Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot.

CONTEXT: Bone marrow (BM) in adult long bones is rich in adipose tissue, but the functions of BM adipocytes are largely unknown. We set out to elucidate the metabolic and molecular characteristics of BM adipose tissue (BMAT) in humans. OBJECTIVE: Our aim was to determine if BMAT is an insulin-sensitive tissue, and whether the insulin sensitivity is altered in obesity or type 2 diabetes (T2DM). DESIGN: This was a cross-sectional and longitudinal study. SETTING: The study was conducted in a clinical research center. PATIENTS OR OTHER PARTICIPANTS: Bone marrow adipose tissue glucose uptake (GU) was assessed in 23 morbidly obese subjects (9 with T2DM) and 9 healthy controls with normal body weight. In addition, GU was assessed in another 11 controls during cold exposure. Bone marrow adipose tissue samples for molecular analyses were collected from non-DM patients undergoing knee arthroplasty. INTERVENTION(S): Obese subjects were assessed before and 6 months after bariatric surgery and controls at 1 time point. MAIN OUTCOME MEASURE: We used positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose tracer to characterize GU in femoral and vertebral BMAT. Bone marrow adipose tissue molecular profile was assessed using quantitative RT-PCR. RESULTS: Insulin enhances GU in human BMAT. Femoral BMAT insulin sensitivity was impaired in obese patients with T2DM compared to controls, but it improved after bariatric surgery. Furthermore, gene expression analysis revealed that BMAT was distinct from brown and white adipose tissue. CONCLUSIONS: Bone marrow adipose tissue is a metabolically active, insulin-sensitive and molecularly distinct fat depot that may play a role in whole body energy metabolism.

Can combined online and face-to-face continuing medical education improve the clinical knowledge and skills of family doctors in Vietnam? A cluster randomised controlled trial.

OBJECTIVES: To assess the effectiveness of a combined online and face-to-face continuing medical education (CME) programme, for improvement in clinical knowledge and skills of family doctors, in comparison with a control group; and to explore the self-reported satisfaction, competencies and confidence of those in the intervention group. METHODS: We used a cluster randomised controlled trial, with pre- and post-testing, and a feedback survey at the end of the 18-month CME programme. The measurements consisted of a multiple-choice test, an objective structured clinical examination test and an anonymously self-administered questionnaire. RESULTS: There were 58 family doctors from four provinces in the intervention group and 32 doctors from three provinces in control group, both in the Mekong Delta region in Vietnam. The mean age of participants was 47.8 years, and the female/male ratio was 1/2.9. After training, the intervention group had significantly higher scores on overall knowledge (mean difference = 1.4, 95% CI 1.0-1.86, P < 0.001; Cohen's d 1.36, Pearson's r 0.53), in four of the five education modules: peptic disorders, diabetes, hypertension and bone-muscle-joint diseases (Pearson's r 0.56, 0.56, 0.34 and 0.4, respectively), and in problem-solving skills (Pearson's r 0.27). Self-reports showed a positive learning attitude, strong interest and improved confidence and competency among doctors in the intervention group. CONCLUSIONS: A combined online and face-to-face CME programme proved applicable and effective for improving the clinical knowledge and problem-solving skills of family doctors in Vietnam.

OBJECTIFS: Evaluer l'efficacité d'une combinaison d'un programme de formation médicale continue (FMC), en ligne et en face-à-face pour l' amélioration des connaissances cliniques et les compétences des médecins de famille, par rapport à un groupe témoin et explorer la satisfaction, les compétences et la confiance autodéclarées des participants dans le groupe d'intervention. Méthodes Nous avons utilisé un essai contrôlé randomisé en grappes , avec pré et post-test, et une enquête de rétroaction à la fin du programme de FMC de 18 mois. Les mesures consistaient en un test à choix multiple, un test d'examen clinique objectif structuré et un questionnaire anonyme administré. Résultats Il y avait 58 médecins de famille de 4 provinces dans le groupe d'intervention et 32 médecins de 3 provinces dans le groupe témoin, tous deux dans la région du delta du Mékong au Vietnam. L'âge moyen des participants était de 47,8 ans, et le ratio femmes/hommes était de 1/2,9. Après la formation, le groupe d'intervention avaient des scores significativement plus élevés sur l' ensemble des connaissances (moyenne de différence = 1,4 ; IC95%: 1,0 à 1,86 ; p < 0,001 ; d de Cohen: 1,36 ; r de Pearson 0,53), dans 4 des 5 modules d'éducation: troubles gastro-duodénaux, diabète, hypertension et maladies des os-muscles- articulaires (r de Pearson 0,56 ; 0,56 ; 0,34 et 0,4, respectivement), et dans les compétences à résoudre des problèmes (r de Pearson: 0,2 7). Les auto-évaluations ont montré une attitude d'apprentissage positive, un vif intérêt et une amélioration de la confiance et des compétences chez les médecins du groupe d'intervention. CONCLUSIONS: Une FMC combiné basé sur Internet et en direct est applicable et efficace pour l'amélioration des connaissances cliniques et les compétences à résoudre les problèmes chez les médecins de famille au Vietnam.

Can a family medicine rotation improve medical students' knowledge, skills and attitude towards primary care in Vietnam? A pre-test-post-test comparison and qualitative survey.

OBJECTIVES: Well-designed studies on the impact of a family medicine rotation on medical students are rare, and very few studies include a qualitative component. This study aimed to determine the improvement of medical students' knowledge, communication skills and attitude towards primary care and explore their perceptions after rotations, in comparison with a control group. METHODS: We used a mixed-methods design, comprising a pre-test-post-test comparison between a sample of trained students who took family medicine rotations and a control group and a qualitative survey. The measurement of improvement included (i) multiple choice question testing, (ii) objective structured checklist examinations, (iii) self-reporting and (iv) interviews and focus group discussions. Data were collected from August 2017 to June 2018. RESULTS: There were 696 students in the trained group and 617 controls. The two groups' baseline scores in knowledge, communication skills and attitude were not significantly different. Knowledge covering five domains of family medicine (Pearson's r from 0.6 to 0.9) improved significantly, as did attitudes towards primary care in the trained group. There were no differences in communication and counselling skills between the two groups for four situations, but for two-health check-ups and mental health care-skills were significantly improved (Pearson's r from 0.28 to 0.43). The qualitative survey showed highly positive feedback from trained students. CONCLUSIONS: The family medicine rotation significantly improved students' knowledge and attitude towards primary care and some communication skills. Further studies should investigate students' interest in and career choice for this discipline.

OBJECTIFS: Des études bien conçues sur l'impact d'une rotation de la médecine familiale sur les étudiants en médecine sont rares et très peu d'études comprennent une composante qualitative. Cette étude visait à mesurer l'amélioration des connaissances, des compétences en communication et de l'attitude des étudiants en médecine à l'égard des soins primaires, et à explorer leurs perceptions après les rotations, en comparaison avec un groupe témoin. MÉTHODES: Nous avons utilisé un concept de méthodes mixtes, comprenant une comparaison pre-test et post-test entre un échantillon d'étudiants formés qui ont effectué des rotations de la médecine familiale et un groupe témoins, et une enquête qualitative. La mesure de l'amélioration comprenait (1) des tests de questions à choix multiples, (2) des examens objectifs structurés de listes, (3) des rapports personnels et (4) des entretiens et des discussions focalisées de groupes. Les données ont été collectées d'août 2017 à juin 2018. RÉSULTATS: Il y avait 696 élèves dans le groupe formé et 617 témoins. Les scores de référence des deux groupes en termes de connaissances, de communication et d'attitude n'étaient pas significativement différents. Les connaissances couvrant cinq domaines de la médecine familiale se sont considérablement améliorées (r de Pearson de 0,6 à 0,9), tout comme l'attitude à l'égard des soins primaires dans le groupe formé. Il n'y avait pas de différence dans les compétences de communication et de conseil entre les deux groupes pour quatre situations, mais pour deux (bilan de santé et soins de santé mentale) les compétences ont été significativement améliorées (r de Pearson de 0. 28 à 0. 43). L'enquête qualitative a montré une rétroaction très positive des étudiants formés. CONCLUSIONS: La rotation de la médecine familiale a amélioré de manière significative la connaissance et l'attitude des étudiants à l'égard des soins primaires et certaines compétences de communications. Des études ultérieures devraient examiner l'intérêt des étudiants et le choix de carrière pour cette discipline.

The Vietnamese Version of the Brief Illness Perception Questionnaire and the Beliefs about Medicines Questionnaire: Translation and Cross-cultural Adaptation.

OBJECTIVE: To translate and cross-culturally adapt the Brief Illness Perception Questionnaire (BIPQ) and the Beliefs about Medicines Questionnaire (BMQ) into Vietnamese. METHODS: We followed the guideline by Beaton et al. (2000 & 2007). Stage I: two translators (informed and uninformed) translated the questionnaires. Stage II: the translations were synthesised. Stage III: back translation was performed by two translators fluent in both Vietnamese and English but naïve to the outcome measurement. Stage IV: seven experts reached consensus on the pre-final Vietnamese version (BIPQ-V and BMQ-V). Stage V: field test of the questionnaires on 16 twelve-year-old students and 31 Vietnamese patients. In addition, we determined the internal consistency and test-retest reliability of the questionnaires in 34 Vietnamese patients with acute coronary syndrome. RESULTS: All experts agreed that there was semantic, idiomatic, experiential and conceptual equivalence between the original and pre-final Vietnamese versions of the BIPQ and BMQ. Cronbach's alpha coefficients of the internal consistency were acceptable for the BMQ-V Specific-Necessity (0.64), BMQ-V Specific-Concerns (0.62) and BMQ-V General-Harm (0.60), with the exception of BMQ-V General-Overuse (0.27). Intra-class correlation coefficients of the test-retest reliability were acceptable for the subscales of BMQ-V (range: 0.77-0.86), and BIPQ-V items (range: 0.62-0.85) with the exception of BIPQ-V 1 (0.44, 95% CI -014 to 0.72) and BIPQ-V 4 (0.57, 95% CI 0.22-0.81). CONCLUSIONS: The Vietnamese version of BIPQ and BMQ are reliable tools to assess illness perceptions and beliefs about medicines of patients with acute coronary syndrome. Psychometric properties of these questionnaires should be tested in different patient populations.

OBJECTIF: Traduire en vietnamien et adapter culturellement le Bref Questionnaire sur la Perception de la Maladie (BIPQ) et le Questionnaire sur les Croyances relatives aux Médicaments (BMQ). MÉTHODES: Nous avons suivi les directives de Beaton et al. (2000 et 2007). Etape I: deux traducteurs (informés et non informés) ont traduit les questionnaires. Etape II: les traductions ont été synthétisées. Etape III: une re-traduction a été effectuée par deux traducteurs parlant couramment le vietnamien et l'anglais mais naïfs sur la mesure des résultats. Etape IV: sept experts sont parvenus à un consensus sur la version vietnamienne pré-finale (BIPQ-V et BMQ-V). Etape V: test sur le terrain des questionnaires sur 16 étudiants de 12 ans et 31 patients vietnamiens. En outre, nous avons déterminé la cohérence interne et la fiabilité du test/re-test des questionnaires chez 34 patients vietnamiens atteints de syndrome coronarien aigu. RÉSULTATS: Tous les experts ont convenu qu'il existait une équivalence sémantique, idiomatique, expérientielle et conceptuelle entre les versions originales et pré-finale vietnamiennes du BIPQ et du BMQ. Les coefficients alpha de cohérence interne de Cronbach étaient acceptables pour la nécessité spécifique du BMQ-V (0,64), les préoccupations spécifiques du BMQ-V (0,62) et la nocivité générale du BMQ-V (0,60), à l'exception de la qualité générale du BMQ-V (0,27). Les coefficients de corrélation intra-classe de la fiabilité du test/re-test étaient acceptables pour les sous-échelles de BMQ-V (plage: 0,77-0,86) et les éléments du BIPQ-V (plage: 0,62-0,85) à l'exception du BIPQ-V 1 (0,44; IC95%: −014-0,72) et du BIPQ-V 4 (0,57; IC95%: 0,22-0,81). CONCLUSIONS: Les versions vietnamiennes du BIPQ et du BMQ constituent des outils fiables pour évaluer les perceptions relatives à la maladie et les croyances concernant les médicaments destinés aux patients atteints du syndrome coronarien aigu. Les propriétés psychométriques de ces questionnaires doivent être testées dans différentes populations de patients.

Pharmacist-Led Intervention to Enhance Medication Adherence in Patients With Acute Coronary Syndrome in Vietnam: A Randomized Controlled Trial.

Background: Patient adherence to cardioprotective medications improves outcomes of acute coronary syndrome (ACS), but few adherence-enhancing interventions have been tested in low-income and middle-income countries. Objectives: We aimed to assess whether a pharmacist-led intervention enhances medication adherence in patients with ACS and reduces mortality and hospital readmission. Methods: We conducted a randomized controlled trial in Vietnam. Patients with ACS were recruited, randomized to the intervention or usual care prior to discharge, and followed 3 months after discharge. Intervention patients received educational and behavioral interventions by a pharmacist. Primary outcome was the proportion of adherent patients 1 month after discharge. Adherence was a combined measure of self-reported adherence (the 8-item Morisky Medication Adherence Scale) and obtaining repeat prescriptions on time. Secondary outcomes were (1) the proportion of patients adherent to medication; (2) rates of mortality and hospital readmission; and (3) change in quality of life from baseline assessed with the European Quality of Life Questionnaire - 5 Dimensions - 3 Levels at 3 months after discharge. Logistic regression was used to analyze data. Registration: ClinicalTrials.gov (NCT02787941). Results: Overall, 166 patients (87 control, 79 intervention) were included (mean age 61.2 years, 73% male). In the analysis excluding patients from the intervention group who did not receive the intervention and excluding all patients who withdrew, were lost to follow-up, died or were readmitted to hospital, a greater proportion of patients were adherent in the intervention compared with the control at 1 month (90.0% vs. 76.5%; adjusted OR = 2.77; 95% CI, 1.01-7.62) and at 3 months after discharge (90.2% vs. 77.0%; adjusted OR = 3.68; 95% CI, 1.14-11.88). There was no significant difference in median change of EQ-5D-3L index values between intervention and control [0.000 (0.000; 0.275) vs. 0.234 (0.000; 0.379); p = 0.081]. Rates of mortality, readmission, or both were 0.8, 10.3, or 11.1%, respectively; with no significant differences between the 2 groups. Conclusion: Pharmacist-led interventions increased patient adherence to medication regimens by over 13% in the first 3 months after ACS hospital discharge, but not quality of life, mortality and readmission. These results are promising but should be tested in other settings prior to broader dissemination.

Enhancing prescribing of guideline-recommended medications for ischaemic heart diseases: a systematic review and meta-analysis of interventions targeted at healthcare professionals.

OBJECTIVES: Ischaemic heart diseases (IHDs) are a leading cause of death worldwide. Although prescribing according to guidelines improves health outcomes, it remains suboptimal. We determined whether interventions targeted at healthcare professionals are effective to enhance prescribing and health outcomes in patients with IHDs. METHODS: We systematically searched PubMed and EMBASE for studies published between 1 January 2000 and 31 August 2017. We included original studies of interventions targeted at healthcare professionals to enhance prescribing guideline-recommended medications for IHDs. We only included randomised controlled trials (RCTs). Main outcomes were the proportion of eligible patients receiving guideline-recommended medications, the proportion of patients achieving target blood pressure and target low-density lipoprotein-cholesterol (LDL-C)/cholesterol level and mortality rate. Meta-analyses were performed using the inverse-variance method and the random effects model. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: We included 13 studies, 4 RCTs (1869 patients) and 9 cluster RCTs (15 224 patients). 11 out of 13 studies were performed in North America and Europe. Interventions were of organisational or professional nature. The interventions significantly enhanced prescribing of statins/lipid-lowering agents (OR 1.23; 95% CI 1.07 to 1.42, P=0.004), but not other medications (aspirin/antiplatelet agents, beta-blockers, ACE inhibitors/angiotensin II receptor blockers and the composite of medications). There was no significant association between the interventions and improved health outcomes (target LDL-C and mortality) except for target blood pressure (OR 1.46; 95% CI 1.11 to 1.93; P=0.008). The evidence was of moderate or high quality for all outcomes. CONCLUSIONS: Organisational and professional interventions improved prescribing of statins/lipid-lowering agents and target blood pressure in patients with IHDs but there was little evidence of change in other outcomes. PROSPERO REGISTRATION NUMBER: CRD42016039188.

Association between in-hospital guideline adherence and postdischarge major adverse outcomes of patients with acute coronary syndrome in Vietnam: a prospective cohort study.

OBJECTIVE: We aimed to determine the association between physician adherence to prescribing guideline-recommended medications during hospitalisation and 6-month major adverse outcomes of patients with acute coronary syndrome in Vietnam. DESIGN: Prospective cohort study. SETTING: The study was carried out in two public hospitals in Vietnam between January and October 2015. Patients were followed for 6 months after discharge. PARTICIPANTS: Patients who survived during hospitalisation with a discharge diagnosis of acute coronary syndrome and who were eligible for receiving at least one of the four guideline-recommended medications. EXPOSURES: Guideline adherence was defined as prescribing all guideline-recommended medications at both hospital admission and discharge for eligible patients. Medications were antiplatelet agents, beta-blockers, ACE inhibitors or angiotensin II receptor blockers and statins. MAIN OUTCOME MEASURE: Six-month major adverse outcomes were defined as all-cause mortality or hospital readmission due to cardiovascular causes occurring during 6 months after discharge. Cox regression models were used to estimate the association between guideline adherence and 6-month major adverse outcomes. RESULTS: Overall, 512 patients were included. Of those, there were 242 patients (47.3%) in the guideline adherence group and 270 patients (52.3%) in the non-adherence group. The rate of 6-month major adverse outcomes was 30.5%. A 29% reduction in major adverse outcomes at 6 months after discharge was found for patients of the guideline adherence group compared with the non-adherence group (adjusted HR, 0.71; 95% CI, 0.51 to 0.98; p=0.039). Covariates significantly associated with the major adverse outcomes were percutaneous coronary intervention, prior heart failure and renal insufficiency. CONCLUSIONS: In-hospital guideline adherence was associated with a significant decrease in major adverse outcomes up to 6 months after discharge. It supports the need for improving adherence to guidelines in hospital practice in low-income and middle-income countries like Vietnam.

Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease primarily caused by mutations in genes coding for sarcomeric proteins. A molecular-genetic etiology can be established in ~60% of cases. Evolutionarily conserved mitochondrial DNA (mtDNA) haplogroups are susceptibility factors for HCM. Several polymorphic mtDNA variants are associated with a variety of late-onset degenerative diseases and affect mitochondrial function. We examined the role of private, non-haplogroup associated, mitochondrial variants in the etiology of HCM. In 87 Danish HCM patients, full mtDNA sequencing revealed 446 variants. After elimination of 312 (69.9%) non-coding and synonymous variants, a further 109 (24.4%) with a global prevalence > 0.1%, three (0.7%) haplogroup associated and 19 (2.0%) variants with a low predicted in silico likelihood of pathogenicity, three variants: MT-TC: m.5772G>A, MT-TF: m.644A>G, and MT-CYB: m.15024G>A, p.C93Y remained. A detailed analysis of these variants indicated that none of them are likely to cause HCM. In conclusion, private mtDNA mutations are frequent, but they are rarely, if ever, associated with HCM.

Physicians' adherence to acute coronary syndrome prescribing guidelines in Vietnamese hospital practice: a cross-sectional study.

OBJECTIVES: To determine the extent of physicians' adherence to prescribing guidelines for acute coronary syndrome in Vietnamese hospitals. METHODS: Retrospective cross-sectional study of medical records of all patients with ACS admitted to two public hospitals in Ho Chi Minh City, Vietnam, from January to December 2013. Percentages of eligible patients receiving guideline-recommended medications were determined. Factors associated with non-adherence were identified using multivariate logistic regression. RESULTS: Overall, 711 medical records were reviewed and 284 patients fulfilled inclusion criteria (mean age 64 years; 69.4% male). Of those patients eligible for treatment, aspirin was prescribed for 97.9% at arrival and 96.3% at discharge; dual antiplatelet therapy was prescribed for 92.3% at arrival and 91.7% at discharge; loading doses were prescribed for 79.5% (aspirin) and 55.8% (clopidogrel); beta blockers were prescribed for 58.7% at arrival and 76.7% at discharge; angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were prescribed for 89.1% at arrival or discharge; and statins were prescribed for 94.1% at arrival and 90.7% at discharge. Patients undergoing an invasive procedure were more likely to receive guideline-recommended medications at discharge: dual antiplatelet therapy (OR 3.77; 95% CI 1.23-11.52), beta blocker (OR 3.95; 95% CI 1.86-8.40) and ACEI/ARB (OR 4.01; 95% CI 1.30-12.41). Ninety of the excluded patients were discharged without completing treatment. CONCLUSIONS: In general, physicians closely adhered to ACS prescribing guidelines in Vietnamese hospital practice. Prescribing of beta blockers and clopidogrel loading doses was probably suboptimal. Why patients do not complete treatment needs to be investigated.

Long QT syndrome in South Africa: the results of comprehensive genetic screening.

Congenital long QT syndrome (cLQTS) is a genetic disorder predisposing to ventricular arrhythmia, syncope and sudden death. Over 700 different cLQTS-causing mutations in 13 genes are known. The genetic spectrum of LQTS in 44 South African cLQTS patients (23 known to carry the South African founder mutation p.A341V in KCNQ1) was established by screening for mutations in the coding regions of KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A, the most frequently implicated cLQTS-causing genes (five-gene screening). Fourteen disease-causing mutations were identified, eight (including the founder mutation) in KCNQ1, five in KCNH2 and one in KCNE1. Two mutations were novel. Two double heterozygotes were found among the 23 families (8.5%) carrying the founder mutation. In conclusion, cLQTS in South Africa reflects both a strong founder effect and a genetic spectrum similar to that seen in other populations. Consequently, five-gene screening should be offered as a standard screening option, as is the case internationally. This will disclose compound and double heterozygotes. Fivegene screening will most likely be even more informative in other South African sub-populations with a greater genetic diversity.

Noncovalent assembly of targeted carbon nanovectors enables synergistic drug and radiation cancer therapy in vivo.

Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off-target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. In an in vitro system, we previously demonstrated that targeted drug delivery to cancer cells overexpressing epidermal growth factor receptor (EGFR+) can be achieved by poly(ethylene glycol)-functionalized carbon nanovectors simply mixed with a drug, paclitaxel, and an antibody that binds to the epidermal growth factor receptor, cetuximab. This construct is unusual in that all three components are assembled through noncovalent interactions. Here we show that this same construct is effective in vivo, enhancing radiotherapy of EGFR+ tumors. This targeted nanovector system has the potential to be a new therapy for head and neck squamous cell carcinomas, deserving of further preclinical development.

Noncovalent functionalization of carbon nanovectors with an antibody enables targeted drug delivery.

Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off-target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. We previously demonstrated that poly(ethylene glycol)-functionalized carbon nanovectors are able to sequester paclitaxel, a widely used hydrophobic cancer drug, by simple physisorption and thereby deliver the drug for killing of cancer cells. The cell-killing when these drug-loaded carbon nanoparticles were used was equivalent to when a commercial formulation of paclitaxel was used. Here we show that by further mixing the drug-loaded nanoparticles with Cetuximab, a monoclonal antibody that recognizes the epidermal growth factor receptor (EGFR), paclitaxel is preferentially targeted to EGFR+ tumor cells in vitro. This supports progressing to in vivo studies. Moreover, the construct is unusual in that all three components are assembled through noncovalent interactions. Such noncovalent assembly could enable high-throughput screening of drug/antibody combinations.

Effective drug delivery, in vitro and in vivo, by carbon-based nanovectors noncovalently loaded with unmodified Paclitaxel.

Many new drugs have low aqueous solubility and high therapeutic efficacy. Paclitaxel (PTX) is a classic example of this type of compound. Here we show that extremely small (<40 nm) hydrophilic carbon clusters (HCCs) that are PEGylated (PEG-HCCs) are effective drug delivery vehicles when simply mixed with paclitaxel. This formulation of PTX sequestered in PEG-HCCs (PTX/PEG-HCCs) is stable for at least 20 weeks. The PTX/PEG-HCCs formulation was as effective as PTX in a clinical formulation in reducing tumor volumes in an orthotopic murine model of oral squamous cell carcinoma. Preliminary toxicity and biodistribution studies suggest that the PEG-HCCs are not acutely toxic and, like many other nanomaterials, are primarily accumulated in the liver and spleen. This work demonstrates that carbon nanomaterials are effective drug delivery vehicles in vivo when noncovalently loaded with an unmodified drug.

Sleep apnea in early and advanced chronic kidney disease: Kaiser Permanente Southern California cohort.

BACKGROUND: Sleep apnea (SA) has been reported to be highly prevalent in the dialysis population. The reported rates of SA in dialysis are severalfold greater than the 2 to 4% estimated in the general population. This study sought to determine whether an association exists between SA and early stages of chronic kidney disease (CKD) where SA may represent an important comorbidity and potential risk factor in kidney disease. METHODS: Cross-sectional study of adults from an integrated health plan with documented serum creatinine levels in the period January 1, 2002, through December 31, 2004. SA diagnosis determined by International Classification of Diseases, ninth revision, coding for SA and Current Procedural Terminology coding for positive airway pressure devices. Kidney function was determined by the estimated glomerular filtration rate (eGFR). Logistic was regression used to estimate the relative risk for SA. RESULTS: The overall prevalence of SA was 2.5% in the study population that included subjects with normal renal function and those with CKD. The odds ratios (ORs) for SA by eGFRs of 75 to 89, 60 to 74, 45 to 59, 30 to 44, and 15 to 29 mL/min per 1.73 m(2), respectively, compared to normal kidney function, after adjustment for age, sex, and number of visits, were as follows: 1.22 (95% confidence interval [CI], 1.18 to 1.25); 1.32 (95% CI, 1.27 to 1.37); 1.42 (95% CI, 1.35 to 1.50); 1.37 (95% CI, 1.25 to 1.50); and 1.32 (95% CI, 1.13 to 1.55). The increased ORs for eGFRs > 45 mL/min per 1.73 m(2) were sustained even after controlling for diabetes, heart failure, and hypertension. CONCLUSION: This study demonstrated an increased risk of SA in patients with early CKD. Further evidence of a causal relationship should be sought in the hope that the detection and management of SA may improve the course of CKD.

Prevalence of nondiabetic renal disease in diabetic patients.

BACKGROUND: Diabetic nephropathy is the leading cause of end-stage renal disease in the USA, yet most patients with type 2 diabetes mellitus are not formally evaluated with a renal biopsy. Our aim was to evaluate the prevalence of nondiabetic renal disease (NDRD) in patients with type 2 diabetes mellitus to determine common clinical indicators suggestive of NDRD. METHODS: A retrospective analysis was performed on biopsy reports of patients who had undergone native renal biopsy between January 1, 1995, and December 31, 2005. RESULTS: After exclusion of 57 patients, 233 patients with DM2 were included in our analysis. Mean age at the time of biopsy was 58.1 +/- 13.7 years, and 53.0% of the study population were male. There were 124 cases (53.2%) with a pathologic diagnosis of NDRD, 64 (27.5%) with pure diabetic glomerulosclerosis (DGS) and 45 (19.3%) with concurrent NDRD and DGS (CD). Patients with NDRD tended to be younger than those with DGS and had significantly less associated diabetic retinopathy. Focal segmental glomerulosclerosis was the most common lesion found in patients with NDRD and accounted for 21.0% of all NDRD, followed by minimal-change disease (15.3%). IgA nephropathy (15.6%) and membranous glomerulonephritis (13.3%) were the most prevalent lesions found in patients with CD. CONCLUSIONS: The high prevalence of NDRD found in our population underscores the need for clinicians to consider renal biopsy in diabetic patients with an atypical clinical course, since additional disease-specific therapies may be helpful for this subset of the population.

A novel isoform of glucan, water dikinase phosphorylates pre-phosphorylated alpha-glucans and is involved in starch degradation in Arabidopsis.

An Arabidopsis thaliana gene encoding a homologue of the potato alpha-glucan, water dikinase GWD, previously known as R1, was identified by screening the Arabidopsis genome and named AtGWD3. The AtGWD3 cDNA was isolated, heterologously expressed and the protein was purified to apparent homogeneity to determine the enzymatic function. In contrast to the potato GWD protein, the AtGWD3 primarily catalysed phosphorylation at the C-3 position of the glucose unit of preferably pre-phosphorylated amylopectin substrate with long side chains. An Arabidopsis mutant, termed Atgwd3, with downregulated expression of the AtGWD3 gene was analysed. In Atgwd3 the amount of leaf starch was constantly higher than wild type during the diurnal cycle. Compared with wild-type leaf starch, the level of C-3 phosphorylation of the glucosyl moiety of starch in this mutant was reduced. Taken together, these data indicate that the C-3 linked phospho-ester in starch plays a so far unnoticed specific role in the degradation of transitory starch.