Verbal and General IQ Associate with Supragranular Layer Thickness and Cell Properties of the Left Temporal Cortex.

The left temporal lobe is an integral part of the language system and its cortical structure and function associate with general intelligence. However, whether cortical laminar architecture and cellular properties of this brain area relate to verbal intelligence is unknown. Here, we addressed this using histological analysis and cellular recordings of neurosurgically resected temporal cortex in combination with presurgical IQ scores. We find that subjects with higher general and verbal IQ scores have thicker left (but not right) temporal cortex (Brodmann area 21, BA21). The increased thickness is due to the selective increase in layers 2 and 3 thickness, accompanied by lower neuron densities, and larger dendrites and cell body size of pyramidal neurons in these layers. Furthermore, these neurons sustain faster action potential kinetics, which improves information processing. Our results indicate that verbal mental ability associates with selective adaptations of supragranular layers and their cellular micro-architecture and function in left, but not right temporal cortex.

Meta-analysis and systematic review of ADGRL3 (LPHN3) polymorphisms in ADHD susceptibility.

The gene encoding adhesion G protein-coupled receptor L3 (ADGRL3, also referred to as latrophilin 3 or LPHN3) has been associated with ADHD susceptibility in independent ADHD samples. We conducted a systematic review and a comprehensive meta-analysis to summarize the associations between the most studied ADGRL3 polymorphisms (rs6551665, rs1947274, rs1947275, and rs2345039) and both childhood and adulthood ADHD. Eight association studies (seven published and one unpublished) fulfilled criteria for inclusion in our meta-analysis. We also incorporated GWAS data for ADGRL3. In order to avoid overlapping samples, we started with summary statistics from GWAS samples and then added data from gene association studies. The results of our meta-analysis suggest an effect of ADGRL3 variants on ADHD susceptibility in children (n = 8724/14,644 cases/controls and 1893 families): rs6551665 A allele (Z score = -2.701; p = 0.0069); rs1947274 A allele (Z score = -2.033; p = 0.0421); rs1947275 T allele (Z score = 2.339; p = 0.0978); and rs2345039 C allele (Z score = 3.806; p = 0.0026). Heterogeneity was found in analyses for three SNPs (rs6551665, rs1947274, and rs2345039). In adults, results were not significant (n = 6532 cases/15,874 controls): rs6551665 A allele (Z score = 2.005; p = 0.0450); rs1947274 A allele (Z score = 2.179; p = 0.0293); rs1947275 T allele (Z score = -0.822; p = 0.4109); and rs2345039 C allele (Z score = -1.544; p = 0.1226). Heterogeneity was found just for rs6551665. In addition, funnel plots did not suggest publication biases. Consistent with ADGRL3's role in early neurodevelopment, our findings suggest that the gene is predominantly associated with childhood ADHD.

Performance validity in outpatients with multiple sclerosis and cognitive complaints.

BACKGROUND: Suboptimal performance during neuropsychological assessment renders cognitive test results invalid. However, suboptimal performance has rarely been investigated in multiple sclerosis (MS). OBJECTIVES: To investigate potential underlying mechanisms of suboptimal performance in MS. METHODS: Performance validity testing, neuropsychological assessments, neuroimaging, and questionnaires were analyzed in 99 MS outpatients with cognitive complaints. Based on performance validity testing patients were classified as valid or invalid performers, and based on neuropsychological test results as cognitively impaired or preserved. Group comparisons and correlational analyses were performed on demographics, patient-reported, and disease-related outcomes. RESULTS: Twenty percent displayed invalid performance. Invalid and valid performers did not differ regarding demographic, patient-reported, and disease-related outcomes. Disease severity of invalid and valid performers with cognitive impairment was comparable, but worse than cognitively preserved valid performers. Lower performance validity scores related to lower cognitive functioning, lower education, being male, and higher disability levels (p < 0.05). CONCLUSION: Suboptimal performance frequently occurs in patients with MS and cognitive complaints. In both clinical practice and in cognitive research, suboptimal performance should be considered in the interpretation of cognitive outcomes. Identification of factors that differentiate between suboptimal and optimal performers with cognitive impairment needs further exploration.

Quality of life and functional outcomes after transanal total mesorectal excision for rectal cancer-results from the implementation period in Denmark.

BACKGROUND: The standard operation for mid- and low rectal cancer total mesorectal excision (TME) is routinely performed as minimally invasive surgery. TME is associated with temporary or permanent functional impairment of pelvic organs, causing reduced quality of life (QoL). Concerns have been raised that the newest minimally invasive approach, transanal TME (TaTME), may further reduce urogenital and anorectal functions. OBJECTIVE: To determine if functional outcomes affecting QoL are altered after TaTME. Primary end-point is the impact of TaTME on QoL and functional outcomes. Secondary end-point is assessing differences in QoL and functional outcomes after TME surgery from below (TaTME) or above (transabdominal TME). DESIGN, SETTING, AND PARTICIPANTS: Observational study consisting of prospectively registered self-reported questionnaire data collected at baseline and follow-ups after TaTME. All patients who underwent TaTME during the Danish national implementation phase were included. Central surveillance of the implementation included questionnaires concerning QoL and functional outcomes. Analyses of functional results from the Danish cohort of the ROLARR trial (Jayne et al. in JAMA 318:1569-1580, (2017) are reported separately for perspective, representing the transabdominal approach to TME, i.e., laparoscopic- or robotic-assisted TME (LaTME/RoTME). Applied questionnaires include EORTC QLQ-C30, SF-36, LARS, ICIQ-MLUTS, ICIQ-FLUTS, IPSS, IIEF, SVQ, and FSFI. RESULTS: A total of 115 TaTME procedures were registered August 2016 to April 2019. LaTME/RoTME patients (n = 92) were operated on January 2011 to September 2014. A temporary postoperative decrease of QoL (global health status and functional scales) was observed, yet long-term results were unaffected by surgery in both groups. In TaTME patients, the anorectal dysfunction increased significantly (p < 0.001) from preoperative baseline to 13.5 months follow-up, where 67.5% (n = 52) reported major LARS symptoms. Urinary function was not significantly impaired after TME regardless of technique. The paucity of responses concerning sexual function precludes conclusions. CONCLUSIONS: Although an initial reduction in QoL after TME occurs, it normalizes within the first year postoperatively. In concurrence with international results, we found that significant anorectal dysfunction is common after TaTME. No data on anorectal function was available for LaTME/RoTME patients for comparison. We found no indications that transanal TME is inferior to transabdominal TME surgery concerning urogenital functions or health-related QoL.

Initiation of lactation and the provision of human milk to preterm infants in German neonatal intensive care units from the mothers' perspective.

BACKGROUND: If infants with a very low birth weight (VLBW) are to be fed exclusively with human milk, it is essential to focus on lactation initiation. The aim of the study is to learn more about the current state of lactation initiation and human milk provision in neonatal intensive care units in Germany from the mothers' perspective. METHODS: Written surveys were conducted with mothers of VLBW infants to learn more about the timing of initiation of lactation, pumping frequency during the first three days postpartum and feeding of the preterm infant during hospitalisation. RESULTS: The data of 437 mothers (response rate: 44.7%) were included in the analyses. Of these, only 7.8% stated that they had initiated lactation immediately after delivery and 38.2% within 6 h. In terms of pumping frequency, 50.1% pumped 7-9 times a day within the first 3 days postpartum; 60.9% reported that their infant received formula feedings during the hospital stay. CONCLUSION: Overall, deficits were still evident with regard to the initiation of lactation in mothers of VLBW infants in Germany, resulting in a large proportion of VLBW infants receiving formula in the hospital. TRIAL REGISTRATION: German Clinical Trial Register: DRKS00017755 .

Long-term care, care needs and wellbeing of individuals after cancer in childhood or adolescence (VersKiK): study protocol of a large scale multi-methods non-interventional study.

BACKGROUND: It has been shown previously that a relevant proportion of childhood cancer survivors suffers from late effects, which are often directly related to the cancer itself or its therapy, resulting in particular follow-up needs, additionally burdening healthcare systems. Being diagnosed with cancer at a vulnerable stage of development, this group of cancer survivors is at comparatively higher risk of relapse or subsequent cancer. Although national and international follow-up guidelines based on treatment modalities have been developed, their implementation seems to leave room for improvement. Additionally, they lack a sufficient consideration of the survivors' psychosocial needs, affecting their adherence to them. The aim of the VersKiK study is to provide representative information on late effects in childhood and adolescence cancer survivors in Germany. The main research objectives are: (1) to describe the state of follow-up care among survivors after a cancer diagnosis in childhood or adolescence; (2) to quantify the occurrence of late effects among this group of survivors; (3) to examine the adherence to selected audiological and cardiological follow-up guidelines and to identify factors affecting it; (4) to explore actual follow-up needs of paediatric cancer survivors; (5) to review selected follow-up guidelines with the aim to improve and expand them. METHODS: VersKiK is designed as a mixed-methods non-interventional study. We will use claims data from statutory health insurance companies in combination with individually linked population-based registry data from the German Childhood Cancer Registry (GCCR). This data base will permit us to quantify diagnoses and procedures in comparison to the general population as well as the adherence to existing follow-up guidelines. Additional information will be obtained through interviews with childhood and adolescence cancer survivors and their informal caregivers, as well as in focus groups with healthcare professionals. DISCUSSION: The present study aims to research the actual needs of individuals after cancer diagnosis and treatment in childhood or adolescence - physical, psychological and organisational - in order to improve existing follow-up guidelines. These improvements might further positively affect not only actual care provided to paediatric cancer survivors, but also benefit healthcare systems in general while decreasing consequent medical visits in this group of patients. TRIAL REGISTRATION: Registered at German Clinical Trial Register (ID: DRKS00025960 and DRKS00026092).

Proapoptotic and antiapoptotic stimuli alternation in myocardial infarction experimental model.

Myocardial infarction is a life-threatening complication of the coronary artery disease - the leading cause of premature death worldwide. The severity of this condition is the result of cellular death following the myocardial ischaemia, which occurs via several mechanism including apoptosis. For the research of this condition, animal models are often employed. We established isoprenaline-induced rat model of myocardial infarction, focusing on the immunohistochemical analysis of the expression of antiapoptotic and proapoptotic proteins BCL-2 and BAX, respectively. Apoptosis (based on BAX-positivity) was activated in cardiac muscle cells within the first day, later on day 8 also in fibroblasts of the forming scar tissue. Antiapoptosis in cardiac muscle cells was weak to moderate on the day 1 and 2, on the day 8 macrophages were strongly positive for BCL-2. The results confirmed that programmed cell death as well as mechanisms of antiapoptosis contribute to the pathogenesis of myocardial infarction. Previous research demonstrated that by experimentally affecting proapoptotic and antiapoptotic signals, it is possible to influence various aspects of myocardial infarction including: infarction size, cardiac remodelling and prognosis of the heart failure. Future research is warranted to fully elucidate the role of this process during myocardial infarction, which will result in refined diagnostic and therapeutic strategies (Tab. 1, Fig. 1, Ref. 21). Keywords: myocardial infarction, isoprenaline, apoptosis, necrosis, BCL-2, BAX.

Altered dynamics of lipid metabolism in muscle cells from patients with idiopathic inflammatory myopathy is ameliorated by 6 months of training.

KEY POINTS: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM). In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6-month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics. We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls. A 6-month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids. These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms. ABSTRACT: Exercise improves skeletal muscle function, clinical state and quality of life in patients with idiopathic inflammatory myopathy (IIM). Our aim was to identify disease-related metabolic perturbations and the impact of exercise in skeletal muscle cells of IIM patients. Patients underwent a 6-month intensive supervised training intervention. Muscle function, anthropometric and metabolic parameters were examined and muscle cell cultures were established (m. vastus lateralis; Bergström needle biopsy) before and after training from patients and sedentary age/sex/body mass index-matched controls. [14 C]Palmitate was used to determine fat oxidation and lipid synthesis (thin layer chromatography). Cells were exposed to a chronic (3 days) and acute (3 h) metabolic challenge (the saturated fatty acid palmitate, 100 µm). Reduced oxidative (intermediate metabolites, -49%, P = 0.034) and non-oxidative (diglycerides, -38%, P = 0.013) lipid metabolism was identified in palmitate-treated muscle cells from IIM patients compared to controls. Three days of palmitate exposure elicited distinct regulation of oxidative phosphorylation (OxPHOS) complex IV and complex V/ATP synthase (P = 0.012/0.005) and adipose triglyceride lipase in patients compared to controls (P = 0.045) (immunoblotting). Importantly, 6 months of training in IIM patients improved lipid metabolism (CO2 , P = 0.010; intermediate metabolites, P = 0.041) and activation of AMP kinase (P = 0.007), and nearly normalized palmitate-induced changes in OxPHOS proteins in myotubes from IIM patients, in parallel with improvements of patients' clinical state. Myotubes from IIM patients displayed altered dynamics of lipid metabolism and impaired response to metabolic challenge with saturated fatty acid. Our observations suggest that metabolic defects intrinsic to skeletal muscle could represent non-immune pathomechanisms, which can contribute to muscle weakness in IIM. A 6-month training intervention mitigated disease effects in muscle cells in vitro, indicating the existence of epigenetic regulatory mechanisms.

Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer before chemo-endocrine therapy.

BACKGROUND: We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SETER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). PATIENTS AND METHODS: Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SETER/PR or RNA4 components of SET2,3. RESULTS: SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SETER/PR index. CONCLUSIONS: SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.

Synchrotron CT of an equine digit at the Australian Synchrotron Imaging and Medical Beamline.

Laminitis is an extremely painful and debilitating condition of horses that can affect their athletic ability and even quality of life. The current gold standard for assessment of laminar tissue is histology, which is the only modality that enables detailed visualization of the lamina. Histology requires dissection of the hoof and therefore can only represent one specific time point. The superior spatial and contrast resolution of synchrotron computed tomography (sCT), when compared with readily available imaging modalities, such as radiographs and conventional CT, provides an opportunity for detailed studies of the lamina without the need for hoof dissection and histological assessment. If the resolution of histology can be matched or even approached, dynamic events, such as laminar blood flow, could also be studied on the microscopic tissue level. To investigate this possible application of sCT further, two objectives are presented: (i) to develop a protocol for sCT of an equine digit using cadaver limbs and (ii) to apply the imaging protocol established during (i) for sCT imaging of the vasculature within the foot using an ex vivo perfusion system to deliver the vascular contrast. The hypotheses were that sCT would allow sufficient resolution for detailed visualization to the level of the secondary lamellae and associated capillaries within the equine digit. Synchrotron CT enabled good visualization of the primary lamellae (average length 3.6 mm) and the ex vivo perfusion system was able to deliver vascular contrast agent to the vessels of the lamina. The individual secondary lamellae (average length 0.142 mm) could not be seen in detail, although differentiation between primary and secondary lamellae was achieved. This approaches, but does not yet reach, the current gold standard, histology, for assessment of the lamellae; however, with further refinement of this imaging technique, improved resolution may be accomplished in future studies.

Immunological and virological response to initial antiretroviral therapy among older people living with HIV in the Canadian Observational Cohort (CANOC).

OBJECTIVES: The aim of this study was to assess the adequacy of immunological recovery and virological suppression in response to antiretroviral therapy (ART) in the growing population of older people living with HIV (PLWH), as treatment regimens become more effective and tolerable. METHODS: An interprovincial Canadian cohort of treatment-naïve PLWH who initiated ART after 1 January 2000 was used and age assessed in decades. Longitudinal absolute CD4 count response to treatment was modelled using generalized estimating equations. Cumulative incidence functions and proportional hazards models with a competing risk of death were used to estimate time to: (1) CD4 ≥ 200 cells/µL, (2) CD4 ≥ 500 cells/µL, (3) virological suppression (≤ 50 copies/mL), and (4) virological failure (> 200 copies/mL). RESULTS: In all, 12 489 individuals starting ART between 2000 and 2016 with one or more post-treatment CD4 count or viral load were included in the analysis. Age > 60 years was associated with lower absolute CD4 recovery (adjusted ß = -31 cells/µL) compared with age ≤ 30 years when pre-treatment CD4 count and other covariates were accounted for. Older age groups were less likely to achieve a CD4 ≥ 500 cells/µL, with the greatest effect in the > 60 group [adjusted hazard ratio (aHR) = 0.69, 95% confidence interval (CI): 0.57-0.84 vs. age ≤ 30). Older age groups were more likely to achieve viral suppression (age > 60, aHR = 1.20, 95% CI: 1.05-1.37) and less likely to have virological failure (age > 60, aHR = 0.46, 95% CI: 0.3-0.71) compared with those aged ≤ 30 years. CONCLUSIONS: Older adults have robust virological responses to ART; however, individuals over the age 60 are more likely to experience blunted CD4 recovery.

A protein-free chemically defined medium for the cultivation of various micro-organisms with food safety significance.

AIMS: To develop a broadly applicable medium free of proteins with well-defined and reproducible chemical composition for the cultivation of various micro-organisms with food safety significance. METHODS AND RESULTS: The defined medium was designed as a buffered minimal salt medium supplemented with amino acids, vitamins, trace metals and other nutrients. Various strains commonly used for food safety research were selected to test the new defined medium. We investigated single growth factors needed by different strains and the growth performance of each strain cultivated in the defined medium. Results showed that the tested strains initially grew slower in the defined medium compared to tryptic soy broth, but after an overnight incubation cultures from the defined medium reached adequately high cell densities. CONCLUSIONS: The newly designed defined medium can be widely applied in food safety studies that require media with well-defined chemical constituents. SIGNIFICANCE AND IMPACT OF THE STUDY: Defined media are important in studies of microbial metabolites and physiological properties. A defined medium capable of cultivating different strains simultaneously is needed in the food safety area. The new defined medium has broader applications in comparing different strains directly and provides more reproducible results.

[Personnel assessment in psychiatry and psychotherapy : Results of a feasibility study on the platform model]. / Personalbemessung in der Psychiatrie und Psychotherapie : Ergebnisse einer Machbarkeitsstudie zum Plattform-Modell.

The topic of personnel assessment in psychiatry, psychotherapy and psychosomatics is currently of great importance in terms of health policy. Sufficient empirical evidence for the development of a comprehensive system for staffing is not yet available. The platform model developed by the psychiatric psychosomatic societies and associations pursues a combined empirical normative approach for a future-oriented assessment instrument for the various professional groups. The concept presented has been proven in the health policy discussion as a sensible system of comprehensive personnel assessment; however, an empirically sound control is still lacking as to whether this system can be used practically for the task described and thus can withstand the task of a resilient and future-proof measurement instrument for the necessary personnel. The task of the present study was to examine the extent to which the assumptions of the platform model are confirmed, whether methodological indications can be identified and whether there are limitations of the study that can be used in the validation and foundation of the model. The study confirmed the feasibility of the model and refers to a number of methodological findings and limitations that can be used for the further development of the model. The developed model allows the necessary staffing to be derived and justified, regardless of diagnoses and settings. It is future-oriented and dynamic.

Agenesis of female internal reproductive organs, the Mayer- Rokitansky-Küster-Hauser syndrome.

OBJECTIVES: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is the most common cause of uterine and uterine tubes absence/underdevelopment and the second most common cause of primary amenorrhea. It is characterized by a congenital agenesis of the uterine tubes, uterus, cervix, and upper part of the vagina. This study presents our 10 years of experience with the diagnostics and therapeutic management of patients with MRKH syndrome. We also focused on the description of anatomical deviations of the female reproductive organs. MATERIALS AND METHODS: We studied a cohort of 16 patients hospitalized with MRKH syndrome between 2011-2020. We analysed the age at diagnosis, clinical signs and symptoms, diagnostic techniques, methods of neovagina creation, and anatomical anomalies of the female reproductive organs. RESULTS: The mean age of our patients at the time of diagnosis was 16.75 years. The most frequent clinical manifestations were primary amenorrhea (56.25 %), pelvic pain (31.25 %) and coitus-associated problems. We used two methods of neovagina creation. In six patients we used the non-surgical Frank's dilators method. The vaginal length at the beginning of the dilation was 1.5-2 cm. In 4 patients the vaginal length was under 1 cm, so we performed surgical neovagina creation using the laparoscopic Vecchietti method. An-other two patients could create the vagina via regular sexual intercourse. Based on magnetic resonance imaging and ultrasound examination, the following anomalies were observed: complete agenesis of the uterus (50 % of cases), fibrous band (25 %) and rudimentary uterus (25 %). CONCLUSIONS: Satisfactory results in the attempt to create a neovagina can be obtained by both non-surgical and surgical methods. Modern medicine provides many therapeutic measures, which make it possible for the affected women to have a normal sexual life (Tab. 1, Fig. 3, Ref. 37).

Outcome following local excision of T1 anal cancers-a systematic review.

PURPOSE: In most cases, squamous cell carcinoma of the anus (SCCA) is treated with chemo-radiotherapy preserving sphincter function and offering good long-term survival and low recurrence rates. However, chemo-radiotherapy has several side effects: dyspareunia, impotence, fecal incontinence, pain, and skin symptoms. Small/T1 tumors, without metastatic disease, can be treated with local excision alone. We aimed to systematically review the literature regarding outcome following local excision of T1 SCCA. METHODS: PubMed and Embase databases were searched for studies that investigated outcome following local excision of SCCA. RESULTS: Twenty-three studies were included. Twenty of the studies were retrospective, and three studies included more than 100 patients. Most of the studies were published before the 1980s. Overall there was great heterogeneity and missing data across the included studies when comparing patient demographics, resection margins, definitions on tumor location, and outcome. Overall 5-year survival was 69% (95% CI 66-72) following local excision. Overall 5-year recurrence was 37% (95% CI 30-45) following local excision. No complications were reported following local excision. CONCLUSION: The current literature on outcome following local excision of T1 anal cancers consists predominantly of smaller, retrospective, and heterogenous studies. Overall 5-year survival is acceptable, but worse than following chemo-radiation therapy. However, local excision seems to have no or only few minor complications. Recurrence rates are high. Therefore, a thorough follow-up program is needed when performing local excision as primary treatment for T1 SCCA. There is an evident need for further studies.

Validation of the Danish Colorectal Cancer Group (DCCG.dk) database - on behalf of the Danish Colorectal Cancer Group.

AIM: The aim of this study was to validate the clinical quality database of the Danish Colorectal Cancer Group. The validation is meant to focus on core data regarding staging of the disease, treatment provided, patient-related factors and key complications. METHOD: This was a database validation study assessing the completeness of the database and the accuracy of the data by re-entering core variables into an online module in a blinded fashion and comparing re-entered data with the original database data. A sample of 5% of patients from the years 2014-2017 was randomly selected. RESULTS: The sample of 936 patients was identified and data were re-entered. The completeness of the data retrieved was a median of 96%, 100% and 99% for preoperative, intra-operative and postoperative variables, respectively. The overall accuracy was a median of 95%. The least accurate variable was date of diagnosis (50% perfect agreement), with agreement rising to 96% when near matches defined as correct date ± 30 days were included. Intra-operative variables were of high quality, as were data on surgical complications including anastomotic leakage, where agreement was 97%. CONCLUSION: This was the first major validation of the Danish Colorectal Cancer Group's database. Overall, the completeness and quality of data were high, but the validation process also identified weaknesses, which can be crucial for future users to acknowledge and consider.

Ophthalmic Thelazia callipaeda infections: first feline and new canine imported cases in Germany.

The first case of feline ocular Thelazia callipaeda infection and two new canine imported infections in West Germany are here described. The three animals had a history of recent travel to/from other countries. The young adult cat imported from Spain presented an intermittent unilateral ocular discharge. During in-depth ophthalmic examination, a single alive nematode was removed from the conjunctival compartment of the affected eye. Referring to the canine cases, an adult female dog originated from Kenya presented epiphora and mucous whitish-grey discharge of the right eye. During flushing of the nasolacrimal duct two small, thin and long nematodes were removed. Furthermore, a male Borzoi racing dog with regular visit to racing tracks in different countries presented ocular mucous discharge. At ophthalmologic examination, two transparent-whitish vital nematodes were removed. All nematode specimens of the three cases were morphologically identified as adult T. callipaeda parasites. The animals were treated orally with milbemycin oxime (2.0 mg/kg; cat) or milbemycin oxime/praziquantel (0.5 mg/kg and 5.0 mg/kg; dogs) twice with 1-week interval resulting in complete resolution of symptoms. The repeated introduction of patent T. callipaeda-infected animals, especially from southern and eastern endemic countries, will ease the establishment of ophthalmic thelaziosis in Northern Europe. The male fruit fly, Phortica variegata, an intermediate host of T. callipaeda, is endemic within European countries. Considering the clinical and zoonotic relevance of ophthalmic thelaziosis, enhanced disease awareness of European medical and veterinarian doctors and in-depth eye examination for proper detection of T. callipaeda are crucial for appropriate anthelmintic treatments and to limit spreading of the infection.

Nuclear power plant: state of knowledge of the population living in the area of the Cattenom special intervention plan. A cross-sectional study.

In France information campaigns are periodically conducted within a 10 km radius of nuclear power plants on the protective actions to be adopted in the event of a nuclear accident. The aim of this study was to assess the knowledge of the inhabitants of the Cattenom PPI area on the recommended actions to be adopted in the event of a nuclear accident after the information campaign that took place from 2016 to 2017 and compare its results with a similar study carried out before the information campaign. We performed a cross-sectional study in the Cattenom PPI area after the 2016-2017 information campaign. We administered questionnaires in ten municipalities selected by lot. These questionnaires contained queries on the general protective actions and required approach to taking potassium iodide (KI). The results obtained were compared with the results of a study conducted before the information campaign in the same area. Out of 200 questionnaires administered, 122 people responded. Only 40% of respondents remembered the information campaign. Only 16% knew all of the recommended protective actions. 78% of households had KI and only 60% knew the objective of KI intake. Compared to the results of the study before the information campaign, KI coverage was better (69% versus 78%, p = 0.02) and the dosage was better known (16% versus 28%, p = 0.0003). This study provides an overview of the effectiveness of information campaigns on the procedure in the event of a nuclear accident. This study highlights the insufficient knowledge of people living in the Cattenom PPI area.

Prevalence and predictors of airflow obstruction in an HIV tertiary care clinic in Montreal, Canada: a cross-sectional study.

OBJECTIVES: The reported prevalence of chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWHIV) varies widely. Our objective was to estimate the prevalence of airflow obstruction and COPD in unselected PLWHIV and identify characteristics that increase the risk of nonreversible airflow obstruction in order to guide case finding strategies for COPD. METHODS: All adults attending the Chronic Viral Illness Service were invited to participate in the study, regardless of smoking status or history of known COPD/asthma. Individuals underwent spirometric testing both before and after use of a salbutamol bronchodilator. Airflow obstruction was defined as forced expiratory volume in 1 s (FEV1 )/forced vital capacity (FVC) < 0.7 post-bronchodilation, whereas COPD was defined as FEV1 /FVC < 0.7 post-bronchodilation and Medical Research Council (MRC) score > 2. Multivariate logistic regression was used to evaluate risk factors associated with airflow obstruction, reported as adjusted odds ratios (aORs). RESULTS: Five hundred and three participants successfully completed spirometry testing. The median (Q1; Q3) age was 52 (44; 58) years. The median (Q1; Q3) CD4 count was 598 (438; 784) cells/µL and the median (Q1; Q3) nadir CD4 count was 224 (121; 351) cells/µL. There were 119 (24%) current smokers and 145 (29%) former smokers. Among those screened, 54 (11%) had airflow obstruction whereas three (1%) of the participants had COPD. Factors that were associated with airflow obstruction included a history of smoking [aOR 2.2; 95% confidence interval (CI) 1.1; 4.7], older age (aOR 1.6; 95% CI 1.2; 2.2), and lower CD4 count (aOR 0.8; 95% CI 0.7; 1.0). CONCLUSIONS: Airflow obstruction was relatively uncommon. Our findings suggest that PLWHIV who are ≥50 years old, smokers and those with nadir CD4 counts ≤ 200 cells/µL could be targeted to undergo spirometry to diagnose chronic airflow obstruction.

A Potential Role for the STXBP5-AS1 Gene in Adult ADHD Symptoms.

We aimed to detect Attention-deficit/hyperactivity (ADHD) risk-conferring genes in adults. In children, ADHD is characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity and may persists into adulthood. Childhood and adulthood ADHD are heritable, and are thought to represent the clinical extreme of a continuous distribution of ADHD symptoms in the general population. We aimed to leverage the power of studies of quantitative ADHD symptoms in adults who were genotyped. Within the SAGA (Study of ADHD trait genetics in adults) consortium, we estimated the single nucleotide polymorphism (SNP)-based heritability of quantitative self-reported ADHD symptoms and carried out a genome-wide association meta-analysis in nine adult population-based and case-only cohorts of adults. A total of n = 14,689 individuals were included. In two of the SAGA cohorts we found a significant SNP-based heritability for self-rated ADHD symptom scores of respectively 15% (n = 3656) and 30% (n = 1841). The top hit of the genome-wide meta-analysis (SNP rs12661753; p-value = 3.02 × 10-7) was present in the long non-coding RNA gene STXBP5-AS1. This association was also observed in a meta-analysis of childhood ADHD symptom scores in eight population-based pediatric cohorts from the Early Genetics and Lifecourse Epidemiology (EAGLE) ADHD consortium (n = 14,776). Genome-wide meta-analysis of the SAGA and EAGLE data (n = 29,465) increased the strength of the association with the SNP rs12661753. In human HEK293 cells, expression of STXBP5-AS1 enhanced the expression of a reporter construct of STXBP5, a gene known to be involved in "SNAP" (Soluble NSF attachment protein) Receptor" (SNARE) complex formation. In mouse strains featuring different levels of impulsivity, transcript levels in the prefrontal cortex of the mouse ortholog Gm28905 strongly correlated negatively with motor impulsivity as measured in the five choice serial reaction time task (r2 = - 0.61; p = 0.004). Our results are consistent with an effect of the STXBP5-AS1 gene on ADHD symptom scores distribution and point to a possible biological mechanism, other than antisense RNA inhibition, involved in ADHD-related impulsivity levels.