Sex and pubertal variation in reward-related behavior and neural activation in early adolescents.

This study aimed to characterize the role of sex and pubertal markers in reward motivation behavior and neural processing in early adolescence. We used baseline and two-year follow-up data from the Adolescent Brain and Cognitive DevelopmentSM study (15844 observations; 52% from boys; age 9-13). Pubertal development was measured with parent-reported Pubertal Development Scale, and DHEA, testosterone, and estradiol levels. Reward motivation behavior and neural processing at anticipation and feedback stages were assessed with the Monetary Incentive Delay task. Boys had higher reward motivation than girls, demonstrating greater accuracy difference between reward and neutral trials and higher task earnings. Girls had lower neural activation during reward feedback than boys in the nucleus accumbens, caudate, rostral anterior cingulate, medial orbitofrontal cortex, superior frontal gyrus and posterior cingulate. Pubertal stage and testosterone levels were positively associated with reward motivation behavior, although these associations changed when controlling for age. There were no significant associations between pubertal development and neural activation during reward anticipation and feedback. Sex differences in reward-related processing exist in early adolescence, signaling the need to understand their impact on typical and atypical functioning as it unfolds into adulthood.

Long-term experience on assisted suicide in Switzerland: dementia, mental disorders, age-related polymorbidity and the slippery slope argument.

OBJECTIVES: According to the Swiss medico-ethical guidelines valid between 2004 and 2018, the key criterion for assisted suicide (AS) was that the patients who wished to die suffered with a disease leading to death in the foreseeable future. Critics of AS fears that broadening of the medical indications will lead to an uncontrolled expansion to persons who are not terminally ill (slippery slope argument). We evaluated to what extent this broadening took place in practice over time. STUDY DESIGN: Retrospective national cohort study. METHODS: By using data of the Swiss Federal Statistical Office, we analyzed the long-term development of AS in Switzerland over a 20-year period (1999-2018; n = 8738 cases). We classified the cases into one of three categories regarding the aforementioned key criterion for AS. RESULTS: In 43.6% of AS cases, the criterion 'end of life is near' was met. In 5.3% of cases, this criterion was not met (4.7%: mental disorders; 0.6%: dementia). In 51.1% of cases, the reason underlying AS comprised several, mostly age-related diseases and/or functional impairments; the aforementioned key criterion, however, was probably not met in most of the cases. Over time, the number of cases doubled over each 5-year period; this increase occurred similarly for the three categories. CONCLUSION: The fact that many AS cases took place outside the valid medico-ethical guidelines might be interpreted as a development in the idea of the slippery slope argument. The fact that the percentage distribution of these cases remained unchanged over time argues against it.

An intra-action review conducted by the CDC Foundation during COVID-19 to evaluate emergency response procedures.

OBJECTIVES: During times of emergency response, the CDC Foundation leverages partnerships and relationships to better understand the situation and respond rapidly to save lives. As the COVID-19 pandemic began to unfold, an opportunity became clear to improve our work in emergency response through documentation of lessons learned and incorporating them into best practices. STUDY DESIGN: This was a mixed methods study. METHODS: The CDC Foundation Response, Crisis and Preparedness Unit conducted an internal evaluation via an intra-action review to evaluate and rapidly improve emergency response activities to provide effective and efficient response-related program management. RESULTS: The processes developed during the COVID-19 response to conduct timely and actionable reviews of the CDC Foundation's operations led to the identification of gaps in the work and management processes and to creation of subsequent actions to address these issues. Such solutions include surge hiring, establishing standard operating procedures for processes not yet documented, and creating tools and templates to streamline emergency response operations. CONCLUSIONS: The creation of manuals and handbooks, intra-action reviews, and impact sharing for emergency response projects led to actionable items meant to improve processes and procedures and the ability of the Response, Crisis and Preparedness Unit to quickly mobilize resources directed toward saving lives. These products are now open-source resources that can be used by other organizations to improve their own emergency response management systems.

Perioperative complications and outcomes following partial ear canal ablation and lateral bulla osteotomy in pet rabbits: 20 cases (2009-2021).

OBJECTIVE: To investigate the perioperative complications and outcomes of rabbits undergoing partial ear canal ablation and lateral bulla osteotomy for treatment of chronic otitis. MATERIALS AND METHODS: Surgical logbooks were searched to identify rabbits that underwent partial ear canal ablation and lateral bulla osteotomy between December 2009 and September 2021. Data collected included signalment, history, clinical signs, historical and current medical management, physical examination findings, preoperative diagnostic imaging and aural bacterial culture results, surgical procedure information, duration of hospitalisation, complications and final outcome. RESULTS: Twenty rabbits with chronic, medically unresponsive otitis underwent 27 partial ear canal ablation and lateral bulla osteotomies. Ten rabbits had pre-existing neurologic deficits and 17 had an ear base abscess at the time of surgery. A total of 13 (65%) rabbits developed at least one complication, either in the perioperative period or between discharge and recheck. Three of these rabbits (15%) underwent revision surgery for persistent or recurrent ear base abscess. Complete resolution of clinical signs ultimately occurred in 12 (60%) rabbits. Three (15%) rabbits showed improved but not completely resolved clinical signs (three facial asymmetry). Five (25%) rabbits died of causes potentially related to chronic otitis and/or partial ear canal ablation and lateral bulla osteotomy; two of these rabbits had undergone revision surgery. CLINICAL SIGNIFICANCE: Although this study reports a high complication rate (65%), most complications resolved, with 15 (75%) rabbits having a good to excellent final outcome. Since the majority of rabbits in this study had chronic and severe ear disease, further studies are required to determine if surgical intervention earlier in the disease process could result in a lower complication rate.

High pressure frozen oocytes have improved ultrastructure but reduced cleavage rates compared to conventionally fixed or vitrified oocytes.

CONTEXT: Live birth rates are lower for cryopreserved oocytes than for fresh IVF cycles, indicating a need for improved methodologies. AIMS: The aim of this study was to determine if high pressure freezing (HPF) could improve both ultrastructural preservation and cryopreserved oocyte quality when compared to conventional fixation and vitrification methods. METHODS: Sheep oocytes and embryos were prepared by HPF or vitrification, with or without cryoprotectants. Frozen oocytes were prepared for transmission electron microscopy or warmed, in vitro fertilised and the recovery and cleavage rates recorded. KEY RESULTS: Blastocyst rates were similar between fresh, HPF and vitrified embryos. HPF oocytes had improved ultrastructure compared to conventional fixation or vitrification, but had poorer survival and cleavage rates compared to vitrified oocytes. Freeze-substitution of cryopreserved oocytes and transmission electron microscopy demonstrated disruption of the oocyte ultrastructure in the presence of cryoprotectants. CONCLUSIONS: Superior preservation of ultrastructure was observed in HPF oocytes compared to vitrification or conventional fixation methods. In the presence of CP, both embryos and oocytes could survive HPF and warming but oocytes had reduced development. IMPLICATIONS: The HPF method has potential to be developed and lead to improved oocyte and embryo cryopreservation and outcomes for assisted reproduction.

Sediment-associated organic matter sources and sediment oxygen demand in a Special Area of Conservation (SAC): A case study of the River Axe, UK.

Oxygen demand in river substrates providing important habitats for the early life stages of aquatic ecology, including lithophilous fish, can arise due to the oxidation of sediment-associated organic matter. Oxygen depletion associated with this component of river biogeochemical cycling, will, in part, depend on the sources of such material. A reconnaissance survey was therefore undertaken to assess the relative contributions from bed sediment-associated organic matter sources potentially impacting on the River Axe Special Area of Conservation (SAC), in SW England. Source fingerprinting, including Monte Carlo uncertainty analysis, suggested that the relative frequency-weighted average median source contributions ranged between 19% (uncertainty range 0-82%) and 64% (uncertainty range 0-99%) for farmyard manures or slurries, 4% (uncertainty range 0-49%) and 35% (uncertainty range 0-100%) for damaged road verges, 2% (uncertainty range 0-100%) and 68% (uncertainty range 0-100%) for decaying instream vegetation, and 2% (full uncertainty range 0-15%) and 6% (uncertainty range 0-48%) for human septic waste. A reconnaissance survey of sediment oxygen demand (SOD) along the channel designated as a SAC yielded a mean SOD5 of 4 mg O2 g-1 dry sediment and a corresponding SOD20 of 7 mg O2 g-1 dry sediment, compared with respective ranges of 1-15 and 2-30 mg O2 g-1 dry sediment, measured by the authors for a range of river types across the UK. The findings of the reconnaissance survey were used in an agency (SW region) catchment appraisal exercise for informing targeted management to help protect the SAC.

Crop cover the principal influence on non-crop ground beetle (Coleoptera, Carabidae) activity and assemblages at the farm scale in a long-term assessment.

Ground beetle data were generated using pitfall traps in the 17-year period from 1993 to 2009 and used to investigate the effects of changes in surrounding crop cover on beetle activity and assemblages, together with the effects of weather variability. Beetles were recorded from non-crop field margins (overgrown hedges). Crop cover changes explained far more variation in the beetle assemblages recorded than did temperature and rainfall variation. A reduction in management intensity and disturbance in the crops surrounding the traps, especially the introduction and development of willow coppice, was concomitant with changes in individual species activity and assemblage composition of beetles trapped in non-crop habitat. There were no consistent patterns in either overall beetle activity or in the number of species recorded over the 17-year period, but there was a clear change from assemblages dominated by smaller species with higher dispersal capability to ones with larger beetles with less dispersal potential and a preference for less disturbed agroecosystems. The influence of surrounding crops on ground beetle activity in non-crop habitat has implications for ecosystem service provision by ground beetles as pest predators. These results are contrary to conventional assumptions and interpretations, which suggest activity of pest predators in crops is influenced primarily by adjacent non-crop habitat. The long-term nature of the assessment was important in elucidation of patterns and trends, and indicated that policies such as agri-environment schemes should take cropping patterns into account when promoting management options that are intended to enhance natural pest control.

Short-term spatial and temporal variability in greenhouse gas fluxes in riparian zones.

Recent research indicates that riparian zones have the potential to contribute significant amounts of greenhouse gases (GHG: N2O, CO2, CH4) to the atmosphere. Yet, the short-term spatial and temporal variability in GHG emission in these systems is poorly understood. Using two transects of three static chambers at two North Carolina agricultural riparian zones (one restored, one unrestored), we show that estimates of the average GHG flux at the site scale can vary by one order of magnitude depending on whether the mean or the median is used as a measure of central tendency. Because the median tends to mute the effect of outlier points (hot spots and hot moments), we propose that both must be reported or that other more advanced spatial averaging techniques (e.g., kriging, area-weighted average) should be used to estimate GHG fluxes at the site scale. Results also indicate that short-term temporal variability in GHG fluxes (a few days) under seemingly constant temperature and hydrological conditions can be as large as spatial variability at the site scale, suggesting that the scientific community should rethink sampling protocols for GHG at the soil-atmosphere interface to include repeated measures over short periods of time at select chambers to estimate GHG emissions in the field. Although recent advances in technology provide tools to address these challenges, their cost is often too high for widespread implementation. Until technology improves, sampling design strategies will need to be carefully considered to balance cost, time, and spatial and temporal representativeness of measurements.

Validity and reliability of the Italian Constipation Assessment Scale.

Constipation is a common problem among oncology patients and requires careful assessment. Use of validated instruments is important to improving its management. The aim of this study was to validate the Italian translation of the Constipation Assessment Scale (CAS). To test construct validity, patients and apparently healthy adults were asked to complete the CAS. The results indicated that there was a significant difference between the median CAS of the patient group and that of the apparently healthy group. Test-retest reliability was very high (r=0.96; P=0.0001), and the internal consistency as assessed by Cronbach's alpha was 0.768. These findings suggest that the Italian CAS can be used in clinical practice to document the presence and severity of constipation in cancer patients. However, further studies should be conducted in a larger sample of patients to confirm the results.

Differential Age-related Changes in Bone Geometry between the Humerus and the Femur in Healthy Men.

Muscle pull and weight-bearing are key mechanical determinants of bone geometry which is an important feature of bone strength that declines with adult aging. However, the relative importance of these determinants in young and old adults has not been evaluated systematically. To differentiate the influence of each type of mechanical loading we compared humeral and femoral bone shaft geometry and cross-sectional area (CSA) of the arm and thigh muscles in young and old men. Contiguous transverse MRI (Siemens 1.5T) scans of the arm and thigh were made in 10 young men (21.9 ± 1.0 years) and 10 old men (78.1 ± 4.9 years). Image analysis yielded total (TA), cortical (CA) and medullary (MA) CSA of the humeral and femoral shafts, as well as muscle CSA of the corresponding regions of the arm and thigh. Humeral CA was significantly greater in the young, whereas humeral and femoral MA were significantly greater in the older group. Significant correlations were found between arm muscle CSA and humeral CA (r = 0.73); between thigh muscle CSA and femoral CA (r = 0.69); and between body mass and femoral CA (r = 0.63) and TA (r = 0.55). Moderate correlations between muscle CSA and CA suggest that muscle pull is an important determinant of bone geometry. The significant difference observed between young and old in humeral, but not femoral CA, and the correlation between body mass and femoral, but not humeral cortical area, suggests that weight-bearing attenuates bone loss associated with adult aging.

Malignancy and mortality in a population-based cohort of patients with coeliac disease or "gluten sensitivity".

AIM: To determine the risk of malignancy and mortality in patients with a positive endomysial or anti-gliadin antibody test in Northern Ireland. METHODS: A population-based retrospective cohort study design was used. Laboratory test results used in the diagnosis of coeliac disease were obtained from the Regional Immunology Laboratory, cancer statistics from the Northern Ireland Cancer Registry and mortality statistics from the General Registrar Office, Northern Ireland. Age standardized incidence ratios of malignant neoplasms and standardized mortality ratios of all-cause and cause-specific mortality were calculated. RESULTS: A total of 13 338 people had an endomysial antibody and/or an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There were 490 patients who tested positive for endomysial antibodies and they were assumed to have coeliac disease. There were 1133 patients who tested positive for anti-gliadin antibodies and they were defined as gluten sensitive. Malignant neoplasms were not significantly associated with coeliac disease; however, all-cause mortality was significantly increased following diagnosis. The standardized incidence and mortality ratios for non-Hodgkin's lymphoma were increased in coeliac disease patients but did not reach statistical significance. Lung and breast cancer incidence were significantly lower and all-cause mortality, mortality from malignant neoplasms, non-Hodgkin's lymphoma and digestive system disorders were significantly higher in gluten sensitive patients compared to the Northern Ireland population. CONCLUSION: Patients with coeliac disease or gluten sensitivity had higher mortality rates than the Northern Ireland population. This association persists more than one year after diagnosis in patients testing positive for anti-gliadin antibodies. Breast cancer is significantly reduced in the cohort of patients with gluten sensitivity.

Anti-tissue transglutaminase antibodies and their role in the investigation of coeliac disease.

Coeliac disease (CD), caused by an inappropriate T-cell-mediated immune response to the ingestion of cereal proteins in genetically susceptible individuals, is a common disorder with a prevalence of about 1% in Caucasian populations. It has a strong association with other autoimmune disorders, particularly type 1 diabetes and autoimmune thyroid disease. Although primarily affecting the small bowel, CD is a multisystem disorder and the adult or child patient may initially present to a wide range of clinical specialties. The concept of the 'coeliac iceberg' has been used to emphasize that many cases currently remain undiagnosed. The identification of tissue transglutaminase (TGA)-2 as the antigen against which the autoantibodies are directed has led to a greater understanding of the pathogenesis of CD and to the development of improved serological tests. Enzyme-linked immunoassays using human tissue TGA as antigen have high diagnostic sensitivity and specificity for the detection of CD. This review examines the evidence for adopting IgA anti-tissue TGA as the first-line diagnostic test for CD. It recommends a laboratory algorithm for the use and interpretation of TGA to enable the clinical laboratory to play a full part in detecting and monitoring a disorder that is eminently treatable once the diagnosis has been considered and confirmed.

Increasing numbers at a specialist coeliac clinic: contribution of serological testing in primary care.

BACKGROUND: Serological testing, using IgA class endomysial and tissue transglutaminase antibodies has high sensitivity and specificity for coeliac disease and allows case finding by clinicians other than gastroenterologists. We reviewed new coeliac patients seen over a 9-year period to determine how the availability of serology, particularly to primary care physicians, has changed rates and sources of diagnosis. METHODS: Files of patients attending a specialist coeliac clinic who were diagnosed from 1996 through 2004 were reviewed. Patients with villous atrophy consistent with gluten sensitive enteropathy (Marsh III) on duodenal biopsy were selected. Data analysed included clinical characteristics, endomysial and tissue transglutaminase antibodies status and source of request for serology. RESULTS: Over the study period 347 new coeliac patients, comprising adults and children aged 10 years and over, were identified, of whom 163 (47%) were identified by serological testing in primary care, 152 (44%) at the hospital gastroenterology department and 32 (9%) by other physicians in secondary care. Over three consecutive 3-year periods, the percentage of patients identified in primary care rose from 28% through 47% to 60%, with a rise in total numbers diagnosed from 93 through 118 to 136. There was no change in patient clinical characteristics over the study period. Though tissue transglutaminase antibodies were less sensitive than endomysial antibodies, combined testing obtained a sensitivity of over 90%. Patients identified in primary care were significantly younger and more likely to present with diarrhoea as a primary symptom. CONCLUSION: Currently over half of our coeliac patients are identified by serological testing in primary care, which has resulted in an overall rise in diagnosis rates. Primary care practitioners have an important role in the diagnosis of coeliac disease, particularly of patients who present with non-gastrointestinal symptoms. The contribution of specialists other than gastroenterologists in secondary care is disappointing and may improve with directed education.

Therapeutic administration of Budesonide ameliorates allergen-induced airway remodelling.

BACKGROUND: Airway inflammation and remodelling are important pathophysiologic features of chronic asthma. Although current steroid use demonstrates anti-inflammatory activity, there are limited effects on the structural changes in the lung tissue. OBJECTIVE: We have used a mouse model of prolonged allergen challenge that exhibits many of the salient features of airway remodelling in order to investigate the anti-remodelling effects of Budesonide. METHODS: Treatment was administered therapeutically, with dosing starting after the onset of established eosinophilic airway inflammation and hyper-reactivity. RESULTS: Budesonide administration reduced airway hyper-reactivity and leukocyte infiltration in association with a decrease in production of the Th2 mediators, IL-4, IL-13 and eotaxin-1. A reduction in peribronchiolar collagen deposition and mucus production was observed. Moreover, our data show for the first time that, Budesonide treatment regulated active transforming growth factor (TGF)-beta signalling with a reduction in the expression of pSmad 2 and the concomitant up-regulation of Smad 7 in lung tissue sections. CONCLUSIONS: Therefore, we have determined that administration of Budesonide modulates the progression of airway remodelling following prolonged allergen challenge via regulation of inflammation and active TGF-beta signalling.

Coeliac disease-associated antibodies correlate with psoriasis activity.

BACKGROUND: Antigliadin antibodies (AGA) have been reported in patients with psoriasis. OBJECTIVES: To determine if AGA and other coeliac disease (CD)-associated antibodies correlate with clinical features and activity in patients with psoriasis. METHODS: Patients with psoriasis (n = 130) were investigated for serum IgG and IgA AGA, IgA antitransglutaminase antibody and IgA antiendomysial antibody. Disease characteristics and associated bowel and joint symptoms were determined. All patients were invited to undertake endoscopy with duodenal biopsy. RESULTS: A significantly higher proportion of patients with elevated CD-associated antibody levels was currently on or had previously required systemic immunosuppressants (methotrexate, ciclosporin or etretinate; P = 0.04) or psoralen plus ultraviolet A phototherapy (P = 0.03). One case of CD was diagnosed. CONCLUSIONS: The presence of CD-associated antibodies in psoriasis patients correlates with greater disease activity.

Prolonged allergen challenge in mice leads to persistent airway remodelling.

BACKGROUND: Inflammatory infiltrates, airway hyper-responsiveness, goblet cell hyperplasia and subepithelial thickening are characteristic of chronic asthma. Current animal models of allergen-induced airway inflammation generally concentrate on the acute inflammation following allergen exposure and fail to mimic all of these features. OBJECTIVE: The aim of this study was to use a murine model of prolonged allergen-induced airway inflammation in order to characterize the cells and molecules involved in the ensuing airway remodelling. Moreover, we investigated whether remodelling persists in the absence of continued allergen challenge. METHODS: Acute pulmonary eosinophilia and airways hyper-reactivity were induced after six serial allergen challenges in sensitized mice (acute phase). Mice were subsequently challenged three times a week with ovalbumin (OVA) (chronic phase) up to day 55. To investigate the persistence of pathology, one group of mice were left for another 4 weeks without further allergen challenge (day 80). RESULTS: The extended OVA challenge protocol caused significant airway remodelling, which was absent in the acute phase. Specifically, remodelling was characterized by deposition of collagen as well as airway smooth muscle and goblet cell hyperplasia. Importantly, these airway changes, together with tissue eosinophilia were sustained in the absence of further allergen challenge. Examination of cytokines revealed a dramatic up-regulation of IL-4 and tumour growth factor-beta1 during the chronic phase. Interestingly, while IL-4 levels were significantly increased during the chronic phase, levels of IL-13 fell. Levels of the Th1-associated cytokine IFN-gamma also increased during the chronic phase. CONCLUSION: In conclusion, we have demonstrated that prolonged allergen challenge results in persistent airway wall remodelling.