100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial).

BACKGROUND: This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer (OC). METHODS: This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III-IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for ≥20 months. RESULTS: Of the 1119 women included, 66.9% had Stage III disease, 11.7% had a deleterious BRCA mutation, and 26.6% received bevacizumab; 40.8% and 39.3% underwent primary debulking surgery (PDS) and interval debulking surgery (IDS), respectively. Of the patients who underwent PDS, 55.5% had no visible residual disease (VRD); 63.9% of the IDS patients had no VRD. According to physician-assessed responses (at the first assessment after diagnosis and treatment), 53.2% of the total population had a complete response and 25.7% had a partial response to first-line chemotherapy after surgery. After ≥20 months of follow-up, 32.9% of the patients were disease-free, 46.4% had progressive disease, and 20.6% had died. Bevacizumab use had a significant positive effect on overall survival (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91; p = .01). A deleterious BRCA status had a significant positive effect on progression-free survival (HR, 0.60; 95% CI, 0.41-0.84; p < .01). CONCLUSIONS: Women with advanced high-grade serous or endometrioid OC have a poor prognosis. Bevacizumab use and a deleterious BRCA status were found to improve survival in this real-world population. LAY SUMMARY: Patients with advanced (Stage III or IV) ovarian cancer (OC) have a poor prognosis. The standard treatment options of surgery and chemotherapy extend life beyond diagnosis for 5 years or more in only approximately 45% of patients. This study was aimed at describing the standard of care in eight Western countries and estimating how many patients who are diagnosed with high-grade serous or endometrioid OC could potentially be eligible for first-line poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) maintenance therapy. The results highlight the poor prognosis for these patients and suggest that a significant proportion (79%) would potentially be eligible for first-line PARPi maintenance treatment.

Microfluidic-Derived Detection of Protein-Facilitated Copper Flux Across Lipid Membranes.

Measurement of protein-facilitated copper flux across biological membranes is a considerable challenge. Here, we demonstrate a straightforward microfluidic-derived approach for visualization and measurement of membranous Cu flux. Giant unilamellar vesicles, reconstituted with the membrane protein of interest, are prepared, surface-immobilized, and assessed using a novel quencher-sensor reporter system for detection of copper. With the aid of a syringe pump, the external buffer is exchanged, enabling consistent and precise exchange of solutes, without causing vesicle rupture or uneven local metal concentrations brought about by rapid mixing. This approach bypasses common issues encountered when studying heavy metal-ion flux, thereby providing a new platform for in vitro studies of metal homeostasis aspects that are critical for all cells, health, and disease.

Mortality and cause of death in persons with chronic hepatitis B virus infection versus healthy persons from the general population in Denmark.

The study aimed to determine adjusted all-cause mortality and cause of death in persons with chronic hepatitis B virus (HBV) infection compared with age- and sex-matched persons from the general population. We used nationwide registers to identify persons aged ≥18 years with chronic HBV infection in 2002-2017 in Denmark and included 10 age- and sex-matched controls for each. Follow-up was from 6 months after diagnosis until death, emigration, or 31 December 2017. Mortality rate ratios (MRRs) adjusted for age, sex, employment, origin and comorbidity were calculated using Poisson regression. Unadjusted cause-specific mortality rate ratios with 95% confidence intervals were calculated assuming a Poisson distribution. A total of 6988 persons with chronic HBV infection and 69,847 controls were included. During a median follow-up of 7.7 years (range 0.0-15.5), 315 (5%) persons with-and 1525 (2%) without-chronic HBV infection died. The adjusted all-cause MRR was 1.5 (95% CI 1.2-2.0). Persons with chronic HBV infection had increased mortality due to liver disease including hepatocellular carcinoma (MRR 12.3 [8.6-17.7]), external causes (MRR 3.3 [2.5-4.7]), endocrine disease (MRR 3.2 [1.8-5.4]), genitourinary disease (MRR 3.2 [1.2-7.6]) and neoplasms (except hepatocellular carcinoma; MRR 1.6 [1.2-2.0]). In conclusion, this study showed an increased all-cause mortality in persons with chronic HBV infection in comparison with age- and sex-matched persons without chronic HBV infection which remained after adjustment for several confounding factors. Excess mortality was mainly associated with liver disease, but also external factors, endocrine disease, genitourinary disease and neoplasms (excluding hepatocellular carcinoma).

Risk of Anal High-grade Squamous Intraepithelial Lesions Among Renal Transplant Recipients Compared With Immunocompetent Controls.

BACKGROUND: Renal transplant recipients (RTRs) have increased risk of human papillomavirus (HPV)-related cancers, including anal cancer. We investigated the prevalence of anal high-grade intraepithelial lesions (HSILs) in RTRs compared with immunocompetent controls and risk factors for anal HSIL in RTRs. METHODS: We included 247 RTRs and 248 controls in this cross-sectional study. We obtained anal samples for HPV testing with INNO-LiPA and performed high-resolution anoscopy on all participants. The participants completed a questionnaire on lifestyle and sexual habits. We used logistic regression to estimate odds ratios (ORs) of histologically confirmed anal HSIL in RTRs vs controls and risk factors for anal HSIL in RTRs, stratified by sex and anal high-risk (hr) HPV status, adjusting for age, smoking, lifetime sexual partners, and receptive anal sex. RESULTS: RTRs had higher anal HSIL prevalence than controls, both among men (6.5% vs 0.8%; adjusted OR [aOR], 11.21 [95% confidence interval {CI}, 1.46-291.17]) and women (15.4% vs 4.0%; aOR, 6.41 [95% CI, 2.14-24.10]). Among those with anal hrHPV, RTRs had higher anal HSIL prevalence than controls (33.8% vs 9.5%; aOR, 6.06 [95% CI, 2.16-20.27]). Having had receptive anal sex (aOR, 6.23 [95% CI, 2.23-19.08]) or genital warts (aOR, 4.21 [95% CI, 1.53-11.48]) were risk factors for anal HSIL in RTRs. All HSIL cases occurred in individuals with anal hrHPV. CONCLUSIONS: RTRs had increased risk of anal HSIL compared with immunocompetent controls, with particularly high prevalence in female RTRs. Receptive anal sex, previous genital warts, and anal hrHPV infection were risk factors for anal HSIL in RTRs. Screening for anal HSIL in RTRs should be considered. CLINICAL TRIALS REGISTRATION: NCT03018927.

Peptide-Oleate Complexes Create Novel Membrane-Bound Compartments.

A challenging question in evolutionary theory is the origin of cell division and plausible molecular mechanisms involved. Here, we made the surprising observation that complexes formed by short alpha-helical peptides and oleic acid can create multiple membrane-enclosed spaces from a single lipid vesicle. The findings suggest that such complexes may contain the molecular information necessary to initiate and sustain this process. Based on these observations, we propose a new molecular model to understand protocell division.

Risk of Anogenital Warts in Renal Transplant Recipients Compared with Immunocompetent Controls: A Cross-sectional Clinical Study.

Renal transplant recipients have increased risk of human papilloma virus-related anogenital (pre)cancers. Less is known about their risk of anogenital warts. The aim of this study was to estimate the prevalence and odds of anogenital warts in renal transplant recipients compared with immunocompetent controls, and to assess risk factors for intra- and perianal warts in renal transplant recipients. The study examined 248 renal transplant recipients and 250 controls for cutaneous and mucosal anogenital warts. Participants completed a questionnaire on lifestyle and sexual habits. For external anogenital warts (including penile, vulvar and perianal warts), renal transplant recipients had higher prevalence and odds than controls, both in men (8.1% vs 1.6%, adjusted odds ratio (ORadjusted)=5.09, 95% confidence interval (95% CI), 1.03-25.04) and women (11.3% vs 1.6%, ORadjusted=8.09, 95% CI 1.69-38.82). For intra-anal warts, there was no clear pattern of higher odds in renal transplant recipients than controls. Current smoking and having had receptive anal sex increased the risk of intra-/perianal warts in renal transplant recipients. In conclusion, renal transplant recipients in this study had higher odds of external anogenital warts than controls.

Cemented hemiarthroplasty for femoral neck fracture patients: collarless, polished tapered stem (CPT) versus anatomic matte stem (Lubinus SP2).

BACKGROUND: Cemented hemiarthroplasty is a well-documented treatment for patients with femoral neck fractures (FNFs). However, there are not many cohort studies comparing different types of hemiarthroplasty (HA). OBJECTIVE: To compare CPT and Lubinus SP2 HA for FNF patients concerning complications and radiological measurements. METHODS: From January 1, 2013, CPT was introduced instead of Lubinus SP2 as the new cemented HA due to a regional procurement. Data were retrieved 3 years prior and after the introduction. All patient health records were retrospectively reviewed for types of implant, American Society of Anesthesiologists (ASA) score and duration of admission. All X-ray images were analyzed for radiological measurements concerning offset, stem angulation and cement filling. Mortality and major complications within 1 year were retrieved from patient health records as well as the Danish National Patient Registry. Major complications were defined as dislocations, periprosthetic fractures and revisions. RESULTS: 584 cemented HA were included, 300 CPT and 284 with Lubinus SP2. The mean age (SD) was 82 (8.2) years, and there was no baseline difference between the groups concerning age, sex, ASA score and mortality. There were 8.7% major complications for CPT and 9.2% for Lubinus SP2 (p = 0.836). There were, however, seven periprosthetic fractures in the CPT group and one in the Lubinus SP2 group (p = 0.04). In contrast, there were 20 dislocations in the Lubinus SP2 group and 10 in the CPT group (p = 0.042). There was no statistical difference between the stem angulation and periprosthetic fractures (p = 0.824) or major complications (p = 0.602). The Lubinus SP2 had a mean plus 2.7 mm offset postoperatively (p = 0.001), while the CPT had plus 10.6 mm (p < 0.000). The mean (SD) angle of the stems was 1.39 (1.75) degrees for Lubinus SP2 and 2.46 (1.99) for CPT. There was no difference in cementation (p = 0.308). CONCLUSION: There was no overall statistical difference between the CPT and Lubinus SP2 stem regarding major complications. However, the CPT had a higher prevalence of periprosthetic fractures, while the Lubinus SP2 had a higher dislocation prevalence. The CPT stem had overcorrection of offset and a higher degree of varus positioning.

Campylobacter concisus is prevalent in the gastrointestinal tract of patients with microscopic colitis.

OBJECTIVES: Microscopic colitis (MC) is potentially induced by an inflammatory reaction to a luminal gut factor. The emerging pathogen Campylobacter concisus is associated with prolonged diarrhoea and subsequently increased risk of MC. We aimed to examine the prevalence of C. concisus in clinical samples from MC patients, analyse the subtypes collagenous colitis (CC) and lymphocytic colitis (LC), and characterise C. concisus isolates from MC patients by genomic sequencing. METHODS: Mucosal biopsies were collected by sigmoidoscopy in 55 MC patients (CC n = 34, LC n = 21). Saliva and faecal samples were also collected. A two-step cultivation method and PCR established C. concisus prevalence. Biopsy and faecal isolates were sequenced for genomic analysis. RESULTS: Cultivation revealed C. concisus in saliva 55/55, faeces 14/55 and biopsies 69/436, which was confirmed by PCR in faeces 28/55 and biopsies 215/430. Interestingly, biopsy prevalence was higher in CC patients than in LC patients both by cultivation (50/270 vs.19/166, p = .058) and by PCR (175/270 vs. 40/160, p < .0001). Long disease duration also affected biopsy prevalence both by cultivation 30/244 (<2 years) vs. 39/192 (>2 years) (p = .025) and by PCR 103/239 (<2 years) vs. 112/191 (>2 years) (p = .002). Genomic analysis on sixty biopsy and twenty faecal isolates revealed division into two clusters/genomospecies and a high presence of various, putative virulence genes (zot, exotoxin 9 and hcp). CONCLUSIONS: Campylobacter concisus was prevalent in MC patients. Interestingly, the biopsy prevalence differed in biopsies from CC and LC patients and with regard to disease duration. Further studies are needed to elucidate this possible association.

Prevalence, type distribution and risk factors for oral HPV in Danish renal transplant recipients.

OBJECTIVE: To assess the prevalence and type distribution of oral human papillomavirus (HPV) among renal transplant recipients (RTRs) and healthy controls and to examine risk factors for oral HPV among RTRs. MATERIALS AND METHODS: During 2016-2017 we recruited 250 RTRs and 250 controls. Oral samples were tested for HPV DNA with INNO-LiPA HPV Genotyping Extra II. All participants answered a questionnaire on lifestyle and sexual behaviour, and characteristics of RTRs were obtained from medical files. We assessed prevalence and type distribution of oral HPV. Using logistic regression, the risk of oral HPV and risk factors for oral HPV among RTRs were estimated as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Overall, 30 RTRs (12.1%) and 26 controls (10.4%) were oral HPV positive (OR = 1.14; 95% CI: 0.64-2.05). Female RTRs tended to have a higher oral HPV prevalence than controls (OR = 1.73; 95% CI: 0.63-4.77), while no difference was observed among men. HPV51 was the commonest genotype. Sexual behaviour tended to be associated with oral HPV among RTRs. CONCLUSIONS: There was no overall difference in oral HPV prevalence between RTRs and controls, but female RTRs tended to have a higher prevalence of oral HPV than controls.

Effect of Hydrogen Bonds on the Dielectric Properties of Interfacial Water.

The dielectric constant for water is reduced under confinement. Although this phenomenon is well known, the underlying physical mechanism for the reduction is still in debate. In this work, we investigate the effect of the orientation of hydrogen bonds on the dielectric properties of confined water using molecular dynamics simulations. We find a reduced rotational diffusion coefficient for water molecules close to the solid surface. The reduced rotational diffusion arises due to the hindered rotation away from the plane parallel to the channel walls. The suppressed rotation in turn affects the orientational polarization of water, leading to a low value for the dielectric constant at the interface. We attribute the constrained out-of-plane rotation to originate from a higher density of planar hydrogen bonds formed by the interfacial water molecules.

Reproducibility of the stability-based classification for ankle fractures.

BACKGROUND: Classification of ankle fracture is important when deciding for operative or conservative treatment. This study rates the reproducibility of ankle stability assessment and compares it with the classification by Lauge-Hansen and Arbeitsgemeinschaft für Osteosyntesefragen (AO) in adult patients with primary ankle fractures. METHODS: A total of 496 consecutive ankle fractures were included, and the X-ray images were reviewed 2 times by 2 medical students, 2 residents, and 1 consultant in orthopedic traumatology. The raters were blinded to each other and to their own results. Unweighted Kappa statistics were used to assess reproducibility. RESULTS: Overall mean (95% CI) interrater Kappa results were 0.65 (0.64; 0.68) for Lauge-Hansen, 0.62 (0.60; 0.63) for AO and 0.61 (0.57; 0.62) for the stability assessment. The intrarater results ranged from a mean Kappa of 0.64-0.80 for the medical students, 0.65-0.81 for the residents and 0.82-0.84 for the consultant. CONCLUSION: The stability assessment has substantial to almost-perfect agreement which is comparable to the Lauge-Hansen and AO classifications.

Grazoprevir, ruzasvir, and uprifosbuvir for hepatitis C virus after NS5A treatment failure.

People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682-011 and -012) were open-label, multicenter studies. Participants who had previously relapsed following an NS5A inhibitor-containing all-oral regimen were retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was sustained virologic response (HCV RNA below the limit of quantitation [<15 IU/mL]) 12 weeks after treatment completion (SVR12). In C-SURGE, SVR12 was achieved by 49/49 (100%) and 43/44 (98%) genotype (GT)1 participants in the 24-week no ribavirin arm and the 16-week plus ribavirin arm (lost to follow-up, n = 1), respectively. In C-CREST Part C, SVR12 was achieved by 23/24 (96%) participants treated for 16 weeks with ribavirin (GT1, 2/2 [100%]; GT2, 13/14 [93%]; GT3, 8/8 [100%]). One participant with GT2 infection discontinued study medication after a single dose of grazoprevir, ruzasvir, and uprifosbuvir plus ribavirin due to serious adverse events of vomiting and tachycardia. The presence of baseline resistance-associated substitutions had no impact on SVR12. No participant who completed treatment in either study experienced virologic failure. CONCLUSION: Grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, for 16 or 24 weeks was safe and highly effective in participants with HCV infection who had previously failed NS5A inhibitor-containing therapy. (Hepatology 2017;66:1794-1804).

Mannose-binding lectin genotypes and outcome in end-stage renal disease: a prospective cohort study.

Background: Patients with end-stage renal disease (ESRD) have high morbidity and mortality rates, with cardiovascular diseases and infections being the major causes of death. Mannose-binding lectin (MBL) has been suggested to play a protective role in this regard. The aim of this study was to investigate a possible clinical association of MBL genotypes (MBL2) with outcome among patients on dialysis or with a functioning graft. Methods: A total of 98 patients with ESRD accepted for living-donor renal transplantation or on the waiting list for transplantation were included and prospectively followed for an average of 9 years (range 7.5-9.9). Medical records were evaluated regarding transplantation status, diabetes mellitus, vascular parameters and infections for all the patients. Cox regression models and logistic regression analysis were used for statistical analyses. The cohort was divided into two groups according to the MBL2 genotype (normal A/A versus variant A/O or O/O). Results: We found no evidence for an association between the MBL2 genotype and all-cause mortality, cardiovascular events or bacterial infections (pneumonia, urinary tract infection, fistula infection or other infections). Conclusion: In this cohort, the MBL2 genotype did not seem to be associated with any long-term clinical effects in ESRD patients on dialysis or with a functioning graft.

Is early measles vaccination associated with stronger survival benefits than later measles vaccination?

BACKGROUND: Measles vaccine (MV) may protect against non-measles mortality. We tested whether survival depended on age of measles vaccination. METHODS: Bandim Health Project follows children under 5 years of age through a Health and Demographic Surveillance System in rural Guinea-Bissau. Children aged 6-36 months with a vaccination card inspected were followed to the next visit or for a maximum of 6 months. In Cox proportional-hazards models adjusted for age and village cluster, we compared the survival of children vaccinated with MV early (< 9 months), as recommended (9-11 months) or late (> 12+ months) with the survival of measles-unvaccinated children. Among measles-vaccinated children, we modelled the effect of age at measles vaccination linearly to assess mortality changes per month increase in vaccination age. RESULTS: From 1999 to 2006, 14,813 children (31,725 observations) were included. Children vaccinated with MV had a Hazard Ratio (HR) of 0.76 (95% CI: 0.63-0.91) compared with measles-unvaccinated children; censoring measles deaths did not change the results (HR = 0.79 (0.65-0.95)). For early MV the HR was 0.68 (0.53-0.87), for MV as recommended the HR was 0.77 (0.62-0.96) and for late MV the HR was 0.86 (0.67-1.11). Limiting the analysis to measles-vaccinated children, age at measles vaccination was associated with a 2.6% (0.4-5.1%) increase in mortality per month increase in vaccination age. CONCLUSION: Early MV was associated with a large survival advantage. The current policy to increase vaccination age, when measles control improves, may not optimize the impact of MV on child survival.

Does Left Atrial Appendage Amputation During Routine Cardiac Surgery Reduce Future Atrial Fibrillation and Stroke?

PURPOSE OF REVIEW: Stroke is the most feared complication of atrial fibrillation. To prevent stroke, left atrial appendage exclusion has been targeted, as it is the prevalent site for formation of heart thrombi during atrial fibrillation. We review the historic development of methods for exclusion of the left atrial appendage and the evidence to support its amputation during routine cardiac surgery. RECENT FINDINGS: Evidence is not yet sufficient to routinely recommend left atrial exclusion during heart surgery, despite a high prevalence of postoperative atrial fibrillation. Observational studies indicate that electrical isolation of scarring from clip or suture techniques reduces the arrhythmogenic substrate. Randomized studies comparing different methods of closure of the left atrial appendage before amputation do not exist. Such studies are therefore warranted, as well as studies that can elucidate whether amputation is superior to leaving the left atrial appendage stump. Potentially, thrombogenic remaining pouch after closure should be addressed.

Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins.

Orthodox aquaporins are transmembrane channel proteins that facilitate rapid diffusion of water, while aquaglyceroporins facilitate the diffusion of small uncharged molecules such as glycerol and arsenic trioxide. Aquaglyceroporins play important roles in human physiology, in particular for glycerol metabolism and arsenic detoxification. We have developed a unique system applying the strain of the yeast Pichia pastoris, where the endogenous aquaporins/aquaglyceroporins have been removed and human aquaglyceroporins AQP3, AQP7, and AQP9 are recombinantly expressed enabling comparative permeability measurements between the expressed proteins. Using a newly established Nuclear Magnetic Resonance approach based on measurement of the intracellular life time of water, we propose that human aquaglyceroporins are poor facilitators of water and that the water transport efficiency is similar to that of passive diffusion across native cell membranes. This is distinctly different from glycerol and arsenic trioxide, where high glycerol transport efficiency was recorded.

The impact of kidney transplantation on insulin sensitivity.

To investigate the impact of kidney transplantation (KTx) on insulin sensitivity affecting glucose metabolism. 9 nondiabetic patients awaiting living donor KTx were examined prior to transplantation with an oral glucose tolerance test and a 3-h hyperinsulinaemic-euglycaemic clamp. The clamp was repeated 6 months after KTx. Nine age-, gender- and body mass index (BMI)-matched individuals with normal kidney function served as controls. Endogenous glucose production and glucose disappearance rate (N = 6) were measured in a subgroup of patients with corresponding controls. Results presented as mean [range]. Two patients had pretransplant prediabetes, whereas all others had normal glucose tolerance. After KTx, average glucose infusion rate to maintain euglycaemia during clamp declined significantly from 15.1 [9.1-23.7] to 9.8 [2.8-14.6] µmol/kg/min (P < 0.01) with 20.2 [9.9-33.7] µmol/kg/min in controls. Endogenous glucose production increased from 7.0 [4.8-8.5] to 9.4 [7.4-11.8] µmol/kg/min (P < 0.05) with 7.0 [-3.8 to 10.1] µmol/kg/min in controls. Glucose disappearance rate was unchanged (18.1 [12.9-24.5] vs. 17.1 [12.2-22.7] µmol/kg/min, NS) with 22.3 [14.6-34.3] in controls. In conclusion, insulin sensitivity is reduced 6 months after KTx and characterized mainly by impaired suppression of the endogenous glucose production.