Familial atrial fibrillation mutation M1875T-SCN5A increases early sodium current and dampens the effect of flecainide.

AIMS: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Pathogenic variants in genes encoding ion channels are associated with familial AF. The point mutation M1875T in the SCN5A gene, which encodes the α-subunit of the cardiac sodium channel Nav1.5, has been associated with increased atrial excitability and familial AF in patients. METHODS AND RESULTS: We designed a new murine model carrying the Scn5a-M1875T mutation enabling us to study the effects of the Nav1.5 mutation in detail in vivo and in vitro using patch clamp and microelectrode recording of atrial cardiomyocytes, optical mapping, electrocardiogram, echocardiography, gravimetry, histology, and biochemistry. Atrial cardiomyocytes from newly generated adult Scn5a-M1875T+/- mice showed a selective increase in the early (peak) cardiac sodium current, larger action potential amplitude, and a faster peak upstroke velocity. Conduction slowing caused by the sodium channel blocker flecainide was less pronounced in Scn5a-M1875T+/- compared to wildtype atria. Overt hypertrophy or heart failure in Scn5a-M1875T+/- mice could be excluded. CONCLUSION: The Scn5a-M1875T point mutation causes gain-of-function of the cardiac sodium channel. Our results suggest increased atrial peak sodium current as a potential trigger for increased atrial excitability.

A systematic review on outcome reporting in randomised controlled trials assessing treatment interventions in pregnant women with pregestational diabetes.

BACKGROUND: Pregestational diabetes mellitus (PGDM) is associated with adverse pregnancy outcomes. Studies assessing interventions to improve maternal and infant outcomes have increased exponentially over recent years. Several outcomes in this field of maternal diabetes are rare, making it difficult to synthesise evidence. OBJECTIVES: To collect outcomes reported in studies assessing treatment interventions in pregnant women with PGDM. SEARCH STRATEGY: CENTRAL, Web of Science, Medline, CINAHL, Embase and ClinicalTrials.gov from their inception until 27 January 2020. SELECTION CRITERIA: Any randomised controlled trial assessing treatment interventions in pregnant women with PGDM reported in English. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed the suitability of articles and retrieved the data. Outcomes extracted from the literature were broadly categorised into maternal, fetal/infant or other outcomes by the study advisory group. MAIN RESULTS: Sixty-seven of the 1475 studies identified fulfilled the inclusion criteria. The median number of outcomes reported per study was 15 (range 1-46). The majority of studies were from North America and Europe. Insulin and metformin were the most commonly investigated pharmacological interventions. Glucose monitoring was the most assessed technological intervention. In all, 131 unique outcomes were extracted: maternal (n = 69), fetal/infant (n = 61) and other (n = 1). CONCLUSIONS: Outcome reporting in treatment interventions trials of pregnant women with PGDM is varied, making it difficult to synthesise evidence, especially for rare outcomes. Systems are needed to standardise outcome reporting in future clinical trials and so facilitate evidence synthesis in this area of maternal diabetes. REGISTRATION: The systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO) database (Registration number CRD42020173549). TWEETABLE ABSTRACT: Outcome reporting is heterogeneous in intervention trials of pregnant women with diabetes existing before pregnancy.

A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

When to Admit to Observation: Predicting Length of Stay for Anticoagulated Elderly Fall Victims.

BACKGROUND: Geriatric patients who fall while taking an anticoagulant have a small but significant risk of delayed intracranial hemorrhage requiring observation for 24 h. However, the medical complexity associated with geriatric care may necessitate a longer stay in the hospital. Little is known about the factors associated with a successful observational status stay (<2 d) for this population. MATERIALS AND METHODS: Elderly patients who fell while taking an anticoagulant admitted from 2012 to 2017 at an ACS level II trauma center were included in a retrospective cohort study to determine what factors were associated with a stay consistent with observational status. INCLUSION CRITERIA: age> 65 y old, negative initial head CT, and one of the following: INR>3.5 if on warfarin, GCS<14, external signs of trauma, or focal neurological deficits. RESULTS: The cohort included 369 patients. Factors associated with decreased likelihood of successful observational status included the need for services after discharge such as an extended care facility (OR 0.06, 95% CI 0.02-0.19, P < 0.001) or visiting nurse agency services (OR 0.27, 95% CI 0.10-0.75, P < 0.001), a dementia diagnosis (OR 0.17, 95% CI 0.04-0.70, P = 0.014), increasing number of medications (OR 0.91, 95% CI 0.84-0.99, P = 0.031), and the use of coumadin (OR 0.28, 95% CI 0.12-0.70, P = 0.006). CONCLUSIONS: For trauma providers, knowing your patient's medication use and particularly type of anticoagulant, comorbidities including dementia, and likely need for services after discharge will help guide the decision to admit the patient for what may be a reasonably lengthy stay versus a brief observation in the hospital for elderly fall victims on anticoagulation.

Transverse cardiac slicing and optical imaging for analysis of transmural gradients in membrane potential and Ca2+ transients in murine heart.

KEY POINTS: A robust cardiac slicing approach was developed for optical mapping of transmural gradients in transmembrane potential (Vm ) and intracellular Ca2+ transient (CaT) of murine heart. Significant transmural gradients in Vm and CaT were observed in the left ventricle. Frequency-dependent action potentials and CaT alternans were observed in all ventricular regions with rapid pacing, with significantly greater incidence in the endocardium than epicardium. The observations demonstrate the feasibility of our new approach to cardiac slicing for systematic analysis of intrinsic transmural and regional gradients in Vm and CaT. ABSTRACT: Transmural and regional gradients in membrane potential and Ca2+ transient in the murine heart are largely unexplored. Here, we developed and validated a robust approach which combines transverse ultra-thin cardiac slices and high resolution optical mapping to enable systematic analysis of transmural and regional gradients in transmembrane potential (Vm ) and intracellular Ca2+ transient (CaT) across the entire murine ventricles. The voltage dye RH237 or Ca2+ dye Rhod-2 AM were loaded through the coronary circulation using a Langendorff perfusion system. Short-axis slices (300 µm thick) were prepared from the entire ventricles (from the apex to the base) by using a high-precision vibratome. Action potentials (APs) and CaTs were recorded with optical mapping during steady-state baseline and rapid pacing. Significant transmural gradients in Vm and CaT were observed in the left ventricle, with longer AP duration (APD50 and APD75 ) and CaT duration (CaTD50 and CaTD75 ) in the endocardium compared with that in the epicardium. No significant regional gradients were observed along the apico-basal axis of the left ventricle. Interventricular gradients were detected with significantly shorter APD50 , APD75 and CaTD50 in the right ventricle compared with left ventricle and ventricular septum. During rapid pacing, AP and CaT alternans were observed in most ventricular regions, with significantly greater incidence in the endocardium in comparison with epicardium. In conclusion, these observations demonstrate the feasibility of our new approach to cardiac slicing for systematic analysis of intrinsic transmural and regional gradients in Vm and CaT in murine ventricular tissue.

KIT mutations and CD117 overexpression are markers of better progression-free survival in vulvar melanomas.

BACKGROUND: Few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas. OBJECTIVES: To evaluate the clinicopathological features of 95 cases of vulvar melanoma. METHODS: p53, CD117, Ki-67, neurofibromin, brafv600e and nrasq61r immunostains, and molecular analyses by either targeted next-generation or direct sequencing, were performed on available archival materials. RESULTS: Molecular testing detected mutations in KIT (44%), BRAF (25%), NF1 (22%), TP53 (17%), NRAS (9%) and TERT promoter (9%). Co-mutation of KIT and NF1 and of KIT and NRAS were identified in two and one cases, respectively. KIT mutations were significantly associated with better progression-free survival in univariate analyses. In multivariate analyses CD117 expression was significantly associated with better progression-free survival. Tumour thickness was significantly associated with worse progression-free and overall survival, and perineural invasion significantly correlated with reduced melanoma-specific survival and reduced overall survival. Cases were from multiple centres and only a subset of samples was available for molecular testing. CONCLUSIONS: KIT mutations and CD117 overexpression are markers of better progression-free survival. In addition to its prognostic value, molecular testing may identify cases that might respond to targeted agents or immunotherapeutic approaches.

Effect of the interaction of seaweed extracts containing laminarin and fucoidan with zinc oxide on the growth performance, digestibility and faecal characteristics of growing piglets.

Seaweed extracts (SWE) rich in laminarin and fucoidan have shown promise as a supplement for weaned piglets. However, successful application in pig nutrition depends on their bioactivity in the presence of additives such as ZnO. In the present study, a 2 × 2 factorial experiment was carried out to investigate the effect of the interaction between SWE and ZnO on the growth performance, digestibility and faecal characteristics of 192 weaned piglets (6·5 kg). The piglets were penned in groups of 4 (n 12 pens). The study consisted of two phases after weaning: a starter diet period from the day of weaning (0 d) to 21 d and a transition diet period from 21 to 40 d. The dietary treatments were as follows: (1) control diet; (2) control diet+ZnO; (3) control diet+SWE; (4) control diet+ZnO+SWE. Diets containing ZnO improved the faecal consistency of the piglets throughout the experimental period (0-40 d). An effect of the interaction between ZnO and SWE on several variable was observed. The diet containing only SWE or ZnO improved the feed conversion efficiency of the piglets during the transition diet period; however, this effect was not observed when the diet containing both ZnO and SWE was fed. The diet containing only SWE increased the N and organic matter digestibility of the piglets; however, this effect was not observed in the presence of ZnO. An interaction between ZnO and SWE was observed, whereby the faecal counts of Escherichia coli were decreased when piglets were fed the diet containing only SWE, but not when fed the diet containing both SWE and ZnO. In summary, SWE and ZnO improve growth performance when given alone, but not when given in combination. The biological effect of SWE on selected digestibility and faecal characteristics was markedly different when compared with that of ZnO.

Effect of maternal supplementation with seaweed extracts on growth performance and aspects of gastrointestinal health of newly weaned piglets after challenge with enterotoxigenic Escherichia coli K88.

In the present study, a 2 × 2 factorial arrangement was conducted to investigate the effect of maternal supplementation with seaweed extracts ( - SWE v. +SWE, n 20) from day 83 of gestation until weaning (day 28) on post-weaning (PW) growth performance, faecal score, faecal enterotoxigenic Escherichia coli (ETEC) toxin quantification, intestinal histology and cytokine mRNA of unchallenged and ETEC-challenged pigs. Pigs were ETEC challenged on day 9 PW. There was a maternal treatment × challenge (SWE × ETEC) interaction effect on growth performance and faecal score (P< 0.05). Pigs from SWE-supplemented sows and ETEC-challenged (SE) had higher average daily gain (ADG) during 0-13 d PW and reduced faecal score during 0-72 h post-challenge than those from basal-fed sows and ETEC-challenged (BE) (P< 0.05). However, there was no difference between unchallenged pigs from the SWE-supplemented sows (SC) and basal-fed sows (BC) (P>0.10). Pigs from the SWE-supplemented sows had reduced heat-labile enterotoxin gene copy numbers than those from the basal-fed sows (P< 0.05). Maternal SWE supplementation increased the villus height in the ileum of pigs (P< 0.05). There was a SWE × ETEC interaction effect (P< 0.05) on IL-6 mRNA and a SWE × gastrointestinal (GI) region interaction effect (P< 0.05) on transforming growth factor-ß1 (TGF-ß1) and TNF-α mRNA. IL-6 mRNA was down-regulated in SC pigs than BC pigs (P< 0.05). However, there was no difference in IL-6 mRNA between SE and BE pigs. The mRNA of TGF-ß1 and TNF-α was down-regulated in the colon of pigs from the SWE-supplemented sows compared with those from the basal-fed sows (P< 0.05). However, there was no difference in TGF-ß1 and TNF-α mRNA in the ileum between the pigs from the SWE-supplemented sows and basal-fed sows. In conclusion, maternal SWE supplementation improves ADG and the aspects of GI health of weaned pigs following an ETEC challenge.

Effect of seaweed-derived laminarin and fucoidan and zinc oxide on gut morphology, nutrient transporters, nutrient digestibility, growth performance and selected microbial populations in weaned pigs.

In the present study, two experiments were conducted to (1) evaluate the effect of laminarin and/or fucoidan on ileal morphology, nutrient transporter gene expression and coefficient of total tract apparent digestibility (CTTAD) of nutrients and (2) determine whether laminarin inclusion could be used as an alternative to ZnO supplementation in weaned pig diets. Expt 1 was designed as a 2 × 2 factorial arrangement, comprising four dietary treatments (n 7 replicates, weaning age 24 d, live weight 6·9 kg). The dietary treatments were as follows: (1) basal diet; (2) basal diet+300 ppm laminarin; (3) basal diet+240 ppm fucoidan; (4) basal diet+300 ppm laminarin and 240 ppm fucoidan. There was an interaction between laminarin and fucoidan on the CTTAD of gross energy (GE) (P< 0·05) and the expression of sodium-glucose-linked transporter 1 (SGLT1/SLC5A1) and GLUT1/SLC2A1 and GLUT2/SLC2A2 (P< 0·05) in the ileum. The laminarin diet increased the CTTAD of GE and increased the expression of SGLT1, GLUT1 and GLUT2 compared with the basal diet. However, there was no effect of laminarin supplementation on these variables when combined with fucoidan. Expt 2 was designed as a complete randomised design (n 8 replicates/treatment, weaning age 24 d, live weight 7·0 kg), and the treatments were (1) basal diet, (2) basal diet and laminarin (300 ppm), and (3) basal diet and ZnO (3100 ppm, 0-14 d, and 2600 ppm, 15-32 d post-weaning). The laminarin diet increased average daily gain and gain:feed ratio compared with the basal diet during days 0-32 post-weaning (P< 0·01) and had an effect similar to the ZnO diet. These results demonstrate that laminarin provides a dietary means to improve gut health and growth performance post-weaning.

Eruptive cutaneous squamous cell carcinoma and psoriasis: response to cetuximab.

Cutaneous squamous cell carcinomas (CSCCs) comprise 20-30% of nonmelanoma skin cancers (NMSCs), and continue to increase in incidence. We report a case of a patient with severe psoriasis who had recurrent and eruptive CSCCs on her leg, which were successfully treated with cetuximab and radiotherapy. The patient had successful long-term clearance of her skin tumours, with the additional finding of resolution of psoriasis while on cetuximab therapy.

Expanding the Cell-Free Reporter Protein Toolbox by Employing a Split mNeonGreen System to Reduce Protein Synthesis Workload.

The cell-free system offers potential advantages in biosensor applications, but its limited time for protein synthesis poses a challenge in creating enough fluorescent signals to detect low limits of the analyte while providing a robust sensing module at the beginning. In this study, we harnessed split versions of fluorescent proteins, particularly split superfolder green fluorescent protein and mNeonGreen, to increase the number of reporter units made before the reaction ceased and enhance the detection limit in the cell-free system. A comparative analysis of the expression of 1-10 and 11th segments of beta strands in both whole-cell and cell-free platforms revealed distinct fluorescence patterns. Moreover, the integration of SynZip peptide linkers substantially improved complementation. The split protein reporter system could enable higher reporter output when sensing low analyte levels in the cell-free system, broadening the toolbox of the cell-free biosensor repertoire.

Effect of dietary laminarin and fucoidan on selected microbiota, intestinal morphology and immune status of the newly weaned pig.

A 2 × 2 factorial experiment was conducted to investigate the interactions between laminarin (LAM; 0 and 300 parts per million (ppm)) and fucoidan (FUC; 0 and 240 ppm) levels on intestinal morphology, selected microbiota and inflammatory cytokine gene expression in the weaned pig. There was an interaction between LAM and FUC supplementation on the Enterobacteriaceae population (P< 0·05) and the abundance of attaching and effacing Escherichia coli (AEEC) strains (P< 0·05) in the colon. Pigs offered the FUC diet had a reduced Enterobacteriaceae population compared with pigs offered the basal diet. However, the effect of FUC on the Enterobacteriaceae population was not observed when combined with LAM. Pigs offered the LAM diet had reduced abundance of AEEC strains compared with pigs offered the basal diet. However, there was no effect of LAM on the abundance of AEEC strains when combined with FUC. There was an interaction between LAM and FUC supplementation on villous height (P< 0·01) and the villous height:crypt depth ratio (P< 0·01) in the duodenum. Pigs offered the LAM or FUC diet had an increased villous height and villous height:crypt depth ratio compared with pigs offered the basal diet. However, there was no effect of the LAM and FUC combination diet on intestinal morphology. Pigs offered the LAM-supplemented diets had a lower IL-6 (P< 0·05), IL-17A (P< 0·01) and IL-1ß (P< 0·01) mRNA expression in the colon compared with pigs offered the diets without LAM. In conclusion, supplementation with either LAM or FUC alone modified intestinal morphology and selected intestinal microbiota, but these effects were lost when offered in combination.

Management of cases that might benefit from radiotherapy: a standardised patient study in primary care.

The aim of this study was to assess general practitioner (GP) consultations with standardised patients presenting with cancer-related problems that might benefit from radiotherapy. Standardised patient scenarios were constructed with indications for radiotherapy or with side effects of radiotherapy. Six GPs consulted six standardised patients. All consultations were video recorded. Two GPs independently rated the consultation performance using the Leicester Assessment Package (LAP). Each consultation was also assessed by two radiation oncologists to assess specific decisions taken or advice offered to 'patients' in each case. The mean duration of consultations was 13 min and 55 s. Three GPs differed significantly (P < 0.025) in competencies measured by the LAP, but not as assessed by radiation oncologists. There was no significant difference in LAP scores when reviewed by scenario. However, there was significant differences in the management of the case with prostate cancer (P= 0.005) and data suggest that GPs management of different problems presented varied widely. These data are consistent with the published literature which suggests that in practice not all patients are appropriately advised or referred. There is a need for innovations to support GPs to manage patients who would benefit from radiotherapy.

Use of modifying phrases in surgical pathology reports: is there a different understanding between pathologists and treating physicians?

When not all the histopathologic and clinical features necessary for a pathology diagnosis are present in a particular specimen, pathologists may use modifying phrases to convey various degrees of certainty, e.g., "consistent with…" and "suggestive of…." However, it is unclear whether pathologists use such phrases consistently or whether treating physicians fully understand their intended meaning. A questionnaire concerning six common modifying phrases ("consistent with, suggestive of, suspicious for, highly consistent with, highly suggestive of, some features of") was sent to all physicians from a single institution who either issued or routinely received surgical pathology reports. Physicians were asked to rank their understanding of each phrase on a printed scale between 1 ("no evidence of") and 10 ("diagnostic of"). One hundred sixty physicians (74.3%) responded. Despite wide variation, there was a hierarchy (from more to less diagnostic): highly consistent > highly suspicious > consistent > suspicious > suggestive > some features (p < 1 × 10-7). There were no significant differences between pathologists and treating physicians (p = 0.72) or attendings and residents (p = 0.9). Pathologists and treating physicians share an overall common understanding of their hierarchical relationship, albeit with wide ranges. Based upon our results, we propose to use only three qualifying phrases to convey the degree of certainty for a particular diagnosis: "suggestive of" (> 25 ≤ 50% certainty), "suspicious for" (> 50 ≤ 75%), and "consistent with" (> 75%). The phrase "no evidence of" should probably be used only when there is ≤ 5% confidence in a diagnosis, and conversely, "diagnostic of" should probably be used only when there is ≥ 95% confidence in a diagnosis.

The development of a urinary tract infection is associated with increased mortality in trauma patients.

BACKGROUND: In October 2008, Medicare and Medicaid stopped paying for care associated with catheter-related urinary tract infections (UTIs). Although most clinicians agree UTIs are detrimental, there are little data to support this belief. METHODS: This is a retrospective review of trauma registry data from a Level I trauma center between 2003 and 2008. Two proportional hazards regressions were used for analyses. The first predicted acquisition of UTI as a function of indwelling urinary catheter use, adjusting for age, diabetes, gender, and injury severity. The second predicted hospital mortality as a function of UTI, covarying for age, gender, chronic obstructive pulmonary disease, congestive heart failure, hypertension, diabetes, pneumonia, and injury severity. RESULTS: After excluding patients who stayed in the hospital <3 days and those with a UTI on arrival, 5,736 patients were included in the study. Of these patients, 680 (11.9%) met criteria for a UTI, with 487 (71.6%) indwelling urinary catheter-related infections. Predictors of UTI included the interaction between age and gender (p = 0.0018), Injury Severity Score (p = 0.0021), and indwelling urinary catheter use (p < 0.001). The development of a UTI predicted the risk of in-hospital death as a patient's age increased (p = 0.002). Similar results were seen when only catheter-associated UTIs are included in the analysis. CONCLUSIONS: Indwelling urinary catheter use is connected to the development of UTIs, and these infections are associated with a greater mortality as the age of a trauma patients increases.

Impact of socioethnic factors on outcomes following traumatic brain injury.

BACKGROUND: Ethnic minorities and low income families tend to be in poorer health and have worse outcomes for a spectrum of diseases. Health care provider bias has been reported to potentially affect the distribution of care away from poorer communities, minorities, and patients with a history of substance abuse. Trauma is perceived as a disease of the poor and medically underserved. Minorities are overrepresented in low income populations and are also less likely to possess health insurance leading to a potential overlapping effect. Traumatic brain injury (TBI) is a predominant cause of mortality and long-term morbidity, which imposes a considerable social and financial burden. We therefore sought to determine the independent effect on outcome after TBI from race, insurance status, intoxication on presentation, and median income. METHODS: A 5-year retrospective chart review of admitted trauma patients aged 18 years and older to a Level I trauma center. Zip code of residency was a surrogate marker for socioeconomic status, because median income for each zip code is available from the US Census. Charts review included race, insurance status, mechanisms of trauma, and injuries sustained. Outcomes were placement of tracheostomy, hospital length of stay (HLOS), leaving Against Medical Advice (AMA), and discharge to home versus rehabilitation and mortality. RESULTS: A total of 3,101 TBI patients were included in the analyses. Multivariable logistic and proportional hazard regression analyses were undertaken adjusting for age, gender, Injury Severity Score, and mechanism. Rates of tracheostomy placement were unaffected by race, median income, or insurance status. Race and median income did not affect HLOS, but private insurance was associated with shorter HLOS and intoxication was associated with longer HLOS. Neither race nor intoxication affected rates of AMA, but higher income and private insurance was associated with lower rates of AMA. Non-Caucasian race and lack of insurance had significantly lower likelihood of placement in a rehabilitation center. Mortality was unaffected by race, increased in intoxicated patients, was variably affected by median income, and was lowest in patients with private insurance. CONCLUSIONS: An extremely complex interplay exists between socioethnic factors and outcomes after TBI. Few physicians would claim overt discrimination. Tracheostomy, the factor most directed by the surgeon, was unbiased by race, income, or insurance status. The likelihood of placement in a rehabilitation center was significantly impacted by both race and insurance status. Future prospective studies are needed to better address causation.

Effects of dietary supplementation with a laminarin-rich extract on the growth performance and gastrointestinal health in broilers.

Restriction in antimicrobial use in broiler chicken production is driving the exploration of alternative feed additives that will support growth through the promotion of gastrointestinal health and development. The objective of this study was to determine the effects of dietary inclusion of laminarin on growth performance, the expression of nutrient transporters, markers of inflammation and intestinal integrity in the small intestine and composition of the caecal microbiota in broiler chickens. Two-hundred-and-forty day-old male Ross 308 broiler chicks (40.64 (3.43 SD) g) were randomly assigned to: (T1) basal diet (control); (T2) basal diet + 150 ppm laminarin; (T3) basal diet + 300 ppm laminarin (5 bird/pen; 16 pens/treatment). The basal diet was supplemented with a laminarin-rich Laminaria spp. extract (65% laminarin) to achieve the two laminarin inclusion levels (150 and 300 ppm). Chick weights and feed intake was recorded weekly. After 35 days of supplementation, one bird per pen from the control and best performing (300 ppm) laminarin groups were euthanized. Duodenal, jejunal and ileal tissues were collected for gene expression analysis. Caecal digesta was collected for microbiota analysis (high-throughput sequencing and QPCR). Dietary supplementation with 300 ppm laminarin increased both final body weight (2033 vs. 1906 ± 30.4, P < 0.05) and average daily gain (62.3 vs. 58.2 ± 0.95, P < 0.05) compared to the control group and average daily feed intake (114.1 vs. 106.0 and 104.5 ± 1.77, P < 0.05) compared to all other groups. Laminarin supplementation at 300 ppm increased the relative and absolute abundance of Bifidobacterium (P < 0.05) in the caecum. Laminarin supplementation increased the expression of interleukin 17A (IL17A) in the duodenum, claudin 1 (CLDN1) and toll-like receptor 2 (TLR2) in the jejunum and IL17A, CLDN1 and SLC15A1/peptide transporter 1 (SLC15A1/PepT1) in the ileum (P < 0.05). In conclusion, supplementation with laminarin is a promising dietary strategy to enhance growth performance and 300 ppm was the optimal inclusion level with which to promote a beneficial profile of the gastrointestinal microbiota in broiler chickens.

Normal presenting vital signs are unreliable in geriatric blunt trauma victims.

BACKGROUND: Normal vital signs are typically associated with improved outcomes in trauma patients. Whether this association is true for geriatric patients is unclear. METHODS: A Level 1 trauma center retrospective chart review of vital signs on presentation (heart rate [HR] and blood pressure) in young (aged 17-35 years) and geriatric (aged 65 years or older) blunt trauma victims from September 2003 to September 2008 was preformed. Generalized nonlinear using piecewise regression for the linear portion of standard logistic models was used to model risk of mortality as a function of HR and blood pressure. Independent models were selected for elderly and young trauma patients based on blood pressure and HR. Models of the same complexity were then fit within each gender and age. RESULTS: There were 2,194 geriatric and 2,081 young patients. Two hundred fifty-one (11.4%) geriatric and 49 (2.4%) young patients died. At all points of "normality," the mortality of the geriatric patients was higher than the young group. Mortality increases considerably in the elderly patients for HRs >90 beats per minute (bpm), an association not seen until HR of 130 bpm in the young group. Mortality significantly increases with systolic blood pressure (SBP) <110 mm Hg in the geriatric patients but not until a SBP of 95 mm Hg in the young patients. HR and mortality association was most variable in the male geriatric patients. CONCLUSIONS: Vital signs on presentation are less predictive of mortality in geriatric blunt trauma victims. Geriatric blunt trauma patients warrant increased vigilance despite normal vital signs on presentation. New trauma triage set points of HR >90 or SBP <110 mm Hg should be considered in the geriatric blunt trauma patients.

The multiply injured trauma patient: resuscitation, rehabilitation, recovery.

The care of the acutely injured patient requires a multidisciplinary approach from the moment of injury through rehabilitation and reintegration into society. In addition to the doctors and nurses providing many aspects of the acute and chronic medical care, the rehabilitation component is delivered by several skilled specialists focused on maximizing functional outcomes.