Helicobacter pylori Chronic Infection Selects for Effective Colonizers of Metaplastic Glands.

Chronic gastric infection with Helicobacter pylori can lead to progressive tissue changes that culminate in cancer, but how H. pylori adapts to the changing tissue environment during disease development is not fully understood. In a transgenic mouse gastric metaplasia model, we found that strains from unrelated individuals differed in their ability to infect the stomach, to colonize metaplastic glands, and to alter the expression of the metaplasia-associated protein TFF3. H. pylori isolates from different stages of disease from a single individual had differential ability to colonize healthy and metaplastic gastric glands. Exposure to the metaplastic environment selected for high gastric colonization by one of these strains. Complete genome sequencing revealed a unique alteration in the frequency of a variant allele of the putative adhesin sabB, arising from a recombination event with the related sialic acid binding adhesin (SabA) gene. Mutation of sabB in multiple H. pylori strain backgrounds strongly reduced adherence to both normal and metaplastic gastric tissue, and highly attenuated stomach colonization in mice. Thus, the changing gastric environment during disease development promotes bacterial adhesin gene variation associated with enhanced gastric colonization. IMPORTANCE Chronic infection with Helicobacter pylori is the primary risk factor for developing stomach cancer. As disease progresses H. pylori must adapt to a changing host tissue environment that includes induction of new cell fates in the cells that line the stomach. We tested representative H. pylori isolates collected from the same patient during early and later stages of disease in a mouse model where we can rapidly induce disease-associated tissue changes. Only the later-stage H. pylori strains could robustly colonize the diseased stomach environment. We also found that the ability to colonize the diseased stomach was associated with genetic variation in a putative cell surface adhesin gene called sabB. Additional experiments revealed that SabB promotes binding to stomach tissue and is critical for stomach colonization by the late-stage strains. Thus, H. pylori diversifies its genome during disease progression and these genomic changes highlight critical factors for bacterial persistence.

Surgical results of the Lung Cancer Mutation Consortium 3 trial: A phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non-small cell lung cancer.

OBJECTIVE: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery. METHODS: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was major pathological response in patients without EGFR/ALK+ alterations. Pre- and post-treatment computed tomography, positron emission tomography, pulmonary function tests, and biospecimens were obtained. Adverse events were recorded by Common Terminology Criteria for Adverse Events v.4.0. RESULTS: From April 2017 to February 2020, 181 patients were entered in the study. Baseline characteristics were mean age, 65.1 years; female, 93 of 181 (51%); nonsquamous histology, 112 of 181 (62%); and clinical stages IIB to IIIB, 147 of 181 (81%). In patients without EGFR/ALK alterations who underwent surgery, the major pathological response rate was 20% (29/143; 95% confidence interval, 14-28) and the pathological complete response rate was 6% (8/143; 95% confidence interval, 2-11). There were no grade 4/5 treatment-related adverse events preoperatively. Of 159 patients (87.8%) undergoing surgery, 145 (91%) had pathologic complete resection. There were 5 (3%) intraoperative complications, no intraoperative deaths, and 2 postoperative deaths within 90 days, 1 treatment related. Median disease-free and overall survival have not been reached. CONCLUSIONS: Neoadjuvant atezolizumab in resectable stage IB to IIIB non-small cell lung cancer was well tolerated, yielded a 20% major pathological response rate, and allowed safe, complete surgical resection. These results strongly support the further development of immune checkpoint inhibitors as preoperative therapy in locally advanced non-small cell lung cancer.

The contact structure of Great Britain's salmon and trout aquaculture industry.

We analyse the network structure of the British salmonid aquaculture industry from the perspective of infectious disease control. We combine for the first time live fish transport (or movement) data covering England and Wales with data covering Scotland and include network layers representing potential transmission by rivers, sea water and local transmission via human or animal vectors in the immediate vicinity of each farm or fishery site. We find that 7.2% of all live fish transports cross the England-Scotland border and network analysis shows that 87% of English and Welsh nodes and 72% of Scottish nodes are reachable from cross-border connections via live fish transports alone. Consequently, from a disease-control perspective, the contact structures of England and Wales and of Scotland should not be considered in isolation. We also show that large epidemics require the live fish movement network and so control strategies targeting movements can be very effective. While there is relatively low risk of widespread epidemics on the live fish transport network alone, the potential risk is substantially amplified by the combined interaction of multiple network layers.

Using biological-physical modelling for informing sea lice dispersal in Loch Linnhe, Scotland.

Sea lice are a constraint on the sustainable growth of Scottish marine salmonid aquaculture. As part of an integrated pest management approach, farms coordinate procedures within spatial units. We present observations of copepodids being at relatively greater density than nauplii in upper waters, which informs the development of surface layer sea lice transmission modelling of Loch Linnhe, Scotland, for informing farm parasite management. A hydrodynamic model is coupled with a biological particle-tracking model, with characteristics of plankton sea lice. Simulations are undertaken for May and October 2011-2013, forced by local wind data collected for those periods. Particles are continually released from positions representing farm locations, weighted by relative farm counts, over a 2-week period and tracked for a further 5 days. A comparison is made between modelled relative concentrations against physical and biological surveys to provide confidence in model outputs. Connectivity between farm locations is determined in order to propose potential coordination areas. Generally, connectivity depends on flow patterns in the loch and decreases with increased farm separation. The connectivity indices are used to estimate the origins of the sea lice population composition at each site, which may influence medicinal regimens to avoid loss of efficacy.

Influence of body condition on the population dynamics of Atlantic salmon with consideration of the potential impact of sea lice.

Atlantic salmon Salmo salar is an iconic species of high conservation and economic importance. At sea, individuals typically are subject to sea lice infestation, which can have detrimental effects on their host. Over recent decades, the body condition and marine survival in NE Atlantic stocks have generally decreased, reflected in fewer adults returning to rivers, which is partly attributable to sea lice. We developed a deterministic stage-structured population model to assess condition-mediated population dynamics resulting in changing fecundity, age at sexual maturation and marine survival rate. The model is parameterized using data from the North Esk system, north-east Scotland. Both constant and density-dependent juvenile survival rates are considered. We show that even small sea lice-mediated changes in mean body condition of MSW can cause substantial population declines, whereas 1SW condition is less influential. Density dependence alleviates the condition-mediated population effect. The resilience of the population to demographic perturbations declines as adult condition is reduced. Indirect demographic changes in salmonid life-history traits (e.g., body condition) are often considered unimportant for population trajectory. The model shows that Atlantic salmon population dynamics can be highly responsive to sea lice-mediated effects on adult body condition, thus highlighting the importance of non-lethal parasitic long-term effects.

Predictors of Postpartum Depression in Dubai, a Rapidly Growing Multicultural Society in the United Arab Emirates.

BACKGROUND: Postpartum depression (PPD) is a significant public health problem adversely affecting mothers, their newborns, and other members of the family. Although PPD is common and potentially dangerous, only a minority of the cases are identified in primary health care settings during routine care, and the majority of depressed mothers in the community lies unrecognized and therefore untreated. SUBJECTS AND METHODS: In this study, a total of 1500 mothers were approached randomly, 808 accepted to participate, and 504 were within the inclusion criteria (women who had a birth of a singleton full-term healthy infant, had an uncomplicated pregnancy, and were within their one week to six months postpartum). The participants completed the Edinburgh Postnatal Depression Scale. RESULTS: A total of 168 women had an EPDS score ≥10, yielding a crude prevalence rate of 33%. The prevalence of suicidal ideation was 14 out of 504 (3%), among which 11 (79%) had EPDS score of ≥10. We fitted multiple linear regression models to evaluate the predictors of variables measured on the EPDS scale. This model was statistically significant p<0.0001 in predicting the total EPDS score. Women's employment status, baby's birth weight, stressful life event and marital conflict were statistically significant predictors. CONCLUSIONS: The findings of this study are anticipated to entail the government and policy makers in the region to pay more attention to the apparently high prevalence of unrevealed PPD in the community. It is crucial to enhance screening mechanisms for early detection, providing interventions to manage symptoms, and at the same time mandating local guidelines to address the PPD pathology as a high priority for the UAE population.

Simulated environmental transport distances of Lepeophtheirus salmonis in Loch Linnhe, Scotland, for informing aquaculture area management structures.

In the majority of salmon farming countries, production occurs in zones where practices are coordinated to manage disease agents such as Lepeophtheirus salmonis. To inform the structure of zones in specific systems, models have been developed accounting for parasite biology and system hydrodynamics. These models provide individual system farm relationships, and as such, it may be beneficial to produce more generalized principles for informing structures. Here, we use six different forcing scenarios to provide simulations from a previously described model of the Loch Linnhe system, Scotland, to assess the maximum dispersal distance of lice particles released from 12 sites transported over 19 day. Results indicate that the median distance travelled is 6.1 km from release site with <2.5% transported beyond 15 km, which occurs from particles originating from half of the release sites, with an absolute simulated distance of 36 km observed. This provides information suggesting that the disease management areas developed for infectious salmon anaemia control may also have properties appropriate for salmon lice management in Scottish coastal waters. Additionally, general numerical descriptors of the simulated relative lice abundance reduction with increased distance from release location are proposed.

Evidence-based case report: acute diabetic complication risks of Ramadan fasting in type 2 diabetics.

AIM: to investigate causal relationship between Ramadan fasting and acute diabetic complications in adult controlled type 2 diabetics. METHODS: a Pubmed's Clinical Queries and Embase search was conducted and resulted in 2 useful articles: 1 systematic review and 1 cohort study to be critically appraised. RESULTS: the incidence of acute diabetic complications is higher during Ramadan, with the relative risk for adult type 2 diabetics who fast during Ramadan is 1.36 and number needed to harm 50. CONCLUSION: Ramadan fasting was related with acute diabetic complications in adult controlled type 2 diabetics, but the risk was only slightly higher. It is acceptable for type 2 diabetics to fast during Ramadan.

Development and assessment of a biophysical dispersal model for sea lice.

Salmon aquaculture in Scotland continues to increase; however, one of the potential limitations to its further sustainable growth is the ectoparasitic sea louse Lepeophtheirus salmonis. The industry in Scotland undertakes coordinated management procedures to control the levels of sea lice on farms in designated production areas. We developed a biophysical sea lice dispersal model for Loch Linnhe, one of the largest fjords on the west coast of Scotland, to provide further information to help establish more effective farm management areas. We successfully extend modelling principles previously applied to a small Scottish fjordic system. Modelling scenarios demonstrate heterogeneity in the distribution of sea lice within the system and simulations, suggesting that lice could be transmitted up to 30 km. The scenarios are assessed by comparing model predictions against lice sampled by both planktonic trawls and settlement on sentinel caged fish. The model predicts the ranked abundance of both planktonic and settled lice assuming that the lice input to the system is relative to host biomass. Data collection is ongoing for undertaking and assessing additional scenarios.

Role of HFE gene mutations on developing iron overload in beta-thalassaemia carriers in Egypt.

A case-control study aimed to determine the prevalence of C282Y, H63D and S65C mutations of the HFE gene in beta-thalassaemia carriers and investigate their influence on iron absorption. A total of 41 beta-thalassaemia carriers and 40 control subjects without haemoglobinopathies were screened for the C282Y, H63D and S65C mutations by polymerase chain reaction-restriction fragment-length polymorphism. The iron status in these subjects was studied and correlated with the HFE gene mutations. H63D, S65C and C282Y allele frequencies were 30.5%, 13.4% and 7.3% respectively in beta-thalassaemia carriers and 10.0%, 2.5% and 0.0% respectively in the control group. Compound heterozygosis was found in 10 carriers (24.4%). The transferrin saturation level was high in compound heterozygote cases. Our study has shown that the HFEgene mutations are common in Egypt among beta-thalassaemia carriers compared with normal controls.

Incidence of tetracycline residues in chicken meat and liver retailed to consumers.

The incidence of tetracyclines' (TCs) residue (oxytetracycline, tetracycline, chlorotetracycline and doxycycline) in fresh chicken samples (meat and liver) collected during one year was recorded. TC residues were analysed using an HPLC-DAD method. The limit of detection for meat was 4.4, 5, 10 and 7 ng g(-1) for OTC, TTC, CTC and DOC, respectively, compared with 5.5, 6, 12 and 9 ng g(-1) stated for liver. The recovery of the method ranged from 91% to 70% depending upon both matrix type and tetracycline kind. The results revealed that 66 (44%) samples contained TC residues including 21 (42%) breast, 19 (38%) thigh and 26 (52%) liver samples. The corresponding contaminated ranges were 124-5812, 107-6010 and 103-8148 µg kg(-1). A total of 12 (8%), 13 (7.33%) and 20 (13.33%) samples of breast, thigh and liver, respectively, had TC residues above the Codex maximum residue limit (MRL). Liver samples had a higher incidence and level than those found in breast or thigh samples.

Role of HFE gene mutations on developing iron overload in beta thalassaemia carriers in Egypt

A case-control study aimed to determine the prevalence of C282Y, H63D and S65C mutations of the HFE gene in beta thalassaemia carriers and investigate their influence on iron absorption. A total of 41 beta-thalassaemia carriers and 40 control subjects without haemoglobinopathies were screened for the C282Y, H63D and S65C mutations by polymerase chain reaction-restriction fragment-length polymorphism. The iron status in these subjects was studied and correlated with the HFE gene mutations. H63D, S65C and C282Y allele frequencies were 30.5%, 13.4% and 7.3% respectively in [3-thalassaemia carriers and 10.0%, 2.5% and 0.0% respectively in the control group. Compound heterozygosis was found in 10 carriers [24.4%]. The transferrin saturation level was high in compound heterozygote cases. Our study has shown that the HFE gene mutations are common in Egypt among beta-thalassaemia carriers compared with normal controls

Numerical studies of biocontrol efficacies of foliar plant pathogens in relation to the characteristics of a biocontrol agent.

A previously published generic mathematic model has been used in a numerical study to understand the dynamics of foliar pathogens in relation to mechanisms, and timing and coverage of biocontrol agent (BCA) applications. With the model parameter values used, it was demonstrated that a BCA possessing either competition or induced resistance as the main mechanism of biological control was more effective in reducing disease development than a BCA with either mycoparasitism or antibiosis as its mechanism. Application coverage, ranging from 50 to 90%, had little effect on biocontrol efficacy, particularly for a BCA with competition and induced resistance as the main mechanism of biocontrol. Conversely, delayed application of BCA had more profound effects on biocontrol efficacy for those with competition or induced resistance as their main mechanism than those with mycoparasitism and antibiosis. Biocontrol efficacy was greatest for a single BCA combining competition with mycoparasitism or antibiosis. The efficacy for a single BCA combining induced resistance with competition critically depended on application time; the efficacy was greatly reduced for delayed applications. The present study suggests that development of an effective strategy for BCA application is critically dependent upon our quantitative understanding of several key biocontrol processes and their interactions. Without reliable quantitative estimation of these processes, it is impossible to make quantitative predictions about biological control and hence to optimize BCA application strategies.

Lymphoproliferative disorder of nasopharynx after long-standing cyclosporin therapy for psoriatic arthritis.

BACKGROUND: The increased risk of developing lymphoproliferative disorders, mainly linked with Epstein-Barr virus infection, is well documented in patients with cyclosporin-induced immunosuppression following organ transplantation. Lymphoproliferative disease is extremely rare in the non-transplant setting. METHODS: We present the first published case of non-Epstein-Barr virus associated lymphoproliferative disease in a patient receiving long-standing cyclosporin therapy for psoriatic arthritis, which presented as a recurrent nasopharyngeal mass. RESULTS: Histological examination showed lymphoid hyperplasia in repeated biopsies. Macroscopic clearance was persistently followed by aggressive recurrence. Spontaneous regression occurred upon cyclosporin withdrawal. CONCLUSION: This rare complication of cyclosporin therapy in non-transplant patients is highlighted from an otolaryngological perspective, as the sole presentation may be a recurrent nasopharyngeal mass. Repeated biopsies showing lymphoid hyperplasia, together with aggressive recurrence, should prompt immediate drug withdrawal to reduce immunosuppression and promote spontaneous regression.

Effects of exposure to a mobile phone on sexual behavior in adult male rabbit: an observational study.

The accumulating effects of exposure to electromagnetic radiation emitted by a conventional mobile phone (MP) on male sexual behaviour have not yet been analyzed. Therefore, we studied these effects in 18 male rabbits that were randomly divided into phone and control groups. Six female teasers were taken successively to the male's cage and the copulatory behavior was recorded. Serum total testosterone, dopamine and cortisol were evaluated. The animals of the phone group were exposed to MPs (800 MHz) in a standby position for 8 h daily for 12 weeks. At the end of the study, the copulatory behavior and hormonal assays were re-evaluated. Mounts without ejaculation were the main mounts in the phone group and its duration and frequency increased significantly compared with the controls, whereas the reverse was observed in its mounts with ejaculation. Ejaculation frequency dropped significantly, biting/grasping against teasers increased notably and mounting latency in accumulated means from the first to the fourth teasers were noted in the phone group. The hormonal assays did not show any significant differences between the study groups. Therefore, the pulsed radiofrequency emitted by a conventional MP, which was kept on a standby position, could affect the sexual behavior in the rabbit.

Benefit from the minimally invasive sinus technique.

INTRODUCTION: Sinus drainage is impeded by the transition spaces that the anterior paranasal sinuses drain into, not the ostia themselves. Addressing the transition spaces and leaving the ostia intact, using the minimally invasive sinus technique, should reverse chronic rhinosinusitis. AIM: To assess patient benefit following use of the minimally invasive sinus technique for chronic rhinosinusitis. METHOD: One hundred and forty-three consecutive patients underwent the minimally invasive sinus technique for chronic rhinosinusitis. Symptoms (i.e. blocked nose, poor sense of smell, rhinorrhoea, post-nasal drip, facial pain and sneezing) were recorded using a visual analogue scale, pre-operatively and at six and 12 weeks post-operatively. Patients were also surveyed using the Glasgow benefit inventory, one and three years post-operatively. RESULTS: We found a significant reduction in all nasal symptom scores at six and 12 weeks post-operatively, and increased total quality of life scores at one and three years post-operatively (25.2 and 14.8, respectively). CONCLUSION: The patient benefits of treatment with the minimally invasive sinus technique compare with the published patient benefits for functional endoscopic sinus surgery.

WITHDRAWN: Sex differences in the expression of sodium/calcium exchanger influence the arrhythmia phenotype in the long QT syndrome type 2.

The paper entitled "Sex differences in the expression of sodium/calcium exchanger influence the arrhythmia phenotype in the long QT syndrome type 2" by Salama et al, which was published online on 19 May 2008, has been withdrawn at the authority of the editor and the publisher.

A review of the current management of impacted foreign bodies in the oesophagus in adults.

Patients with acute oesophageal obstruction, either due to a foreign body or food bolus, present to any of the specialties of Otorhinolaryngology, General Surgery, Cardiothoracic Surgery or Gastroenterology. To review current routine management of this condition, we conducted a postal survey of all the consultants in the aforementioned specialties in the South Thames region. The aims of the survey were to assess current practice and to produce a standardized management plan for these patients.