Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B

YMDD variants of hepatitis B virus (HBV) emerge in some patients with chronic hepatitis B who receive lamivudine. YMDD variants were examined in 794 patients in 4 controlled studies of 1 year's duration. The long-term effects of YMDD variants were examined in a subset of patients treated up to 4 years. YMDD variants were detected by polymerase chain reaction (PCR) and restriction fragment-length polymorphism assays. After 1 year, YMDD variants were detected in 81 (24%) of 335 patients. In these patients, the median serum HBV DNA concentration at 1 year was <20% of the baseline level, and serum alanine transaminase (ALT) levels and liver histologic findings had significantly improved. In patients with YMDD variants who were treated for up to 4 years, median HBV DNA and ALT levels showed improvements. Sex, baseline body mass index, and HBV DNA level were associated with emergence of YMDD variants. Patients with YMDD variants losing clinical response with a significant increase in the HBV DNA and ALT levels may require additional therapy.published_or_final_versio

Magnetic resonance imaging sequence evaluation of an MR Linac system; early clinical experience.

Objectives:To systematically identify the preferred magnetic resonance imaging (MRI) sequences following volunteer imaging on a 1.5 Tesla (T) MR-Linear Accelerator (MR Linac) for future protocol development. Methods:Non-patient volunteers were recruited to a Research and Ethics committee approved prospective MR-only imaging study on a 1.5T MR Linac system. Volunteers attended 1-3 imaging sessions that included a combination of mDixon, T1w, T2w sequences using 2-dimensional (2D) and 3-dimensional (3D) acquisitions. Each sequence was acquired over 2-7 minutes and reviewed by a panel of 3 observers to evaluate image quality using a visual grading analysis based on a 4-point Likert scale. Sequences were acquired and modified iteratively until deemed fit for purpose (online image matching or re-planning) and all observers agreed they were suitable in 3 volunteers. Results:26 volunteers underwent 31 imaging sessions of six general anatomical regions. Images were acquired in one or two of six general anatomical regions: male pelvis (n = 9), female pelvis (n = 4), chestwall/breast (n = 5), lung/oesophagus (n = 5), abdomen (n = 3) and head and neck (n = 5). Images were acquired using a pre-defined exam-card that on average, included six sequences (range 2-10), with a maximum scan time of approximately one hour. The majority of observers preferred T2-weighted sequences. The thorax teams were the only groups to prefer T1-weighted imaging. Conclusions:An iterative process identified sequence agreement in all anatomical regions. These sequences will now be evaluated in patient volunteers. Advances in knowledge:This manuscript is the first publication sharing the results of the first systematic selection of MRI sequences for use in on-board MRI-guided radiotherapy by end-users (therapeutic radiographers and clinical oncologists) in healthy volunteers

Laimaphelenchus suberensis sp. nov. associated with Quercus suber in Portugal

Laimaphelenchus suberensis sp. nov. obtained from declining Quercus suber trees of Herdade da Gouveia de Baixo, Alentejo, Portugal, is described and illustrated based on morphological, biometrical and molecular characters. The diagnosis of Laimaphelenchus species has been commonly based on the presence or absence of a vulval flap and on the shape structure of the tail tip. The species described here has been included in the Laimaphelenchus group without vulval flap, and can be distinguished from morphologically similar species by its tail tip shape structure that has a stalk-like terminus and three diffuse tubercles with 4–6 finger-like protrusions. For the molecular analyses, the mitochondrial DNA region from the cytochrome oxidase subunit I (mtCOI), the D2-D3 expansion segments of the large subunit (LSU) and small subunit (SSU) of rRNA gene were amplified and sequenced. Sequences of L. suberensis sp. nov. clustered separately from all Laimaphelenchus spp. with available sequences in Genbank, confirming its identification as a new species. This is the second report of the genus Laimaphelenchus in Portugal, associated with Q. suber: L. heidelbergi and L. suberensis sp. nov.This research was supported by CFE, CIEPQPF and FEDER funds through the ‘Programa Operacional Factores de Competitividade – COMPETE’ and by national funds through FCT–Fundação para a Ciência e a Tecnologia under the projects UID/BIA/04004/2013, PEst-C/EQB/UI0102/2013 and FCOMP-01-0124-008937 (Ref. PTDC/BIA–BEC/102834/2008) and by Instituto do Ambiente, Tecnologia e Vida (IATV). Carla Maleita (SFRH/BPD/85736/2012) and Sofia Costa (SFRH/BPD/ 102438/2014) were financed by MEC National funding and The European Social Fund through POCH (Programa Operacional Capital Humano).info:eu-repo/semantics/publishedVersio

The time course of exogenous and endogenous control of covert attention

Studies of eye-movements and manual response have established that rapid overt selection is largely exogenously driven toward salient stimuli, whereas slower selection is largely endogenously driven to relevant objects. We use the N2pc, an event-related potential index of covert attention, to demonstrate that this time course reflects an underlying pattern in the deployment of covert attention. We find that shifts of attention that occur soon after the onset of a visual search array are directed toward salient, task-irrelevant visual stimuli and are associated with slow responses to the target. In contrast, slower shifts are target-directed and are associated with fast responses. The time course of exogenous and endogenous control provides a framework in which some inconsistent results in the capture literature might be reconciled; capture may occur when attention is rapidly deployed

Delayed gastric emptying and reduced postprandial small bowel water content of equicaloric whole meal bread versus rice meals in healthy subjects: novel MRI insights

BACKGROUND/OBJECTIVES: Postprandial bloating is a common symptom in patients with functional gastrointestinal (GI) diseases. Whole meal bread (WMB) often aggravates such symptoms though the mechanisms are unclear. We used magnetic resonance imaging (MRI) to monitor the intragastric fate of a WMB meal (11% bran) compared to a rice pudding (RP) meal. SUBJECTS/METHODS: 12 healthy volunteers completed this randomised crossover study. They fasted overnight and after an initial MRI scan consumed a glass of orange juice with a 2267 kJ WMB or an equicaloric RP meal. Subjects underwent serial MRI scans every 45 min up to 270 min to assess gastric volumes and small bowel water content and completed a GI symptom questionnaire. RESULTS: The MRI intragastric appearance of the two meals was markedly different. The WMB meal formed a homogeneous dark bolus with brighter liquid signal surrounding it. The RP meal separated into an upper, liquid layer and a lower particulate layer allowing more rapid emptying of the liquid compared to solid phase (sieving). The WMB meal had longer gastric half emptying times (132±8 min) compared to the RP meal (104±7 min), P<0.008. The WMB meal was associated with markedly reduced MRI-visible small bowel free mobile water content compared to the RP meal, P<0.0001. CONCLUSIONS: WMB bread forms a homogeneous bolus in the stomach which inhibits gastric sieving and hence empties slower than the equicaloric rice meal. These properties may explain why wheat causes postprandial bloating and could be exploited to design foods which prolong satiation

Breast cancer risk reduction:is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

BackgroundBreast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reductionThis study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP).MethodsA 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity. At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women¿s, coaches and radiographers¿ experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effectResultsA pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58¿±¿5.6 years, mean BMI was 29.2¿±¿7.0 kg/m2 and many (44%) reported a family history of breast cancer.The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95%CI ¿3.24 kg to ¿0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others.ConclusionsRecruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects.Trial registrationThe trial was registered with Current Controlled Trials (ISRCTN56223933)

The REgulate your SItting Time (RESIT) intervention for reducing sitting time in individuals with Type 2 diabetes: findings from a randomised-controlled feasibility trial

Trial registration: The trial was registered with ISRCTN (number ISRCTN14832389).Electronic supplementary material is available online at: https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-024-01336-6#Sec29 .Background: Reducing and breaking up sitting is recommended for optimal management of Type 2 diabetes mellitus (T2DM). Yet, there is limited evidence of interventions targeting these outcomes in individuals with this condition. The primary aim of this study was to assess the feasibility and acceptability of delivering and evaluating a tailored online intervention to reduce and break up sitting in adults with T2DM. Methods: A mixed-methods two-arm randomised controlled feasibility trial was conducted in ambulatory adults with T2DM who were randomised 1:1 to the REgulate your SItting Time (RESIT) intervention or usual care control group. The intervention included online education, self-monitoring and prompt tools (wearable devices, smartphone apps, computer apps) and health coaching. Feasibility outcomes were recruitment, attrition, data completion rates and intervention acceptability. Measurements of device-assessed sitting (intended primary outcome for definitive trial), standing and stepping, and physical function, psychosocial health and wellbeing were taken at baseline, 3 months and 6 months. Individual semi-structured interviews were conducted at six-months (post intervention) to explore acceptability, feasibility and experiences of the trial and intervention using the Framework Method. Results: Seventy participants aged 55 ± 11 years were recruited. Recruitment rate (proportion of eligible participants enrolled into the study) was 67% and participant retention rate at 6 months was 93% (n = 5 withdrawals). Data completion rates for daily sitting were 100% at baseline and ranged from 83 to 91% at 3 months and 6 months. Descriptive analysis demonstrated potential for the intervention to reduce device-measured sitting, which was 30.9 ± 87.2 and 22.2 ± 82.5 min/day lower in the intervention group at 3 and 6 months, respectively, compared with baseline. In the control group, sitting was 4.4 ± 99.5 and 23.7 ± 85.2 min/day lower at 3 and 6 months, respectively. Qualitative analysis identified three themes: reasons for participating in the trial, acceptability of study procedures, and the delivery and experience of taking part in the RESIT intervention. Overall, the measurement visits and intervention were acceptable to participants. Conclusions: This study demonstrated the feasibility and acceptability of the RESIT intervention and evaluation methods, supporting a future definitive trial. If RESIT is found to be clinically effective, this could lead to changes in diabetes healthcare with a focus on reducing sitting.Diabetes UK grant number [19/0005972]

Induction of humoral immune response to multiple recombinant Rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission

BACKGROUND: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiological agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect feeding success and possibly reduce tick-borne transmission of T. parva. Here we report the evaluation of a multivalent vaccine cocktail of tick antigens for their ability to reduce R. appendiculatus feeding success and possibly reduce tick-transmission of T. parva in a natural host-tick-parasite challenge model. METHODS: Cattle were inoculated with a multivalent antigen cocktail containing recombinant tick protective antigen subolesin as well as two additional R. appendiculatus saliva antigens: the cement protein TRP64, and three different histamine binding proteins. The cocktail also contained the T. parva sporozoite antigen p67C. The effect of vaccination on the feeding success of nymphal and adult R. appendiculatus ticks was evaluated together with the effect on transmission of T. parva using a tick challenge model. RESULTS: To our knowledge, this is the first evaluation of the anti-tick effects of these antigens in the natural host-tick-parasite combination. In spite of evidence of strong immune responses to all of the antigens in the cocktail, vaccination with this combination of tick and parasite antigens did not appear to effect tick feeding success or reduce transmission of T. parva. CONCLUSION: The results of this study highlight the importance of early evaluation of anti-tick vaccine candidates in biologically relevant challenge systems using the natural tick-host-parasite combination

Metastasis of a cecal adenocarcinoma to the prostate five years after a right hemicolectomy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Prostatic metastasis from a primary bowel adenocarcinoma has been only rarely reported in the medical literature. The case reported here is rare in the fact that the primary tumor was from a right-sided bowel adenocarcinoma. It is unusual because initial immunostaining was not fully conclusive, and so a relatively new method of immunostaining, CDX2, was used to ascertain its histopathology.</p> <p>Case presentation</p> <p>We describe the case of a 54-year-old Caucasian man who had a right hemicolectomy for a primary cecal adenocarcinoma, which was completely excised. Following the procedure, he received adjuvant chemotherapy. Computed tomography scans showed no evidence of local recurrence or metastatic disease. Then, five years later, he presented to his general practitioner with urinary symptoms. An abnormal prostate was palpated on digital rectal examination. Trans-rectal prostatic biopsies were performed, which showed colorectal metastases within the prostate gland. This was confirmed with CDX2 immunohistochemistry. There was no further evidence of distant metastases on positron emission tomography-computed tomography scans.</p> <p>Conclusions</p> <p>This case demonstrates a rare isolated hematogenous spread to the prostate from a primary cecal adenocarcinoma, several years after definitive treatment and excision. This highlights the importance of accurate immunohistochemistry and imaging in planning further management and treatment.</p