Pharmacotherapy and Lung Function Decline in Patients with Chronic Obstructive Pulmonary Disease. A Systematic Review.

Rationale: Whether pharmacological therapy alters decline in FEV1 in chronic obstructive pulmonary disease remains controversial. Because pharmacotherapy improves health status, exacerbation rate, and symptoms, it may be unethical to complete placebo-controlled long-term studies aimed at modifying FEV1 decline.Objectives: We conducted a systematic review of placebo-controlled pharmacological trials lasting ≥1 year to address the question of whether therapy alters FEV1 decline.Methods: A literature search for randomized trials that included repeated spirometry with at least one active and one placebo arm was conducted. Articles were excluded if study duration was <1 year, <3 spirometric measurements, or <100 subjects per arm. Study design was assessed using the Jadad score. To combine studies and find the estimated effect, we used random effects methodology to account for both within-study and between-study variation.Measurements and Main Results: There were 33,051 patients in the analysis (active component, n = 21,941; placebo, n = 11,110 in nine studies). The active treatment arms demonstrated a 5.0 ml/yr reduction (95% confidence interval, 0.8-9.1 ml/yr; P < 0.001) in the rate of FEV1 decline compared with the placebo arms. The relative FEV1 differences between active and placebo arms were within the range of differences reported for health status and for the exacerbation rate in the same studies.Conclusions: In chronic obstructive pulmonary disease, pharmacotherapy ameliorates rate of lung function decline. The relative benefit observed is within the range of those reported for health status and exacerbations in the same studies. Guidelines should be adjusted according to these findings.

Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease.

Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations. Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.Objectives: Report ACM and impact of stepping down therapy, following collection of additional vital status data.Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg following a run-in on their COPD therapies. Time to ACM was prespecified. Additional vital status data collection and subsequent analyses were performed post hoc.Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n = 10,355), documenting 98 (2.36%) deaths on FF/UMEC/VI, 109 (2.64%) on FF/VI, and 66 (3.19%) on UMEC/VI. For FF/UMEC/VI, the hazard ratio for death was 0.72 (95% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 0.67-1.16; P = 0.387) versus FF/VI. Independent adjudication confirmed lower rates of cardiovascular and respiratory death and death associated with the patient's COPD.Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations.

Indicators of potential health-related social needs and the association with perceived health and well-being outcomes among community-dwelling medicare beneficiaries.

PURPOSE: Health-related social needs (HRSNs) can make older adults' more vulnerable and impact their health, well-being, and ability to age-in-place. The current study assessed the prevalence of potential HRSNs (pHRSNs) across several domains (e.g., transportation, social isolation) and explored the associations with health and well-being outcomes in a sample of Medicare beneficiaries. METHODS: Cross-sectional analyses were conducted with a representative sample of community-dwelling Medicare beneficiaries (N = 5758) from the 2012 National Health and Aging Trends Study. Binary indicators of pHRSNs were created for five domains: medical and utility financial needs (MUFN), housing, nutrition, social isolation, and transportation. Outcomes were depression/anxiety, self-rated health, meaning/satisfaction, perceived control/adaptability. Variables were weighted, and multivariate regression models assessed associations between pHRSN variables and outcomes, controlling for sociodemographics and health conditions. RESULTS: Of the estimated 32 million community-dwelling beneficiaries, approximately 13.3 million were positive for ≥ 1 pHRSN and 11.4 million for ≥ 2 pHRSNs. The prevalence by domain was 7% for housing, 8% for transportation, 12% for UMFN and nutrition, and 33% for social isolation. Each domain, except for housing, was significantly (p < .05) associated with at least two of the four outcomes, where being positive for a pHRSN was associated with greater depression/anxiety and poorer self-rated general health. CONCLUSIONS: Over 40% of Medicare beneficiaries had ≥ 1 pHRSN indicators, which means they are more vulnerable and that may limit their ability to age-in-place. Given the growing aging population, better measures and methods are needed to identify, monitor, and address HRSNs. For example, leveraging existing community-based services through coordinated care may be an effective strategy to address older adults' HRSNs.

Adjudication of cardiovascular events in patients with chronic obstructive pulmonary disease: SUMMIT trial.

BACKGROUND: Adjudicated cause-specific mortality has been used in major trials of chronic obstructive pulmonary disease. However, there is less experience with adjudicated major adverse cardiovascular events as a key efficacy outcome in chronic obstructive pulmonary disease trials. The Study to Understand Mortality and Morbidity in chronic obstructive pulmonary disease trial required a Clinical Endpoint Committee to adjudicate the outcomes of modified major adverse cardiovascular events and cause-specific mortality. METHODS AND RESULTS: A six-member Clinical Endpoint Committee reviewed adverse event and serious adverse event reports included in a list of 204 Medical Dictionary for Regulatory Activities terms. Adverse events were triaged by one Clinical Endpoint Committee member, and then reviewed by three reviewers (round 1). If these three disagreed on the adjudication, the event was discussed by the full committee to reach a consensus (round 2). Among 16,485 participants, 48,105 adverse events were reported, among which 3314 were reviewed by the Clinical Endpoint Committee. After triage, 1827 were adjudicated in round 1; 338 required committee consensus in round 2, yielding 450 myocardial infarctions, strokes, unstable anginas or transient ischaemic attacks. Only 20/1627 (1%) non-serious adverse events were adjudicated as cardiovascular events. Only 45/204 Medical Dictionary for Regulatory Activities terms reviewed yielded cardiovascular events. A total of 430 deaths were adjudicated in round 1 and 631 in round 2, yielding 459 cardiovascular deaths. Adjudication of chest pain and sudden death often required additional information from site investigators. Site assessment of cardiovascular death was moderately specific (501/602 = 83%) but not sensitive (256/459 = 56%). CONCLUSION: A Clinical Endpoint Committee is useful for adjudication of major adverse cardiovascular events in chronic obstructive pulmonary disease trials but requires considerable resources and effort by investigators. This process can be streamlined by reviewing only serious adverse events and filtering by selected Medical Dictionary for Regulatory Activities terms.

Home and community-based services coordination for homebound older adults in home-based primary care.

BACKGROUND: Medically complex vulnerable older adults often face social challenges that affect compliance with their medical care plans, and thus require home and community-based services (HCBS). This study describes how non-medical social needs of homebound older adults are assessed and addressed within home-based primary care (HBPC) practices, and to identify barriers to coordinating HCBS for patients. METHODS: An online survey of members of the American Academy of Home Care Medicine (AAHCM) was conducted between March through November 2016 in the United States. A 56-item survey was developed to assess HBPC practice characteristics and how practices identify social needs and coordinate and evaluate HCBS. Data from 101 of the 150 surveys received were included in the analyses. Forty-four percent of respondents were physicians, 24% were nurse practitioners, and 32% were administrators or other HBPC team members. RESULTS: Nearly all practices (98%) assessed patient social needs, with 78% conducting an assessment during the intake visit, and 88% providing ongoing periodic assessments. Seventy-four percent indicated 'most' or 'all' of their patients needed HCBS in the past 12 months. The most common needs were personal care (84%) and medication adherence (40%), and caregiver support (38%). Of the 86% of practices reporting they coordinate HCBS, 91% followed-up with patients, 84% assisted with applications, and 83% made service referrals. Fifty-seven percent reported that coordination was 'difficult.' The most common barriers to coordinating HCBS included cost to patient (65%), and eligibility requirements (63%). Four of the five most frequently reported barriers were associated with practices reporting it was 'difficult' or 'very difficult' to coordinate HCBS (OR from 2.49 to 3.94, p-values < .05). CONCLUSIONS: Despite the barriers to addressing non-medical social needs, most HBPC practices provided some level of coordination of HCBS for their high-need, high-cost homebound patients. More efforts are needed to implement and scale care model partnerships between medical and non-medical service providers within HBPC practices.

Operation and challenges of home-based medical practices in the US: findings from six aggregated case studies.

BACKGROUND: Home-based primary care (HBPC) is a multidisciplinary, ongoing care strategy that can provide cost-effective, in-home treatment to meet the needs of the approximately four million homebound, medically complex seniors in the U.S. Because there is no single model of HBPC that can be adopted across all types of health organizations and U.S. geographic regions, we conducted a six-site HBPC practice assessment to better understand different operation structures, common challenges, and approaches to delivering HBPC. METHODS: Six practices varying in size, care team composition and location agreed to participate. At each site we conducted unstructured interviews with key informants and directly observed practices and procedures in the field and back office. RESULTS: The aggregated case studies revealed important issues focused on team composition, patient characteristics, use of technology and urgent care delivery. Common challenges across the practices included provider retention and unmet community demand for home-based care services. Most practices, regardless of size, faced challenges around using electronic medical records (EMRs) and scheduling systems not designed for use in a mobile practice. Although many practices offered urgent care, practices varied in the methods used to provide care including the use of community paramedics and telehealth technology. CONCLUSIONS: Learnings compiled from these observations can inform other HBPC practices as to potential best practices that can be implemented in an effort to improve efficiency and scalability of HBPC so that seniors with multiple chronic conditions can receive comprehensive primary care services in their homes.

Personal and professional challenges confronted by hospital staff following hurricane sandy: a qualitative assessment of management perspectives.

BACKGROUND: Adequate hospital staffing during and after a disaster is critical to meet increased health care demands and to ensure continuity of care and patient safety. However, when a disaster occurs, staff may become both victim and responder, decreasing their ability and willingness to report for work. This qualitative study assessed the personal and professional challenges that affected staff decisions to report to work following a natural disaster and examined the role of management in addressing staff needs and concerns. METHODS: Semi-structured interviews were conducted with individuals who filled key management roles in the United States Department of Veterans Affairs New York Harbor Healthcare System's response to Superstorm Sandy and during the facility's initial recovery phase. All interviews were audio recorded and transcribed. Three major themes were identified: 1) Barriers to reporting ("Barriers"), 2) Facilitators to reporting ("Facilitators"), and 3) Responses to staff needs and concerns ("Responses"). Atlas.ti 7.1.6 software program was used for the management and analysis of the transcripts. RESULTS: Results indicated that staff encountered several barriers that impeded their ability to report to work at mobile vans at the temporarily nonoperational Manhattan campus or at two other VA facilities in Brooklyn and the Bronx in the initial post-Sandy period including transportation problems, personal property damage, and communication issues. In addition, we found evidence of facilitators to reporting as expressed through descriptions of professional duty. Our findings also revealed that management was aware of the challenges that staff was facing and made efforts to reduce barriers and accommodate staff affected by the storm. CONCLUSIONS: During and after a disaster event, hospital staff is often confronted with challenges that affect decisions to report for work and perform effectively under potentially harsh conditions. This study examined barriers and facilitators that hospital staff encountered following a major natural disaster from the management perspective. Insights gained from this study can be used to inform future disaster planning and preparedness efforts, and help ensure that there is adequate staffing to mount an effective response when a disaster occurs, and to recover from its aftermath.

Memory for sequences of events impaired in typical aging.

Typical aging is associated with diminished episodic memory performance. To improve our understanding of the fundamental mechanisms underlying this age-related memory deficit, we previously developed an integrated, cross-species approach to link converging evidence from human and animal research. This novel approach focuses on the ability to remember sequences of events, an important feature of episodic memory. Unlike existing paradigms, this task is nonspatial, nonverbal, and can be used to isolate different cognitive processes that may be differentially affected in aging. Here, we used this task to make a comprehensive comparison of sequence memory performance between younger (18-22 yr) and older adults (62-86 yr). Specifically, participants viewed repeated sequences of six colored, fractal images and indicated whether each item was presented "in sequence" or "out of sequence." Several out of sequence probe trials were used to provide a detailed assessment of sequence memory, including: (i) repeating an item from earlier in the sequence ("Repeats"; e.g., AB A: DEF), (ii) skipping ahead in the sequence ("Skips"; e.g., AB D: DEF), and (iii) inserting an item from a different sequence into the same ordinal position ("Ordinal Transfers"; e.g., AB 3: DEF). We found that older adults performed as well as younger controls when tested on well-known and predictable sequences, but were severely impaired when tested using novel sequences. Importantly, overall sequence memory performance in older adults steadily declined with age, a decline not detected with other measures (RAVLT or BPS-O). We further characterized this deficit by showing that performance of older adults was severely impaired on specific probe trials that required detailed knowledge of the sequence (Skips and Ordinal Transfers), and was associated with a shift in their underlying mnemonic representation of the sequences. Collectively, these findings provide unambiguous evidence that the capacity to remember sequences of events is fundamentally affected by typical aging.

A Sequence of events model of episodic memory shows parallels in rats and humans.

A critical feature of episodic memory is the ability to remember the order of events as they occurred in time, a capacity shared across species including humans, nonhuman primates, and rodents. Accumulating evidence suggests that this capacity depends on a network of structures including the hippocampus and the prefrontal cortex, but their respective contributions remain poorly understood. As addressing this important issue will require converging evidence from complementary investigative techniques, we developed a cross-species, nonspatial sequence memory task suitable for behavioral and neurophysiological studies in rodents and in humans. The task involves the repeated presentation of sequences of items (odors in rats and images in humans) and requires subjects to make a judgment as to whether each item is presented "in sequence" or "out of sequence." To shed light on the cognitive processes and sequence representations supporting performance, different types of "out of sequence" probe trials were used including: (i) repeating an item from earlier in the sequence (Repeats; e.g., ABAD), (ii) skipping ahead in the sequence (Skips; e.g., ABD), and (iii) inserting an item from a different sequence into the same ordinal position (Ordinal Transfers; e.g., A2CD). We found a remarkable similarity in the performance of rats and humans, particularly in the pattern of results across probe trial types. Thus, the results suggest that rats and humans not only remember the sequences of events, but also use similar underlying cognitive processes and mnemonic representations. This strong cross-species correspondence validates this task for use in future basic and clinical interdisciplinary studies aimed at examining the neural mechanisms underlying episodic memory.

Fluticasone propionate/salmeterol 250/50 µg versus salmeterol 50 µg after chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Inhaled long-acting beta2 agonists used alone and in combination with an inhaled corticosteroid reduce the risk of exacerbations in patients with stable COPD. However, the relative efficacy of these agents in preventing recurrent exacerbations in those recovering from an initial episode is not known. This study compared the rate of COPD exacerbations over the 26 weeks after an initial exacerbation in patients receiving the combination of fluticasone propionate and salmeterol (FP/SAL) or SAL alone. METHODS: Patients (n = 639) aged ≥40 years were randomized to either twice-daily inhaled FP/SAL 250/50 µg or SAL 50 µg. Primary, and secondary, endpoints were rates of recurrent severe, and moderate/severe, exacerbations of COPD. Lung function, health outcomes and levels of biomarkers of systemic inflammation were also assessed. RESULTS: There was no statistically significant treatment difference in rates of recurrent severe exacerbations (treatment ratio 0.92 [95% CI: 0.58, 1.45]) and moderate/severe exacerbations (0.82 [0.64, 1.06]) between FP/SAL and SAL in the intent-to-treat population. Pre-dose morning FEV1 change from baseline was greater (0.10 L [0.04, 0.16]) with FP/SAL than SAL. No treatment difference was seen for other endpoints including patient-reported health outcomes and biomarker levels for the full cohort. CONCLUSIONS: No significant treatment difference between FP/SAL and SAL was seen in COPD exacerbation recurrence for the complete cohort. Treatment benefit with FP/SAL over SAL (treatment ratio 0.68 [0.47, 0.97]) was seen in patients having FEV1 ≥ 30% and prior exposure to ICS. No unexpected safety issues were identified with either treatment. Patients with the most severe COPD may be more refractory to treatment. TRIAL REGISTRATION: ClinicalTrials.gov (identifier NCT01110200). This study was funded by GlaxoSmithKline (study number ADC113874).

The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans.

Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron-rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans.

The role of the dentate gyrus in the formation of contextual representations.

The hippocampus is involved in encoding and integrating contextual information. Recently, it has been suggested that the dorsal dentate gyrus (dDG) hippocampal subregion may mediate the formation of contextual representations of the spatial environment through a conjunctive encoding process whereby incoming multimodal information is integrated into a single higher-order representation. Despite anatomical evidence in support of this claim, behavioral evidence is limited. Therefore, a contextual associative learning paradigm was used to determine whether the dDG supports the formation of integrated contextual representations. Male Long-Evans rats were randomly assigned as controls or to receive bilateral intracranial infusions of colchicine into the dDG. Following recovery from surgery, each rat was tested on an appetitive task that required animals to form an association between a cue (odor) and a context to receive a food reward. Each rat received 10 trials per day and was tested for 10 consecutive days. Upon completion of testing, animals were tested on an additional two-choice olfactory and contextual discrimination task. The testing order was counterbalanced across animals. Results showed that control animals successfully acquired the contextual associative learning task for olfactory stimuli as indicated by improved performance across the 10 testing days. In contrast, animals with dDG lesions were impaired in the ability to acquire the odor-context associations. Results from follow-up odor and context discrimination tests indicated that both groups acquired the discriminations at similar rates. Therefore, it is unlikely that deficits in performance on the contextual associative learning task were due to an inability to discriminate between odors or contexts. The present findings provide further support for DG involvement in the formation of conjunctive contextual representations.

Algoriphagus machipongonensis sp. nov., co-isolated with a colonial choanoflagellate.

A Gram-negative, non-motile, non-spore-forming bacterial strain, PR1(T), was isolated from a mud core sample containing colonial choanoflagellates near Hog Island, Virginia, USA. Strain PR1(T) grew optimally at 30 °C and with 3 % (w/v) NaCl. Strain PR1(T) contained MK-7 as the major menaquinone as well as carotenoids but lacked pigments of the flexirubin-type. The predominant fatty acids were iso-C(15 : 0) (29.4 %), iso-C(17 : 1)ω9c (18.5 %) and summed feature 3 (C(16 : 1)ω6c and/or C(16 : 1)ω7c; 11.3 %). The major polar lipids detected in strain PR1(T) were phosphatidylethanolamine, an unknown phospholipid, an aminophospholipid, an aminolipid and two lipids of unknown character. The DNA G+C content was 38.7 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain PR1(T) fell within the cluster comprising the genus Algoriphagus and was most closely related to Algoriphagus halophilus JC 2051(T) (95.4 % sequence similarity) and Algoriphagus lutimaris S1-3(T) (95.3 % sequence similarity). The 16S rRNA gene sequence similarity between strain PR1(T) and the type strains of other species of the genus Algoriphagus were in the range 91-95 %. Differential phenotypic properties and phylogenetic and genetic distinctiveness of strain PR1(T) demonstrated that this strain was distinct from other members of the genus Algoriphagus, including its closest relative, A. halophilus. Based on phenotypic, chemotaxonomic, phylogenetic and genomic data, strain PR1(T) should be placed in the genus Algoriphagus as a representative of a novel species, for which the name Algoriphagus machipongonensis sp. nov. is proposed. The type strain is PR1(T) (= ATCC BAA-2233(T) = DSM 24695(T)).

Rare Presentation of Stercoral Ulcer Spontaneous Perforation Without Preceding Radiographic Evidence of Colonic Inflammation and Fecal Impaction.

Stercoral ulcers are caused by persistent fecal impaction. A life-threatening consequence of stercoral ulcers is colonic perforation, which is rare. A high index of clinical suspicion should be held for patients with stercoral ulcer, as colonic perforation is a medical emergency, requiring immediate surgical intervention. Here, we report a case of a 45-year-old female admitted with sepsis of unknown picture and subsequently developed stercoral ulcer perforation (SUP), diagnosed intraoperatively, without prior radiographic evidence of colonic inflammation. She was successfully managed with emergency laparotomy and left colectomy with sigmoid colectomy.

Selective lesions of the dentate gyrus produce disruptions in place learning for adjacent spatial locations.

The hippocampus (HPP) plays a known role in learning novel spatial information. More specifically, the dentate gyrus (DG) hippocampal subregion is thought to support pattern separation, a mechanism for encoding and separating spatially similar events into distinct representations. Several studies have shown that lesions of the dorsal DG (dDG) in rodents result in inefficient spatial pattern separation for working memory; however, it is unclear whether selective dDG lesions disrupt spatial pattern separation for reference memory. Therefore, the current study investigated the role of the dDG in pattern separation using a spatial reference memory paradigm to determine whether the dDG is necessary for acquiring spatial discriminations for adjacent locations. Male Long-Evans rats were randomly assigned to receive bilateral intracranial infusions of colchicine or saline (control) into the dDG. Following recovery from surgery, each rat was pseudo-randomly assigned to an adjacent arm or separate arm condition and subsequently tested on a place-learning task using an eight-arm radial maze. Rats were trained to discriminate between a rewarded arm and a nonrewarded arm that were either adjacent to one another or separated by a distance of two arm positions. Each rat received 10 trials per day and was tested until the animal reached a criterion of nine correct choices out of 10 consecutive trials across 2 consecutive days of testing. Both groups acquired spatial discriminations for the separate condition at similar rates. However, in the adjacent condition, dDG lesioned animals required significantly more trials to reach the learning criterion than controls. The results suggest that dDG lesions decrease efficiency in pattern separation resulting in impairments in the adjacent condition involving greater overlap among the distal cues. Conversely, in the separate condition, there was less overlap among distal cues during encoding and less need for pattern separation. These findings provide further support for a critical role for the dDG in spatial pattern separation by demonstrating the importance of a processing mechanism that is capable of reducing interference among overlapping spatial inputs across a variety of memory demands.

Age-related source memory deficits persist despite superior item memory.

Source and item memory for faces of former United States Presidents were assessed in nondemented older adults over 65 years of age (n = 20) and young adults 18 to 25 years of age (n = 20). During the study phase, a male and a female source each presented pictures of faces to the participant one at a time. To assess source memory, the participant was asked to indicate whether a face from the study phase was presented by the male or female. To assess item memory, a study phase face and distractor face were presented and the participant was asked to indicate which was presented previously. Older adults displayed significantly better item memory for the faces of presidents compared to young adults. However, despite showing superior item memory, source memory still was impaired in older adults compared to young adults. The ability of older adults to efficiently integrate source and item information may be compromised to such a large extent that enhanced item memory does not appear to minimize or negate age-related source memory deficits. The findings demonstrate the robust effects of aging on source memory.

Xenopus sonic hedgehog guides retinal axons along the optic tract.

The role of classic morphogens such as Sonic hedgehog (Shh) as axon guidance cues has been reported in a variety of vertebrate organisms (Charron and Tessier-Lavigne [2005] Development 132:2251-2262). In this work, we provide the first evidence that Xenopus sonic hedgehog (Xshh) signaling is involved in guiding retinal ganglion cell (RGC) axons along the optic tract. Xshh is expressed in the brain during retinal axon extension, adjacent to these axons in the ventral diencephalon. Retinal axons themselves express Patched 1 and Smoothened co-receptors during RGC axon growth. Blocking Shh signaling causes abnormal ventral pathfinding, and targeting errors at the optic tectum. Misexpression of exogenous N-Shh peptide in vivo also causes pathfinding errors. Retinal axons grown in culture respond to N-Shh in a dose-dependent manner, either by decreasing extension at lower concentrations, or retracting axons in the presence of higher doses. These data suggest that Shh signaling is required for normal RGC axon pathfinding and tectal targeting in the developing visual system of Xenopus. We propose that Shh serves as a ventral optic tract repellent that helps to define the caudal boundary for retinal axons in the diencephalon, and that this signaling is also required for initial target recognition at the optic tectum.

Using malnutrition and food insecurity screening to identify broader health-related social needs amongst older adults receiving emergency department care in the Southeastern United States: A cross-sectional study.

Unmet health-related social needs are common amongst older US adults and impact both quality of life and health outcomes. One of the ways that unmet health-related social needs impact health is through malnutrition, an imbalance in a person's intake of energy and/or nutrients. Lack of reliable access to a sufficient quantity of nutritious food is a specific health-related social need that can be assessed rapidly and, when unmet, is a direct risk factor for malnutrition and may be indicative of a broader range of unmet health-related social needs. We conducted a cross-sectional study to characterise malnutrition and food insecurity amongst older adults receiving emergency department (ED) care using brief, validated measures and to assess the burden of a broader range of health-related social needs amongst these patients. Patients were asked about their need for and willingness to receive a range of social services. The study was conducted in an academic ED serving a racially and socioeconomically diverse population in the Southeastern United States. A convenience sample of noncritically ill adults aged 60 years and older was approached between November 2018 and April 2019. Study patients (n = 127) were predominantly non-Hispanic white (67%), community dwelling (91%) and urban residents (66%) with 28% screening positive for malnutrition risk, 16% for food insecurity and 5% for both. Of those at risk for malnutrition, 25 (69%) reported ≥2 unmet health-related social needs and 14 (38%) were receptive to social services. Amongst food insecure patients, 18 (90%) reported additional unmet health-related social needs and 13 (65%) were receptive to receiving social services. In conclusion, a brief set of questions can identify subgroups of older ED patients who are food insecure or at risk for malnutrition. Individuals who screen positive for food insecurity have a high burden of unmet health-related social needs.

Prefrontal and hippocampal contributions to encoding and retrieval of spatial memory.

The prefrontal cortex is thought to be critical for goal-directed action and the hippocampus is known to be importantly involved in spatial memory. Several studies have been suggestive of a role for the orbitofrontal cortex (OFC) in spatial navigation. However, the medial prefrontal cortex (mPFC) receives projections directly from the intermediate CA1 (iCA1) region of hippocampus and this link may be critical for spatial navigation. The purpose of the present investigation was to test the performance of rats receiving bilateral or disconnection infusions of lidocaine into OFC, mPFC, or iCA1 to determine the contribution of these structures to encoding and retrieval of spatial memory using the Hebb-Williams maze. A total of 92 male Long-Evans rats received chronic bilateral, contralateral, or ipsilateral implantation of cannulas into OFC, mPFC, or iCA1. Prior to testing on day 1 or day 2, subjects received central infusions of saline or lidocaine. The number of errors committed on the first five trials compared to the second five trials of day 1 was used to determine encoding, whereas retrieval was determined by comparing the second five trials of day 1 with the first five trials of day 2. The present findings suggest that mPFC and iCA1 are necessary and interact during encoding and retrieval; however, the OFC does not appear to be essential for either process. While the nature of the interaction between mPFC and iCA1 during encoding and retrieval is unclear, it may be supported by the integration of goals and spatial cues or strategy switching.

"It's Not Just a Simple Meal. It's So Much More": Interactions Between Meals on Wheels Clients and Drivers.

Background and Objectives: Meals on Wheels (MOW) programs provide home-delivered meals to over 1.5 million older adults; yet, very little is known about the drivers who make meal deliveries possible. Specifically, we do not have clear insight into their interaction with clients or the benefits that they may receive through their service. The objective of this article is to describe the characteristics of MOW drivers, the interactions among drivers and clients, and the benefits of the program to both. Research Design and Method: This qualitative research study reports on interviews with 84 MOW staff (leadership, case managers/client assessors, volunteer coordinators) and drivers at six geographically and operationally distinct programs across the United States. Results: Qualitative analysis of the interviews with MOW staff and drivers revealed the following key themes: (a) clients have multiple vulnerabilities; (b) clients appear to derive social, as well as nutritional benefit from receiving meals; (c) drivers report they provide additional support to their clients beyond delivering the meal; (d) social bonds between drivers and clients were reported to strengthen over time; (e) drivers claim that they, too, derive validation and personal benefit through their meal delivery. Discussion and Implications: This research highlights the significant contributions that meal delivery drivers made in the lives of MOW clients beyond the actual meal itself. This research also spotlights the perceived benefits experienced by the drivers and points to the importance of conducting further research to determine the effects of meal delivery on client and drivers' outcomes, more broadly.