The quantum twisting microscope.

The invention of scanning probe microscopy revolutionized the way electronic phenomena are visualized1. Whereas present-day probes can access a variety of electronic properties at a single location in space2, a scanning microscope that can directly probe the quantum mechanical existence of an electron at several locations would provide direct access to key quantum properties of electronic systems, so far unreachable. Here, we demonstrate a conceptually new type of scanning probe microscope-the quantum twisting microscope (QTM)-capable of performing local interference experiments at its tip. The QTM is based on a unique van der Waals tip, allowing the creation of pristine two-dimensional junctions, which provide a multitude of coherently interfering paths for an electron to tunnel into a sample. With the addition of a continuously scanned twist angle between the tip and sample, this microscope probes electrons along a line in momentum space similar to how a scanning tunnelling microscope probes electrons along a line in real space. Through a series of experiments, we demonstrate room-temperature quantum coherence at the tip, study the twist angle evolution of twisted bilayer graphene, directly image the energy bands of monolayer and twisted bilayer graphene and, finally, apply large local pressures while visualizing the gradual flattening of the low-energy band of twisted bilayer graphene. The QTM opens the way for new classes of experiments on quantum materials.

Cascade of phase transitions and Dirac revivals in magic-angle graphene.

Twisted bilayer graphene near the magic angle1-4 exhibits rich electron-correlation physics, displaying insulating3-6, magnetic7,8 and superconducting phases4-6. The electronic bands of this system were predicted1,2 to narrow markedly9,10 near the magic angle, leading to a variety of possible symmetry-breaking ground states11-17. Here, using measurements of the local electronic compressibility, we show that these correlated phases originate from a high-energy state with an unusual sequence of band population. As carriers are added to the system, the four electronic 'flavours', which correspond to the spin and valley degrees of freedom, are not filled equally. Rather, they are populated through a sequence of sharp phase transitions, which appear as strong asymmetric jumps of the electronic compressibility near integer fillings of the moiré lattice. At each transition, a single spin/valley flavour takes all the carriers from its partially filled peers, 'resetting' them to the vicinity of the charge neutrality point. As a result, the Dirac-like character observed near charge neutrality reappears after each integer filling. Measurement of the in-plane magnetic field dependence of the chemical potential near filling factor one reveals a large spontaneous magnetization, further substantiating this picture of a cascade of symmetry breaking. The sequence of phase transitions and Dirac revivals is observed at temperatures well above the onset of the superconducting and correlated insulating states. This indicates that the state that we report here, with its strongly broken electronic flavour symmetry and revived Dirac-like electronic character, is important in the physics of magic-angle graphene, forming the parent state out of which the more fragile superconducting and correlated insulating ground states emerge.

Specific T-cell receptor beta-rearrangements of gluten-triggered CD8+ T-cells are enriched in celiac disease patients' duodenal mucosa.

Celiac disease (CeD) is an autoimmune disorder affecting the small intestine with gluten as disease trigger. Infections including Influenza A, increase the CeD risk. While gluten-specific CD4+ T-cells, recognizing HLA-DQ2/DQ8 presented gluten-peptides, initiate and sustain the celiac immune response, CD8+ α/ß intraepithelial T-cells elicit mucosal damage. Here, we subjected TCRs from a cohort of 56 CeD patients and 22 controls to an analysis employing 749 published CeD-related TCRß-rearrangements derived from gluten-specific CD4+ T-cells and gluten-triggered peripheral blood CD8+ T-cells. We show, that in addition to TCRs from gluten-specific CD4+ T-cells, TCRs of gluten-triggered CD8+ T-cells are significantly enriched in CeD duodenal tissue samples. TCRß-rearrangements of gluten-triggered CD8+ T-cells were even more expanded in patients than TCRs from gluten-specific CD4+ T-cells (p < 0.0002) and highest in refractory CeD. Sequence alignments with TCR-antigen databases suggest that a subgroup of these most likely indirectly gluten-triggered TCRs recognize microbial, viral, and autoantigens.

Local and Nonlocal Transport Spectroscopy in Planar Josephson Junctions.

We report simultaneously acquired local and nonlocal transport spectroscopy in a phase-biased planar Josephson junction based on an epitaxial InAs-Al hybrid two-dimensional heterostructure. Quantum point contacts at the junction ends allow measurement of the 2×2 matrix of local and nonlocal tunneling conductances as a function of magnetic field along the junction, phase difference across the junction, and carrier density. A closing and reopening of a gap was observed in both the local and nonlocal tunneling spectra as a function of magnetic field. For particular tunings of junction density, gap reopenings were accompanied by zero-bias conductance peaks (ZBCPs) in local conductances. End-to-end correlation of gap reopening was strong, while correlation of local ZBCPs was weak. A model of the device, with disorder treated phenomenologically, shows comparable conductance matrix behavior associated with a topological phase transition. Phase dependence helps distinguish possible origins of the ZBCPs.

The Naming Assessment in Multicultural Europe (NAME): Development and Validation in a Multicultural Memory Clinic.

OBJECTIVE: Traditional naming tests are unsuitable to assess naming impairment in diverse populations, given the influence of culture, language, and education on naming performance. Our goal was therefore to develop and validate a new test to assess naming impairment in diverse populations: the Naming Assessment in Multicultural Europe (NAME). METHOD: We carried out a multistage pilot study. First, we generated a list of 149 potentially suitable items - e.g. from published cross-linguistic word lists and other naming tests - and selected those with a homogeneous age of acquisition and word frequency across languages. We selected three to four colored photographs for each of the 73 remaining items; 194 controls selected the most suitable photographs. Thirteen items were removed after a pilot study in 15 diverse healthy controls. The final 60-item test was validated in 39 controls and 137 diverse memory clinic patients with subjective cognitive impairment, neurological/neurodegenerative disease or psychiatric disorders in the Netherlands and Turkey (mean age: 67, SD: 11). Patients were from 15 different countries; the majority completed primary education or less (53%). RESULTS: The NAME showed excellent reliability (Spearman-Brown coefficient: 0.95; Kuder-Richardson coefficient: 0.94) and robust correlations with other language tests (ρ = .35-.73). Patients with AD/mixed dementia obtained lower scores on most (48/60) NAME items, with an area under the curve of 0.88. NAME scores were correlated with age and education, but not with acculturation or sex. CONCLUSIONS: The NAME is a promising tool to assess naming impairment in culturally, educationally, and linguistically diverse individuals.

Prognostic impact of activin subunit inhibin beta A in gastric and esophageal adenocarcinomas.

PURPOSE: Adenocarcinomas of the esophagus (AEG) and stomach (AS) are among the most common cancers worldwide. Novel markers for risk stratification and guiding treatment are strongly needed. Activin is a multi-functional cytokine with context specific pro- and anti-tumorigenic effects. We aimed to investigate the prognostic role of activin tumor protein expression in AEG/ASs. METHODS: Tissue from a retrospective cohort of 277 patients with AEG/AS treated primarily by surgery at the Charité - Universitätsmedizin Berlin was collected and analyzed by immunohistochemistry using a specific antibody to the activin homodimer inhibin beta A. Additionally, we evaluated T-cell infiltration and PD1 expression as well as expression of PD-L1 by immunohistochemistry as possible confounding factors. Clinico-pathologic data were collected and correlated with activin protein expression. RESULTS: Out of 277 tumor samples, 72 (26.0%) exhibited high activin subunit inhibin beta A protein expression. Higher expression was correlated with lower Union for International Cancer Control (UICC) stage and longer overall survival. Interestingly, activin subunit expression correlated with CD4+ T-cell infiltration, and the correlation with higher overall survival was exclusively seen in tumors with high CD4+ T-cell infiltration, pointing towards a role of activin in the tumor immune response in AEG/ASs. CONCLUSION: In our cohort of AEG/AS, higher activin subunit levels were correlated with longer overall survival, an effect exclusively seen in tumors with high CD4+ cell infiltration. Further mechanistic research is warranted discerning the exact effect of this context specific cytokine.

Cerebellar Grey Matter Volume in Older Persons Is Associated with Worse Cognitive Functioning.

The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e. symptoms of depression and apathy) and general daily functioning in a population of community-dwelling older persons with mild cognitive deficits, but without dementia. In 194 participants of the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden, the association between cerebellar GMV, WMHs, LIs and MBs and measures of cognitive, psychological and general daily functioning was analysed with linear regression analysis, adjusted for age, sex, education and cerebral volume. Cerebellar GMV was associated with the overall cognition score (standardised beta 0.20 [95% CI, 0.06-0.33]). Specifically, posterior cerebellar GMV was associated with executive function (standardised beta 0.18 [95% CI, 0.03-0.16]). No relation was found between vascular pathology and cognition. Also, no consistent associations were found on the cerebellar GMV and vascular pathology measures and psychological and general daily functioning. In this population of community-dwelling elderly, less posterior cerebellar GMV but not vascular pathology was associated with worse cognitive function, specifically with poorer executive function. No relation was found between cerebellar pathology and psychological and general daily functioning.

Differences in Discriminability and Response Bias on Rey Auditory Verbal Learning Test Delayed Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.

OBJECTIVE: Episodic memory is impaired in Alzheimer's disease (AD) dementia but thought to be relatively spared in behavioral variant frontotemporal dementia (bvFTD). This view is challenged by evidence of memory impairment in bvFTD. This study investigated differences in recognition memory performance between bvFTD and AD. METHOD: We performed a retrospective analysis on the recognition trial of the Rey Auditory Verbal Learning Test in patients with bvFTD (n = 85), AD (n = 55), and control participants (n = 59). Age- and education-adjusted between-group analysis was performed on the total score and indices of discriminative ability and response bias. Correlations between recognition and measures of memory, language, executive functioning, and construction were examined. RESULTS: Patients with AD had a significantly lower total recognition score than patients with bvFTD (control 28.8 ± 1.5; bvFTD 24.8 ± 4.5; AD 23.4 ± 3.6, p < .01). Both bvFTD and AD had worse discriminative ability than controls (A' control 0.96 ± 0.03; bvFTD 0.87 ± 0.03; AD 0.84 ± 0.10, p < .01), but there was no difference in response bias (B" control 0.9 ± 0.2; bvFTD 1.6 ± 1.47; AD 1.4± 1.4, p < .01). AD had worse discriminability than bvFTD (p < .05). Discriminability was associated with memory for both patient groups (median correlation coefficient r = .34) and additionally associated with language (r = .31), but not executive functioning (r = -.03) in bvFTD. Response bias was unrelated to other cognitive functions (r = -.02). CONCLUSIONS: Discriminability, but not response bias, differentiated patients with bvFTD from AD. The presence of an impaired discrimination index suggests a "pure" (recognition) memory deficit in bvFTD.

Primary human testicular PDGFRα+ cells are multipotent and can be differentiated into cells with Leydig cell characteristics in vitro.

STUDY QUESTION: Is it possible to differentiate primary human testicular platelet-derived growth factor receptor alpha positive (PDGFRα+) cells into functional Leydig cells? SUMMARY ANSWER: Although human testicular PDGFRα+ cells are multipotent and are capable of differentiating into steroidogenic cells with Leydig cell characteristics, they are not able to produce testosterone after differentiation. WHAT IS KNOWN ALREADY: In rodents, stem Leydig cells (SLCs) that have been identified and isolated using the marker PDGFRα can give rise to adult testosterone-producing Leydig cells after appropriate differentiation in vitro. Although PDGFRα+ cells have also been identified in human testicular tissue, so far there is no evidence that these cells are true human SLCs that can differentiate into functional Leydig cells in vitro or in vivo. STUDY DESIGN, SIZE, DURATION: We isolated testicular cells enriched for interstitial cells from frozen-thawed fragments of testicular tissue from four human donors. Depending on the obtained cell number, PDGFRα+-sorted cells of three to four donors were exposed to differentiation conditions in vitro to stimulate development into adipocytes, osteocytes, chondrocytes or into Leydig cells. We compared their cell characteristics with cells directly after sorting and cells in propagation conditions. To investigate their differentiation potential in vivo, PDGFRα+-sorted cells were transplanted in the testis of 12 luteinizing hormone receptor-knockout (LuRKO) mice of which 6 mice received immunosuppression treatment. An additional six mice did not receive cell transplantation and were used as a control. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular interstitial cells were cultured to Passage 3 and FACS sorted for HLA-A,B,C+/CD34-/PDGFRα+. We examined their mesenchymal stromal cell (MSC) membrane protein expression by FACS analyses. Furthermore, we investigated lineage-specific staining and gene expression after MSC trilineage differentiation. For the differentiation into Leydig cells, PDGFRα+-sorted cells were cultured in either proliferation or differentiation medium for 28 days, after which they were stimulated either with or without hCG, forskolin or dbcAMP for 24 h to examine the increase in gene expression of steroidogenic enzymes using qPCR. In addition, testosterone, androstenedione and progesterone levels were measured in the culture medium. We also transplanted human PDGFRα+-sorted testicular interstitial cells into the testis of LuRKO mice. Serum was collected at several time points after transplantation, and testosterone was measured. Twenty weeks after transplantation testes were collected for histological examination. MAIN RESULTS AND THE ROLE OF CHANCE: From primary cultured human testicular interstitial cells at Passage 3, we could obtain a population of HLA-A,B,C+/CD34-/PDGFRα+ cells by FACS. The sorted cells showed characteristics of MSC and were able to differentiate into adipocytes, chondrocytes and osteocytes. Upon directed differentiation into Leydig cells in vitro, we observed a significant increase in the expression of HSD3B2 and INSL3. After 24 h stimulation with forskolin or dbcAMP, a significantly increased expression of STAR and CYP11A1 was observed. The cells already expressed HSD17B3 and CYP17A1 before differentiation but the expression of these genes were not significantly increased after differentiation and stimulation. Testosterone levels could not be detected in the medium in any of the stimulation conditions, but after stimulation with forskolin or dbcAMP, androstenedione and progesterone were detected in culture medium. After transplantation of the human cells into the testes of LuRKO mice, no significant increase in serum testosterone levels was found compared to the controls. Also, no human cells were identified in the interstitium of mice testes 20 weeks after transplantation. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was performed using tissue from only four donors because of limitations in donor material. Because of the need of sufficient cell numbers, we first propagated cells to passage 3 before FACS of the desired cell population was performed. We cannot rule out this propagation of the cells resulted in loss of stem cell properties. WIDER IMPLICATIONS OF THE FINDINGS: A lot of information on Leydig cell development is obtained from rodent studies, while the knowledge on human Leydig cell development is very limited. Our study shows that human testicular interstitial PDGFRα+ cells have different characteristics compared to rodent testicular PDGFRα+ cells in gene expression levels of steroidogenic enzymes and potential to differentiate in adult Leydig cells under comparable culture conditions. This emphasizes the need for confirming results from rodent studies in the human situation to be able to translate this knowledge to the human conditions, to eventually contribute to improvements of testosterone replacement therapies or establishing alternative cell therapies in the future, potentially based on SLCs. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Amsterdam UMC, location AMC, Amsterdam, the Netherlands. All authors declare no competing interests.

Obstetric outcomes in patients with primary thrombotic and obstetric antiphospholipid syndrome and its relation to the antiphospholipid antibody profile.

Introduction: Previous studies suggested different obstetric outcomes between patients with thrombotic or obstetric antiphospholipid syndrome, but the data are inconclusive. Aims: To investigate obstetric outcomes and their relation to the antiphospholipid antibody profile in primary thrombotic or obstetric antiphospholipid syndrome patients and compare those to a control population. Materials and methods: A retrospective single-centre study on a cohort of 30 pregnant women with primary antiphospholipid syndrome treated at Karolinska University Hospital Solna, Sweden between 2000 and 2016. The pregnancy outcomes were compared to the outcomes of all pregnancies in Stockholm County during the same period. Results: Preeclampsia (p < 0.001), low birth weight at delivery (p = 0.001), Apgar < 7 at 5 minutes (p < 0.001) and small infants (p < 0.001) were more common in antiphospholipid syndrome patients compared to controls. Obstetric antiphospholipid syndrome patients had a higher incidence of small infants (p = 0.023), lower birth weight (p = 0.013) and infants born with complications (p=0.004) compared to thrombotic antiphospholipid syndrome. Mothers with triple antibody positivity had a higher incidence of preeclampsia (p = 0.03), preterm delivery (p = 0.011), small infants (p=0.002) and infants born with complications (p = 0.012). Conclusions: Patients with primary antiphospholipid syndrome, especially those with obstetric antiphospholipid syndrome and triple antibody positivity, are at higher risk for adverse pregnancy outcomes, even under antithrombotic treatment. More frequent antenatal controls in high-risk patients can further improve outcomes.

Operative results, sexual function and quality of life after gracilis muscle transposition in complex rectovaginal fistulas.

AIM: Successful treatment of complex rectovaginal fistulas (RVFs) continues to be a surgical challenge. Interposition of well-perfused tissue, such as gracilis muscle, is one treatment option. The aim of this study was to investigate the operative results, sexual function and quality of life after gracilis muscle transposition (GMT) in the authors' own group of patients. METHOD: The study included 19 women with RVF (mean age 48 years). The postoperative outcome was evaluated by a questionnaire and clinical examination. RESULTS: The postoperative follow-up period was 7 months to 3.5 years (mean 23 months). GMT led to primary healing of RVF in 10 (53%) patients. Recurrences were observed in nine (47%) patients with RVF, in four (44%) of whom healing was achieved as a result of further interventions. Following GMT, two complications (abscess formation) requiring revision occurred. Although 42% of the patients reported certain limitations following muscle removal, GMT is a procedure that has a positive influence on the healing rate (74%), quality of life, continence and patient satisfaction. CONCLUSION: GMT is a procedure that allows healing in the majority of patients with RVFs, and it should be considered especially in patients with recurrent fistulas, in whom a correlation between decreasing healing rates and the number of previous operations has been demonstrated.

Evaluation of antimicrobial textiles for atopic dermatitis.

BACKGROUND: Functional textiles have been proposed as safe adjunct treatment for atopic dermatitis (AD). Some data have been published regarding their antimicrobial properties and their clinical efficacy. OBJECTIVE: This study examined the physical and functional properties of 11 commercially available functional textiles, including their antimicrobial activity in vitro, as a function of multiple laundering cycles. METHODS: All materials were weighed and examined under scanning electron microscopy (SEM) before and after laundering for fibre morphology and silver coating. Bioburden of newly purchased textiles was assessed by measuring bacterial colony forming units (CFU). Deliverable antimicrobial efficacy was evaluated in vitro for each specimen, before and after 30, 70, 100, 150 and 200 laundering cycles. RESULTS: Textile weight showed high variability. Damaged silver coating of variable degree was observed under SEM in most materials after laundering. Products made of silk showed smoother and tighter fibre morphology compared to cotton. The bacterial load of unwashed material ranged from <1 CFU to 35 CFU per 50 × 50 mm specimen. Most silver-containing products lost their antimicrobial activity rapidly after laundering. Silk and cotton retrieved products had no deliverable antimicrobial effect even in their original state. CONCLUSION: Elastic, lightweight textiles with smooth fibres are comfortable for daily use. Functional textiles rapidly losing their deliverable antimicrobial activity in vitro are not advisable for AD patients. Recommendations for functional textiles should be based on a combination of in vitro analysis of products in their original state and after laundering, together with real-life data obtained from controlled clinical trials.

Cognitive functioning and structural brain abnormalities in people with Type 2 diabetes mellitus.

AIMS: Type 2 diabetes mellitus is associated with cognitive dysfunction, but the underlying structural brain correlates are uncertain. This study examined the association between cognitive functioning and structural brain abnormalities in people with long-standing Type 2 diabetes. METHODS: Ninety-three people with Type 2 diabetes (age 62.3 ± 5.4 years, diabetes duration 9.7 ± 6.7 years; HbA1c 65 ± 10 mmol/mol, 8.1 ± 1.3%) were included. Cognitive functioning was assessed by a test battery covering the domains memory, processing speed and executive functioning. Brain tissue volumes and white matter hyperintensity volumes were automatically determined on MRI. Linear regression analyses were performed adjusted for age, sex and education. RESULTS: In people with Type 2 diabetes, increased white matter hyperintensity volume was associated with decreased processing speed [regression B coefficient = -0.22 (-0.38 to -0.06), P = 0.009], but not with memory or executive function (P > 0.05). Brain tissue volumes were not significantly related to cognitive functioning (P > 0.05). CONCLUSIONS: In people with long-standing, less strictly controlled Type 2 diabetes, white matter hyperintensities volumes were associated with decreased processing speed. This suggests that cerebral small vessel disease is an underlying disease mechanism of cognitive dysfunction in these individuals.

Pharmacokinetics of ceftiofur sodium in equine pregnancy.

Eleven pregnant pony mares (D270-326) were administered ceftiofur sodium intramuscularly at 2.2 mg/kg (n = 6) or 4.4 mg/kg (n = 5), once daily. Plasma was obtained prior to ceftiofur administration and at 0.5, 1, 2, 4, 8, 12, and 24 hr after administration. Eight pony mares were re-enrolled in the study at least 3 days from expected foaling to ensure steady-state concentrations of drug at the time of foaling. Mares were administered ceftiofur sodium (4.4 mg/kg, IM) daily until foaling. Parturition was induced using oxytocin 1 hr after ceftiofur sodium administration. Allantoic and amniotic fluid, plasma, and colostrum samples were collected at time of foaling. Serial foal plasma samples were obtained. Placental tissues were collected. Desfuroylceftiofur acetamide (DCA) concentrations were measured in samples by high-performance liquid chromatography (HPLC). Mean (±SD) peak serum concentrations of DCA were 3.97 ± 0.50 µg/ml (low dose) and 7.45 ± 1.05 µg/ml (high dose). Terminal half-life was significantly (p = .014) shorter after administration of the low dose (2.91 ± 0.59 hr) than after administration of the high dose (4.10 ± 0.72 hr). The mean serum concentration of DCA from mares at time of foaling was 7.96 ± 1.39 µg/ml. The mean DCA concentration in colostrum was 1.39 ± 0.70 µg/ml. DCA concentrations in allantoic fluid, amniotic fluid, placental tissues, and foal plasma were below the limit of quantification (<0.1 µg/ml) and below the minimum inhibitory concentration of ceftiofur against relevant pathogens. These results infer incomplete passage of DCA across fetal membranes after administration of ceftiofur sodium to normal pony mares.

Case-finding for cognitive impairment among people with Type 2 diabetes in primary care using the Test Your Memory and Self-Administered Gerocognitive Examination questionnaires: the Cog-ID study.

AIM: To evaluate two cognitive tests for case-finding for cognitive impairment in older patients with Type 2 diabetes. METHODS: Of 1243 invited patients with Type 2 diabetes, aged ≥70 years, 228 participated in a prospective cohort study. Exclusion criteria were: diagnosis of dementia; previous investigation at a memory clinic; and inability to write or read. Patients first filled out two self-administered cognitive tests (Test Your Memory and Self-Administered Gerocognitive Examination). Secondly, a general practitioner, blinded to Test Your Memory and Self-Administered Gerocognitive Examination scores, performed a structured evaluation using the Mini-Mental State Examination. Subsequently, patients suspected of cognitive impairment (on either the cognitive tests or general practitioner evaluation) and a random sample of 30% of patients not suspected of cognitive impairment were evaluated at a memory clinic. Diagnostic accuracy and area under the curve were determined for the Test Your Memory, Self-Administered Gerocognitive Examination and general practitioner evaluation compared with a memory clinic evaluation to detect cognitive impairment (mild cognitive impairment or dementia). RESULTS: A total of 44 participants were diagnosed with cognitive impairment. The Test Your Memory and Self-Administered Gerocognitive Examination questionnaires had negative predictive values of 81 and 85%, respectively. Positive predictive values were 39 and 40%, respectively. The general practitioner evaluation had a negative predictive value of 83% and positive predictive value of 64%. The area under the curve was ~0.70 for all tests. CONCLUSIONS: Both the tests evaluated in the present study can easily be used in case-finding strategies for cognitive impairment in patients with Type 2 diabetes in primary care. The Self-Administered Gerocognitive Examination had the best diagnostic accuracy and therefore we would have a slight preference for this test. Applying the Self-Administered Gerocognitive Examination would considerably reduce the number of patients in whom the general practitioner needs to evaluate cognitive functioning to tailor diabetes treatment.

Results of the Gore Bio-A fistula plug implantation in the treatment of anal fistula: a multicentre study.

BACKGROUND: The aim of this prospective study was to determine the efficiency of the Gore Bio-A synthetic plug in the treatment of anal fistulas. METHODS: A synthetic bioabsorbable anal fistula plug was implanted in 60 patients. All fistulas were transsphincteric and cryptoglandular in origin. RESULTS: The healing rate after 1 year of follow-up was 52 % (31 out of 60 patients). No patient was lost to follow-up. The treatment had no effect on the incontinence score. The plug dislodgement rate was 10 % (6 out of 60 patients). Thirty-four per cent of the patients (16 out of 47) required reoperation. The average operating time was 32 ± 10.2 min, and the average length of hospital stay was 3.3 ± 1.8 days. CONCLUSIONS: Synthetic plugs may be an alternative to bioprosthetic fistula plugs in the treatment of transsphincteric anal fistulas. This method might have better success rates than treatment with bioprosthetic fistula plugs.

Enhancement of superconductivity near a nematic quantum critical point.

We consider a low T_{c} metallic superconductor weakly coupled to the soft fluctuations associated with proximity to a nematic quantum critical point (NQCP). We show that (1) a BCS-Eliashberg treatment remains valid outside of a parametrically narrow interval about the NQCP, (2) the symmetry of the superconducting state (d wave, s wave, p wave) is typically determined by the noncritical interactions, but T_{c} is enhanced by the nematic fluctuations in all channels, and (3) in 2D, this enhancement grows upon approach to criticality up to the point at which the weak coupling approach breaks down, but in 3D, the enhancement is much weaker.

[Situation-adjusted Treatment of Haemorrhoidal Disease]. / Situationsadaptierte Therapie des Hämorrhoidenleidens.

In addition to the stage several factors influence the treatment of haemorrhoids. The adequate treatment of haemorrhoids is not solely dependent on the stage, thus a situation-adapted therapy should be preferred. Advantages, disadvantages and specific characteristics of different therapy strategies in addition to potential complication risks have to be evaluated in order to obtain an effective and low-risk course. Also requests and personal living conditions of the patient as well as the expertise and experience of the physician have to be considered. A review of the current literature has been performed and a "four columns concept" has been developed that constitutes the fundament of a situation-adjusted treatment of haemorrhoids. The "four columns" that should be considered when therapy strategies are determined are composed of the following key factors: diagnostic findings, treatment alternatives, physician, and patient.

[Practical Implementation of the "Four-column Concept" in the Situation-Adjusted Therapy for Haemorrhoidal Disease in the Daily Routine of a Proctology Department]. / Praktische Anwendung des "4-Säulen-Konzepts" der situationsadaptierten Therapie des Hämorrhoidalleidens im alltäglichen Arbeitsfeld einer proktologischen Abteilung.

INTRODUCTION: In addition to the stage, several factors influence the treatment of haemorrhoids. The aim of this study was the elaboration of an individual therapy concept which is situation-adjusted. In this context, our own experience and approaches are presented. MATERIALS AND METHODS: In the Department of Coloproctology of the Prosper-Hospital Recklinghausen, from January 2009 to August 2012, 903 haemorrhoidectomies (2nd to 4th degree) have been performed. We report our results on the practical implementation of a situation-adjusted treatment of haemorrhoidal disease. In this context we present an overview of effective modifications of surgical techniques. Retrospectively the perioperative course and postoperative outcome were evaluated. RESULTS: Even in a collective with a large number of high-risk patients (26 %) respecting the "four columns" that constitute the fundament of a situation-adjusted treatment of haemorrhoids, high patient satisfaction and good outcome with low complication (7 %) and recurrence (0 %) rates could be attained. CONCLUSION: The "four columns" (findings of examination, therapeutic options, physician and patient) form the fundament of an effective treatment of haemorrhoidal disease without many complications and guarantee an individually tailored therapy for each patient.

Fish and omega-3 fatty acid intake in relation to circulating fibroblast growth factor 23 levels in renal transplant recipients.

BACKGROUND AND AIMS: A high circulating fibroblast growth factor 23 (FGF23) level is an independent risk factor for cardiovascular mortality in renal transplant recipients and the general population. N-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) may contribute to cardiovascular risk reduction. We investigated whether fish and EPA-DHA intake are related to FGF23 levels in renal transplant recipients. METHODS AND RESULTS: We performed a cross-sectional analysis in 619 stable renal transplant recipients (mean age 53 years, 57% male, estimated glomerular filtration rate [eGFR] 53 ± 20 mL/min/1.73 m(2)). Dietary intake was assessed by a 177-item food frequency questionnaire. Serum intact FGF23 was measured by ELISA. We examined differences in FGF23 levels across categories of fish and EPA-DHA intake using analysis of variance models adjusted for age, sex, dietary and lifestyle factors and key determinants of FGF23. Patients consumed on average 15 g of fish and 139 mg EPA-DHA/day. Median FGF23 was 62 pg/mL (IQR 43-98 pg/mL). Higher dietary EPA-DHA and fish intake were associated with lower serum FGF23 levels. Subgroup analyses revealed that particularly in patients with reduced renal function (eGFR <60 mL/min/1.73 m(2)), adjusted FGF23 levels (114, 79, 75 pg/mL, P = 0.0001) were inversely associated with tertiles of EPA-DHA intake. Similarly, we observed an inverse association between fish consumption and serum FGF23 levels in adjusted analyses. CONCLUSION: A higher intake of fish and dietary n-3 fatty acids (EPA-DHA) is related to lower circulating FGF23 levels in renal transplant recipients. Further research is needed to assess the causality of this association and the clinical implications.