The pattern of cortical thickness associated with executive dysfunction in MCI and SCC: The MEMENTO cohort.

BACKGROUND: The association between the pattern of cortical thickness (CT) and executive dysfunction (ED) in mild cognitive impairment (MCI) and subjective cognitive complaints (SCC) is still poorly understood. We aimed to investigate the association between CT and ED in a large French cohort (MEMENTO) of 2323 participants with MCI or SCC. METHODS: All participants with available CT and executive function data (verbal fluency and Trail Making Test [TMT]) were selected (n=1924). Linear regressions were performed to determine relationships between executive performance and the brain parenchymal fraction (BPF) and CT using FreeSurfer. RESULTS: The global executive function score was related to the BPF (sß: 0.091, P<0.001) and CT in the right supramarginal (sß: 0.060, P=0.041) and right isthmus cingulate (sß: 0.062, P=0.011) regions. Literal verbal fluency was related to the BPF (sß: 0.125, P<0.001) and CT in the left parsorbitalis region (sß: 0.045, P=0.045). Semantic verbal fluency was related to the BPF (sß: 0.101, P<0.001) and CT in the right supramarginal region (sß: 0.061, P=0.042). The time difference between the TMT parts B and A was related to the BPF (sß: 0.048, P=0.045) and CT in the right precuneus (sß: 0.073, P=0.019) and right isthmus cingulate region (sß: 0.054, P=0.032). CONCLUSIONS: In a large clinically based cohort of participants presenting with either MCI or SCC (a potential early stage of Alzheimer's disease [AD]), ED was related to the BPF and CT in the left pars orbitalis, right precuneus, right supramarginal, and right isthmus cingulate regions. This pattern of lesions adds knowledge to the conventional anatomy of ED and could contribute to the early diagnosis of AD.

[ARENA-Project atrial fibrillation in the Rhein-Neckar region]. / ARENA ­ Projekt Vorhofflimmern in der Rhein-Neckar-Region.

Atrial fibrillation (AF) is the most common form of cardiac tachyarrhythmia. It is estimated that in the Rhein-Neckar region approximately 40,000-50,000 out of 2 million people are affected. Due to demographic changes in the near future there will be a significant increase in the prevalence of AF within the next decades. The ARENA project was initiated by the Foundation Institute for Cardiac Infarction Research (IHF) Ludwigshafen in cooperation with cardiological and neurological departments of neighboring hospitals, resident doctors and pharmacies to improve the awareness and care of patients with AF. The particular aim is the prevention of stroke as one of the most dreaded complications. The project focusses on the following three subtopics: interventions, medication, migration. The aim of the intervention project is to raise awareness of AF as a risk factor for stroke and to improve the diagnostic work-up and care for patients with diagnosed or unknown AF. The subproject medication focusses on the adherence of patients with AF to the prescribed antithrombotic medication. To evaluate differences concerning patients with and without a migration background the subproject migration was initiated.

Assessing forest availability for wood supply in Europe.

The quantification of forests available for wood supply (FAWS) is essential for decision-making with regard to the maintenance and enhancement of forest resources and their contribution to the global carbon cycle. The provision of harmonized forest statistics is necessary for the development of forest associated policies and to support decision-making. Based on the National Forest Inventory (NFI) data from 13 European countries, we quantify and compare the areas and aboveground dry biomass (AGB) of FAWS and forest not available for wood supply (FNAWS) according to national and reference definitions by determining the restrictions and associated thresholds considered at country level to classify forests as FAWS or FNAWS. FAWS represent between 75 and 95 % of forest area and AGB for most of the countries in this study. Economic restrictions are the main factor limiting the availability of forests for wood supply, accounting for 67 % of the total FNAWS area and 56 % of the total FNAWS AGB, followed by environmental restrictions. Profitability, slope and accessibility as economic restrictions, and protected areas as environmental restrictions are the factors most frequently considered to distinguish between FAWS and FNAWS. With respect to the area of FNAWS associated with each type of restriction, an overlap among the restrictions of 13.7 % was identified. For most countries, the differences in the FNAWS areas and AGB estimates between national and reference definitions ranged from 0 to 5 %. These results highlight the applicability and reliability of a FAWS reference definition for most of the European countries studied, thereby facilitating a consistent approach to assess forests available for supply for the purpose of international reporting.

Explorative Randomized Phase II Clinical Study of the Efficacy and Safety of Finafloxacin versus Ciprofloxacin for Treatment of Complicated Urinary Tract Infections.

The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic conditions. This phase II clinical study compared the efficacies and safeties of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with 800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a 10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68% for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients (64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent-to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin on patients with an acidic urine pH (80% of patients) were reduced, whereas the effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated. Overall, 43.4% of the patients in the FINA05 group, 42.7% in the FINA10 group, and 54.2% in the CIPRO10 group experienced mostly mild and treatment-emergent but unrelated adverse events. A short-course regimen of 5 days of finafloxacin resulted in high eradication and improved clinical outcome rates compared to those for treatment with ciprofloxacin for 10 days. In contrast to those of ciprofloxacin, the clinical effects of finafloxacin were not reduced by acidic urine pH. Hospitalized adults were randomized 1:1:1 to finafloxacin treatment (800 mg q.d.) for either 5 or 10 days or to ciprofloxacin treatment (400 mg/500 mg b.i.d.) for 10 days with an optional switch from intravenous (i.v.) to oral administration at day 3. The primary endpoint was the combined microbiological and clinical response at the TOC visit in the microbiological intent-to-treat population. (This study has been registered at ClinicalTrials.gov under identifier NCT01928433.).

[Ultrasound diagnostics for myotendinous injuries and insertion tendinopathies of the elbow joint]. / Ultraschalldiagnostik bei muskuloligamentären Verletzungen sowie Insertionstendinopathien am Ellenbogengelenk.

INTRODUCTION: Acute capsular injuries of the elbow joint and its ligaments predominantly occur after joint dislocation or subluxation. Together with lateral and medial epicondylitis they represent a common injury pattern in radiology, orthopedic and trauma surgery. CLINICAL ISSUE: Because of the complexity of the elbow joint, knowledge of the elbow dislocation and injury pattern as well as the anatomy is essential in order to adequately estimate the injury severity and joint stability. This is crucial for the correct diagnosis and choice of treatment. Systematic physical examination and careful radiographic evaluation are components of an adequate management of acute soft tissue elbow injuries. DIAGNOSTIC WORK-UP: The cost-effective ultrasound has emerged as a useful imaging modality for the diagnosis of acute joint and soft tissue pathologies especially in the acute phase after injury. Ultrasound as a diagnostic tool enables visualization of motion sequences during dynamic examination and therefore a better understanding of pathologies. Ultrasound examinations of the most common injuries of the elbow joint are presented in this overview.

[CEUS-application possibilities in the musculoskeletal system]. / CEUS ­ Einsatzmöglichkeiten am Bewegungsapparat.

METHODICAL ISSUE: Contrast-enhanced ultrasound (CEUS) offers easily accessible visualization and quantification of the skeletal muscle microcirculation and other tissues in vivo and in real-time with almost no side effects. AIM: The aim of this review is to present the increasing number of musculoskeletal CEUS applications. METHODICAL INNOVATIONS/PERFORMANCE: CEUS applications regarding the musculoskeletal system include applications at bone and joints extending beyond the visualization of only the muscular microcirculation. Besides basic muscle physiology, impaired microcirculation in patients with peripheral artery disease or diabetes mellitus and the diagnosis of inflammatory myopathies have been the subject of previous CEUS studies. More recent studies in orthopedics and traumatology have focused on osseous and muscular perfusion characteristics, e. g., in differentiating infected and aseptic non-unions or the impact of different types of implants and prostheses on muscular microcirculation as a surrogate marker of clinical success. PRACTICAL RECOMMENDATIONS: CEUS of the musculoskeletal system is used in clinical trials or off-label. Therefore, it is not well established in clinical routine. However, considering the increasing number of musculoskeletal CEUS applications, this could change in the future.

[Tibial defects and infected non-unions : Treatment results after Masquelet technique]. / Tibiadefekt- und Infektpseudarthrosen : Behandlungsergebnisse nach Masquelet-Technik.

BACKGROUND: The treatment of non-unions with large bone defects or osteitis is a major challenge in orthopedic and trauma surgery. A new concept of therapy is a two-step procedure: Masquelet technique according to the diamond concept. METHODS: Between February 2010 and June 2014, 55 patients with tibia non-unions or infections were treated in a two-step Masquelet technique in our center. The patients' average age was 48 (median 50; minimum 15-maximum 72) with an average BMI (body mass index) of 28 (27; 18-52). There were 10 (18 %) female and 45 (82 %) male patients in the group. All study patients went through a follow up. Bone healing and clinical functional data were collected, as well as data according to subjective patient statements about pain and everyday limitations. RESULTS: In 42 cases (76.4 %) the outcome was a sufficient bony consolidation. On average, the time to heal was 10.3 (8, 5; 3-40) months, defect gaps were 4 cm (3 cm; 0,6-26 cm), and on average the patients had had 6 (median 4; range 1-31) previous operations . In all cases patients received osteosynthesis as well as a defect filling with RIA (reamer-irrigator-aspirator), and growth factor BMP-7 (bone morphogenetic protein-7). In 13 cases (23.6 %) there was no therapeutic success. In the evaluation of the SF12 questionnaire the mental health score increased from 47.4 (49.1; 27.6-65.7) to 49.8 (53.0; 28.7-69.4) and the well-being score from 32.7 (32.7;16.9-55.7) to 36.6 (36.5; 24.6-55.9). CONCLUSION: The two-step bone grafting method in the Masquelet technique used for tibia non-unions according to the diamond concept is a promising treatment option. Its application for tibia shaft non-unions with large bone defects or infections means a high degree of safety for the patient.

Risk adjustment models for short-term outcomes after surgical resection for oesophagogastric cancer.

BACKGROUND: Outcomes for oesophagogastric cancer surgery are compared with the aim of benchmarking quality of care. Adjusting for patient characteristics is crucial to avoid biased comparisons between providers. The study objective was to develop a case-mix adjustment model for comparing 30- and 90-day mortality and anastomotic leakage rates after oesophagogastric cancer resections. METHODS: The study reviewed existing models, considered expert opinion and examined audit data in order to select predictors that were consequently used to develop a case-mix adjustment model for the National Oesophago-Gastric Cancer Audit, covering England and Wales. Models were developed on patients undergoing surgical resection between April 2011 and March 2013 using logistic regression. Model calibration and discrimination was quantified using a bootstrap procedure. RESULTS: Most existing risk models for oesophagogastric resections were methodologically weak, outdated or based on detailed laboratory data that are not generally available. In 4882 patients with oesophagogastric cancer used for model development, 30- and 90-day mortality rates were 2·3 and 4·4 per cent respectively, and 6·2 per cent of patients developed an anastomotic leak. The internally validated models, based on predictors selected from the literature, showed moderate discrimination (area under the receiver operating characteristic (ROC) curve 0·646 for 30-day mortality, 0·664 for 90-day mortality and 0·587 for anastomotic leakage) and good calibration. CONCLUSION: Based on available data, three case-mix adjustment models for postoperative outcomes in patients undergoing curative surgery for oesophagogastric cancer were developed. These models should be used for risk adjustment when assessing hospital performance in the National Health Service, and tested in other large health systems.

Chronic hepatitis C patients prior to broad access to interferon-free treatments in Germany.

In 2014, the first interferon-free treatment options for chronic Hepatitis C (CHC) became available in Europe introducing a new era of highly effective and well tolerated oral treatment options for CHC. The data from the cross-sectional study CURRENT-C highlights the epidemiological characteristics of patients with CHC in Germany. During the period that the study was conducted, the approval of the combination drugs for the treatment of CHC was imminent.Between June and November 2014, 1471 CHC-patients not receiving anti-HCV treatment were included nationwide in 40 German centers specializing in viral hepatitis. The mean age was 52.4 years with 41.2 % of the patients being female. Presumed route of infection in male patients was most frequently drug use (46.2 %) and blood products in females (22.8 %). The route of infection was unknown in 28.2 % of male and 43.1 % of female patients. Compared to male patients, female patients were older (55.6 vs. 50.1 years) and longer diagnosed with HCV (18 vs. 15 years). First language of the patients was most frequently German (72.2 %), followed by Russian (14.2 %), and Polish (2.9 %). HCV genotype (GT) 1 was found in 73.8 % (1a 29.0 %, 1b 38.4 %), GT2 in 3.5 %, GT3 in 18.3 %, GT4 in 4.2 %, GT5 in 0.2 %, and GT6 in 0.3 %. Liver cirrhosis was diagnosed in 15.7 % of the patients (17.1 % male, 13.7 % female). 43.2 % of the patients had already received HCV treatment, most frequently dual therapy with pegIFN + RBV (75.8 %) or triple therapy with telaprevir or boceprevir (20.3 %). Compared to treatment-naïve patients, pretreated HCV patients were older (55.1 vs. 50.3 years) and more frequently had liver cirrhosis as clinical diagnosis (22.2 % vs. 10.8 %). Patients scheduled for HCV treatment within the next 3 months had higher rates of pre-treatment (49.4 % vs. 37.0 %), and liver cirrhosis (21.4 % vs. 10.0 %).Compared to epidemiological data of Hüppe et al. 1 from 2003 to 2006, Klass et al. 2 stated in 2012 in a comparable setting that the German CHC population were older and had more advanced liver disease. The current data seem to support this ongoing trend towards more difficult to treat patients with an urgent need for new treatment options.

Quantitative ultrasonometry during pregnancy and lactation: a longitudinal study.

UNLABELLED: This study describes bone mass changes during pregnancy and lactation measured by a special ultrasound method. Pregnant women showed a decrease of bone mass followed by a stable bone mass while breast-feeding afterwards. Later in life, there is a recovery of bone mass loss. INTRODUCTION: The aim of this study was to evaluate bone changes during pregnancy using the radiation-free method of quantitative ultrasonometry (QUS). METHODS: One hundred twenty-five pregnant women who underwent prenatal care were included in this study. Ultrasound measurement of the calcaneus was performed in each trimester and then 6 weeks, 3 months, and 1 year postpartum. The calcaneal QUS measurements were carried out using the Achilles plus device (GE/Lunar Corporation, Madison, WI). Three ultrasound variables were measured: speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz), and the "stiffness index" (expressed as the percentage of the mean value in young adults). SOS and BUA raw data result in the t-score and z-score. RESULTS: A complete panel of six measurements was acquired over the time period in 101 patients (80.8%). Forty-two percent of the included patients were primipara, while 58% had given birth to at least one child (47%) previously. There was a statistically significant change of the t-score (tv = 2.14, p = 0.035) and the stiffness index (tv = 2.46, p = 0.016) from the second to the third trimester, followed by a plateau during lactation. Interestingly, the t-score remained stable during lactation, regardless of the duration of lactation (<3 months, 3-6 months, and >6 months). CONCLUSIONS: Young primiparas who had a sedentary adolescence were at the highest risk of bone loss during pregnancy. Bone loss that occurred during pregnancy was typically recovered later on, based on unknown molecular and biochemical mechanisms that must be elucidated with further studies.

Loss of function of PGAP1 as a cause of severe encephalopathy identified by Whole Exome Sequencing: Lessons of the bioinformatics pipeline.

We evaluated a multiple consanguineous Turkish family with two children, a boy and a girl, affected by severe encephalopathy, hypotonia, microcephaly and retinal dystrophy by a combination of linkage analysis and Whole Exome Sequencing (WES). We analyzed the sequence data by two different bioinformatics pipelines which did not differ in overall processing strategy but involved differences in software used, minor allele frequency (MAF) thresholds and reference data sets, the usage of in-house control exomes and filter settings to prioritize called variants. Assuming autosomal recessive mode of inheritance, only homozygous variants present in both children were considered. The resulting variant lists differed partially (nine variants identified by both pipelines, ten variants by only one pipeline). Major reasons for this discrepancy were different filters for MAF and different variant prioritizations. Combining the variant lists with the results of linkage analysis and further prioritization by expression data and prediction tools, an intronic homozygous splice variant (c.1090-2A>G; IVS9-2A>G; p.?) in PGAP1 (Post-GPI Attachment To Proteins 1) was identified and validated by cDNA analysis. PGAP1 ensures the first step of maturation of GPI (glycosylphosphatidylinositol)-anchor proteins. Recently, a homozygous loss-of-function mutation in PGAP1 has been reported in one family with two children affected by a similar phenotype. The present report not only illustrates the possible influence of specific filtering settings on the results of WES but also confirms PGAP1 as a cause of severe encephalopathy.

[Anatomic Success of Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment during the Changeover from 20 to 23 Gauge - A Study on 313 Consecutive Cases]. / Anatomischer Erfolg der Pars-plana-Vitrektomie bei rhegmatogener Netzhautablösung im Rahmen der Umstellung von 20 auf 23 Gauge - eine Studie an 313 konsekutiven Fällen.

BACKGROUND: The aim of this investigation was to evaluate the effect on the anatomic surgical success with the changeover from 20 Gauge (G) (n = 206) to 23 G (n = 107) pars plana vitrectomy (PPV) in rhegmatogenous retinal detachment. METHODS: 313 consecutive patients were retrolective-prospectively analysed. Several parameters including lens status, number of retinal breaks, extent of retinal detachment, proliferative vitreoretinopathy (PVR) and refractive error were examined. Primary success rate was defined as anatomic success after a minimum follow-up of 6 months. The secondary success rate was determined as anatomic success after one further operation if necessary. Moreover recurring retinal detachment after initial success was registered. In additional to the analysis over all patients, cases were grouped according to the severity of the preoperative baseline situation. RESULTS: Primary success rate was 87.4 % for 20 G PPV and 87.9 % for 23 G PPV, secondary success rate was 95.6 % for 20 G PPV and 94.4 % for 23 G PPV. 13.9 % (20 G) and 7.4 % (23 G) of patients with initially reattached retina after one surgery developed recurrent retinal detachment in the follow-up and were successfully treated in 17/25 and 7/7 cases. With 20 G PPV a primary success rate of 85 % was obtained in phakic eyes and 89.6 % in pseudophakic eyes, respectively. However, primary success rate with 23 G PPV was 90.4 % for phakic eyes and 85.5 % for pseudophakic eyes. For simple, medium and severe cases, the primary success rate decreased from 97.1 to 92.4 and 74.2 % in 20 G PPV, whereas no obvious tendency appeared for 23 G PPV (93.9, 83.7, 88 %). In 20 G PPV surgery the lens status had no influence on the primary success rate (p > 0.05), for medium and severe cases in 23 G PPV better results were obtained in phakic eyes (88.5 and 93.3 %) compared to pseudophakic eyes (78.3 and 80 %, n. s.). CONCLUSION: 20 G PPV as well as 23 G PPV are good surgical techniques in rhegmatogenous retinal detachment. Overall the miniaturisation of surgical instruments seems to be without any disadvantage for the surgical success.

Simplified gyral pattern in severe developmental microcephalies? New insights from allometric modeling for spatial and spectral analysis of gyrification.

The strong positive-allometric relationship between brain size, cortical extension and gyrification complexity, recently highlighted in the general population, could be modified by brain developmental disorders. Indeed, in case of brain growth insufficiency, the pathophysiological relevance of the "simplified gyral pattern" phenotype is strongly disputed since almost no genotype-phenotype correlations have been found in primary microcephalies. Using surface scaling analysis and newly-developed spectral analysis of gyrification (Spangy), we tested whether the gyral simplification in groups of severe microcephalies related to ASPM, PQBP1 or fetal-alcohol-syndrome could be fully explained by brain size reduction according to the allometric scaling law established in typically-developing control groups, or whether an additional disease effect was to be suspected. We found the surface area reductions to be fully explained by scaling effect, leading to predictable folding intensities measured by gyrification indices. As for folding pattern assessed by spectral analysis, scaling effect also accounted for the majority of the variations, but an additional negative or positive disease effect was found in the case of ASPM and PQBP1-linked microcephalies, respectively. Our results point out the necessity of taking allometric scaling into account when studying the gyrification variability in pathological conditions. They also show that the quantitative analysis of gyrification complexity through spectral analysis can enable distinguishing between even (predictable, non-specific) and uneven (unpredictable, maybe disease-specific) gyral simplifications.

Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes.

Elevated interleukin-6 (IL-6) levels are associated with type 2 diabetes, but its role in glucose metabolism is controversial. We investigated the effect of IL-6 on insulin-stimulated glucose metabolism in type 2 diabetes patients and hypothesized that an acute, moderate IL-6 elevation would increase the insulin-mediated glucose uptake. Men with type 2 diabetes not treated with insulin [n = 9, age 54.9 ± 9.7 (mean ± SD) yr, body mass index 34.8 ± 6.1 kg/m(2), HbA1c 7.0 ± 1.0%] received continuous intravenous infusion with either recombinant human IL-6 (rhIL-6) or placebo. After 1 h with placebo or rhIL-6, a 3-h hyperinsulinemic-isoglycemic clamp was initiated. Whole body glucose metabolism was measured using stable isotope-labeled tracers. Signal transducer and activator of transcription 3 (STAT3) phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression were measured in muscle biopsies. Whole body energy expenditure was measured using indirect calorimetry. In response to the infusion of rhIL-6, circulating levels of IL-6 (P < 0.001), neutrophils (P < 0.001), and cortisol (P < 0.001) increased while lymphocytes decreased (P < 0.01). However, IL-6 infusion did not change glucose infusion rate, rate of appearance, or rate of disappearance during the clamp. While IL-6 enhanced phosphorylation of STAT3 in skeletal muscle (P = 0.041), the expression of SOCS3 remained unchanged. Whole body oxygen uptake (P < 0.01) and expired carbon dioxide (P < 0.01) increased during rhIL-6 infusion. In summary, although IL-6 induced local and systemic responses, the insulin-stimulated glucose uptake was not affected. While different contributing factors may be involved, our results are in contrast to our hypothesis and previous findings in young, healthy men.

Pattern of Tuber melanosporum extramatrical mycelium expansion over a 20-year chronosequence in Quercus ilex-truffle orchards.

Successful cultivation of black truffle (Tuber melanosporum) requires a long-term investment and the maintenance of the symbiosis throughout its preproductive and productive years. Monitoring the symbiosis over time is challenging, as it requires methods that can detect the belowground proliferation of the fungus associated with its host tree. In this study, we used a chronosequence design to study the expansion pattern of this fungus as the host tree grows. We hypothesize that this expansion can be estimated by monitoring T. melanosporum DNA from soil beneath host trees of different ages (3, 5, 7, 10, 14, and 20 years old) and at different distances from the trunk of the trees (40, 100, and 200 cm). We also wished to evaluate the presences of Tuber brumale and Tuber indicum, potentially problematic truffle species, in these plantations. To detect the mycelium of T. melanosporum in these soils, we extracted DNA and performed polymerase chain reaction (PCR) with Tuber species-specific primers, and to estimate DNA amount, we measured relative band intensities from the amplicons in agarose gels. Both age and distance were related to T. melanosporum DNA quantity, which was more abundant in the oldest age classes, reaching a plateau in 5-7 years. At 40 cm from the tree, there were no differences in T. melanosporum DNA amounts in orchards of different ages, but at 100 and 200 cm, younger orchards had less T. melanosporum DNA. We did not detect DNA from T. brumale or T. indicum in any of our samples.

Effect of dorsolateral prefrontal cortex structural measures on neuroplasticity and response to paired-associative stimulation in Alzheimer's dementia.

Long-term potentiation (LTP)-like activity can be induced by stimulation protocols such as paired associative stimulation (PAS). We aimed to determine whether PAS-induced LTP-like activity (PAS-LTP) of the dorsolateral prefrontal cortex (DLPFC) is associated with cortical thickness and other structural measures impaired in Alzheimer's dementia (AD). We also explored longitudinal relationships between these brain structures and PAS-LTP response after a repetitive PAS (rPAS) intervention. Mediation and regression analyses were conducted using data from randomized controlled trials with AD and healthy control participants. PAS-electroencephalography assessed DLPFC PAS-LTP. DLPFC thickness and surface area were acquired from T1-weighted magnetic resonance imaging. Fractional anisotropy and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF)-a tract important to induce PAS-LTP-were measured with diffusion-weighted imaging. AD participants exhibited reduced DLPFC thickness and increased SLF MD. There was also some evidence that reduction in DLPFC thickness mediates DLPFC PAS-LTP impairment. Longitudinal analyses showed preliminary evidence that SLF MD, and to a lesser extent DLPFC thickness, is associated with DLPFC PAS-LTP response to active rPAS. This study expands our understanding of the relationships between brain structural changes and neuroplasticity. It provides promising evidence for a structural predictor to improving neuroplasticity in AD with neurostimulation. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Nuclear quadrupole moments as a microscopic probe to study the motion of atomic tunneling systems in amorphous solids.

The properties of amorphous solids below 1 K are dominated by atomic tunneling systems. A basic description is given by the standard tunneling model. Despite its success, the standard tunneling model still remains phenomenological and little is known about the microscopic nature of tunneling systems in amorphous solids. We present dielectric polarization echo experiments on partially deuterated amorphous glycerol. Nuclear quadrupoles, introduced by the deuteration, influence the echo amplitude in a characteristic way and allow us to draw for the first time detailed conclusions about the microscopic nature of the tunneling processes in amorphous glycerol.

Plasma follistatin is elevated in patients with type 2 diabetes: relationship to hyperglycemia, hyperinsulinemia, and systemic low-grade inflammation.

BACKGROUND: Plasma follistatin is elevated in patients with low-grade inflammation and insulin resistance as observed with polycystic ovary syndrome. In the present study, we evaluated plasma follistatin in patients with type 2 diabetes characterised by low-grade inflammation and assessed the acute effects of hyperglycemia, hyperinsulinemia and LPS on plasma follistatin. METHODS: Baseline plasma follistatin and inflammatory biomarkers were measured in a cross-sectional study that involved 95 patients with type 2 diabetes and 103 matched controls. To determine the acute effect of hyperglycemia and hyperinsulinemia on follistatin, hyperglycemic and hyperinsulinemic-euglycemic clamps were performed in five healthy males. Furthermore, 15 patients with type 2 diabetes and 22 healthy controls were challenged with low-dose LPS to determine the effect on follistatin. RESULTS: Patients with type 2 diabetes have higher HOMA2-IR values mean [95% CI] 1.64 [1.40-1.93] versus mean 0.86 [0.75-0.99], p < 0.001 and inflammatory markers compared with controls. Baseline plasma follistatin is elevated in patients with type 2 diabetes compared with controls mean 1564 [1456-1680] versus mean 1328 [1225-1440] ng/L, p = 0.003 and correlates with fasting glucose levels (r = 0.44, p < 0.0001), 2 h glucose (r = 0.48, p < 0.0001), HbA1c (r = 0.41, p < 0.0001), triacylglycerol (r = 0.28, p = 0.008) and total cholesterol (r = 0.33, p = 0.004) in patients but not in controls. No correlation exists between plasma follistatin and inflammatory biomarkers in either of the groups. Neither hyperglycemia, hyperinsulinemia nor LPS increase plasma follistatin. CONCLUSIONS: Plasma follistatin is moderately elevated in patients with type 2 diabetes. Our findings suggest that this is not likely caused by hyperglycemia, hyperinsulinemia or systemic low-grade inflammation.

Dermanyssus gallinae (chicken mite): an underdiagnosed environmental infestation.

Dermanyssus gallinae is a mite that normally parasitizes small birds but may occasionally bite humans. We report an unusual case of an 82-year-old woman who presented with pruritus and bite-like lesions over her trunk. Other members of the household were also affected. On physical examination, mites < 1 mm in size were found on the patient's body. The family were residing in the city centre and had no pets, but there were pigeon nests in close proximity to the house. Most dermatologists have difficulties identifying ectoparasitosis. In the case of D. gallinae, the small size of the mites and the fact that they leave the host after feeding means that they may not be seen at presentation, thus such infestations are likely to be underdiagnosed. Physicians should be aware that infection with this mite is possible even in patients from urban areas, and it should be included in the differential diagnosis of conditions causing recurrent pruritus unresponsive to standard treatments.