Cognitive versatility and adaptation to fluid participation in hospital emergency department teams.

Role-based frameworks have long been the cornerstone of organizational coordination, providing clarity in role expectations among team members. However, the rise of "fluid participation"-a constant shift in team composition and skill sets-poses new challenges to traditional coordination mechanisms. In particular, with fluid participation, a team's roles can oscillate between disconnected and intersecting, or between lacking and having overlap in the capabilities and expectations of different roles. This study investigates the possibility that a disconnected set of roles creates a structural constraint on the flexible coordination needed to perform in volatile contexts, as well as the mitigating role of cognitive versatility in a team's strategically-central member. Utilizing a sample of 342 teams from a hospital Emergency Department, we find that teams with a disconnected role set are less effective than teams with an intersecting role set as demonstrated by longer patient stays and increased handoffs during shift changes. Importantly, the presence of a cognitively versatile attending physician mitigates these negative outcomes, enhancing overall team effectiveness. Our findings remain robust even after accounting for other variables like team expertise and familiarity. This research extends the Carnegie School's seminal work on fluid participation by integrating insights from psychology and organizational behavior, thereby identifying key individual attributes that can bolster team coordination in dynamic settings.

Suppression of the pancreatic duodenal homeodomain transcription factor-1 (Pdx-1) promoter by sterol regulatory element-binding protein-1c (SREBP-1c).

Overexpression of sterol regulatory element-binding protein-1c (SREBP-1c) in ß cells causes impaired insulin secretion and ß cell dysfunction associated with diminished pancreatic duodenal homeodomain transcription factor-1 (PDX-1) expression in vitro and in vivo. To identify the molecular mechanism responsible for this effect, the mouse Pdx-1 gene promoter (2.7 kb) was analyzed in ß cell and non-ß cell lines. Despite no apparent sterol regulatory element-binding protein-binding sites, the Pdx-1 promoter was suppressed by SREBP-1c in ß cells in a dose-dependent manner. PDX-1 activated its own promoter. The E-box (-104/-99 bp) in the proximal region, occupied by ubiquitously expressed upstream stimulatory factors (USFs), was crucial for the PDX-1-positive autoregulatory loop through direct PDX-1·USF binding. This positive feedback activation was a prerequisite for SREBP-1c suppression of the promoter in non-ß cells. SREBP-1c and PDX-1 directly interact through basic helix-loop-helix and homeobox domains, respectively. This robust SREBP-1c·PDX-1 complex interferes with PDX-1·USF formation and inhibits the recruitment of PDX-1 coactivators. SREBP-1c also inhibits PDX-1 binding to the previously described PDX-1-binding site (-2721/-2646 bp) in the distal enhancer region of the Pdx-1 promoter. Endogenous up-regulation of SREBP-1c in INS-1 cells through the activation of liver X receptor and retinoid X receptor by 9-cis-retinoic acid and 22-hydroxycholesterol inhibited PDX-1 mRNA and protein expression. Conversely, SREBP-1c RNAi restored Pdx-1 mRNA and protein levels. Through these multiple mechanisms, SREBP-1c, when induced in a lipotoxic state, repressed PDX-1 expression contributing to the inhibition of insulin expression and ß cell dysfunction.

Eating until feeling full and rapid eating both increase metabolic risk factors in Japanese men and women.

OBJECTIVE: To investigate the association between eating behaviour and metabolic risk in the broader population. DESIGN: The association between metabolic risk factors (overweight, hypertension, hyperglycaemia, hypertriacylglycerolaemia, low HDL cholesterol, hyperuricaemia and fatty liver) and various eating behaviours were compared for four groups defined by subjective reporting: not eating until feeling full and not eating rapidly (G1); eating until feeling full only (G2); eating rapidly only (G3); and eating both rapidly and until feeling full (G4). SETTING: A medical centre for health examinations in Tokyo, Japan. SUBJECTS: Men (n 8240) and women (n 2955) who underwent health examinations. RESULTS: The distribution of participants in G1 to G4 was 49·8 %, 11·5 %, 26·3 % and 12·4 % among men and 55·3 %, 15·0 %, 19·0 % and 10·7 % among women, respectively. Compared with G1, the age-adjusted OR (95 % CI) for overweight were significantly higher in G2 to G4, being respectively 1·85 (1·58, 2·17), 1·98 (1·76, 2·23) and 3·46 (2·99, 4·01) for men and 2·20 (1·62, 2·97), 2·59 (1·97, 3·39) and 3·12 (2·27, 4·26) for women. The age-adjusted OR were also significantly higher for hypertriacylglycerolaemia, hyperuricaemia and fatty liver in G2 and for all risks in G3 and G4 among men; and for hyperuricaemia in G2, for hyperglycaemia, hypertriacylglycerolaemia and fatty liver in G3 and for hypertriacylglycerolaemia and fatty liver in G4 among women. CONCLUSIONS: Both eating until feeling full and eating rapidly increase metabolic risk factors. Although the mechanism between rapid eating and metabolic risk requires further exploration, eating slowly and ending meals shortly before feeling full are important public health messages for reducing metabolic risk factors.

Molecular features of 23 patients with glycogen storage disease type III in Turkey: a novel mutation p.R1147G associated with isolated glucosidase deficiency, along with 9 AGL mutations.

Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency in the glycogen debranching enzyme (gene symbol: AGL) with two enzyme activities: transferase and glucosidase. A missense mutation causing isolated glucosidase deficiency has never been reported. In this study, we examined 23 patients of Turkish ancestry and identified a novel missense mutation p.R1147G with isolated glucosidase deficiency, along with nine AGL mutations: six nonsense mutations (p.W373X, p.R595X, p.Q667X, p.Q1205X, p.W1327X and p.Q1376X), one deletion (c.1019delA) and two splicing mutation (c.293+2T>G and c.958+1G>A). As p.R1147G impaired glucosidase activity, but maintained transferase activity in vitro, a 12-year-old girl homozygous for p.R1147G was diagnosed with having isolated glucosidase deficiency. Of nine other mutations, p.W1327X and c.1019delA were recurrent, whereas seven mutations were novel. Six patients with p.W1327X were all from two nearby cities on the East Black Sea and shared the same AGL haplotype, indicating a founder effect in Turkish patients. Patients with the same mutations had identical haplotypes. Our results provide the first comprehensive overview of clinical and molecular features of Turkish GSD III patients and the first description of the missense mutation associated with isolated glucosidase deficiency.

Egyptian glycogen storage disease type III - identification of six novel AGL mutations, including a large 1.5 kb deletion and a missense mutation p.L620P with subtype IIId.

BACKGROUND: Glycogen storage disease type III (GSD III) is caused by mutations in AGL which encodes for a single protein with two enzyme activities: oligo-1, 4-1, 4-glucantransferase (transferase) and amylo-1, 6-glucosidase. Activity of both enzymes is lost in most patients with GSD III, but in the very rare subtype IIId, transferase activity is deficient. Since the spectrum of AGL mutations is dependent on the ethnic group, we investigated the clinical and molecular characteristics in Egyptian patients with GSD III. METHODS: Clinical features were examined in five Egyptian patients. AGL was sequenced and AGL haplotypes were determined. RESULTS: Six novel AGL mutations were identified: a large deletion (c.3481-3588+1417del1525 bp), two insertions (c.1389insG and c.2368insA), two small deletions (c.2223-2224delGT and c.4041delT), and a missense mutation (p.L620P). p.L620P was found in a patient with IIId. Each mutation was located on a different AGL haplotype. CONCLUSIONS: Our results suggest that there is allelic and phenotypic heterogeneity of GSD III in Egypt. This is the second description of a large deletion in AGL. p.L620P is the second mutation found in GSD IIId.

Impact of elevated serum lipoprotein (a) concentrations on the risk of coronary heart disease in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus is associated with a marked increase of coronary heart disease (CHD). We aimed to assess the impact of elevated serum lipoprotein (a) (Lp[a]) concentrations on the risk of CHD in patients with type 2 diabetes mellitus. A consecutive series of 352 outpatients was investigated. We determined the serum lipid profile and checked the patients for a history of CHD and of its traditional risk factors. Furthermore, the patients were divided into 3 groups according to the degree of elevation of the serum Lp(a) concentration: serum Lp(a) concentrations greater than 50 mg/dL, between 30 and 50 mg/dL, and less than 30 mg/dL, a presumed high normal value; and the prevalence of CHD was compared among the 3 groups. The serum Lp(a) concentrations in the subjects varied widely from 0.4 to 163.6 mg/dL. Patients with CHD had significantly higher serum Lp(a) concentrations than those without CHD (P = .0045). Logistic regression analysis to identify factors associated with the presence of CHD revealed that elevated serum Lp(a) is a significant risk factor (P = .0246). The prevalence of CHD increased with increasing serum Lp(a) concentrations (P = .048). Patients with serum Lp(a) concentrations greater than 50 mg/dL had a significantly higher prevalence of CHD than those with serum Lp(a) concentrations less than 30 mg/dL: the odds ratio of an elevated serum Lp(a) concentration was 3.346 (P = .039). In conclusion, elevated serum Lp(a) is a significant risk factor; and the risk of CHD appears to increase with increasing serum Lp(a) concentrations. Serum Lp(a) concentration of 50 mg/dL might represent a threshold level in relation to the risk of CHD in patients with type 2 diabetes mellitus.

Biphasic dyslipidemia in a patient with painless thyroiditis.

In this case study, we followed the thyroid function and serum lipid levels of a patient with painless thyroiditis. Serum lipid levels were decreased during the hyperthyroid phase and elevated during the hypothyroid phase. Both serum lipid levels and thyroid function returned to normative values following a course of thyroid replacement treatment.

Impact of markedly elevated serum lipoprotein(a) levels (> or = 100 mg/dL) on the risk of coronary heart disease.

The serum lipoprotein(a) [Lp(a)] concentration is under genetic control, and most humans have values lower than 30 mg/dL. Subjects with markedly elevated serum Lp(a) concentrations, that is, > or =100 mg/dL, are rarely encountered, and these subjects have not yet been fully characterized from the clinical point of view. In the present investigation, we studied a total of 223 subjects, comprising 123 males and 100 females, with serum Lp(a) values of more than 100 mg/dL. Many of these subjects had a variety of underlying diseases, including metabolic disorders, renal diseases, and hypertension. We focused our attention on the patients with metabolic disorders, namely, familial hypercholesterolemia (FH), primary non-FH hypercholesterolemia (HC), and type 2 diabetes mellitus (DM), and conducted a comparative study of the patients of these 3 disease groups with the corresponding disease controls with serum Lp(a) levels of less than 30 mg/dL, a presumed high normal value. The frequency of markedly elevated serum Lp(a) levels in the general population has not been reported previously. We determined the frequencies in a consecutive series of patients at our Diabetes and Lipid Outpatient Clinic; the results revealed that the frequencies were 6.4% (8/125), 2.6% (6/232), and 0.9% (3/352) in patients with FH, HC, and type 2 DM, respectively. In an attempt to further demonstrate the impact of markedly elevated serum Lp(a) concentrations on the risk of coronary heart disease (CHD), we compared the prevalence of CHD among the study subjects with that among the corresponding disease controls. The results revealed a significantly higher CHD prevalence in the study subjects of all the 3 groups as compared with that in the corresponding disease controls: the odds ratios of a markedly elevated serum Lp(a) level were 5.429 (95% confidence interval [CI], 1.353-21.782), 8.243 (95% CI, 2.793-24.327), and 5.981 (95% CI, 2.530-14.139) for FH, HC, and type 2 DM, respectively. In the present study, we examined some characteristics of this rare population of subjects with markedly elevated serum Lp(a) levels and demonstrated a very high prevalence of CHD among these patients with FH, HC, and type 2 DM, strongly suggesting the significance of Lp(a) as a risk factor for CHD.

A 60-y-old chylomicronemia patient homozygous for missense mutation (G188E) in the lipoprotein lipase gene showed no accelerated atherosclerosis.

BACKGROUND: Familial lipoprotein lipase (LPL) deficiency is a rare autosomal recessive disorder caused by mutations in the LPL gene. Patients with LPL deficiency have chylomicronemia; however, whether they develop accelerated atherosclerosis remains unclear. METHODS: We investigated clinical and mutational characteristics of a 60-y-old Japanese patient with chylomicronemia. RESULTS: The patient's fasting plasma triglyceride levels were >9.0 mmol/l. In postheparin plasma, one fifth of the normal LPL protein mass was present; however, LPL activity was undetectable. Molecular analysis of the LPL gene showed the patient to be a homozygote of missense mutation replacing glycine with glutamine at codon 188 (G188E), which had been known to produce mutant LPL protein lacking lipolytic activity. Ultrasonographic examination of the patient's carotid and femoral arteries showed no accelerated atherosclerosis. Moreover, 64-slice mechanical multidetector-row computer tomography (MDCT) angiography did not detect any accelerated atherosclerotic lesions in the patient's coronary arteries. The patient had none of the risk factors such as smoking, hypertension, and diabetes. CONCLUSIONS: Our case suggests that accelerated atherosclerosis may not develop in patients with LPL deficiency, when they have no risk factors.

Severe hypertriglyceridemia in Japan: Differences in causes and therapeutic responses.

BACKGROUND: Severe hypertriglyceridemia (>1000 mg/dL) has a variety of causes and frequently leads to life-threating acute pancreatitis. However, the origins of this disorder are unclear for many patients. OBJECTIVE: We aimed to characterize the causes of and responses to therapy in rare cases of severe hypertriglyceridemia in a group of Japanese patients. METHODS: We enrolled 121 patients from a series of case studies that spanned 30 years. Subjects were divided into 3 groups: (1) primary (genetic causes); (2) secondary (acquired); and (3) disorders of uncertain causes. In the last group, we focused on 3 possible risks factors for hypertriglyceridemia: obesity, diabetes mellitus, and heavy alcohol intake. RESULTS: Group A (n = 20) included 13 patients with familial lipoprotein lipase deficiency, 3 patients with apolipoprotein CII deficiency, and other genetic disorders in the rest of the group. Group B patients (n = 15) had various metabolic and endocrine diseases. In Group C (uncertain causes; n = 86), there was conspicuous gender imbalance (79 males, 3 females) and most male subjects were heavy alcohol drinkers. In addition, 18 of 105 adult patients (17%) had histories of acute pancreatitis. CONCLUSION: The cause of severe hypertriglyceridemia is uncertain in many patients. In primary genetic forms of severe hypertriglyceridemia, genetic diversity between populations is unknown. In the acquired forms, we found fewer cases of estrogen-induced hypertriglyceridemia than in Western countries. In our clinical experience, the cause of most hypertriglyceridemia is uncertain. Our work suggests that genetic factors for plasma triglyceride sensitivity to alcohol should be explored.

Data from a pre-publication independent replication initiative examining ten moral judgement effects.

We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that researchers can use to better understand reproducibility and irreproducibility in science.

Association of HLA-DQ genotype in autoantibody-negative and rapid-onset type 1 diabetes.

OBJECTIVE: Some type 1 diabetic patients have a distinct phenotype characterized by the absence of pancreatic autoantibodies and fulminant clinical symptoms at onset, including marked hyperglycemia, severe diabetic ketoacidosis, and normal to near-normal HbA(1c) levels with complete destruction of beta-cells. However, little is known about genetic factors of this distinct subtype of diabetes (fulminant autoantibody-negative type 1 diabetes). RESEARCH DESIGN AND METHODS: We analyzed HLA-DQ genotypes in fulminant autoantibody-negative type 1 diabetes (n = 22) and autoantibody-positive type 1 diabetes (immune-mediated type 1 diabetes, n = 78) recruited from a cohort between 1980 and 2000. RESULTS: Fulminant autoantibody-negative type 1 diabetes had a significantly high prevalence of the HLA-DQA1*0303-DQB1*0401 haplotype in a homozygous manner (RR 39) or in a heterozygous manner with the HLA-DQA1*0302-DQB1*0303 haplotype (RR 13). In contrast, autoantibody-positive type 1 diabetic patients had a high prevalence of the HLA-DQA1*0302-DQB1*0303 haplotype in a homozygous manner (RR 10) or in a heterozygous manner with the HLA-DQA1*0303-DQB1*0401 haplotype (RR 12). CONCLUSIONS: Pathogenic roles of genotypic combinations of specific HLA-DQ haplotypes in a homozygous manner are suggested as causative mechanisms of aggressive beta-cell damage in a subtype of autoantibody-negative type 1 diabetes with fulminant clinical features.

Apolipoprotein C-II Tuzla: a novel large deletion in APOC2 caused by Alu-Alu homologous recombination in an infant with apolipoprotein C-II deficiency.

BACKGROUNDS: Familial apolipoprotein (apo) C-II deficiency is a very rare inherited disorder characterized by chylomicronemia. Since the discovery in 1978, reports on apo C-II deficient patients have been limited and only 13 different mutations in APOC2, a gene encoding apo C-II protein, were identified. OBJECTIVES: The objective is to investigate the biochemical and genetic features of a 3-month-old Bosniak girl with chylomicronemia whose apo C-II protein was undetectable in her plasma. METHODS: APOC2, LPL, APOA5, and GPIHBP1 were sequenced. Isoelectrofocusing and immunoblotting of chylomicrons and VLDL fraction from the patient were performed. RESULTS: Sequence analysis demonstrated a large deletion of 2978 base pairs in APOC2, which encompassed exons 2, 3, and 4. The patient was homozygous for the deletion. The 5' part of the breakpoint was located in an Alu Sx repetitive element in intron 1 of APOC2, whereas the 3' part of the breakpoint was in another Alu Sx between APOC2 and CLPTM1, a gene flanking APOC2. We speculate that the deletion was caused by a homologous recombination between two Alu Sx elements. No mutations were detected in LPL, APOA5, and GPIHBP1. Isoelectrofocusing and immunoblotting confirmed the absence of apo C-II protein. CONCLUSIONS: We diagnosed the patient as having apo C-II deficiency and designated the novel large deletion as apo C-II Tuzla. This is the first description of apo C-II deficiency caused by Alu-Alu recombination in APOC2.

The dendrites of granule cell layer neurons are the primary injury sites in the "Brain Diabetes" rat.

We previously demonstrated that rats that receive dorsal third ventricle (3V) streptozotocin (STZ) injections (STZ-3V-rats) exhibit cognitive decline as measured by the Morris Water Maze (MWM) and can be used as an animal model of Alzheimer's disease (AD). Immunohistochemical studies of the hippocampal formations of these animals have revealed significant changes in cerebral insulin signalling pathways, as well as marked increases of amyloid beta (Ab) deposition. Here, we performed Sholl analyses of granule cell layer dendrites and measured dendrite spine densities to assess the effect of STZ on hippocampal morphology. In STZ-3V rats as the results, more branching, complex dendrite arborisation, and increased soma size of the granule cells were observed, while spine densities were decreased in all three spine types. An intraventricular injection of a long-acting insulin analogue improved STZ-induced behavioural and immunohistochemical changes. Nevertheless, dendrite spine densities remained diminished, presumably due to overall null changes since new spine formation due to insulin stimulation has been compensated by loss of old spines. It is concluded that cognitive decline in the "Brain Diabetes" rats is primarily due to impaired intracerebral insulin signalling and the ultimate results were injured excitatory inputs through the perforant pathway.

Molecular and clinical delineation of 12 patients with glycogen storage disease type III in Western Turkey.

BACKGROUND: Glycogen storage disease type III (GSD III; MIM #232400) is an autosomal recessive inherited disorder characterized by fasting hypoglycemia, growth retardation, hepatomegaly, progressive myopathy, and cardiomyopathy. GSD III is caused by deficiency in the glycogen debranching enzyme (gene symbol: AGL). Molecular analyses of AGL have indicated heterogeneity depending on ethnic groups. In Turkey we reported 13 different AGL mutations from GSD III patients in the Eastern region; however, the full spectrum of AGL mutations in Turkish population remains unclear. Here we investigated 12 GSD III patients mostly from Western Turkey. METHODS: The full coding exons, their relevant exon-intron boundaries, and the 5'- and 3'-flanking regions of the patients' AGL were sequenced. AGL haplotypes were determined. Splicing mutations were characterized by RNA transcript analysis. RESULTS: Twelve different mutations were identified: 7 novel AGL mutations [69-base pair deletion (c.1056_1082+42del69), 21-base par deletion (c.3940_3949+11del21), two small duplications (c.364_365dupCT and c.1497_1500dupAGAG), and 3 splicing mutations (c.1736-11A>G, c.3259+1G>A and c.3588+2T>G)], along with 5 known mutations (c.1019delA, c.958+1G>A, c.4161+5G>A, p.R864X and p.R1218X). Transcripts of splicing mutations (c.1736-11A>G, c.3588+2T>G and c.4161+5G>A) were shown to cause aberrant splicing. AGL haplotype analyses suggested that c.1019delA and c.958+1G>A are founder mutations in Turkish patients, while p.R864X is a recurrent mutation. CONCLUSIONS: Our study broadens the spectrum of AGL mutations and demonstrates that mutations in Western Turkey are different from those in the Eastern region.

Seven novel sequence variants in the human low density lipoprotein receptor related protein 5 (LRP5) gene.

We identified seven novel polymorphisms in the human low density lipoprotein receptor related protein 5 (LRP5) gene. Two of them are predicted to replace amino acid in LRP5 protein (c.314A>G: Q89R and c.4037T>C: V1330A), whereas three are silent mutations in the coding region (c.2268T>C: N740N, c.3405A>G: V1119V, and c.4137C>T: D1363D) and two are polymorphisms in introns (IVS10+6T>C and IVS17-30G>A). Since LRP5 recognizes apolipoprotein E and is genetically linked with type 1 diabetes, these novel polymorphisms will be useful in genetic studies of hyperlipoproteinemia and diabetes. To our knowledge, this is the first report in the literature of sequence variants in the human LRP5 gene.

Unique epitopes of glutamic acid decarboxylase autoantibodies in slowly progressive type 1 diabetes.

Disease-specific epitope profiles of glutamic acid decarboxylase (GAD)65 autoantibodies (GAD65Ab) were studied in slowly progressive type 1 (insulin-dependent) diabetes mellitus (SPIDDM) and acute onset type 1 (insulin-dependent) diabetes mellitus (AIDDM) using seven kinds of GAD65/67 chimeric molecules. Sera obtained from Japanese SPIDDM (n = 17) and AIDDM (n = 46) patients followed prospectively were analyzed by immunoprecipitation, ELISA, and Western blotting. GAD65Ab in all SPIDDM samples reacted specifically with an N-terminal linear epitope located on the membrane anchoring domain between amino acids 17-51 and C-terminal conformational epitope between amino acids 443-585 of GAD65. The binding of GAD65Ab with N-terminal 83 residues in SPIDDM inversely correlated with the period in which insulin was not required. GAD65Ab in AIDDM did not react with N-terminal epitope located between amino acids 1-83, irrespective of the titer of GAD65Ab. A novel epitope of GAD65Ab in AIDDM residing between amino acids 244-360 was identified in 17% (8 of 46) of patients whose age of onset was younger than other AIDDM patients. In conclusion, GADAb in SPIDDM has unique N-terminal linear epitopes that are located on the anchoring domain of GAD65 molecules. Association is suggested between GAD65Ab targeted to this region and slowly progressive beta-cell failure in SPIDDM.