Deletion of Wntless in myeloid cells exacerbates liver fibrosis and the ductular reaction in chronic liver injury

Background: Macrophages play critical roles in liver regeneration, fibrosis development and resolution. They are among the first responders to liver injury and are implicated in orchestrating the fibrogenic response via multiple mechanisms. Macrophages are also intimately associated with the activated hepatic progenitor cell (HPC) niche or ductular reaction that develops in parallel with fibrosis. Among the many macrophage-derived mediators implicated in liver disease progression, a key role for macrophage-derived Wnt proteins in driving pro-regenerative HPC activation towards a hepatocellular fate has been suggested. Wnt proteins, in general, however, have been associated with both pro-and anti-fibrogenic activities in the liver and other organs. We investigated the role of macrophage-derived Wnt proteins in fibrogenesis and HPC activation in murine models of chronic liver disease by conditionally deleting Wntless expression, which encodes a chaperone essential for Wnt protein secretion, in LysM-Cre-expressing myeloid cells (LysM-Wls mice)

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Acute confusion in patients with systemic cancer

To determine the incidence, the causes and the prognostic value for survival of acute confusion (delirium) in patients admitted to a general cancer hospital.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Caregivers’ Malaria Knowledge, Beliefs and Attitudes, and Related Factors in the Bata District, Equatorial Guinea

Adequate community knowledge about malaria is crucial in order to improve prevention by reducing exposure to the disease. Malaria is a major cause of morbidity and mortality among children of less than five years of age in Equatorial Guinea. However, information concerning the accuracy of community knowledge is insufficient. This study aimed at assessing the depth of caregivers' knowledge of malaria, their beliefs and attitudes about this disease, and their socioeconomic determinants in the Bata district of Equatorial Guinea.A cross-sectional study was conducted in the district of Bata, involving 440 houses selected from 18 rural villages and 26 urban neighbourhoods. A combined "Malaria Knowledge Score" was generated based on caregivers' knowledge about transmission, symptoms, prevention, the treatment of children, and best place to seek treatment. Multivariate logistic regressions analyses were performed to assess those factors that are associated with knowledge about malaria.A total of 428 caregivers were interviewed; 255 (59.6%) and 173 (40.4%) lived in urban and rural areas respectively. Significant differences between rural and urban households were observed in caregivers' malaria knowledges and beliefs. Almost 42% of urban and 65% of rural caregivers were unaware as to how malaria is transmitted (OR = 2.69; 95% CI: 1.78-4.05). Together with rurality, the factors most significantly associated with the Malaria Knowledge were the level of education of the caregiver and the socioeconomic status of the household.Improvements in educational programs are needed to empower the most vulnerable households such that they can pro-actively implement malaria control measures. This could be achieved by a comprehensive communication strategy aimed at changing individual and community behaviours, and delivered by suitably trained community health workers and indoor residual spraying personnel

Aging Clin Exp Res

BACKGROUND: The incidence of cancer is an age-related phenomenon; therefore, the interest on clinical manifestations, diagnostic approach and treatment strategies for older patients diagnosed with cancer has increased lately. Neurologic symptoms are one of the main reasons for consultation and a common cause of decreased quality of life among cancer patients. AIMS: To identify the neurologic manifestations of patients >/= 65 years of age diagnosed with cancer and compare them to those presented by a younger population. METHODS: Cross-sectional study of cancer patients referred to neuro-oncologic consultation at a Cancer Center. Sociodemographic, health and oncologic characteristics were obtained through clinical interviews. Clinical symptoms and final diagnoses were also recorded. Bivariate logistic regression analyses were carried out. RESULTS: More than 17,000 neuro-oncologic consultations in 3015 patients were given, 27% (n = 811) of them were >/= 65 years of age. Most frequent primary neoplasms in elderly patients were: breast cancer, hematologic neoplasms, gynecological, urologic, skin and head and neck cancers. Elderly patients had an increased risk of having the following diagnoses: abnormal movements, stroke, peripheral vertigo, dementia, degenerative spine disorder, and delirium. DISCUSSION: Elderly patients are considered a vulnerable population. The present study found that the main neoplasms associated with neurological manifestations are similar to the reported previously. We described the main symptoms that led to a neuro-oncological assessment. Moreover, we enlisted the final diagnoses made on elderly patients and compared them with others reports. To the best of our knowledge, this study provides valuable information, since there is scarce evidence in the literature about this topic. CONCLUSION: Identifying the frequency and correlation of neurologic manifestations in older cancer patients will allow for the implementation of timely multidisciplinary care in an attempt to improve these patients' health-related quality of life

Suppression of inflammatory immune responses in celiac disease by experimental hookworm infection

We present immunological data from two clinical trials where the effect of experimental human hookworm (Necator americanus) infection on the pathology of celiac disease was evaluated. We found that basal production of Interferon- (IFN-)γ and Interleukin- (IL-)17A from duodenal biopsy culture was suppressed in hookworm-infected participants compared to uninfected controls. Increased levels of CD4+CD25+Foxp3+ cells in the circulation and mucosa are associated with active celiac disease. We show that this accumulation also occurs during a short-term (1 week) oral gluten challenge, and that hookworm infection suppressed the increase of circulating CD4+CD25+Foxp3+ cells during this challenge period. When duodenal biopsies from hookworm-infected participants were restimulated with the immunodominant gliadin peptide QE65, robust production of IL-2, IFN-γ and IL-17A was detected, even prior to gluten challenge while participants were strictly adhering to a gluten-free diet. Intriguingly, IL-5 was produced only after hookworm infection in response to QE65. Thus we hypothesise that hookworm-induced TH2 and IL-10 cross-regulation of the TH1/TH17 inflammatory response may be responsible for the suppression of these responses during experimental hookworm infection