The rostro-caudal gradient in the prefrontal cortex and its modulation by subthalamic deep brain stimulation in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) alleviates motor symptoms in Parkinson's disease (PD) but also affects the prefrontal cortex (PFC), potentially leading to cognitive side effects. The present study tested alterations within the rostro-caudal hierarchy of neural processing in the PFC induced by STN-DBS in PD. Granger-causality analyses of fast functional near-infrared spectroscopy (fNIRS) measurements were used to infer directed functional connectivity from intrinsic PFC activity in 24 PD patients treated with STN-DBS. Functional connectivity was assessed ON stimulation, in steady-state OFF stimulation and immediately after the stimulator was switched ON again. Results revealed that STN-DBS significantly enhanced the rostro-caudal hierarchical organization of the PFC in patients who had undergone implantation early in the course of the disease, whereas it attenuated the rostro-caudal hierarchy in late-implanted patients. Most crucially, this systematic network effect of STN-DBS was reproducible in the second ON stimulation measurement. Supplemental analyses demonstrated the significance of prefrontal networks for cognitive functions in patients and matched healthy controls. These findings show that the modulation of prefrontal functional networks by STN-DBS is dependent on the disease duration before DBS implantation and suggest a neurophysiological mechanism underlying the side effects on prefrontally-guided cognitive functions observed under STN-DBS.

The impact of physiological noise on hemodynamic-derived estimates of directed functional connectivity.

Measuring the strength of directed functional interactions between brain regions is fundamental to understand neural networks. Functional near-infrared spectroscopy (fNIRS) is a suitable method to map directed interactions between brain regions but is based on the neurovascular coupling. It, thus, relies on vasomotor reactivity and is potentially biased by non-neural physiological noise. To investigate the impact of physiological noise on fNIRS-based estimates of directed functional connectivity within the rostro-caudal hierarchical organization of the prefrontal cortex (PFC), we systematically assessed the effects of pathological perturbations of vasomotor reactivity and of externally triggered arterial blood pressure (aBP) fluctuations. Fifteen patients with unilateral stenosis of the internal carotid artery (ICA) underwent multi-channel fNIRS during rest and during metronomic breathing, inducing aBP oscillations at 0.1 Hz. Comparisons between the healthy and pathological hemispheres served as quasi-experimental manipulation of the neurovascular system's capability for vasomotor reactivity. Comparisons between rest and breathing served as experimental manipulation of two different levels of physiological noise that were expected to differ between healthy and pathological hemispheres. In the hemisphere affected by ICA stenosis, the rostro-caudal hierarchical organization of the PFC was compromised reflecting the pathological effect on the vascular and neural level. Breathing-induced aBP oscillations biased the magnitude of directed interactions in the PFC, but could be adjusted using either the aBP time series (intra-individual approach) or the aBP-induced fNIRS signal variance (inter-individual approach). Multi-channel fNIRS, hence, provides a sound basis for analyses of directed functional connectivity as potential bias due to physiological noise can be effectively controlled for.

[Atrioventricular block and left ventricular wall mobility disorder in a 44-year-old female patient : A case report of a rarity with pitfalls]. / Atrioventrikuläre Blockierung und linksventrikuläre Wandbewegungsstörung bei einer 44-jährigen Patientin : Fallbericht über eine Rarität mit Tücken.

Eosinophilic myocarditis is a rare condition with good treatment options, which can be difficult to diagnose. The clinical presentation can vary from asymptomatic to life-threatening forms. This article describes the case of a 44-year-old woman who suffered from vertigo, chest pain and dyspnea. The woman presented with an intermittent atrioventricular (AV) block II Mobitz type II° and mild impairment of left ventricular ejection fraction. Hypereosinophilia in the peripheral blood, cardiac magnetic resonance imaging (MRI) and endomyocardial biopsy led to the diagnosis of eosinophilic myocarditis, most likely as a result of an allergic reaction to Aspergillus fumigatus. A general treatment recommendation cannot be made due to the lack of evidence-based guidelines; however, recent scientific studies confirmed timely, high-dose steroid administration over several months to be the mainstay of treatment of eosinophilic myocarditis. The following article may be helpful in the early diagnosis and treatment of this underdiagnosed and insidious disease.

Functionally dissociating ventro-dorsal components within the rostro-caudal hierarchical organization of the human prefrontal cortex.

Cognitive control is proposed to rely on a rostral-to-caudal hierarchy of neural processing within the prefrontal cortex (PFC), with more rostral parts exerting control over more caudal parts. Anatomical and functional data suggest that this hierarchical organization of the PFC may be separated into a ventral and a dorsal component. Furthermore, recent studies indicate that the apex of the hierarchy resides within the mid-lateral rather the rostral PFC. However, investigating the hierarchical aspect of rostro-to-caudal processing requires quantification of the directed interactions between PFC regions. Using functional near-infrared spectroscopy (fNIRS) in a sample of healthy young adults we analyzed directed interactions between rostral and caudal PFC during passive watching of nature documentaries. Directed coherence (DC) as a measure of directed interaction was computed pairwise between 38 channels evenly distributed over the lateral prefrontal convexity. Results revealed an overall predominance of rostral-to-caudal directed interactions in the PFC that further dissociated along a ventro-dorsal axis: Dorsal regions exerted stronger rostro-caudally directed interactions on dorsal than on ventral regions and vice versa. Interactions between ventral and dorsal PFC were stronger from ventral to dorsal areas than vice versa. Results further support the notion that the mid-dorsolateral PFC constitutes the apex of the prefrontal hierarchy. Taken together these data provide novel evidence for parallel dorsal and ventral streams within the rostro-caudal hierarchical organization of the PFC. FNIRS-based analyses of directed interactions put forward a new perspective on the functional architecture of the prefrontal hierarchy and complement previous insights from functional magnetic resonance imaging.

Correction to: Electric cauterization of the hernia sac in laparoscopic ventral hernia repair reduces the incidence of postoperative seroma: a propensity score-matched analysis.

In the original publication, first author's given name was incorrectly updated.

Micropropagation and Cryoconservation of the Endangered Plant Species Artemisia laciniata (Asteraceae).

BACKGROUND: Artemisia laciniata, mainly distributed in Siberia and Central Asia, is classified as critically endangered in Europe. OBJECTIVES: This study developed a protocol for its micropropagation and cryopreservation. MATERIALS AND METHODS: In vitro cultures from fresh seed and in vivo shoots were initiated. Micropropagation and cryopreservation protocols were developed. Bacteria detected after cryopreservation were investigated using 16S rRNA analysis. Genome size measurements of regenerated plants after cryopreservation using flow cytometry and carbon isotope measurements to evaluate stress status were also carried out. RESULTS: A. laciniata from both starting materials could be successfully propagated on MS medium with 0.5 uM BAP. Material initiated from in vivo shoots yielded lower regeneration percentages (16%) after cryopreservation than material generated from seed (57 and 63%) using the droplet-vitrification method and PVS3. Bacteria occurring after cryopreservation belonged to the genera Sphingomonas, Staphylococcus, Curtobacterium and Gordonia. There was no significant difference in the genome size and stress status between non-cryopreserved and cryopreserved plants. CONCLUSION: A. laciniata could be readily micropropagated and cryopreserved. No negative effects of cryopreservation on plant water use efficiency or on genetic stability were found.

Electric cauterization of the hernia sac in laparoscopic ventral hernia repair reduces the incidence of postoperative seroma: a propensity score-matched analysis.

BACKGROUND: Laparoscopic intraperitoneal mesh repair has become one of the most commonly performed minimally invasive procedures. Nevertheless, despite improved overall outcome, postoperative seroma formation remains the most frequent complication. Our objective was to investigate the effectiveness of cauterization of the hernia sac in terms of reducing the incidence of postoperative seroma formation. METHODS: A retrospective analysis of 94 patients who underwent standard laparoscopic intraperitoneal mesh repair without closure of the central defect (sIPOM) between June 2011 and December 2014 was conducted. In 20 of those cases, electric cauterization of the hernia sac was additionally performed (csIPOM). One-to-one propensity score analysis was conducted to overcome patient selection bias between the two surgical techniques. The case-control group was matched by gender, body mass index (BMI), patient comorbidities, and surface of the hernia defect. Patient demographics, pre- and postoperative pain score (using a ten-point Likert scale), operative data, and complications were collected. At follow-up, postoperative seroma, hernia recurrence, and chronic pain were evaluated. RESULTS: Patient demographics, hernia size, comorbidities, and BMI were similar between the two groups. The csIPOM patient group had significantly lower rate of seroma formation, compared to the sIPOM control [csIPOM vs. sIPOM 0 vs. 25% (n = 5), p < 0.05]. There was no difference noted regarding postoperative pain between the two techniques. Hernia recurrence rate was found to be higher in the sIPOM group [csIPOM vs. sIPOM 0 vs 12.5% (n = 2), p < 0.05]. CONCLUSION: The present study confirms our hypothesis that laparoscopic sIPOM combined with electric cauterization of the hernia sac (csIPOM) significantly reduces the rate of postoperative seroma compared to the sIPOM technique in patients with ventral and incisional hernias. Further randomized trials are required to verify our findings.

Arsenic-containing hydrocarbons: effects on gene expression, epigenetics, and biotransformation in HepG2 cells.

Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-specific endonuclease 1 (FEN1) as well as xeroderma pigmentosum group A complementing protein (XPA) and (cytosine-5)-methyltransferase 3A (DNMT3A) showed time- and concentration-dependent alterations in gene expression, thereby indicating an impact on genomic stability. In the subsequent analysis of epigenetic markers, within 72 h, neither AsHC 332 nor AsHC 360 showed an impact on the global DNA methylation level, whereas incubation with AsHC 360 increased the global DNA hydroxymethylation level. Analysis of cell extracts and cell media by HPLC-mass spectrometry revealed that both AsHCs were considerably biotransformed. The identified metabolites include not only the respective thioxo-analogs of the two AsHCs, but also several arsenic-containing fatty acids and fatty alcohols, contributing to our knowledge of biotransformation mechanisms of arsenolipids.

Enhanced topical delivery of dexamethasone by ß-cyclodextrin decorated thermoresponsive nanogels.

Highly hydrophilic, responsive nanogels are attractive as potential systems for the topical delivery of bioactives encapsulated in their three-dimensional polymeric scaffold. Yet, these drug carrier systems suffer from drawbacks for efficient delivery of hydrophobic drugs. Addressing this, ß-cyclodextrin (ßCD) could be successfully introduced into the drug carrier systems by exploiting its unique affinity toward dexamethasone (DXM) as well as its role as topical penetration enhancer. The properties of ßCD could be combined with those of thermoresponsive nanogels (tNGs) based on dendritic polyglycerol (dPG) as a crosslinker and linear thermoresponsive polyglycerol (tPG) inducing responsiveness to temperature changes. Electron paramagnetic resonance (EPR) studies localized the drug within the hydrophobic cavity of ßCD by differences in its mobility and environmental polarity. In fact, the fabricated carriers combining a particulate delivery system with a conventional penetration enhancer, resulted in an efficient delivery of DXM to the epidermis and the dermis of human skin ex vivo (enhancement compared to commercial DXM cream: ∼2.5 fold in epidermis, ∼30 fold in dermis). Furthermore, DXM encapsulated in ßCD tNGs applied to skin equivalents downregulated the expression of proinflammatory thymic stromal lymphopoietin (TSLP) and outperformed a commercially available DXM cream.

Pushing the limits of automated glycan assembly: synthesis of a 50mer polymannoside.

Automated glycan assembly (AGA) enables rapid access to oligosaccharides. The overall length of polymers created via automated solid phase synthesis depends on very high yields at every step to obtain full length products. The synthesis of long polymers serves as the ultimate test of the efficiency and reliability of synthetic processes. A series of Man-(1 → 6)-α-Man linked oligosaccharides up to a 50mer, the longest synthetic sequence yet assembled from monosaccharides, has been realized via a 102 step synthesis. We identified a suitable mannose building block and applied a capping step in the final five AGA cycles to minimize (n - 1) deletion sequences that are otherwise difficult to remove by HPLC.

Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.

BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. SUBJECTS/METHODS: To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. RESULTS: Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.

Test-retest reliability of the Tower of London Planning Task (TOL-F).

Test-retest reliability is difficult to establish for measures of executive functioning that rely on task novelty. Correspondingly, evidence on the test-retest reliability of the commonly used Tower of London (TOL) planning task is, as yet, equivocal and only based on indices of relative consistency, rather than absolute agreement of individual scores. Further, the stability of planning latencies over repeated testing has not been investigated. The present study assessed test-retest reliability of planning performance measures using a structurally balanced problem set implemented in the TOL-Freiburg version (TOL-F). The TOL-F was administered in 2 structurally identical versions to a sample of young, healthy adults over a 1-week interval. For planning accuracy, the Pearson correlation and intraclass correlation coefficient for relative consistency were adequate (r = .739 and .734), with the intraclass correlation coefficient for absolute agreement only slightly decreased (r = .690). For initial thinking and movement execution times, relative consistency and absolute agreement reliability indices were uniformly low (all r between .274 and .519). Given adequate planning accuracy test-retest reliability, the TOL-F can be reliably used to measure planning ability in group-based studies and with individual participants, as is important for clinical testing. Planning latencies, however, should only be used as complementary, but not sole measures of planning ability, particularly for normative evaluations in clinical assessment. In sum, TOL-F planning accuracy possesses adequate absolute and relative test-retest reliability for experimental utility. Future studies should assess whether this indeed translates into clinical utility of the TOL-F for measuring planning ability in patients.

Spatial mapping of dynamic cerebral autoregulation by multichannel near-infrared spectroscopy in high-grade carotid artery disease.

The exact spatial distribution of impaired cerebral autoregulation in carotid artery disease is unknown. In this pilot study, we present a new approach of multichannel near-infrared spectroscopy (mcNIRS) for non-invasive spatial mapping of dynamic autoregulation in carotid artery disease. In 15 patients with unilateral severe carotid artery stenosis or occlusion, cortical hemodynamics in the bilateral frontal cortex were assessed from changes in oxyhemoglobin concentration using 52-channel NIRS (spatial resolution ∼2 cm). Dynamic autoregulation was graded by the phase shift between respiratory-induced 0.1 Hz oscillations of blood pressure and oxyhemoglobin. Ten of 15 patients showed regular phase values in the expected (patho) physiological range.Five patients had clearly outlying irregular phase values mostly due to artifacts. In patients with a regular phase pattern, a significant side-to-side difference of dynamic autoregulation was observed for the cortical border zone area between the middle and anterior cerebral artery (p < 0.05). In conclusion, dynamic cerebral autoregulation can be spatially assessed from slow hemodynamic oscillations with mcNIRS. In high-grade carotid artery disease,cortical dynamic autoregulation is affected mostly in the vascular border zone. Spatial mapping of dynamic autoregulation may serve as a powerful tool for identifying brain regions at specific risks for hemodynamic infarction.

Risk factors for oral mucositis in children receiving hematopoietic cell transplantation for primary immunodeficiencies: a retrospective study.

OM is a frequent complication for patients undergoing HSCT. The aim of this study was to evaluate the possible risk factors for OM in children undergoing HSCT for PI. A retrospective study was carried out on 55 consecutive medical records of patients with PI (including osteopetrosis) who underwent HSCT. Age at the time of HSCT, gender, diagnosis, type of donor, conditioning regimen, engraftment, graft-versus-host disease, and severity and duration of OM were collected at the beginning of the conditioning until day 100 post-HSCT or death. OM was measured using the WHO scale. Patients' age range at the time of HSCT was quite wide; 59.2% of the patients who were under nine months (n = 13) developed OM vs. 87.8% of the patients older than nine months (n = 29) (p = 0.01). T-cell positive patients had a statistically significant higher risk of developing OM (p = 0.04), as did those receiving a more intensive conditioning regimen (p < 0.01). PI patients undergoing HSCT are at higher risk of developing OM if the PI is a T-lymphocyte-positive disease and/or if the HSCT recipient is over nine months of age.

Genetic variants associated with predisposition to prostate cancer and potential clinical implications.

Prostate cancer is the commonest cancer in the developed world. There is an inherited component to this disease as shown in familial and twin studies. However, the discovery of these variants has been difficult. The emergence of genome-wide association studies has led to the identification of over 46 susceptibility loci. Their clinical utility to predict risk, response to treatment, or treatment toxicity, remains undefined. Large consortia are needed to achieve adequate statistical power to answer these genetic-clinical and genetic-epidemiological questions. International collaborations are currently underway to link genetic with clinical/epidemiological data to develop risk prediction models, which could direct screening and treatment programs.

Aetiology of acute gastro-enteritis in children at Saint Camille Medical Centre, Ouagadougou, Burkina Faso.

UNLABELLED: The present study aims at identifying the infectious agents responsible for child Acute GastroEnteritis (AGE) in Ouagadougou. From May 5 2006 to June 22 2008, 648 children aged from 2 to 41 months, with at least an average of 3 loose stools per day have been enrolled for coproculture, parasitology and virology test. Among them, 34 (5.25%) were HIV seropositive. A single sample of faeces from each child was used to identify enteropathogens. An infectious aetiology was identified in 41.20% of cases. The pathogenic agents detected as responsible for the AGE are: Rotavirus 21.1%; Adenovirus 1.9%; Giardia 7.6% Entamoeba; 1.08%; entero-pathogenic E. coli 41.7%; Salmonella 3.40%; Shigella 1.85% and Yersinia 1.70%. CONCLUSION: Therefore, these AGE etiologic agents constitute a problem of public health in Burkina Faso. Their control for the child would require: (1) a regular paediatric and clinical follow up; (2) health education of the population for food hygiene and (3) in case of absence of HIV infection in the mother, a promotion of exclusive breast-feeding up to the age of 4 months.

Stem cell transplantation for primary immunodeficiencies.

BMT is curative in almost 75% of children affected by severe primary immunodeficiencies (PIDs). Recently, the chance of cure has increased thanks to the availability of matched unrelated donors (MUDs). Nevertheless, besides the conventional indications to BMT (profound or absent T-cell function, profound or absent natural killer function, known syndromes with T-cell deficiencies), indications to BMT for PIDs affecting the quality of life or having an expectation of life that does not exceed the third-fourth decade remain unclear. Infact, if it is evident that the survival rate in an infant grafted for a PID with a MUD is expected to be more than 80%, alternative treatments such as gene therapy are now available.

Noninvasive coronary angiography using 64-slice spiral computed tomography in an unselected patient collective: effect of heart rate, heart rate variability and coronary calcifications on image quality and diagnostic accuracy.

OBJECTIVE: The aim of this study was to assess the impact of heart rate, heart rate variability and calcification on image quality and diagnostic accuracy in an unselected patient collective. SUBJECTS AND METHODS: One hundred and two consecutive patients with known or suspected coronary artery disease underwent both 64-MSCT and invasive coronary angiography. Image quality (IQ) was assessed by independent observers using a 4-point scale from excellent (1) to non-diagnostic (4). Accuracy of MSCT regarding detection or exclusion of significant stenosis (>50%) was evaluated on a per segment basis in a modified AHA 13-segment model. Effects of heart rate, heart rate variability, calcification and body mass index (BMI) on IQ and accuracy were evaluated by multivariate regression. IQ and accuracy were further analysed in subgroups of significant predictor variables and simple regression performed to calculate thresholds for adequate IQ. RESULTS: Mean heart rate was 68.2+/-13.3 bpm, mean heart rate variability 11.5+/-16.0 beats per CT-examination (bpct) and median Agatston score 226.5. Average IQ score was 2+/-0.6 whilst diagnostic quality was obtained in 89% of segments. Overall sensitivity, specificity, PPV or NPV was 91.2%, 99.2%, 95.3% or 98.3%. According to multivariate regression, overall IQ was significantly related to heart rate and calcification (P=0.0038; P<0.0001). The effect of heart rate variability was limited to IQ of RCA segments (P=0.018); BMI was not related to IQ (P=0.52). Calcification was the only predictor variable with significant effect on the number of non-diagnostic segments (P<0.0001). In a multivariate regression, calcification was also the single factor with impact on diagnostic accuracy (P=0.0049). CONCLUSION: Whilst heart rate, heart rate variability and calcification all show an inverse correlation to IQ, severe calcium burden remains the single factor with translation of such effect into decrease of diagnostic accuracy.

[Epidemiology of sexually transmitted diseases in the catchment area of the Rostock University Dermatology Clinic after 1945]. / Die Epidemiologie der sexuell übertragbaren Krankheiten im Einzugsgebiet der Universitäts-Hautklinik Rostock nach 1945.

The decline of STD in the region of Rostock, Germany, since 1945 is explained by a decreasing incidence of gonorrhoea and trichomoniasis. On the other hand chlamydial and candidal infections have increased. The rate of chlamydia infections was about 45% in our venerological patients, as common as gonorrhea used to be. Genital candidal infections were to be found in 23%. Mycoplasmas were identified in 15%, usually combined with other pathogens except in some cases of vaginitis.