Laser-Particle Collider for Multi-GeV Photon Production.

As an alternative to Compton backscattering and bremsstrahlung, the process of colliding high-energy electron beams with strong laser fields can more efficiently provide both a cleaner and brighter source of photons in the multi-GeV range for fundamental studies in nuclear and quark-gluon physics. In order to favor the emission of high-energy quanta and minimize their decay into electron-positron pairs, the fields must not only be sufficiently strong, but also well localized. We here examine these aspects and develop the concept of a laser-particle collider tailored for high-energy photon generation. We show that the use of multiple colliding laser pulses with 0.4 PW of total power is capable of converting more than 18% of multi-GeV electrons passing through the high-field region into photons, each of which carries more than half of the electron initial energy.

Maternal body mass index in early pregnancy and offspring asthma, rhinitis and eczema up to 16 years of age.

BACKGROUND: Maternal obesity has been linked to offspring asthma; however, other allergy-related diseases, as well as the association beyond early school age, are largely unstudied. OBJECTIVE: To examine the associations between maternal body mass index (BMI) in pregnancy and offspring asthma, rhinitis, eczema and sensitization up to 16 years of age. METHODS: A total of 3294 children from the Swedish birth cohort BAMSE were included in the analyses. Maternal BMI was assessed around week 10 in pregnancy. Information on asthma, rhinitis, eczema, lifestyle factors and environmental exposures was obtained by parental questionnaires at 1, 2, 4, 8, 12 and 16 years. Sensitization was defined from IgE levels of inhalant allergens at 4, 8 and 16 years in a subsample of 2850 children. Generalized estimated equation models were used to analyse the associations between maternal BMI and the outcomes at 1-16 years. RESULTS: Maternal BMI was positively associated with overall risk of asthma up to age of 16 years (adj OR per 5 kg/m(2) increase: 1.23; 95% CI 1.07-1.40 for prevalent asthma) excluding underweight mothers. In contrast, no significant associations were found for rhinitis, eczema or sensitization. The association with asthma was restricted to obese, rather than overweight mothers, but was attenuated when adjusting for overweight in the offspring. A causal inference test at 16 years further indicated that the child's own overweight is a mediator in the suggested association between maternal BMI and offspring asthma at 16 years. CONCLUSIONS AND CLINICAL RELEVANCE: Maternal BMI is associated with an increased risk of asthma, but not rhinitis, eczema or sensitization; however, overweight in the offspring seems to have a mediating role. Prevention strategies of maternal pre-pregnancy and childhood obesity might be important to reduce the prevalence of childhood asthma.

Difference in early all-cause mortality among patients having hip arthroplasty a Swedish perioperative registry study 2013-2022.

INTRODUCTION: Hip arthroplasty is a common orthopaedic procedure worldwide. There is an ongoing debate related to the fixation and anaesthesia impact on the 30-day mortality, particularly in the aging population with higher American Society of Anaesthesiology (ASA) Physical-Status. AIM: To study the 30-day all-cause mortality in patients undergoing primary hip arthroplasty, with regards to the impact of age, ASA-class, anaesthesia techniques, indication for surgery and fixation techniques. MATERIALS AND METHODS: Perioperative data for primary hip arthroplasty procedures for osteoarthritis and hip fractures registered in the Swedish Perioperative Registry (SPOR) between 2013 and June 2022 were collected. Binary logistic regressions were performed to assess the impact of age, ASA-class, anaesthetic technique, indication for surgery and fixation on odds ratio for 30-day mortality in Sweden. RESULTS: In total, 79,114 patients, 49,565 with osteoarthritis and 29,549 with hip fractures were included in the main study cohort. Mortality was significantly higher among hip fracture patients compared with osteoarthritis, cumulative 8.2% versus 0.1% at 30-days respectively (p < 0.001). Age above 80 years (OR3.7), ASA 3-5 (OR3.3) and surgery for hip fracture (OR 21.5) were associated with significantly higher odds ratio, while hybrid fixation was associated with a significantly lower odds ratio (OR0.4) of 30-day mortality. In the same model, for the subgroups of osteoarthritis and hip fracture, only age (OR 3.7) and ASA-class (OR 3.3) had significant impact, increasing the odds ratio for 30-day mortality. Hemi arthroplasty was commonly used among the hip fracture patients 20.453 (69.2%), and associated with a significantly higher odds ratio for all-cause 30-day mortality as compared to total hip arthroplasty when adjusting for age and ASA-class and fixation 2.3 (95%CI 1.9-2.3, p < 0.001). CONCLUSIONS: All-cause 30-day mortality associated with arthroplasty differed significantly between the two cohorts, hip fracture, and osteoarthritis (8.2% and 0.1% respectively) and mortality expectedly increased with age and higher ASA-class. Anaesthetic method and cement-fixation did not impact the odds ratio for all-cause 30-day mortality after adjustment for age and ASA-class.

Genome-wide association study of body mass index in 23 000 individuals with and without asthma.

BACKGROUND: Both asthma and obesity are complex disorders that are influenced by environmental and genetic factors. Shared genetic factors between asthma and obesity have been proposed to partly explain epidemiological findings of co-morbidity between these conditions. OBJECTIVE: To identify genetic variants that are associated with body mass index (BMI) in asthmatic children and adults, and to evaluate if there are differences between the genetics of BMI in asthmatics and healthy individuals. METHODS: In total, 19 studies contributed with genome-wide analysis study (GWAS) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. RESULTS: We report associations between several DENND1B variants (P = 2.2 × 10(-7) for rs4915551) on chromosome 1q31 and BMI from a meta-analysis of GWAS data using 2691 asthmatic children (screening data). The top DENND1B single nucleotide polymorphisms(SNPs) were next evaluated in seven independent replication data sets comprising 2014 asthmatics, and rs4915551 was nominally replicated (P < 0.05) in two of the seven studies and of borderline significance in one (P = 0.059). However, strong evidence of effect heterogeneity was observed and overall, the association between rs4915551 and BMI was not significant in the total replication data set, P = 0.71. Using a random effects model, BMI was overall estimated to increase by 0.30 kg/m(2) (P = 0.01 for combined screening and replication data sets, N = 4705) per additional G allele of this DENND1BSNP. FTO was confirmed as an important gene for adult and childhood BMI regardless of asthma status. CONCLUSIONS AND CLINICAL RELEVANCE: DENND1B was recently identified as an asthma susceptibility gene in a GWAS on children, and here, we find evidence that DENND1B variants may also be associated with BMI in asthmatic children. However, the association was overall not replicated in the independent data sets and the heterogeneous effect of DENND1B points to complex associations with the studied diseases that deserve further study.

Antioxidant intake and allergic disease in children.

BACKGROUND: Antioxidant intake may reduce the risk of allergic disease by protecting against oxidative tissue damage. Major sources of antioxidants in the Western world are fruits, vegetables (vitamin C, ß-carotene, α-tocopherol), meat and milk (selenium, magnesium, zinc). Children may exclude or eat less of some fruits and vegetables due to cross-reactivity between pollen and these foods, complicating assessment of causal relationships. OBJECTIVE: To investigate the association between dietary antioxidant intake and allergic disease, taking potential reverse causation into account. METHODS: Data on 2442 8-year-old children from the Swedish birth cohort study BAMSE were analysed. Children with completed parental questionnaires on exposures and health, including a food-frequency questionnaire and who provided a blood sample were included. Associations between antioxidant intake during the past year and current allergic disease were analysed using logistic regression. RESULTS: An inverse association was observed between intake of ß-carotene and rhinitis (OR(adj), highest vs. lowest quartile, 0.67, 95% CI 0.49-0.93). Magnesium intake was inversely related to asthma (OR(adj), 0.65, 95% CI 0.42-1.00) and atopic sensitisation (OR(adj), 0.78, 95% CI 0.61-1.00). Following exclusion of children who avoided certain fruits, vegetables or milk due to allergic symptoms (n = 285), the inverse association remained between magnesium intake and asthma (OR(adj), 0.58, 95% CI 0.35-0.98), whereas all other associations became non-significant. CONCLUSION AND CLINICAL RELEVANCE: Diet modifications due to allergy may affect the antioxidant intake and needs to be considered when investigating the relationship between diet and allergic disease. Magnesium intake seems to have a protective effect on childhood asthma.

Adolescent multiple risk behaviour: an asset approach to the role of family, school and community.

BACKGROUND: Engagement in risk behaviours may pose a significant threat to health if involvement spans multiple behaviours. The asset model suggests that contextual aspects of young people's lives, such as factors related to family, school and community, serve as a protective function against health risk behaviours. METHODS: A risk-taking index was created from the English health behaviour in school-aged children study on 15 years olds, substance use and sexual activity. Using a multinomial regression, potential asset variables relating to school, family, peers, community and family affluence were tested for their association with levels of risk behaviours. RESULTS: Sense of neighbourhood belonging, strong school belonging and parental involvement in decision-making about leisure time were related to lower engagement in health risk behaviours. A weaker sense of family belonging was associated with increased risk behaviours if connectedness with teachers was also low. Factors related to school and community played a greater role in adolescent participation in health-related risk behaviours than family-related factors, including family affluence. CONCLUSIONS: Feelings of safety and belonging in the out-of-home settings of adolescents were positively associated with reduced risk behaviours, and indicate the importance of the wider community alongside parents and school as protective assets for health.

Evaluation of polymeric films for buccal drug delivery.

The objective of this study was to evaluate the suitability of the bioadhesive polymers Carbopol 981 NF, Carbopol 1382 and sodium alginate as possible carriers for films for buccal drug delivery. Films were prepared by casting and solvent evaporation method, using propylene glycol as plasticizer and hydoxypropylmethyl cellulose to modify the properties of the films. The bioadhesive and mechanical properties of the films were evaluated with a TA-XT2i Texture Analyser. The alginate films exhibited greater bioadhesion and showed higher tensile strength and elasticity than the Carbopol films. There was a marked difference in the way the polymeric films hydrated in simulated saliva solution. Upon swelling the diameter of the alginate films did not increase but their thickness increases slightly, however the surface area of the Carbopol films increased significantly which points to them being unsuitable for drug delivery to the buccal mucosa. Excessive hydration of a polymeric film for buccal delivery could lead to decreasing adhesive strength and possibly loss of adhesion and hence shorter duration of retention. HPMC appeared to improve the properties of the films, affecting the bioadhesiveness and increasing tensile strength. For the alginate films an increase in HPMC leads to an increase in elasticity but for the Carbopol polymers this was not the case. The release profile of a model drug, sumatriptan succinate, showed that drug release was by diffusion rather than due to disintegration of the films. The results indicate that sodium alginate may be a suitable carrier for polymeric films for use in the buccal cavity.

Sustainability of the relationship between preoperative symptoms and postoperative improvement in quality of life after inguinal hernia repair.

PURPOSE: Chronic pain and discomfort are common before and after inguinal hernia repair (IHR) and pain is clearly linked to reduced quality of life (QoL). The long-term effect of IHR on QoL in relation to preoperative symptoms is incompletely described. METHODS: 309 men (18-75 years) undergoing IHR under local anesthesia and day care surgery were included. Pre- and postoperative symptoms, pain and QoL (SF-36) were measured before and up to 3 years after surgery. RESULTS: Before surgery, 197 patients (64%) reported pain (VAS 0.9-5.4) from their inguinal hernia. 102 patients (33%) had other inguinal symptoms, and 26% were asymptomatic. Patients with preoperative groin pain (P) scored their physical QoL (PCS) lower compared with controls (C) (median (IQR) 43.5 (34.7-50.3) vs. 53.9 (47.8-56.9, p < 0.001)), whereas patients with no pain (N) did not (53.0 (47.9-55.9), p = 0.57). Mental QoL was not affected before or after surgery. At 1, 2 and 3 years after surgery, 14, 12 and 7% of patients, respectively, reported groin pain. In P, PCS increased from 43.5 before surgery to 55.3 (p < 0.001) at 36 months, but was unchanged in N (53.0 vs 55.9, p = ns). CONCLUSIONS: The incidence of inguinal pain decreases over time after inguinal hernia repair. Both preoperative reduction and long-term improvement in physical QoL are strongly associated with the presence of preoperative groin pain. This supports, from a QoL perspective, that patients with preoperative pain are those who benefit the most from IHR, also from a long-term perspective.

Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors.

PURPOSE: The purpose of this study was to investigate the albumin-binding compound 111In-C4-DTPA as an imaging agent for the detection of endogenous albumin accumulation in tumors. METHODS: 111In-C4-DTPA was injected in healthy nude mice for pharmacokinetic and biodistribution studies (10 min, 1, 6, 24, and 48 h, n = 4) and subsequently in tumor-bearing mice for single-photon emission computed tomography/X-ray-computed tomography (SPECT/CT) imaging studies. Four different human tumor xenograft models (LXFL529, OVXF899, MAXFTN401, and CXF2081) were implanted subcutaneously unilaterally or bilaterally (n = 4-8). After intravenous administration of 111In-C4-DTPA, SPECT/CT images were collected over 72 h at 4-6 time points. Additionally, gamma counting was performed for the blood, plasma, lungs, heart, liver, spleen, kidneys, muscle, and tumors at 72 h post-injection. RESULTS: 111In-C4-DTPA bound rapidly to circulating albumin upon injection, and the radiolabeled albumin conjugate thus formed was stable in murine and human serum. SPECT/CT images demonstrated a time-dependent uptake with a maximum of 2.7-3.8% ID/cm3 in the tumors at approximately 24 h post-injection and mean tumor/muscle ratios in the range of 3.2-6.2 between 24 and 72 h post-injection. The kidneys and bladder were the predominant elimination organs. Gamma counting at 72 h post-injection showed 1.3-2.5% ID/g in the tumors and mean tumor/muscle ratios in the range of 4.9-9.4. CONCLUSION: 111In-C4-DTPA bound rapidly to circulating albumin upon injection and showed time-dependent uptake in the tumors demonstrating a potential for clinical application as a companion imaging diagnostic for albumin-binding anticancer drugs.

MHC loci affecting cervical cancer risk: distinguishing the effects of HLA-DQB1 and non-HLA genes TNF, LTA, TAP1 and TAP2.

Cervical cancer has been associated with specific human leukocyte antigen (HLA) haplotypes/alleles and with polymorphisms at the nearby non-HLA loci TNF, LTA, TAP1 and TAP2. Distinguishing effects of individual loci in the major histocompatibility complex (MHC) region are difficult due to the complex linkage disequilibrium (LD) pattern characterized by high LD, punctuated by recombination hot spots. We have evaluated the association of polymorphism at HLA class II DQB1 and the TNF, LTA, TAP1 and TAP2 genes with cervical cancer risk, using 1306 familial cases and 288 controls. DQB1 was strongly associated; alleles *0301, *0402 and (*)0602 increased cancer susceptibility, whereas *0501 and *0603 decreased susceptibility. Among the non-HLA loci, association was only detected for the TAP2 665 polymorphism, and interallelic disequilibrium analysis indicated that this could be due to LD with DQB1. As the TAP2 665 association was seen predominantly in non-carriers of DQB1 susceptibility alleles, we hypothesized that TAP2 665 may have an effect not attributable to LD with DQB1. However, a logistic regression analysis suggested that TAP2 665 was strongly influenced by LD with DQB1. Our results emphasize the importance of large sample sizes and underscore the necessity of examining both HLA and non-HLA loci in the MHC to assign association to the correct locus.

Rates of and methods used at reoperation for recurrence after primary inguinal hernia repair with Prolene Hernia System and Lichtenstein.

INTRODUCTION: Since the introduction of tension-free mesh repair of inguinal hernia ad modum Lichtenstein (L), recurrence rates have been reduced to 1-2%. The bi-layer mesh Prolene Hernia System (PHS) is an alternative mesh with a theoretical potential to further reduce recurrence rates. However, a reoperation due to recurrence after PHS might be technically difficult since both the anterior and posterior space has been utilized. METHODS: Data on all males 18-75 years undergoing primary inguinal hernia repair (IHR) with PHS or L between January 1999 and October 2010 was collected from the Swedish Hernia Register (SHR). Moreover, data was collected for all operations due to recurrence after primary IHR with PHS or L between January 1st 1999 and December 31st 2014. RESULTS: A total of 1229 primary IHR with PHS and 78,230 with L was identified. Rates of reoperation for recurrence after PHS was significantly lower compared to L (1.5 vs. 2.7 %), [OR 0.38 (0.20-0.74)]. A medial recurrence was most common in both groups. At reoperation, an open anterior mesh repair was used in 74 % after PHS and a posterior mesh repair was performed in 58 % after L. Re-operating time was shorter, although not statistically significant in the PHS group (47 vs. 58 min, p = 0.29). Complication rates after surgery due to recurrence did not differ between groups. CONCLUSION: The findings from this dataset suggest that recurrence rates after primary IHR with PHS might be lower and that reoperation due to recurrence after PHS is not more complicated than after L.

Age at adiposity rebound and body mass index trajectory from early childhood to adolescence; differences by breastfeeding and maternal immigration background.

OBJECTIVE: This paper aims to assess association between breastfeeding and maternal immigration background and body mass index development trajectories from age 2 to 16 years. METHODS: A cohort of children born in Stockholm during 1994 to 1996 was followed from age 2 to 16 years with repeated measurement of height and weight at eight time points (n = 2278). Children were categorized into groups by breastfeeding status during the first 6 months of life and maternal immigration background. Body mass index (BMI) trajectories and age at adiposity rebound were estimated using mixed-effects linear models. RESULTS: Body mass index trajectories were different by breastfeeding and maternal immigration status (P-value < 0.0001). Compared with exclusively breastfed counterparts, never/short breastfed children of Swedish mothers had a higher BMI trajectory, whereas never/short breastfed children of immigrant mothers followed a lower BMI trajectory. Ages at adiposity rebound were earlier for higher BMI trajectories regardless of maternal immigration background. CONCLUSION: Differences in BMI trajectories between offspring of immigrant and of Swedish mothers suggest a lack of beneficial association between breastfeeding and long-term BMI development among children of immigrant mothers. Given the relation between long-term BMI development and risk of overweight/obesity, these differences challenge the notion that exclusive breastfeeding is always beneficial for children's BMI development and subsequent risk of overweight/obesity.

Androgens in women after allogeneic hematopoietic cell transplantation: impact of chronic GvHD and glucocorticoid therapy.

Low androgen levels may contribute to sexual dysfunction in women after allogeneic hematopoietic cell transplantation (alloHCT). However, data on serum androgens in women after alloHCT are limited. The aim of this study was to assess androgen levels and their association with chronic GvHD (cGvHD) and glucocorticoid (GC) therapy. Included were 65 allografted women, 33 with cGvHD, and 23 of these were on GC therapy. Controls were 94 healthy, age-matched women. Supportive study groups were women after autologous HCT (autoHCT; n=20) and non-transplanted women on GC therapy (n=26). Compared with controls, free testosterone (free T) and dehydroepiandrosterone sulfate (DHEAS) levels were lower in both the alloHCT group and GC groups; P<0.0001 and P<0.05, respectively. Androgens in the autoHCT group were similar or higher than controls. In the subgroup of alloHCT patients without cGvHD, free T was similar to controls (7.2 vs 8.6 pmol/L; P=0.42), whereas DHEAS levels was lower than controls (1.7 vs 2.5 µmol/L; P=0.008). Compared with controls, cGvHD without GC (n=10) was associated with lower free T and DHEAS; P=0.004 and P=0.0004, respectively). The lowest androgen levels were seen in women with both cGvHD and GC therapy. In conclusion, low serum androgens were associated with cGvHD and GC therapy, prompting for studies assessing a possible association between low androgens and sexual dysfunction and quality of life in allografted women.

Alterations in glucose homeostasis in SSTR1 gene-ablated mice.

SSTR1 is found on the majority of human pancreatic beta cells, however, its role in insulin secretion has yet to be elucidated. In this study, we used the SSTR1 knockout mouse model to examine the role of SSTR1 in insulin secretion and glucose homeostasis in mice. Despite the reported effect of SSTR1 in inhibiting growth hormone secretion, SSTR1-/- mice had significantly reduced body weight with growth retardation. Perfusion of isolated mouse pancreata at 3 months of age demonstrated a significant increase in insulin secretion in SSTR1-/- mice compared with that of WT controls. We also found that at 3 months of age, SSTR1-/- mice had significantly decreased levels of systemic insulin secretion and were glucose intolerant. However, SSTR1 gene-ablated mice had a much higher rate of insulin clearance compared to WT mice at the same age. When challenged at 12 months of age, we found SSTR1-/- mice had increased glucose tolerance with exaggerated increase of insulin levels at the end of the experiment. Immunochemical analysis showed that the pancreatic islets of SSTR1-/- mice had significantly decreased levels of somatostatin staining and a significant decrease of SSTR5 expression. These results demonstrate that SSTR1 plays an important role in the regulation of insulin secretion in the endocrine pancreas in mice.

Linked models to assess the impacts of climate change on nitrogen in a Norwegian river basin and FJORD system.

Dynamically downscaled data from two Atmosphere-Ocean General Circulation Models (AOGCMs), ECHAM4 from the Max-Planck Institute (MPI), Germany and HadAm3H from the Hadley Centre (HAD), UK, driven with two scenarios of greenhouse gas emissions (IS92a and A2, respectively) were used to make climate change projections. These projections were then used to drive four effect models linked to assess the effects on hydrology, and nitrogen (N) concentrations and fluxes, in the Bjerkreim river basin (685-km(2)) and its coastal fjord, southwestern Norway. The four effect models were the hydrological model HBV, the water quality models MAGIC, INCA-N and the NIVA FJORD model. The downscaled climate scenarios project a general temperature increase in the study region of approximately 1 degrees C by 2030-2049 (MPI IS92a) and approximately 3 degrees C by 2071-2100 (HAD A2). Both scenarios imply increased winter precipitation, whereas the projections of summer and autumn precipitation are quite different, with the MPI scenario projecting a slight increase and the HAD scenario a significant decrease. As a response to increased winter temperature, the HBV model simulates a dramatic reduction of snow accumulation in the upper parts of the catchment, which in turn lead to higher runoff during winter and lower runoff during snowmelt in the spring. With the HAD scenario, runoff in summer and early autumn is substantially reduced as a result of reduced precipitation, increased temperatures and thereby increased evapotranspiration. The water quality models, MAGIC and INCA-N project no major changes in nitrate (NO(3)(-)) concentrations and fluxes within the MPI scenario, but a significant increase in concentrations and a 40-50% increase in fluxes in the HAD scenario. As a consequence, the acidification of the river could increase, thus offsetting ongoing recovery from acidification due to reductions in acid deposition. Additionally, the increased N loading may stimulate growth of N-limited benthic algae and macrophytes along the river channels and lead to undesirable eutrophication effects in the estuarine area. Simulations made by the FJORD model and the HAD scenario indicate that primary production in the estuary might increase up to 15-20%, based on the climate-induced changes in river flow and nitrate concentrations alone.

UltraPro Hernia System, Prolene Hernia System and Lichtenstein for primary inguinal hernia repair: 3-year outcomes of a prospective randomized controlled trial.

PURPOSE: Chronic pain and discomfort are common after inguinal hernia repair (IHR). In this study, results from a 3-year follow-up from a randomized controlled study comparing three different mesh repairs for postoperative pain, discomfort, Quality of Life (QoL) and patient satisfaction are reported. METHODS: Between November 1, 2006 and January 31, 2009, 309 men, who underwent day surgery for primary unilateral inguinal hernia under local anesthesia, were randomized to three different mesh repairs; UltraPro Hernia System (U), Prolene Hernia System (P) and Lichtenstein procedure (L). RESULTS: Preoperatively, there were no differences between groups regarding demographics, symptoms, inguinal pain or QoL (SF-36 and a hernia-specific questionnaire). Operating time, postoperative pain, complications and time to full recovery were similar. At 36 months, 21 patients indicated pain [L, n = 6, P, n = 6 and U, n = 9; VAS (median (IQR)): L 0.4 (0.2-1.7), P 0.2 (0.1-2.3) and U 1.6 (0.7-4.6), p = ns]. Physical QoL was reduced in all groups before surgery and was similarly increased to normal levels after 3 months without further changes throughout the study. Although 92 % of participants were satisfied, sixteen percent reported any discomfort from the groin (ns between groups). Five recurrences were reported (L, n = 2, P, n = 1 and U, n = 2, p = ns). CONCLUSIONS: After 3 years of follow-up, all three procedures provided equally good results regarding, pain, discomfort and QoL and could therefore be recommended for primary IHR in LA.

SSTR5 ablation in islet results in alterations in glucose homeostasis in mice.

Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, betaSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the betaSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in betaSSTR5Kd mice pancreata. In addition, betaSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in betaSSTR5Kd mice. Further studies of betaSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.

Incidence of Hepatitis E Antibodies in Swedish Lung Transplant Recipients.

BACKGROUND: Hepatitis E virus (HEV) is an important cause of acute and chronic hepatitis in solid organ transplant recipients, especially liver transplant recipients. However, less is known of the incidence and prevalence of HEV in lung transplant recipients. METHODS: In a prospective study, 62 patients were observed during the first year after lung transplantation. Sera were analyzed for anti-HEV immunoglobulin G (IgG) and IgM at 12 months after transplantation. Samples positive for anti-HEV were also analyzed for HEV RNA by polymerase chain reaction. Pretransplantation samples were analyzed for patients with detectable anti-HEV 1 year after transplantation. RESULTS: Eight patients (13%) had anti-HEV IgG at the 12-month follow-up sample. HEV RNA could not be detected in any of these samples. One of these patients seroconverted during the follow-up without developing acute or chronic hepatitis. CONCLUSIONS: Our results show that the prevalence of HEV antibodies among Swedish lung transplant recipients is similar when compared to the general population. It also suggests that the risk for HEV antibody seroconversion during first year is limited.

High frequency of LOH, MSI and abnormal expression of FHIT in gastric cancer.

The FHIT gene is a putative tumour suppressor gene. In this study, we analysed a set of 50 gastric tumours for alterations of FHIT, and found 38 of 45 tumours (84%) exhibiting loss of heterozygosity (LOH) within the FHIT gene. We used both nested Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and single step RT-PCR to analyse the FHIT transcripts and found 34 of 39 (87%) tumours and seven of the 11 (64%) corresponding non-cancerous tissues showed low or aberrant expression of FHIT mRNA and the appearance of the aberrant FHIT transcripts depended on the conditions of the RT-PCR. In these aberrant transcripts, frequent deletions and/or insertions were detected by direct sequencing. All breakpoints for deletions and insertions were at splicing sites. All insertions came from the adjacent introns, whose appearance was completely in accordance with the 'GU-AG' rule for pre-mRNA splicing. It may be suggested that an alternative splicing mechanism functions in the formation of these aberrant transcripts. The fragile nature of FRA3B within the FHIT gene could be responsible for the formation of the aberrant mRNA. Negative or reduced Fhit expression was detected in 39 of 50 tumours (78%). Moreover, an association was found between abnormal Fhit expression and positive node status (P=0.012). Thirteen of 48 tumours (27%) displayed microsatellite instability (MSI), among which 10 tumours also showed MSI within the FHIT gene. Furthermore, we detected an association between MSI and negative node status (P=0.02). We conclude that the abnormalities of FHIT, presumably associated with the unstable nature of FRA3B within the FHIT gene, are involved in the carcinogenesis of gastric cancer, and lack of mismatch repair (MMR) could possibly promote its alteration in a subset of gastric tumours.

Chemical induction of nondisjunction in drosophila.

Tests for chemically induced nondisjunction and loss of the sex chromosomes in Drosophila were performed. Of 31 compounds tested four gave rise only to an increase of XO exceptions, indicating the induction of chromosome loss. Six compounds, all known spindle inhibitors (colchicine, organic mercury, lead, and tin compounds) gave rise to an increase both of XXY and XO or of only XXY. The effect by metalloorganic compounds of which methylmercury was studied particularly closely, follows a peculiar pattern. In females with structurally normal X chromosomes only an increase of XX gametes is obtained, while with X chromosomes heterozygous for long inversions only O gametes are increased. The data indicates that the effect of the metal compounds occurs at first meiosis and that the process is connected with a meiotic drive, giving rise to a preferential segregation of the two X chromosomes to the functioning pole. The increase only of O gametes with structurally heterozygous X chromosomes can tentatively be explained by a loss due to crossing over within the inversion. An increase of the effect of methyl mercury was obtained where the normal pairing of the X chromosomes was interfered with by means of autosomal inversions. Likewise a synergistic increase of nondisjunction was obtained when a temperature chock of 10 degrees C was applied together with treatment with methylmercury. It is concluded that chemical induction of nondisjunction can be studied in Drosophila, but the sensitivity of the test is rather low and large amount of material is required.