hospital., Participants: Fifty adult patients, six nurses, five occupational therapy practitioners, and one speech-language pathologist., Outcomes and Measures: Interrater reliability for the AM-PAC ACISF among therapists and nurses., Results: Interrater reliability was good among nurses and therapists, with an intraclass correlation coefficient of .88 (95% confidence interval [.79, .93]) for the AM-PAC ACISF., Conclusions and Relevance: Findings suggest that the AM-PAC ACISF is reliable for use among interdisciplinary teams, helps to establish a common language for early identification of cognitive impairment, and can be used for guiding clinical discussions around patient cognition in the acute care setting. Plain-Language Summary: Having an interdisciplinary and standardized process to screen patients early for cognitive impairment is essential for identifying impairments, optimizing patients' function, and facilitating safe discharge planning in the acute care setting. Early identification of cognitive impairment by the interdisciplinary team can also allow for timely occupational therapy and other rehabilitation service interventions. The findings of this study suggest that the Activity Measure for Post-Acute Care Applied Cognitive Inpatient Short Form "6-Clicks" (AM-PAC ACISF) can reliably be used by interdisciplinary teams, establishes a common language for early identification of cognitive impairment, and can be used for guiding clinical discussions around patient cognition in the acute care setting., (Copyright © 2024 by the American Occupational Therapy Association, Inc.)

Background: Promoting safe patient mobility for providers and patients is a safety priority in the hospital setting. Safe patient handling equipment aids safe mobility but can also deter active movement by the patient if used inappropriately. Nurses need guidance to choose equipment that ensures their safety and that of the patients while promoting active mobility and preventing workplace-related injury., Methods: Using a modified Delphi approach with a diverse group of experts, we created the Johns Hopkins Safe Patient Handling Mobility (JH-SPHM) Guide. This diverse group of 10 experts consisted of nurses, nurse leaders, physical and occupational therapists, safe patient handling committee representatives, and a fall prevention committee leader. The application of the tool was then tested in the hospital environment by two physical therapists., Findings: Consensus was reached for safe patient handling (SPH) equipment recommendations at each level of the Johns Hopkins Mobility Goal Calculator (JH-Mobility Goal Calculator). Expert SPH equipment recommendations were then added to JH-Mobility Goal Calculator levels to create the JH-Safe Patient Handling Mobility Guide. JH-Safe Patient Handling Mobility Guide equipment suggestions were compared with equipment recommendations from physical therapists revealing strong agreement ( n = 125, 88%)., Conclusion: The newly created JH-Safe Patient Handling Mobility Guide provides appropriate safe patient-handling equipment recommendations to help accomplish patients' daily mobility goals., Applications to Practice: The Johns Hopkins Safe Patient Handling Mobility Guide simultaneously facilitates patient mobility and optimizes safety for nursing staff through recommendations for safe patient handling equipment for use with hospitalized patients., Competing Interests: Conflict of InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Given the stigma of falls while hospitalized, inpatient rehabilitation facilities often restrict the independent room mobility of their patients. We assessed the psychometric properties of a new tool, the Johns Hopkins In-Room Independence Scale, to evaluate its effectiveness at identifying independence for in-room mobility., Design: Construct validity was assessed by comparing the Johns Hopkins In-Room Independence Scale to its "gold standard" counterparts, The Johns Hopkins Falls Risk Assessment Tool, the Activity Measure for Post-Acute Care Mobility and Activity, and the Centers for Medicare Quality Indicators. Reliability was assessed via Cronbach α., Results: One hundred ninety-seven episodes were included. In construct validity, the Johns Hopkins In-Room Independence Scale had significantly negative low correlation to the Johns Hopkins Falls Risk Assessment Tool (Spearman ρ = -0.281), and a significant moderate correlation to the Activity Measure for Post-Acute Care Activity and Activity Measure for Post-Acute Care Mobility (Spearman ρ =0.678 and 0.530, respectively). The Johns Hopkins In-Room Independence Scale was moderately positively correlated to the quality indicators for mobility and activity (Spearman ρ = 0.577 and 0.643, respectively). All two-tailed, α levels were 0.01. The Johns Hopkins In-Room Independence Scale reliability was strong (Cronbach α = 0.822, 15 items). Sensitivity and specificity were both 100%., Conclusions: Given the moderate validity, strong reliability, and high sensitivity/specificity, our study suggests that the Johns Hopkins In-Room Independence Scale be used to identify patients who have the capacity to mobilize independently in their room., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Falls are one of the most common adverse events in hospitals, and patient mobility is a key risk factor. In hospitals, risk assessment tools are used to identify patient-centered fall risk factors and guide care plans, but these tools have limitations. To address these issues, we examined daily patient mobility levels before injurious falls using the Johns Hopkins Highest Level of Mobility, which quantifies key patient mobility milestones from low-level to community distances of walking. We aimed to identify longitudinal characteristics of patient mobility before a fall to help identify fallers before the event. Conducting a retrospective matched case-control analysis, we compared mobility levels in the days leading up to an injurious fall between fallers and nonfallers. We observed that patients who experienced an injurious fall, on average, spent 28% of their time prefall at a low mobility level (Johns Hopkins Highest Level of Mobility levels 1-4), compared with nonfallers who spent 19% of their time at a low mobility level (mean absolute difference, 9%; 95% confidence interval, 1%-16%; P = 0.026; relative difference, 44%). This suggests that assessing a patient's mobility levels over time can help identify those at an increased risk for falls and enable hospitals to manage mobility problems more effectively., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Staff injuries adversely affect the health of staff members as well the ability of health care teams to effectively care for patients. Identifying patients who pose an increased risk of injury may allow for the planning of risk mitigation strategies, but few studies have examined patient factors associated with staff injury risk., Aims: Examine the relationship between staff injury and patient mobility, which has been linked to other key hospital outcomes., Methods: Linking occupational health and electronic medical record data, we examined documented patient mobility levels, based on the Activity Measure for Post-Acute Care (AM-PAC) and the Johns Hopkins Highest Level of Mobility (JH-HLM) Scale, on the day prior to injury. In addition, we created a matched cohort of control patients not associated with staff injury to examine the influence of patient mobility on the odds of staff injury., Results: We identified 199 staff injuries associated with 181 patients with 1063 matched controls. Patients had median scores of 11 and 3 on the AM-PAC and JH-HLM, respectively, indicating moderate-severe mobility impairments. In addition, scores in the lowest AM-PAC tertile (6-15) and lowest JH-HLM tertile (1-4) were associated with a 4.46-fold and 2.90-fold increase in the odds of nurse injury, respectively., Conclusions: These results indicate that moderate-severe mobility impairments are associated with increased risk of nurse injury. Hospitals and clinical care teams should consider documenting mobility routinely and utilizing these values to identify patients who pose an increased risk of nurse injury., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Importance: Assessing patients' activities of daily living (ADLs) function early in hospitalization may help identify patients at risk for poor outcomes., Objective: To investigate the association between patients' ADL function at hospital admission and length of stay, inpatient falls, hospital-acquired pressure injuries, and discharge disposition., Design: Retrospective cohort study using scores collected on the Activity Measure for Post-Acute Care Inpatient Activity Short Form (AM-PAC IASF) in routine care at admission., Setting: Two inpatient units at the Johns Hopkins Hospital., Participants: Hospitalized patients with various diagnoses, including neurosurgical, stroke, and general neurology (N = 1,899)., Results: People with lower AM-PAC scores (every 10-point difference) had increased odds (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.4-1.8) of being in the highest length-of-stay quartile (≥8 days), having an injurious fall (OR = 1.7; 95% CI = 1.3-2.2), acquiring a pressure injury (OR = 2.7; 95% CI = 1.5-5.3), and being discharged to a postacute care facility (OR = 3.02; 95% CI = 2.1-2.7)., Conclusions and Relevance: Greater functional impairments in ADLs, measured with the AM-PACS IASF, were significantly associated with worse outcomes. AM-PAC IASF scores may be useful in identifying patients with ADL deficits and targeting occupational therapy services for patients who are at higher risk for negative outcomes. What This Article Adds: Early assessment of ADL function in routine care of hospitalized patients may aid in treatment and care plan decisions, particularly for inpatients who may be at higher risk for adverse outcomes., (Copyright © 2023 by the American Occupational Therapy Association, Inc.)

Bacteria have evolved different systems to sense and adapt to acid stress. For example, Vibrio campbellii, a marine pathogen for invertebrates, encounters acidic conditions in the digestive glands of shrimp. The main acid resistance system of V. campbellii is the Cad system, which is activated when cells are in a low-pH, amino acid-rich environment. The Cad system consists of the pH-responsive transcriptional activator CadC, the lysine decarboxylase CadA, and the lysine/cadaverine antiporter CadB. In many Vibrio species, the LysR-type transcriptional regulator AphB is involved in the regulation of the Cad system, but its precise role is unclear. Here, we examined AphB of V. campbellii in vivo and in vitro in the context of Cad activation. At low pH, an aphB deletion mutant was less able to grow and survive compared with the wild-type because it did not excrete sufficient alkaline cadaverine to increase the extracellular pH. AphB was found to upregulate the transcription of cadC, thereby increasing its protein copy number per cell. Moreover, AphB itself was shown to be a pH-sensor, and binding to the cadC promoter increased under low pH, as shown by surface plasmon resonance spectroscopy. By monitoring the activation of the Cad system over a wide range of pH values, we found that AphB-mediated upregulation of cadC not only adjusts CadC copy numbers depending on acid stress strength, but also affects the response of individual cells and thus the degree of heterogeneous Cad system activation in the V. campbellii population. IMPORTANCE Acid resistance is an important property not only for neutralophilic enteric bacteria such as Escherichia, Yersinia , and Salmonella, but also for Vibrio . To counteract acidic threats, the marine Vibrio campbellii, a pathogen for various invertebrates, activates the acid-resistance Cad system. The transcriptional activator of the Cad system is CadC, an extracellular pH-sensor. The expression of cadC is upregulated by the transcriptional regulator AphB to achieve maximum expression of the components of the Cad system. In vitro studies demonstrate that AphB binds more tightly to the DNA under low pH. The interplay of two pH-responsive transcriptional activators allows tight control of the activity of the Cad system.

Background: Bedrest is toxic for inpatients and consumer grade physical activity monitors offer an economical solution to monitor patient ambulation. But these devices may not be accurate in debilitated hospitalized patients who frequently ambulate very slowly., Objective: To determine whether measures of physical capacity can help identify inpatients for whom wearable physical activity monitors may accurately measure step count., Methods: Prospective observational study of 54 adult inpatients with acute neurological diagnoses. Patients were assessed using 2 physical capacity assessments (Activity Measure for Post-Acute Care Inpatient Mobility Short Form [AM-PAC IMSF] and Katz Activities of Daily Living [ADL] scale). They also completed a 2-minute walk test (2MWT) wearing a consumer grade physical activity monitor., Results: The wearable activity monitor recorded steps (initiated) in 33 (61%) of the inpatients, and for 94% of inpatients with gait speeds >0.43 m/s. Physical capacity assessments correlated well with gait speed, AM-PAC IMSF r = 0.7, and Katz ADL r = 0.6, p < 0.05. When the physical activity monitor initiated, the mean absolute percent error (SD) comparing device calculated steps to observed steps, was 10% (13). AM-PAC IMSF (T-score >45) and Katz ADL (>5) cutoff scores identified inpatients for whom physical activity monitors initiated with a sensitivity of 94 and 91%, respectively., Conclusions: Physical capacity assessments, such as AM-PAC, and Katz ADL, may be a useful and feasible screening strategy to help identify inpatients where wearable physical activity monitors can measure their mobility., Competing Interests: Conflicts of interest None., (Copyright © 2022 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Hospitalized patients often experience unnecessary immobility and inactivity leading to direct harms and poor outcomes. Despite growing evidence that early and regular mobility and activity are safe and helpful for patients in the hospital, there remains substantial room for improvement in clinical practice. Key to improvement is establishing an interdisciplinary approach to measurement and communication using a common language of function. Here we provide a framework for systematic functional measurement in the hospital. We also provide 3 specific examples of how this framework has been used to improve care: (1) targeting specialized rehabilitation providers to the patients most likely to need their services, (2) generating a daily mobility goal for all patients, and (3) identifying patients early who are likely to require postacute care., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

SignificanceHost-emitted stress hormones significantly influence the growth and behavior of various bacterial species; however, their cellular targets have so far remained elusive. Here, we used customized probes and quantitative proteomics to identify the target of epinephrine and the α-adrenoceptor agonist phenylephrine in live cells of the aquatic pathogen Vibrio campbellii . Consequently, we have discovered the coupling protein CheW, which is in the center of the chemotaxis signaling network, as a target of both molecules. We not only demonstrate direct ligand binding to CheW but also elucidate how this affects chemotactic control. These findings are pivotal for further research on hormone-specific effects on bacterial behavior.

Background: The Johns Hopkins Highest Level of Mobility (JH-HLM) scale is used to document the observed mobility of hospitalized patients, including those patients in the intensive care unit (ICU) setting., Objective: To evaluate the inter-rater reliability of the JH-HLM, completed by physical therapists, across medical, surgical, and neurological adult ICUs at a single large academic hospital., Methods: The JH-HLM is an ordinal scale for documenting a patient's highest observed level of activity, ranging from lying in bed (score = 1) to ambulating >250 feet (score = 8). Eighty-one rehabilitation sessions were conducted by eight physical therapists, with 1 of 2 reference physical therapist rater simultaneously observing the session and independently scoring the JH-HLM. The intraclass correlation coefficient was used to determine the inter-rater reliability., Results: A total of 77 (95%) of 81 assessments had perfect agreement. The overall intraclass correlation coefficient for inter-rater reliability was 0.98 (95% confidence interval: 0.96, 0.99), with similar scores in the medical, surgical, and neurological ICUs. A Bland-Altman plot revealed a mean difference in JH-HLM scoring of 0 (limits of agreement: -0.54 to 0.61)., Conclusion: The JH-HLM has excellent inter-rater reliability as part of routine physical therapy practice, across different types of adult ICUs., (Copyright © 2020 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Membrane proteins account for about one third of the cellular proteome, but it is still unclear how dynamic they are and how they establish functional contacts with cytoplasmic interaction partners. Here, we consider a membrane-integrated one-component receptor that also acts as a transcriptional activator, and analyze how it kinetically locates its specific binding site on the genome. We focus on the case of CadC, the pH receptor of the acid stress response Cad system in E. coli. CadC is a prime example of a one-component signaling protein that directly binds to its cognate target site on the chromosome to regulate transcription. We combined fluorescence microscopy experiments, mathematical analysis, and kinetic Monte Carlo simulations to probe this target search process. Using fluorescently labeled CadC, we measured the time from activation of the receptor until successful binding to the DNA in single cells, exploiting that stable receptor-DNA complexes are visible as fluorescent spots. Our experimental data indicate that CadC is highly mobile in the membrane and finds its target by a 2D diffusion and capture mechanism. DNA mobility is constrained due to the overall chromosome organization, but a labeled DNA locus in the vicinity of the target site appears sufficiently mobile to randomly come close to the membrane. Relocation of the DNA target site to a distant position on the chromosome had almost no effect on the mean search time, which was between four and five minutes in either case. However, a mutant strain with two binding sites displayed a mean search time that was reduced by about a factor of two. This behavior is consistent with simulations of a coarse-grained lattice model for the coupled dynamics of DNA within a cell volume and proteins on its surface. The model also rationalizes the experimentally determined distribution of search times. Overall our findings reveal that DNA target search does not present a much bigger kinetic challenge for membrane-integrated proteins than for cytoplasmic proteins. More generally, diffusion and capture mechanisms may be sufficient for bacterial membrane proteins to establish functional contacts with cytoplasmic targets., Competing Interests: The authors have declared that no competing interests exist.

Transgenic coexpression of a class I-restricted tumor antigen-specific T cell receptor (TCR) and CD8αβ (TCR8) redirects antigen specificity of CD4 + T cells. Reinforcement of biophysical properties and early TCR signaling explain how redirected CD4 + T cells recognize target cells, but the transcriptional basis for their acquired antitumor function remains elusive. We, therefore, interrogated redirected human CD4 + and CD8 + T cells by single-cell RNA sequencing and characterized them experimentally in bulk and single-cell assays and a mouse xenograft model. TCR8 expression enhanced CD8 + T cell function and preserved less differentiated CD4 + and CD8 + T cells after tumor challenge. TCR8 + CD4 + T cells were most potent by activating multiple transcriptional programs associated with enhanced antitumor function. We found sustained activation of cytotoxicity, costimulation, oxidative phosphorylation- and proliferation-related genes, and simultaneously reduced differentiation and exhaustion. Our study identifies molecular features of TCR8 expression that can guide the development of enhanced immunotherapies., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Objective: To expand an existing validated measure of basic mobility (Activity Measure for Post-Acute Care [AM-PAC]) for patients at the lowest levels of function., Design: Item replenishment for existing item response theory (IRT) derived measure via (1) idea generation and creation of potential new items, (2) item calibration and field testing, and (3) longitudinal pilot test., Setting: Two tertiary acute care hospitals., Participants: Consecutive inpatients (N=502) ≥18 years old, with an AM-PAC Inpatient Mobility Short Form (IMSF) raw score ≤15. For the longitudinal pilot test, 8 inpatients were evaluated., Results: Fifteen new AM-PAC items were developed, 2 of which improved mobility measurement at the lower levels of functioning. Specifically, with the 2 new items, the floor effect of the AM-PAC IMSF was reduced by 19%, statistical power and measurement breadth were greater, and there was greater measurement sensitivity in longitudinal pilot testing., Conclusion: Adding 2 new items to the AM-PAC IMSF lowered the floor and increased statistical power, measurement breadth, and sensitivity., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Bacteria have evolved different signaling systems to sense and adapt to acid stress. One of these systems, the CadABC-system, responds to a combination of low pH and lysine availability. In Escherichia coli, the two signals are sensed by the pH sensor and transcription activator CadC and the co-sensor LysP, a lysine-specific transporter. Activated CadC promotes the transcription of the cadBA operon, which codes for the lysine decarboxylase CadA and the lysine/cadaverine antiporter CadB. The copy number of CadC is controlled translationally. Using a bioinformatics approach, we identified the presence of CadC with ribosomal stalling motifs together with LysP in species of the Enterobacteriaceae family. In contrast, we identified CadC without stalling motifs in species of the Vibrionaceae family, but the LysP co-sensor was not identified. Therefore, we compared the output of the Cad system in single cells of the distantly related organisms E. coli and V. campbellii using fluorescently-tagged CadB as the reporter. We observed a heterogeneous output in E. coli, and all the V. campbellii cells produced CadB. The copy number of the pH sensor CadC in E. coli was extremely low (≤4 molecules per cell), but it was 10-fold higher in V. campbellii An increase in the CadC copy number in E. coli correlated with a decrease in heterogeneous behavior. This study demonstrated how small changes in the design of a signaling system allow a homogeneous output and, thus, adaptation of Vibrio species that rely on the CadABC-system as the only acid resistance system. Importance Acid resistance is an important property of bacteria, such as Escherichia coli , to survive acidic environments like the human gastrointestinal tract. E. coli possess both passive and inducible acid resistance systems to counteract acidic environments. Thus, E. coli evolved sophisticated signaling systems to sense and appropriately respond to environmental acidic stress by regulating the activity of its three inducible acid resistance systems. One of these systems is the Cad system that is only induced under moderate acidic stress in a lysine-rich environment by the pH-responsive transcriptional regulator CadC. The significance of our research is in identifying the molecular design of the Cad systems in different Proteobacteria and their target expression noise at single cell level during acid stress conditions., (Copyright © 2020 American Society for Microbiology.)

Importance: Promoting patient mobility during hospitalization is associated with improved outcomes and reduced risk of hospitalization-associated functional decline. Therefore, accurate measurement of mobility with high-information content data may be key to improved risk prediction models, identification of at-risk patients, and the development of interventions to improve outcomes. Remote monitoring enables measurement of multiple ambulation metrics incorporating both distance and speed., Objective: To evaluate novel ambulation metrics in predicting 30-day readmission rates, discharge location, and length of stay using a real-time location system to continuously monitor the voluntary ambulations of postoperative cardiac surgery patients., Design, Setting, and Participants: This prognostic cohort study of the mobility of 100 patients after cardiac surgery in a progressive care unit at Johns Hopkins Hospital was performed using a real-time location system. Enrollment occurred between August 29, 2016, and April 4, 2018. Data analysis was performed from June 2018 to December 2019., Main Outcomes and Measures: Outcome measures included 30-day readmission, discharge location, and length of stay. Digital records of all voluntary ambulations were created where each ambulation consisted of multiple segments defined by distance and speed. Ambulation profiles consisted of 19 parameters derived from the digital ambulation records., Results: A total of 100 patients (81 men [81%]; mean [SD] age, 63.1 [11.6] years) were evaluated. Distance and speed were recorded for more than 14 000 segments in 840 voluntary ambulations, corresponding to a total of 127.8 km (79.4 miles) using a real-time location system. Patient ambulation profiles were predictive of 30-day readmission (sensitivity, 86.7%; specificity, 88.2%; C statistic, 0.925 [95% CI, 0.836-1.000]), discharge to acute rehabilitation (sensitivity, 84.6%; specificity, 86.4%; C statistic, 0.930 [95% CI, 0.855-1.000]), and length of stay (correlation coefficient, 0.927)., Conclusions and Relevance: Remote monitoring provides a high-information content description of mobility, incorporating elements of step count (ambulation distance and related parameters), gait speed (ambulation speed and related parameters), frequency of ambulation, and changes in parameters on successive ambulations. Ambulation profiles incorporating multiple aspects of mobility enables accurate prediction of clinically relevant outcomes.

A complex relationship exists between environmental factors, signaling networks and phenotypic individuality in bacteria. In this review, we will focus on the organization, function and control points of multiple-input histidine kinase-based signaling cascades as a source of phenotypic heterogeneity. In particular, we will examine the quorum sensing cascade in Vibrio harveyi and the pyruvate sensor network in Escherichia coli. We will describe and compare these histidine kinase-based signaling networks in terms of robustness, the molecular mechanisms of signal transduction and the role of RNA switches. Finally, we will discuss the biological significance of phenotypic heterogeneity for the respective bacteria in relation to environmental factors., (Copyright © 2019. Published by Elsevier Ltd.)

Postpartum depression (PPD) is a common but complex condition that is poorly understood and multifactorial in aetiology. It is a condition that can compromise the mother's care for her infant, which may pose challenges to the formation of the mother-infant bond and the infant's overall development. Past research has looked at abnormalities in the brain circuitry and hormonal profiles of mothers with PPD compared to non-depressed mothers. However, abnormalities in PPD that may specifically affect the mother's care of her infant have not been clearly assessed. Thus, the present review aims to synthesise studies of altered brain and hormonal responses in mothers with PPD in relation to their care of their infant. First, we review maternal brain responses and their relation to PPD symptomatology, focusing on the salience/fear network, reward/attachment network and default mode network. Next, we discuss oxytocin and hypothalamic-pituitary-adrenal axis hormones in the context of maternal behaviour and PPD. Finally, we synthesise these findings and propose how future studies may benefit from the combined study of both neural and hormonal activity to better understand the underlying neurobiology of maternal care in PPD., (© 2019 British Society for Neuroendocrinology.)

Strains of the Gram-negative bacterium Vibrio coralliilyticus cause the bleaching of corals due to decomposition of symbiotic microalgae. The V. coralliilyticus strain ATCC BAA-450 (Vc450) encodes a type III secretion system (T3SS). The gene cluster also encodes a protein (locus tag VIC&#95;001052) with sequence homology to the T3SS-secreted nodulation proteins NopE1 and NopE2 of Bradyrhizobium japonicum (USDA110). VIC&#95;001052 has been shown to undergo auto-cleavage in the presence of Ca 2+ similar to the NopE proteins. We have studied the hitherto unknown secondary structure, Ca 2+ -binding affinity and stoichiometry of the "metal ion-inducible autocleavage" (MIIA) domain of VIC&#95;001052 which does not possess a classical Ca 2+ -binding motif. CD and fluorescence spectroscopy revealed that the MIIA domain is largely intrinsically disordered. Binding of Ca 2+ and other di- and trivalent cations induced secondary structure and hydrophobic packing after partial neutralization of the highly negatively charged MIIA domain. Mass spectrometry and isothermal titration calorimetry showed two Ca 2+ -binding sites which promote structure formation with a total binding enthalpy of -110 kJ mol -1 at a low micromolar K d . Putative binding motifs were identified by sequence similarity to EF-hand domains and their structure analyzed by molecular dynamics simulations. The stoichiometric Ca 2+ -dependent induction of structure correlated with catalytic activity and may provide a "host-sensing" mechanism that is shared among pathogens that use a T3SS for efficient secretion of disordered proteins.

All living cells have a large number of proteins that are anchored with one transmembrane helix in the cytoplasmic membrane. Almost nothing is known about their spatiotemporal organization in whole cells. Here we report on the localization and dynamics of one representative, the pH sensor and transcriptional regulator CadC in Escherichia coli . Fluorophore-tagged CadC was detectable as distinct cluster only when the receptor was activated by external stress, which results in DNA-binding. Clusters immediately disappeared under non-stress conditions. CadC variants that mimic the active state of CadC independent of environmental stimuli corroborated the correlation between CadC clustering and binding to the DNA, as did altering the number or location of the DNA-binding site(s) in whole cells. These studies reveal a novel diffusion-and-capture mechanism to organize a membrane-integrated receptor dependent on the DNA in a rod-shaped bacterium., Competing Interests: The authors declare no competing interests.

Background: Hospital-level studies have found an inverse relationship between patient experience and readmissions. However, based on typical survey response time, it is unclear if patients are able to respond to surveys before they get readmitted and whether being readmitted might be a driver of poor experience scores (reverse causation)., Objective: Using patient-level Hospital Consumer Assessment of Healthcare Providers and Systems (HCHAPS) and Press Ganey data to examine the relationship between readmissions and experience scores and to distinguish between patients who responded before or after a subsequent readmission., Design: Retrospective analysis of 10-year HCAHPS data., Setting: Single tertiary care academic hospital., Participants: Patients readmitted within 30 days of an index hospitalization who received an HCAHPS survey linked to index admission comprised the exposure group. This group was divided into those who responded prior to readmission and those who responded after readmission. Nonreadmitted patients comprised the control group., Analysis: Multivariable-logistic regression to analyze the association between HCHAPS and Press Ganey scores and 30-readmission status, adjusted for patient factors., Results: Only 15.8% of the readmitted patients responded to the survey prior to readmission, and their scores were not significantly different from the nonreadmitted patients. The patients who responded after readmission were significantly more dissatisfied with physicians (doctors listened 73.0% vs 79.2%, aOR 0.75, P < .0001), staff responsiveness, (call button 50.0% vs 59.1%, aOR 0.71, P < .0001) pain control, discharge plan, noise, and cleanliness of the hospital., Conclusions: Our findings suggest that poor patient experience may be due to being readmitted, rather than being predictive of readmission., (© 2018 Society of Hospital Medicine.)

Every living cell possesses numerous transmembrane signalling systems that receive chemical and physical stimuli from the environment and transduce this information into an intracellular signal that triggers some form of cellular response. As unicellular organisms, bacteria require these systems for survival in rapidly changing environments. The receptors themselves act as 'sensory organs', while subsequent signalling circuits can be regarded as forming a 'neural network' that is involved in decision making, adaptation and ultimately in ensuring survival. Bacteria serve as useful biosensors in industry and clinical diagnostics, in addition to producing drugs for therapeutic purposes. Therefore, there is a great demand for engineered bacterial strains that contain transmembrane signalling systems with high molecular specificity, sensitivity and dose dependency. In this review, we address the complexity of transmembrane signalling systems and discuss principles to rewire receptors and their signalling outputs., (© 2018 The Authors.)

The lack of suitable target vessels remains a challenge for aortocoronary bypass grafting in end-stage coronary heart disease. This study aimed to investigate the arterialization of cardiac veins as an alternative myocardial revascularization strategy in an experimental long-term model in pigs. Selective retrograde perfusion of a coronary vein (aorta to coronary vein bypass, retrobypass) before ligation of the ramus interventricularis paraconalis (equivalent to the left anterior descending artery in humans) was performed in 20 German Landrace pigs (Sus scrofa domestica). Retroperfusion of the left anterior descending vein was performed in 10 pigs (RP+) but not in the other 10 (RP-), and the vena cordis magna was ligated (L+) in 5 pigs in each of these groups but left open (L-) in the remaining animals. Hemodynamic performance (for example, cardiac output) was significantly better in the group that underwent selective retroperfusion with proximal ligation of vena cordis magna (RP+L+; 4.1 L/min) compared with the other groups (RP+L-, 2.5 L/min; RP-L+, 2.2 L/min; RP-L-, 1.9 L/min). Long-term survival was significantly better in RP+L+ pigs (112±16 d) than in all other groups. Histologic follow-up studies showed significantly less necrosis in the RP+L+ group compared with all other groups. Venous retroperfusion is an effective technique to achieve long-term survival after acute occlusion of the left anterior descending artery in a pig model. In this model, proximal ligation of vena cordis magna is essential.

In ischemic hearts, venous retroperfusion is a potential myocardial revascularization strategy. This study aimed to refine the technical and functional aspects of a pig model of acute myocardial infarction and retroperfusion with respect to the azygos connection. Global retroperfusion after ligation of the ramus interventricularis paraconalis (equivalent to the left anterior descending artery in humans) was performed in 16 Landrace pigs (Sus scrofa domestica). Coronary sinus perfusion was performed in 8 pigs (P+) but not in the other 8 (P-), and the azygos vein was ligated (L+) 4 of the 8 pigs in each of these groups but left open (L-) in the remaining animals. Hemodynamic performance (for example, cardiac output, stroke volume) was significantly better in P+L+ pigs that underwent coronary sinus perfusion with ligation of the azygos vein compared with all other animals. In addition, troponin I release was significant lower in P+L+ pigs (1.7 +/- 1.3 ng/mL) than in P-L- (5.47 +/- 2.1 ng/mL), P-L+ (6.63 +/- 2.4 ng/mL), and P+L- (4.81 +/- 2.3 ng/mL) pigs. Effective retrograde flow and thus hemodynamic stability was achieved by ligation of the azygos vein. Therefore, experiments focusing on global retroperfusion will benefit from effective inhibition of the blood flow through the azygos vein.

Background: Interest in fructooligosaccharides as a health-promoting food component is increasing. Fructooligosaccharides are mainly indigestible and large amounts in the colon may provoke gastrointestinal symptoms., Objective: The symptoms of irritable bowel syndrome (IBS) may be provoked by large quantities of carbohydrates in the colon. The objective of this study was to determine whether regular consumption of fructooligosaccharides worsens gastrointestinal symptoms in patients with IBS., Design: A multicenter, prospective, randomized, double-blind, placebo-controlled parallel group comparison was conducted at 24 sites. The study consisted of a 2-wk, single-blind run-in phase and a 12-wk, double-blind comparative phase. Subjects were randomly assigned to receive 20 g fructooligosaccharides powder/d (n = 52) or a placebo (n = 46). Efficacy was based on the patients' overall response to treatment at completion of the study and on the severity and duration of individual symptoms (abdominal distension, abdominal rumbling, abnormal flatulence, and abdominal pain)., Results: Data from 96 patients (16 men and 80 women) were analyzed. After 4-6 wk of treatment, IBS symptoms improved more in the placebo group than in the fructooligosaccharide group. After completion of the study, there were no significant differences between the 2 groups: symptoms improved in 58% of the fructooligosaccharide group and in 65% of the placebo group and symptoms worsened in 8% of the fructooligosaccharide group and in 13% of the placebo group., Conclusion: Although symptoms worsened in patients with IBS at the onset of treatment with 20 g fructooligosaccharides/d, continuous treatment for 12 wk resulted in no worsening of symptoms.

This study investigated maturational changes in children's ability to discriminate the frequency of short-duration tone pulses. Frequency difference limens (DLs) were measured for digitally generated 1000-Hz tones with pulse durations of 200, 50, and 20 ms using a two-alternative, two-interval, forced-choice procedure. Participants were 16 5-year-old children; 10 children each in the age categories of 7, 9, and 11 years; and a control group of 10 young adults. Eleven of the 5-year-old children were unable to learn the experimental task. All children in the three older groups and the adults successfully completed the study. The five 5-year-old children who completed the task performed similarly to the 7-year-old children. All groups of participants showed an inverse relationship between duration of the signal and the size of the DL. The DLs at all three tone durations were significantly larger for the 7-year-old children than they were for the older children and adults. There were no significant differences in DL size among the 9-year-old, 11-year-old, and adult subjects at any tone duration. These findings suggest that the sensory and/or cognitive skills required to discriminate the frequency of brief-duration tones may not reach maturity until after age 7 years.

Objective: To study processing and fermentability in the human gastro-intestinal tract of a newly isolated, enzymatically modified, soluble, and highly concentrated (> 80% dietary fibres) solubilised potato fibre (SPP)., Setting: Gastroenterological laboratory. DESIGN, SUBJECTS AND INTERVENTIONS: Seven healthy volunteers ingested in random order on seven different days: 20 g SPP; bread made of 180 g wheat flour served with 20 g raw SPP; bread baked of 180 g wheat flour and 20 g SPP; bread made from 180 g what flour; 20 g lactulose; 20 g oat bran; and 20 g wheat bran. The hydrogen breath test was used to evaluate oro-coecal transit time (OCTT) and fermentation., Results: Fermentation of SPP yielded a measurable increase in end-expiratory H2. The total incremental increase in end expiratory H2 due to SPP was unaffected of whether SPP was served alone, as the raw flour served with bread, or baked into bread. The OCTT for raw SPP was significantly delayed compared to lactulose (P = 0.01). The OCTT for SPP baked into bread was significantly delayed compared to raw SPP (P = 0.01), indicating that SPP may be used as a marker of oro-coecal transit time for as well the fluid phase as the solid phase of a meal., Conclusions: SPP is a fermentable, highly concentrated soluble fibre source. Baking SPP did not interfere with the fermentable properties. Thus, SPP may be interesting as a fibre-supplement in fibre-poor diets. The change in oro-coecal transit time for SPP, depending on the composition of the total meal, makes SPP interesting as a marker in studies of gastrointestinal transit.

We have investigated the physicochemical and paramagnetic properties of the new gadolinium complexes of N-(pyrid-2-yl-methyl)-ethylenediamine-N,N,N-triacetic acid (Gd-PEDTA) and N-tris(2-aminoethyl)amine-N,N,N,N,N,N+hexaacetic acid(Gd-TTAHA). The relaxivities as well as the thermodynamic and conditional stability constants of these complexes with respect to the physiological relevance were determined and discussed in comparison with the commercially available gadolinium (III) diethylenetriaminpentaacetic acid/gadopentate dimeglumine (Gd-DTPA, Magnevist). In case of Gd-TTAHA a twofold higher relaxivity and a complex stability similar to Gd-DTPA were determined. It is shown, that lower concentrations of Gd-TTAHA are sufficient for the same signal enhancement in the T1-weighted MR image compared with Gd-DTPA and, thus, the use of the new contrast agent Gd-TTAHA should diminish risks for health. Therefore, Gd-TTAHA might be used potentially as a new contrast agent for clinical MRI application.

Twelve children, ranging in age from 8.9 to 12.4 years, with histories of severe otitis media with effusion (OME) before age 3, were compared to age-matched cohorts in their ability to discriminate the frequency of tone pulses of 20-, 50-, and 200-msec duration. An adaptive procedure was used in combination with a two-alternative forced-choice paradigm to measure difference limens (DLs) for digitally generated 1000-Hz tones. The OME group exhibited larger DLs than the non-OME group at all three stimulus durations. These results provide tentative evidence of possible long-term effects of early OME on brief tone frequency discrimination.

Using a unique three-solvent biphasic method, we have prepared and characterized three new fully conjugated, chalcogen-rich, bridged copper(II) complexes for the preparation of molecular conductors and magnetic materials, having the general formula (Bu(4)N)(2){tto[Cu(L)](2)} (tto = C(2)S(4)(2)(-) = tetrathiooxalato; L = mnt = C(4)N(2)S(2)(2)(-) = 1,2-dicyanoethene-1,2-dithiolato for complex 2, dsit = C(3)Se(2)S(3)(2)(-) = 2-thioxo-1,3-dithiole-4,5-diselenolato for complex 3, dmid = C(3)OS(4)(2)(-) = 2-oxo-1,3-dithiole-4,5-dithiolato for complex 4a). The single-crystal X-ray structures of 2 and 3 have been determined: 2, (Bu(4)N)(2){tto[Cu(mnt)](2)}, monoclinic, space group C2/m, a = 19.549(4) Å, b = 13.519(3) Å, c = 10.162(2) Å, beta = 90.33(1) degrees, Z = 2; 3, (Bu(4)N)(2){tto[Cu(dsit)](2)}, monoclinic, space group P2(1)/c, a = 9.903(1) Å, b = 15.589(1) Å, c = 18.218(1) Å, beta = 90.40(1) degrees, Z = 2. Complex 2 displays perfect planarity, while 3 shows a slight tetrahedral distortion at the metal centers, resulting in a dihedral angle of 24.86(3) degrees. Cyclic voltammetry of (Bu(4)N)(2){tto[Cu(mnt)](2)} (2), (Bu(4)N)(2){tto[Cu(dsit)](2)} (3), and (Bu(4)N)(2){tto[Cu(dmid)](2)} (4a) shows each complex to exhibit two reversible redox processes which can be attributed to {tto[Cu(L)](2)}(2)(-) right arrow over left arrow tto[Cu(L)](2)}(-) and {tto[Cu(L)](2)}(1)(-) right arrow over left arrow {tto[Cu(L)](2)}(0) couples. The structural and electronic properties of 2, 3, and 4a will be compared to those of the recently communicated analogous complex (Bu(4)N)(2){tto[Cu(dmit)](2)} (1).

Tumor seeding of the mediastinoscopy tract has been described. Although it is a rare occurrence, it can present the radiation oncologist with a therapeutic dilemma. Two cases of mediastinoscopy scar recurrences are reported. Their response to treatment and a review of previous cases are included.

Forty-five adult outpatients with endoscopically confirmed gastric ulceration completed a double-blind trial of either cimetidine (1 g/day) or placebo. After six weeks 18 of the 23 patients receiving cimetidine showed complete ulcer healing compared with only six of the 22 patients receiving placebo. The cimetidine group also had fewer days with pain than the placebo group but the difference was not statistically significant. Cimetidine therefore seems to promote healing of gastric ulcers without severe side effects, although its effect on pain is less pronounced than in patients with duodenal ulcers.

Children with cow's milk intolerance, clinically non-confirmed cow's milk intolerance, coeliac disease, non-confirmed malabsorption, other gastrointestinal disorders and normal children were investigated for the presence of precipitins against 40 individual bovine whey proteins by means of the crossed immunoelectrophoresis with intermediate gel technique. In the various groups of children the amount and specificity of bovine whey precipitins were neither connected with the various gastrointestinal disorders nor with alternating diet and challenge with milk. Bovine whey-specific IgE could not be detected in any of the patients clinically suspected for cow's milk intolerance by cutaneous test, RAST or CRIE. The immunoglobulin level of the patients investigated did not differ significantly from the normal ranges. It is concluded that investigations of serum precipitins against bovine whey proteins do not give any significant information concerning cow's milk intolerance.

The purpose was to develop and test an apparatus for objective specification of localization of a moving acoustic target. The system involves computer analysis and graphic display of vectors created from rotational and linear potentiometers that are activated by listeners using a hand-held pointer as they track an acoustic event.

Twenty children from regular classrooms and 20 children from self-contained, learning disability classrooms tracked four different acoustic stimuli through three fixed paths in space. An apparatus specifically designed to provide objective data on accuracy of tracking was used. The results showed that learning disability children as a group were inferior in their abilities to follow a moving speech signal and a moving white noise. The position of the target with respect to the listeners' midlines affected accuracy of tracking, but this was not a function of the hand used to control the pointer.

59 outpatients with irritable bowel syndrome participated in a randomised double-blind trial. The patients in the treatment group received three biscuits daily each containing 10 g of ordinary miller's bran, whereas the patients in the control group received wheat biscuits of a similar appearance. The treatment period was 6 weeks. 52% of the patients in the treatment group noted subjective improvement compared with 65% in the control group. The results of this trial do not support the routine use of miller's bran in irritable bowel syndrome.

Diagnostic value of disaccharide tolerance tests in children. Acta Paediatr Scand, 64:693, 1975.--The diagnostic value of oral lactose and sucrose tolerance tests was investigated in 61 children. A total of 105 oral disaccharide tests were carried out. When the rise in blood sugar was low, the same disaccharide was, as a control measure, instilled directly into the small intestine through a tube. This was carried out in 40 cases. In 21 patients the rise in blood sugar following the two forms of administration was correlated with the disaccharidase activity in a peroral small-intestine biopsy. The incidence of false-positive oral lactose tests was between 23 and 30%, that of false-positive oral sucrose tests between 24 and 33%. A border value of 20 mg per 100 ml in the rise of blood glucose within the first hour following a direct intra-intestinal administration affords a very satisfactory distinction between patients with and without disaccharide malabsorption. Blood glucose determinations exceeding one hour were found to be without diagnostic value.

Plasma fibronectin was determined during normal pregnancy after 15th week, post partum, in cord blood and in cases of EPH gestosis. Non-pregnant women of a comparable age group were examined for plasma fibronectin concentration. Fibronectin at the end of gestation was at about the same level as at the beginning of the second trimester and as in non-pregnant women. The amount of fibronectin remains post partum practically the same. Cord blood fibronectin was about half the concentration of that in adult plasma. In EPH gestosis, levels were significantly elevated.