From the Cover: Chimpanzees play the ultimatum game

Is the sense of fairness uniquely human? Human reactions to reward division are often studied by means of the ultimatum game, in which both partners need to agree on a distribution for both to receive rewards. Humans typically offer generous portions of the reward to their partner, a tendency our close primate relatives have thus far failed to show in experiments. Here we tested chimpanzees (Pan troglodytes) and human children on a modified ultimatum game. One individual chose between two tokens that, with their partner’s cooperation, could be exchanged for rewards. One token offered equal rewards to both players, whereas the other token favored the chooser. Both apes and children responded like humans typically do. If their partner’s cooperation was required, they split the rewards equally. However, with passive partners—a situation akin to the so-called dictator game—they preferred the selfish option. Thus, humans and chimpanzees show similar preferences regarding reward division, suggesting a long evolutionary history to the human sense of fairness.     

Systematic review shows no strong evidence regarding the use of elastic taping for pain improvement in patients with primary knee osteoarthritis

Background:A recent trend in the field of primary knee osteoarthritis suggests that elastic tape (e.g., K-tape) relieves pressure on the joint by increasing tension on fascia. Elastic tape (ET) is expected to decrease pain and help patients to recover faster.Objective:This systematic review aims to analyze the efficacy of this method on pain in patients with knee osteoarthritis by using The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score.Data sources:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard for reporting systematic reviews of qualitative and quantitative evidence, we used 3 electronic databases, PubMed, Cochrane, and EBSCO, and grey literature was included.Study eligibility criteria:Articles were screened for duplicates, screened for inclusion and exclusion criteria, and critically appraised.Participants and Intervention:People older than 45 years old with primary osteoarthritis (OA) and application of ET.Study appraisal and synthesis methods:2005 Oxford standard.Results:Amongst all the papers found, 6 Randomized Control Trials (RCT) for a total of 392 participants met the criteria and were included in our review. Three papers out of the 6 RCT had low risks of bias. When the ET was compared to sham taping, the results show no to moderate decreases of WOMAC scores in patients with primary knee osteoarthritis.Limitations:We focused on a single index test (WOMAC) and could not perform meta-analyses.Conclusion and implications of key findings:Although ET does not provide strong adverse outcomes, our data do not support the use of ET as a treatment alone because of too slight reductions of the WOMAC score for reaching clinical efficiency. Thus, our systematic review shows no strong evidence regarding the use of elastic taping for pain improvement in patients with primary knee osteoarthritis.     

When there is no match,the game is not over: Alternative donor options for hematopoietic stem cell transplantation in sickle cell disease

Many patients with sickle cell disease experience severe morbidity and early mortality. The only curative option remains hematopoietic stem cell transplantation. Although HLA-matched sibling transplantation has been very successful for adults and children, the vast majority of patients with sickle cell disease do not have an HLA-matched sibling. Alternative donor options include haploidentical, unrelated umbilical cord blood, and matched unrelated donor transplantation. This report summarizes major alternative donor transplantation studies reported to date and ongoing and upcoming clinical trials. We conclude that when there is no HLA-match, all these approaches should be systematically considered before ruling out the option of hematopoietic stem cell transplantation.     

HFE genotypes and dietary heme iron: no evidence of strong gene-nutrient interaction on serum ferritin concentrations in middle-aged women

BACKGROUND AND AIM: Hereditary hemochromatosis (HH) is a disorder characterized by inappropriately high intestinal iron absorption. In populations of Northern European descent, HH is most commonly caused by mutations (C282Y/H63D) in the HFE gene. METHODS AND RESULTS: We investigated the effects of dietary heme iron intake and HFE mutations on serum ferritin concentrations in a population-based random sample of 1611 women aged >50 years using analysis of covariance (ANCOVA). Higher heme iron intake was associated with significantly higher serum ferritin concentrations (P(trend) < 0.001). Also, women with the compound or C282Y homozygous genotype had significantly higher serum ferritin concentrations (geometric mean 115.2 microg/L (95% CI 81.4-162.9 microg/L) than women carrying normal alleles (geometric mean 76.6 microg/L (95% CI 72.5-80.9 microg/L). We observed the highest serum ferritin concentrations among postmenopausal women who are compound heterozygous or C282Y homozygous, and who consume relatively high amounts of heme iron (geometric mean 183.9 microg/L (95% CI 97.2-347.8 microg/L). CONCLUSIONS: Even when there are currently no clinical signs, women with the compound or C282Y homozygous genotype may still be at risk for developing iron overload sometime after menopause.     

Human cord blood-derived cells can differentiate into hepatocytes in the mouse liver with no evidence of cellular fusion

BACKGROUND & AIMS: Studies have indicated that stem cells have unexpected plasticity and can differentiate down a multitude of nonhematopoietic cell lineages in rodents. Our aim was to identify whether human cord blood cells, which are a rich source of stem cells, would be able to differentiate into hepatocytes when infused into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. We also wanted to test whether such differentiated cells were the result of cellular fusion or true stem cell transdifferentiation. METHODS: Unsorted mononuclear cell preparations of human cord blood were infused into sublethally irradiated NOD-SCID mice. After death, immunohistologic analysis of murine livers was performed using human specific hepatocyte, biliary, and endothelial markers. Fluorescent in situ hybridization (FISH) for mouse and human DNA was also performed. RESULTS: We show that human cord blood cells have the ability to engraft into NOD-SCID liver and become mature hepatocytes. We were unable to identify any biliary or endothelial differentiation. Furthermore, we do not detect any evidence of cell fusion in any of the human cells found in the mouse liver, suggesting that human cord blood cells are capable of true transdifferentiation into hepatocytes in vivo. CONCLUSIONS: We conclude that hepatocytes can derive from human cord blood cells when infused into NOD-SCID mice in the absence of fusion. The demonstration that human stem cell differentiation can occur in this murine model permits comprehensive study of human stem cell plasticity in vivo.     

Multiple ulcers of the ileum due toCytomegalovirus infection in a patient who showed no evidence of an immunocompromised state

68-year-old woman presented with abdominal pain and vomiting. After initial conservative therapy, laparotomy showed multiple ulcers of the ileum, one of which had perforated and adhered to the uterus. The affected segment of the ileum was resected. Numerous cytomegalic cells, corresponding to endothelia and macrophages, with intranuclear inclusion bodies, were found in microscopic sections of the ulcerated lesions. These findings were consistent with cytomegalic vasculitis and enteritis.Cytomegalovirus infections of the alimentary tract have been, reported mainly in severely immunocompromised patients or those with predisposing disorders such as ulcerative colitis; their prognosis is usually poor. In our patient, there was no obvious immunocompromised state or other gastrointestinal disorders. The postoperative course has been uneventful for 2 years after surgery. The prognosis ofCytomegalovirus-associated lesions in the alimentary tract may be quite good in the immunocompetent patient.     

Skeletal muscle mass is a strong predictor of cardiorespiratory fitness in the Chinese population with obesity

Background and aimsAlthough skeletal muscle is well-known as physiologically related to VO₂max, the independent predictive value of skeletal muscle mass (SMM) VO₂max in people with obesity has not been studied. This study aims to determine the relationships between maximal oxygen uptake (VO₂max) and SMM in the Chinese population with obesity.Methods and resultsOverall, 409 participants with obesity were included in this cross-sectional study. A maximal and graded exercise testing measured VO₂max, and body compositions were measured by bioelectrical impedance analysis. Subsequently, correlation coefficients and stepwise multiple linear regression analyses were used to determine the relationships between VO₂max and body compositions. SMM was found to have a significant correlation with VO₂max (r = 0.290, P < 0.001) after adjusting for sex, age, body mass index (BMI), waist-to-hip ratio, and percent body fat (PBF). In previous studies, BMI was widely recognized as a strong predictor of VO₂max. This study revealed surprising results: after SMM was controlled, the correlation between BMI and VO₂max was reduced (from r = 0.381, P < 0.001 to r = 0.191, P < 0.001). SMM was found the most important independent predictor. In the regression model, the variance of VO₂max was explained by the SMM which accounted for 27.4%.ConclusionsIn summary, SMM is a stronger independent predictor of cardiorespiratory fitness in the Chinese population with obesity than sex, age, BMI, waist-to-hip ratio, and PBF.     

Examination of two genetic polymorphisms within the renin-angiotensin system: no evidence for an association with nephropathy in IDDM

Summary Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n=242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n=187); a geographically defined cohort of newly diagnosed diabetic patients (n=341); and IDDM patients with long duration of disease (>15 years) and no evidence of overt nephropathy (n=166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p=0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p=0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.Abbreviations IDDM Insulin-dependent diabetes mellitus - ACE angiotensin converting enzyme - PCR polymerase chain reaction - LDNN long duration-non-nephropathy group - I/D insertion/deletion - RAS renin-angiotension system     

Recent advances in the management of pleural sepsis: What is the evidence?

The management of pleural sepsis involves early diagnosis, administration of appropriate antibiotics, recognition of poor prognostic features and timely intervention to drain the infected pleural space. Important recent advances in the management of pleural sepsis include better imaging techniques, the use of flexible image-guided drainage catheters, adjunctive intrapleural thrombolytic therapy and the introduction of interventional thoracoscopy. These advances have been augmented, in the past year, by results from prospective controlled studies comparing different therapeutic options. This review describes an evidence-based approach to the management of pleural sepsis which incorporates recent therapeutic advances.     

Combination urate-lowering therapy in the treatment of gout: What is the evidence?

Background

Combination therapy that includes a uricosuric and xanthine oxidase inhibitor (XOI) is recommended in guidelines for patients with gout who do not meet treatment targets with XOI monotherapy alone. While the use of combination therapies has been investigated for many years, we reviewed data from the published studies to investigate the efficacy and safety of this approach.

Diabetes-specific cardiomyopathy in type 1 diabetes mellitus: no evidence for its occurrence in the era of intensive insulin therapy.

Aims The incidence of diabetic cardiomyopathy, independent of arterial hypertension (AH) and coronary heart disease (CHD), remains controversial. The present study aimed to determine the influence of type 1 diabetes mellitus (T1DM) of long duration (>10 years) on myocardial function estimated by echocardiography (ECHO) and serum level of N-terminal pro-B type natriuretic peptide (NT-proBNP) in patients without CHD and AH. We also retrospectively investigated the relationship between the structural changes in the hearts of other deceased T1DM patients, and had their myocardial function echocardiographically assessed before death. Methods and results In 185 patients (96 males) with T1DM (mean duration 22.8 years) and 105 non-diabetic control subjects (57 males), detailed ECHO parameters and NT-proBNP were assessed. No significant differences were found between the respective groups. Histological studies of 17 hearts of deceased T1DM patients were carried out and retrospectively compared with their ECHO performed before death. Histological changes were identified, although without the signs of myocardial dysfunction on ECHO prior to death. Conclusion Even the application of echocardiographic, biochemical and morphologic techniques hardly gives sufficient grounds to believe that type 1 diabetes alone may actually precipitate myocardial dysfunction, despite long-term course of the disease and typical histological changes in the myocardium.     

The absence of evidence is not the evidence of absence: A case report on the challenges in diagnosing ostial left main stenosis

Because left main (LM) coronary artery stenosis is known to have higher mortality and morbidity compared to lesions in other territories, an early diagnosis and management are crucial to prevent worse outcomes. Due to limitations of coronary angiography (CA), the diagnosis of ostial LM stenosis solely based on CA may result in underdiagnosis of such lesions. Therefore, additional testing is often needed either by pressure wire or intravascular ultrasound (IVUS) to make appropriate diagnosis. We, hereby, present a case of left main ostial stenosis in a 56-year-old male that was missed on multiple coronary angiograms, and highlights many of the considerations in the diagnosis of LM disease.     

Development of extramedullary myeloma in the era of novel agents: no evidence of increased risk with lenalidomide–bortezomib combinations

Proteasome inhibitors (PI) and immunomodulatory agents (IMIDs) have improved the overall survival (OS) of patients with multiple myeloma (MM), but concerns have been raised about increased incidence of extramedullary disease (EMD) after the combined use of PIs and IMIDs for upfront therapy. We evaluated whether the addition of lenalidomide to bortezomib‐based front‐line regimens precipitated earlier development of EMD. We reviewed the charts of 117 MM patients (median follow‐up from diagnosis 6·1 years; range 0·1–10·2 years) enrolled in eight clinical trials of first‐line treatment with bortezomib‐based regimens, with or without lenalidomide. We assessed development of EMD as extraosseous (distant from bone) or osseous (originating from bone) plasmacytomas. The primary endpoint was time from diagnosis until development of EMD, based on imaging, biopsy and/or physical examination. Any form of EMD at progression was observed in 40 (34·2%) patients, including 21 (18%) osseous, 8 (7%) extraosseous and 11 (9%) both osseous and extraosseous. Median OS was 0·9 years (range 0·1–4·8 years) after extraosseous EMD development. Sensitivity analyses with follow‐up times truncated at 5 years detected no statistically significant difference in rates of any EMD form between the two groups (P > 0·2 for each comparison). Therefore, we observed no evidence that bortezomib–lenalidomide‐based front‐line therapy precipitates earlier EMD.     

Fat distribution is altered in HIV-infected men without clinical evidence of the HIV lipodystrophy syndrome

Objective

To determine if fat distribution is altered in HIV‐infected men without clinical evidence of lipodystrophy.

Methods

In a cross‐sectional design, 14 protease inhibitor (PI)‐treated men with lipodystrophy and 12 PI‐treated and five PI‐naive men without clinical evidence of lipodystrophy underwent body composition and fat distribution analysis by dual‐energy X‐ray absorptiometry and computed tomography. Their fat distribution was compared to 43 uninfected male controls matched for age and BMI.

Results

The percent of body fat in the trunk of men with HIV lipodystrophy was significantly greater compared to both HIV‐infected and healthy controls. The percentage of body fat in the extremities was significantly lower in men with HIV lipodystrophy compared to both HIV‐infected and healthy controls. HIV‐infected men without clinical evidence of lipodystrophy also had a significantly greater percentage of total body fat in the trunk and a significantly lower percent of body fat in the extremities compared to healthy controls. Among the HIV‐infected men, age was an independent predictor of truncal and extremity adiposity.

Conclusion

This study suggests that a continuum of change is present in the adipose organ of HIV‐infected men on antiretroviral therapy. Physical examination alone can miss significant changes in body fat distribution in HIV‐infected patients.

     

Preclinical and manifest diabetes mellitus in young patients with friedreich's ataxia: no evidence of immune process behind the islet cell destruction

Summary Friedreich's ataxia is known to be associated with diabetes mellitus in up to 20% of the patients. However, type, development and course of diabetes mellitus are not well characterised. We report on 3 patients (2 female and 1 male, age 13–20 years) with the combination of Friedreich's ataxia and diabetes mellitus. Diabetes mellitus was characterised as follows: (1) it was strictly insulin-dependent and ketosis-prone, (2) the average insulin requirement was 1 U/kg body weight, (3) the HLA haplotype was not typical of Type 1 (insulin-dependent) diabetes mellitus, (4) there were no positive immune parameters typical of Type 1 diabetes at the clinical onset of diabetes mellitus and (5) there was no remission. To evaluate a preclinical phase as in common autoimmune Type 1 diabetes, i.v. glucose tolerance tests (0.5 g glucose/kg body weight) were performed in 8 patients with Friedreich's ataxia without diabetes mellitus. Seven patients had normal early phase insulin response. In contrast, the glucose disappearance rate was slow in 4 and normal in 3 patients. One of the 8 patients showed a prediabetic metabolic state: the early-phase insulin response was abolished and the glucose disappearance rate was abnormal. The results suggest that diabetes in Friedreich's ataxia is caused by a loss of islet cells similar to common Type 1 diabetes but without HLA-association and without serologic evidence for autoimmune destruction of the islet cells.     

Analysis of single nucleotide polymorphisms and haplotypes in the neuropeptide Y gene: no evidence for association with alcoholism in a German population sample

Background:  Several lines of evidence from animal and electrophysiological studies indicate that the neuropeptide Y (NPY) gene is involved in the pathophysiology of alcohol dependence. Recent studies have provided evidence for an association between a Leu7Pro polymorphism, as well as 2 promoter single nucleotide polymorphisms (SNPs) in the NPY gene (G-602T, T-399C) and alcohol dependence. The aim of the present study was to analyze these variants in a large sample of the Munich Gene Bank of Alcoholism.
Methods:  We performed single SNP and haplotype studies in 465 alcohol dependent patients and 448 healthy controls with 3 SNPs in the promoter region (−883ins/del, G-602T, T-399C) and the Leu7Pro polymorphism in exon 2 of the NPY gene.
Results:  Neither single SNP-, nor haplotype analysis could detect significant associations with alcohol dependence. Additionally we could not detect any relation to Cloninger's Type 1/2 or Babor's Type A/B classification, to withdrawal symptoms, to the age of onset or to the amount of alcohol intake.
Conclusions:  In conclusion, our results suggest that the analyzed SNPs, as well as the corresponding haplotypes of the NPY gene are unlikely to play a major role in the pathophysiology of alcohol dependence in the investigated sample from the German population. Further analyses are needed to confirm the present results.