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A fetal diagnosis places an unexpected psychological burden on parents and triggers a complex pregnancy experience. Parents who choose to continue the pregnancy have unique perspectives as they prepare for birth. It is crucial to understand these families’ experiences to inform their care and support. This qualitative systematic review explored the psychological adjustment of parents who continued gestation after they received a fetal diagnosis. A systematic database search was conducted with subsequent thematic analysis of fourteen included studies. Parents experienced intense initial emotional reactions to the diagnosis including shock and grief, followed by a complex processing period influenced by personal and social factors. The findings demonstrate a need for improved multidisciplinary parental support for families who receive a fetal diagnosis and add rationale for the addition of psychological services to the care teams of prospective parents. Keywords: prenatal, fetal diagnosis, pregnancy, parents, emotions, process

Despite important advances in the linkage of residents' Medicare claims and Minimum Data Set (MDS) information, the data infrastructure for long-term care remains inadequate for public health surveillance and clinical research. It is widely known that the evidence base supporting treatment decisions for older nursing home residents is scant as residents are systematically excluded from clinical trials. Electronic health records (EHRs) hold the promise to improve this population's representation in clinical research, especially with the more timely and detailed clinical information available in EHRs that are lacking in claims and MDS. The COVID-19 pandemic shined a spotlight on the data gap in nursing homes. To address this need, the National Institute on Aging funded the Long-Term Care (LTC) Data Cooperative, a collaboration among providers and stakeholders in academia, government, and the private sector. The LTC Data Cooperative assembles residents' EHRs from major specialty vendors and facilitates linkage of these data with Medicare claims to create a comprehensive, longitudinal patient record. These data serve 4 key purposes: (1) health care operations and population health analytics; (2) public health surveillance; (3) observational, comparative effectiveness research; and (4) clinical research studies, including provider and patient recruitment into Phase 3 and Phase 4 randomized trials. Federally funded researchers wanting to conduct pragmatic trials can now enroll their partnering sites in this Cooperative to more easily access the clinical data needed to close the evidence gaps in LTC. Linkage to Medicare data facilitates tracking patients' long-term outcomes after being discharged back to the community. As of August 2022, nearly 1000 nursing homes have joined, feedback reports to facilities are being piloted, algorithms for identifying infections are being tested, and proposals for use of the data have been reviewed and approved. This emerging EHR system is a substantial innovation in the richness and timeliness of the data infrastructure of the nursing home population.

On a sunny day in a studio overlooking the Hudson River, a Mark Morris dancer guides a group of medical students in choreographing their patients’ stories. This class in narrative medicine provides a safe laboratory where doctors-to-be learn to view their relationships with future patients as an improvisatory partnered dance in which the choreography adjusts moment to moment as new challenges, details, and possibilities for healing emerge.

Supplemental Digital Content is available in the text., We use simulated data to examine the consequences of depletion of susceptibles for hazard ratio (HR) estimators based on a propensity score (PS). First, we show that the depletion of susceptibles attenuates marginal HRs toward the null by amounts that increase with the incidence of the outcome, the variance of susceptibility, and the impact of susceptibility on the outcome. If susceptibility is binary then the Bross bias multiplier, originally intended to quantify bias in a risk ratio from a binary confounder, also quantifies the ratio of the instantaneous marginal HR to the conditional HR as susceptibles are depleted differentially. Second, we show how HR estimates that are conditioned on a PS tend to be between the true conditional and marginal HRs, closer to the conditional HR if treatment status is strongly associated with susceptibility and closer to the marginal HR if treatment status is weakly associated with susceptibility. We show that associations of susceptibility with the PS matter to the marginal HR in the treated (ATT) though not to the marginal HR in the entire cohort (ATE). Third, we show how the PS can be updated periodically to reduce depletion-of-susceptibles bias in conditional estimators. Although marginal estimators can hit their ATE or ATT targets consistently without updating the PS, we show how their targets themselves can be misleading as they are attenuated toward the null. Finally, we discuss implications for the interpretation of HRs and their relevance to underlying scientific and clinical questions. See video Abstract: http://links.lww.com/EDE/B727.

Increasing evidence suggests the protein arginine methyltransferase PRMT5 as a contributor to tumorigenesis in various cancer types and several inhibitors have entered clinical trials. Robust assays to determine cellular target engagement and selectivity are an important asset for the optimisation of inhibitors and the design of relevant in vivo studies. Here we report a suite of chemical biology assays enabling quantitative assessment of PRMT5 inhibitor in-cell target engagement and global selectivity profiling using a representative set of inhibitors. With the help of a bespoke cellular probe, we assess inhibitor target occupancy in cells in relation to biochemical and functional cellular assays. Investigating the influence of SAM, the natural cofactor of PRMT5, our results support the hypothesis that SAM positively contributes to the engagement of substrate-competitive inhibitors via a PRMT5:SAM:inhibitor ternary complex. Extensive proteomic profiling studies by drug affinity chromatography and thermal profiling further indicate high specificity of the clinical PRMT5 inhibitor GSK3326595 (pemrametostat).Graphical abstract

Angiogenesis is a proven clinical target for the treatment of advanced epithelial ovarian cancer. Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) offer patients potential new treatment regimens as they can be given as monotherapy, in combination with poly(ADP-ribose) polymerase (PARP) inhibitors, or with and following cytotoxic chemotherapy. If VEGFR-TKIs are licensed for use in ovarian cancer, patients will require prompt and effective management of adverse events, including diarrhea, to optimize compliance and benefit. As diarrhea is one of the most prevalent toxicities of this class of drug, it is important to consider the potential causes, be they disease related (bowel obstruction), treatment related (VEGFR-TKI-related or infective/neutropenic septic diarrhea when patients are receiving cytotoxic chemotherapy combined with VEGFR inhibitor treatment), or incurred through diet. Here, we provide an overview of the possible mechanisms responsible for VEGFR-TKI-induced diarrhea. We review potential interventions that can help in the management of diarrhea induced by VEGFR-TKIs, when used in combination or as single agents, and we provide a diarrhea treatment algorithm to serve as a clinical reference point for the management of diarrhea in patients with ovarian cancer treated with a VEGFR-TKI in combination with chemotherapy or PARP inhibitors, or as monotherapy.

Purpose To describe the consistency in the frequency of 5 health outcomes across the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and Tenth Revision, Clinical Modification (ICD-10-CM) eras in the US. Methods We examined the incidence of 3 acute conditions (acute myocardial infarction [AMI], angioedema, ischemic stroke) and the prevalence of 2 chronic conditions (diabetes, hypertension) during the final 5 years of the ICD-9-CM era (January 2010-September 2015) and the first 15 months of the ICD-10-CM era (October 2015-December 2016) in 13 electronic health care databases in the Sentinel System. For each health outcome reviewed during the ICD-10-CM era, we evaluated 4 definitions, including published algorithms derived from other countries, as well as simple-forward, simple-backward, and forward-backward mapping using the General Equivalence Mappings. For acute conditions, we also compared the incidence between April to December 2014 and April to December 2016. Results The analyses included data from approximately 172 million health plan members. While the incidence or prevalence of AMI and hypertension performed similarly across the 2 eras, the other 3 outcomes did not demonstrate consistent trends for some or all the ICD-10-CM definitions assessed. Conclusions When using data from both the ICD-9-CM and ICD-10-CM eras, or when using results from ICD-10-CM data to compare to results from ICD-9-CM data, researchers should test multiple ICD-10-CM outcome definitions as part of sensitivity analysis. Ongoing assessment of the impact of ICD-10-CM transition on identification of health outcomes in US electronic health care databases should occur as more data accrue.

Purpose The US Food and Drug Administration's Sentinel system developed tools for sequential surveillance. Methods In patients with non-valvular atrial fibrillation, we sequentially compared outcomes for new users of rivaroxaban versus warfarin, employing propensity score matching and Cox regression. A total of 36 173 rivaroxaban and 79 520 warfarin initiators were variable-ratio matched within 2 monitoring periods. Results Statistically significant signals were observed for ischemic stroke (IS) (first period) and intracranial hemorrhage (ICH) (second period) favoring rivaroxaban, and gastrointestinal bleeding (GIB) (second period) favoring warfarin. In follow-up analyses using primary position diagnoses from inpatient encounters for increased definition specificity, the hazard ratios (HR) for rivaroxaban vs warfarin new users were 0.61 (0.47, 0.79) for IS, 1.47 (1.29, 1.67) for GIB, and 0.71 (0.50, 1.01) for ICH. For GIB, the HR varied by age

Background Racial minority children, particularly from low-income households, are at risk for obesity. Family meals have a protective effect on child nutritional health. However, the current evidence is limited in racial and socioeconomic diversity. The objective of this study was to evaluate the impact of a family meals intervention, Simple Suppers, on improvements in diet and health outcomes from baseline (T0) to post-intervention (T1) in intervention compared to waitlist control participants, and determine retention of change in outcomes among intervention participants at 10-week follow-up (T2). Methods Simple Suppers was a 10-week family meals intervention implemented as a 2-group quasi-experimental trial. Ten 90-min lessons were delivered weekly. Data were collected at T0 and T1, and from intervention participants at T2. Participants were racially diverse 4–10 year-old children from low-income households. Setting was a faith-based community center. Main outcomes were daily servings of fruit, vegetables, and sugar-sweetened beverages and diet quality; z-scores for body mass index (BMI), waist circumference, systolic and diastolic blood pressure (BP); weight status categories; food preparation skills; and family meals (frequency of dinner, breakfast, TV viewing during meals, meals in dining area). Generalized linear mixed models (GLMMs) and mixed-effects ordinal regression models were used to assess intervention impact (T0:T1). Paired t-tests examined retention of change among intervention participants (T1:T2). Results One hundred forty children enrolled and 126 completed T1 (90% retention); 71 of 87 intervention participants completed T2(79% retention). Mean (SD) age was 6.9(1.9) yr, 62% female, 60% Black, and 42% low-income. Intervention vs waitlist controls had higher food preparation skills (p p = 0.04) at T1.There were no group differences in dietary intake or quality or z-scores for BMI, waist circumference, or BP, however intervention versus waitlist controls experienced a greater change toward healthy weight (p = 0.04) At T2, intervention participants demonstrated a retention of improved food preparation skills. Conclusions Simple Suppers led to improvements in children’s weight status, food preparation skills, and TV viewing during meals, but not diet or z-scores for BMI, waist circumference, or BP. Future research should examine the preventive effects of healthy family mealtime routines in children at greatest risk for obesity. Trial registration NCT02923050; Simple Suppers Scale-up (S3); Retrospectively registered on Oct 2016; First participant enrolled on Jan 2015.

CBP (CREB (cAMP responsive element binding protein) binding protein (CREBBP)) and P300 (adenovirus E1A-associated 300 kDa protein) are two closely related histone acetyltransferases (HATs) that play a key role in the regulation of gene transcription. Both proteins contain a bromodomain flanking the HAT catalytic domain that is important for the targeting of CBP/P300 to chromatin and which offeres an opportunity for the development of protein-protein interaction inhibitors. Here we present the development of CBP/P300 bromodomain inhibitors with 2,3,4,5-tetrahydro-1,4-benzoxazepine backbone, an N-acetyl-lysine mimetic scaffold that led to the recent development of the chemical probe I-CBP112. We present comprehensive SAR of this inhibitor class as well as demonstration of cellular on target activity of the most potent and selective inhibitor TPOP146, which showed 134 nM affinity for CBP with excellent selectivity over other bromodomains.

YEATS domain (YD) containing proteins are an emerging class of epigenetic targets in drug discovery. Dysregulation of these modified lysine binding proteins has been linked to the onset and progression of cancers. We herein report the discovery and characterisation of the first small molecule chemical probe, SGC-iMLLT, for the YD of MLLT1 (ENL/YEATS1) and MLLT3 (AF9/YEATS3). SGC-iMLLT is a potent and selective inhibitor of MLLT1/3 -histone interactions. Excellent selectivity over other human YD proteins (YEATS2/4) and bromodomains was observed. Furthermore, our probe displays cellular target engagement of MLLT1 and MLLT3. The first small molecule X-ray co-crystal structures with the MLLT1 YD are also reported. This first in class probe molecule can be used to understand MLLT1/3 associated biology and the therapeutic potential of small molecule YD inhibitors.

Histone lysine demethylase (KDMs) are involved in the dynamic regulation of gene expression and they play a critical role in several biological processes. Achieving selectivity over the different KDMs has been a major challenge for KDM inhibitor development. Here we report potent and selective KDM5 covalent inhibitors designed to target cysteine residues only present in the KDM5 sub-family. The covalent binding to the targeted proteins was confirmed by MS and time-dependent inhibition. Additional competition assays show that compounds were non 2-OG competitive. Target engagement and ChIP-seq analysis showed that the compounds inhibited the KDM5 members in cells at nano- to micromolar levels and induce a global increase of the H3K4me3 mark at transcriptional start sites.

RIPK2 mediates inflammatory signaling by the bacteria‐sensing receptors NOD1 and NOD2. Kinase inhibitors targeting RIPK2 are a proposed strategy to ameliorate NOD‐mediated pathologies. Here, we reveal that RIPK2 kinase activity is dispensable for NOD2 inflammatory signaling and show that RIPK2 inhibitors function instead by antagonizing XIAP‐binding and XIAP‐mediated ubiquitination of RIPK2. We map the XIAP binding site on RIPK2 to the loop between β2 and β3 of the N‐lobe of the kinase, which is in close proximity to the ATP‐binding pocket. Through characterization of a new series of ATP pocket‐binding RIPK2 inhibitors, we identify the molecular features that determine their inhibition of both the RIPK2‐XIAP interaction, and of cellular and in vivo NOD2 signaling. Our study exemplifies how targeting of the ATP‐binding pocket in RIPK2 can be exploited to interfere with the RIPK2‐XIAP interaction for modulation of NOD signaling.

Purpose To replicate the well-established association between angiotensin-converting enzyme inhibitors versus beta blockers and angioedema in the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) era. Methods We conducted a retrospective, inception cohort study in a large insurance database formatted to the Sentinel Common Data Model. We defined study periods spanning the ICD-9-CM era only, ICD-10-CM era only, and ICD-9-CM and ICD-10-CM era and conducted simple-forward mapping (SFM), simple-backward mapping (SBM), and forward-backward mapping (FBM) referencing the General Equivalence Mappings to translate the outcome (angioedema) and covariates from ICD-9-CM to ICD-10-CM. We performed propensity score (PS)-matched and PS-stratified Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results In the ICD-9-CM and ICD-10-CM eras spanning April 1 to September 30 of 2015 and 2016, there were 152 017 and 145 232 angiotensin-converting enzyme inhibitor initiators and 115 073 and 116 652 beta-blocker initiators, respectively. The PS-matched HR was 4.19 (95% CI, 2.82-6.23) in the ICD-9-CM era, 4.37 (2.92-6.52) in the ICD-10-CM era using SFM, and 4.64 (3.05-7.07) in the ICD-10-CM era using SBM and FBM. The PS-matched HRs from the mixed ICD-9-CM and ICD-10-CM eras ranged from 3.91 (2.69-5.68) to 4.35 (3.33-5.70). Conclusion The adjusted HRs across different diagnostic coding eras and the use of SFM versus SBM and FBM produced numerically different but clinically similar results. Additional investigations as ICD-10-CM data accumulate are warranted.

The bromodomain and plant homeodomain finger-containing (BRPF) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Here, we describe NI-57 (16) as new pan-BRPF chemical probe of the bromodomain (BRD) of the BRPFs. Inhibitor 16 preferentially bound the BRD of BRPF1 and BRPF2 over BRPF3, whereas binding to BRD9 was weaker. Compound 16 has excellent selectivity over nonclass IV BRD proteins. Target engagement of BRPF1B and BRPF2 with 16 was demonstrated in nanoBRET and FRAP assays. The binding of 16 to BRPF1B was rationalized through an X-ray cocrystal structure determination, which showed a flipped binding orientation when compared to previous structures. We report studies that show 16 has functional activity in cellular assays by modulation of the phenotype at low micromolar concentrations in both cancer and inflammatory models. Pharmacokinetic data for 16 was generated in mouse with single dose administration showing favorable oral bioavailability.

The BRPF (bromodomain and PHD finger-containing) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Evaluation of the BRPF family as a potential drug target is at an early stage although there is an emerging understanding of a role in acute myeloid leukemia (AML). We report the optimization of fragment hit 5b to 13-d as a biased, potent inhibitor of the BRD of the BRPFs with excellent selectivity over non-class IV BRD proteins. Evaluation of 13-d in a panel of cancer cell lines showed a selective inhibition of proliferation of a subset of AML lines. Pharmacokinetic studies established that 13-d had properties compatible with oral dosing in mouse models of disease (Fpo 49 %). W e propose that NI-42 (13-d) is a new chemical probe for the BRPFs suitable for cellular and in vivo studies to explore the fundamental biology of these proteins.

Objective. To test the feasibility and acceptability of a nutrition education/cooking program aimed at teaching positive eating behaviors to parents and their preschool children. Methods. A monthly program was delivered over the dinner hour at a child care facility. Questionnaires were completed at baseline, midway, and study end (10 month). Outcomes were program feasibility (retention, attendance) and acceptability (satisfaction); child food preparation skills, dietary intake, and body mass index percentile; parent self-efficacy regarding healthy eating practices; and family meal frequency. Results. Eleven families were recruited, and 10 families completed (91% retention). On average, 74% attended the program. All reported high satisfaction. Certain child diet outcomes improved (increased fruits and vegetables; decreased sugar-sweetened beverages) ( P < .05). No gain in child body mass index percentile was observed. Parent self-efficacy regarding healthy eating practices improved (planning and encouraging; availability) ( P < .05); family meal frequency increased ( P < .05). Conclusions and Implications. We demonstrated feasibility and acceptability and inferred potential efficacy of a child care–based nutrition education/cooking program. Findings point to the promise of such a childhood obesity prevention program and the need for a larger randomized controlled trial.

Bromodomains (BRDs) are epigenetic interaction domains currently recognized as emerging drug targets for development of anticancer or anti-inflammatory agents. In this study, development of a selective ligand of the fifth BRD of polybromo protein-1 (PB1(5)) related to switch/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes is presented. A compound collection was evaluated by consensus virtual screening and a hit was identified. The biophysical study of protein–ligand interactions was performed using X-ray crystallography and isothermal titration calorimetry. Collective data supported the hypothesis that affinity improvement could be achieved by enhancing interactions of the complex with the solvent. The derived SAR along with free energy calculations and a consensus hydration analysis using WaterMap and SZmap algorithms guided rational design of a set of novel analogues. The most potent analogue demonstrated high affinity of 3.3 μM and an excellent selectivity profile, thus comprising a promising lead for the development of chemical probes targeting PB1(5).

Summary The ability to forage and return home is essential to the success of bees as both foragers and pollinators. Pesticide exposure may cause behavioural changes that interfere with these processes, with consequences for colony persistence and delivery of pollination services.We investigated the impact of chronic exposure (5–43 days) to field‐realistic levels of a neonicotinoid insecticide (2·4 ppb thiamethoxam) on foraging ability, homing success and colony size using radio frequency identification (RFID) technology in free‐flying bumblebee colonies.Individual foragers from pesticide‐exposed colonies carried out longer foraging bouts than untreated controls (68 vs. 55 min). Pesticide‐exposed bees also brought back pollen less frequently than controls indicating reduced foraging performance.A higher proportion of bees from pesticide‐exposed colonies returned when released 1 km from their nests; this is potentially related to increased orientation experience during longer foraging bouts. We measured no impact of pesticide exposure on homing ability for bees released from 2 km, or when data were analysed overall.Despite a trend for control colonies to produce more new workers earlier, we found no overall impacts of pesticide exposure on whole colony size. Synthesis and applications. This study shows that field‐realistic neonicotinoid exposure can have impacts on both foraging ability and homing success of bumblebees, with implications for the success of bumblebee colonies in agricultural landscapes and their ability to deliver crucial pollination services. Pesticide risk assessments should include bee species other than honeybees and assess a range of behaviours to elucidate the impact of sublethal effects. This has relevance for reviews of neonicotinoid risk assessment and usage policy world‐wide., This study shows that field‐realistic neonicotinoid exposure can have impacts on both foraging ability and homing success of bumblebees, with implications for the success of bumblebee colonies in agricultural landscapes and their ability to deliver crucial pollination services. Pesticide risk assessments should include bee species other than honeybees and assess a range of behaviours to elucidate the impact of sublethal effects. This has relevance for reviews of neonicotinoid risk assessment and usage policy world‐wide.

Fluorescence Recovery After Photobleaching (FRAP) is an established method for validating chemical probes against the chromatin reading bromodomains, but so far requires constant human supervision. Here, we present Frapid, an automated open source code implementation of FRAP that fully handles cell identification through fuzzy logic analysis, drug dispensing with a custom-built fluid handler, image acquisition & analysis, and reporting. We successfully tested Frapid on 3 bromodomains as well as on spindlin1 (SPIN1), a methyl lysine binder, for the first time.

Protein-protein interactions (PPIs) represent an enormous source of opportunity for therapeutic intervention. We and others have recently pinpointed key rules that will help in identifying the next generation of innovative drugs to tackle this challenging class of targets within the next decade. We used these rules to design an oriented chemical library corresponding to a set of diverse 'PPI-like' modulators with cores identified as privileged structures in therapeutics. In this work, we purchased the resulting 1664 structurally diverse compounds and evaluated them on a series of representative protein-protein interfaces with distinct "druggability" potential using Homogeneous Time-Resolved Fluorescence (HTRF®) technology. For certain PPI classes, analysis of the hit rates revealed up to 100 enrichment factors compared with non-oriented chemical libraries. This observation correlates with the predicted "druggability" of the targets. A specific focus on selectivity profiles, the three-dimensional (3D) molecular modes of action resolved by X-ray crystallography, and the biological activities of identified hits targeting the well-defined "druggable" bromodomains of the bromo and extraterminal (BET) family are presented as a proof-of-concept. Overall, our present study illustrates the potency of machine learning-based oriented chemical libraries to accelerate the identification of hits targeting PPIs. A generalization of this method to a larger set of compounds will accelerate the discovery of original and potent probes for this challenging class of targets.

The objective of this project was to compare neuropsychologic performance and quality of life in a population-based sample of deployed Gulf War (GW) veterans with and without multisymptom complaints.The study participants were obtained from the 30,000 member population-based National Health Survey of GW-era veterans conducted in 1995. Cases (N=25) were deployed to the year 1990 and 1991 GW and met Center for Disease Control and Prevention criteria for multisymptom GW illness (GWI). Controls (N=16) were deployed to the 1990 and 1991 GW but did not meet Center for Disease Control and Prevention criteria for GWI.There were no significant differences in composite scores on the traditional and computerized neuropsychologic battery (automated neuropsychologic assessment metrics) between GW cases and controls using bivariate techniques. Multiple linear regression analyses controlling for demographic and clinical variables revealed composite automated neuropsychologic assessment metrics scores were associated with age (b=-7.8; P=0.084), and education (b=22.9; P=0.0012), but not GW case or control status (b=-63.9; P=0.22). Compared with controls, GW cases had significantly more impairment on the Personality Assessment Inventory and the short form-36.Compared with GW controls, GW cases meeting criteria for GWI had preserved cognition function but had significant psychiatric symptoms and lower quality of life.

Cosmarium reniforme (Zygnematophyceae, Streptophyta) is a green alga that is commonly found in biofilms of wetlands of the Adirondack region, NY (USA). Two distinctive characteristics that are critical to this alga's survival in a benthic biofilm are its elaborate cell morphology and extracellular matrix (ECM). In this study, ultrastructural, immunocytochemical, and experimental methodologies were employed in order to elucidate the cellular characteristics that are critical for survival in a biofilm. The ECM consists of a thick, outwardly lobed cell wall (CW), which contains a patterned network of structurally complex pores. Each pore consists of a narrow channel, terminating internally at a bulb that invaginates localized regions of the plasma membrane. The outer region of the pore contains arabinogalactan protein-like and extensin epitopes that are likely involved in adhesion mechanisms of the cell. External to the CW is the extracellular polymeric substance that is employed in ensheathment of the cell to the substrate and in gliding motility. The architectural design/biochemical make-up of the CW and a secretory system that encompasses the coordinated activities of the endomembrane and cytomotile/cytoskeletal systems provide the organism with effective mechanisms to support life within the biofilm complex.

In patients with multiple sclerosis (MS), attention and information-processing-speed impairment contribute to dysfunction in other cognitive domains (learning, memory). Treatment for MS-related attention and processing-speed deficits may have dual benefits: improvement of function in these domains and in overall cognitive efficiency. The objective of this study was to determine whether adjunctive treatment of fatigue with modafinil ameliorates deficits in attention and cognitive domains reliant on attention. Relapsing-remitting MS patients receiving intramuscular interferon beta-1a (IM IFNβ-1a) were screened for attention problems with four well-validated, reliable, standardized neurocognitive measures sensitive to attention impairment. Those scoring at least 1 standard deviation below normative expectations on at least two of the measures were eligible for continued participation. Participants with normal values on all physical screening measures were randomized to one of two groups: continued IM IFNβ-1a alone or plus modafinil. Significant mean group differences were found at 4 months on multiple measures of fatigue and cognitive functioning. Patients on combination therapy reported significantly less fatigue (P

Talbot's publication of The Pencil of Nature was an extraordinary achievement, a complex project representing the culmination of his invention of photography. In it he demonstrated that light-sensitive chemicals, when applied to paper and exposed to light, produced, with or without a camera, recognizable images of the space of the world and its objects. Talbot demonstrated also that the photograph had economic and cultural value and could have a vital social role. For Talbot, photography was an entirely new means of making the world not simply visible but newly visual, and The Pencil of Nature demonstrated how.

Even among highly vaccinated populations such as Rhode Island (RI), there exists a vulnerability to disease outbreaks. This is the basis for requiring proof of immunization for enrollment into school. Although RI grants medical, temporary, and religious vaccination exemptions, little is known about the beliefs of RI parents who seek exemptions for their children. The purpose of this small-scale, cross-sectional, Web-based survey is to describe the vaccine behaviors and beliefs of parents of children attending private pre-school in Providence, RI. In spite of limitations, the results provided the intended baseline assessment of the target population. While such findings should be interpreted with caution, they can be used as the foundation for future research and interventions.

The retinoblastoma protein (pRB) plays a key role in the control of normal development and proliferation through the regulation of the E2F transcription factors. We generated a mutant mouse model to assess the in vivo role of the predominant E2F family member, E2F4. Remarkably, loss of E2F4 had no detectable effect on either cell cycle arrest or proliferation. However, E2F4 was essential for normal development. E2f4-/- mice died of an increased susceptibility to opportunistic infections that appeared to result from craniofacial defects. They also displayed a variety of erythroid abnormalities that arose from a cell autonomous defect in late stage maturation. This suggests that E2F4 makes a major contribution to the control of erythrocyte development by the pRB tumor suppressor.

To enhance the learner's competence with information geared toward improving processes to capture present-on-admission pressure ulcers.This continuing education activity is intended for physicians and nurses with an interest in skin and wound care.After participating in this educational activity, the participant should be better able to:1. Analyze the research study presented and its effects regarding identification of present-on-admission pressure ulcers (PrUs) and reduction of healthcare-acquired conditions.2. Identify implications of proper admission skin assessment and documentation on reimbursement by the Centers for MedicareMedicaid Services.3. Implement recommendations from the research study for ways to improve PrU documentation on admission assessment.This study was designed to determine if a process could be built to accurately capture present-on-admission (POA) pressure ulcers (PrUs). Will a formalized electronic process designed to identify, communicate, and document assessment findings of POA PrUs from clinical nurses to admitting physicians reduce missed identification of POA PrUs, improve communication processes, improve physicians' documentation, and improve reimbursement for the hospital?A before-and-after study design in a single site over a 4-month period compared with the same period during the previous 2 years.An acute-care, 333-bed hospital in the Midwestern United States.Nurses were the primary study population.The wound assessment screen in the electronic medical record (EMR) was revised to include a new prompt for POA documentation and communication to the admitting physician of the assessment findings.An increase in POA PrU reporting and reduction in hospital-acquired condition (HAC) reported PrUs.A statistically significant change (2010: P.01, z = 2.507; 2011: P.01, z = 2.632) was found for POA; HAC also had a statistically significant change (2010: P = .02, z = 2.411; 2011: P.01, z = 2.781).The implementation of the electronic prompt did not contribute to the improvement in the POA and HAC rates because the reduction occurred before the EMR prompt intervention. Changing processes such as EMR upgrades, shared governance, Magnet journey, participation in the National Database of Nursing Quality Indicators, and unit-based nursing councils and skin care champions may have exerted positive forces and contributed to improvement in the communication process between the admitting physicians and the clinical nurses.

To evaluate the influence of major cross-match on transfusion efficacy based on the change in PCV following packed red blood cell (pRBC) administration in cats.Retrospective study from January 2000 to December 2010.University Teaching Hospital.Two hundred nine cats received 233 type-specific pRBC transfusions as treatment for anemia. Forty-three transfusions were cross-match compatible and 190 were not screened with cross-match.Pretransfusion major cross-match.Signalment, body weight, dosage of pRBC transfusion, pretransfusion PCV, posttransfusion PCV, IV fluid volumes administered between the measurement of the pretransfusion PCV and posttransfusion PCV, time delay between pretransfusion PCV measurement and transfusion administration, time between administration of transfusion and posttransfusion PCV measurement, and major cross-match testing data were extracted from the medical records of cats receiving pRBC transfusions and were evaluated for their influence on posttransfusion PCV scaled to dose of pRBC administered. The mean pretransfusion PCV was significantly lower for cross-match compatible transfusions (13.7 ± 4.2%) compared to noncross-matched transfusions (16.1 ± 4.5%; independent samples t-test, P0.0001). The PCV increase posttransfusion scaled by dose was significantly greater for cross-match compatible transfusions (1.02 ± 0.51%/mL/kg) than for noncross-matched transfusions (0.74 ± 0.65%/mL/kg; independent samples t-test, P = 0.0093). Of age, dose of pRBCs, cross-match status, reason for transfusion, pretransfusion PCV, and dose of IV fluids administered between the pretransfusion and posttransfusion PCV, only pRBC dose, cross-match status, and pretransfusion PCV were independent predictors of change in PCV with transfusion on multiple regression analysis (coefficient = 0.507, P0.0001; coefficient = 1.64, P = 0.041; coefficient = -0.235, P = 0.0009, respectively).In this retrospective study, administration of type-specific, cross-match compatible pRBC transfusions resulted in significantly greater increases in the posttransfusion PCV when compared to administration of typed, noncross-matched pRBCs. Future prospective studies evaluating the effect of cross-match on transfusion efficacy in cats are warranted.

Objectives To describe a specialized early treatment program for persons with disorders of consciousness (DOC) that includes family education; to identify rates of secondary conditions, imaging used, and selected interventions; and to evaluate outcomes. Design A single-center, retrospective, pre-post design using electronic medical record data. Setting A Commission on Accreditation of Rehabilitation Facilities–accredited, long-term acute care hospital that provides acute medical and inpatient rehabilitation levels of care for people with catastrophic injuries. Participants Persons (N=210) aged 14 to 69 years with DOC of primarily traumatic etiology admitted at a mean ± SD of 41.0±27.2 days postinjury; 2% were in coma, 41% were in the vegetative state, and 57% were in the minimally conscious state. Interventions An acute medical level of care with ≥90 minutes of daily interdisciplinary rehabilitation and didactic and hands-on caretaking education for families. Main Outcome Measures Coma Recovery Scale–Revised, Modified Ashworth Scale, and discharge disposition. Results Program admission medical acuity included dysautonomia (15%), airway modifications (79%), infections (eg, pneumonia, 16%; urinary tract infection, 14%; blood, 11%), deep vein thrombosis (17%), pressure ulcers (14%), and marked hypertonia (30% in each limb). There were 168 program interruptions (ie, 139 surgeries, 29 nonsurgical intensive care unit transfers). Mean length of stay ± SD was 39.1±29.4 days (range, 6–204d). Patients showed improved consciousness and respiratory function and reduced presence or severity of pressure ulcers and upper extremity hypertonia. At discharge, 54% showed sufficient emergence from a minimally conscious state to transition to mainstream inpatient rehabilitation, and 29% did not emerge but were discharged home to family with ongoing programmatic support; only 13% did not emerge and were institutionalized. Conclusions Persons with DOC resulting primarily from a traumatic etiology who receive specialized early treatment that includes acute medical care and ≥90 minutes of daily rehabilitation are likely to show improved consciousness and body function; more than half may transition to mainstream inpatient rehabilitation. Families who receive comprehensive education and hands-on training with ongoing follow-up support may be twice as likely to provide care for medically stable persons with DOC in their homes versus nursing facility placement.