Burden of disease and circulating serotypes of rotavirus infection in sub-Saharan Africa: systematic review and meta-analysis.

Two new rotavirus vaccines have recently been licensed in many countries. However, their efficacy has only been shown against certain serotypes commonly circulating in Europe, North America, and Latin America, but thought to be globally important. To assess the potential impact of these vaccines in sub-Saharan Africa, where rotavirus mortality is high, knowledge of prevalent types is essential because an effective rotavirus vaccine is needed to protect against prevailing serotypes in the community. We did two systematic reviews and two meta-analyses of the most recent published data on the burden of rotavirus disease in children aged under 5 years and rotavirus serotypes circulating in countries in sub-Saharan Africa. Eligible studies were selected from PubMed/Medline, Cochrane Library, EmBase, LILACS, Academic Search Premier, Biological Abstracts, ISI Web of Science, and the African Index Medicus. Depending on the heterogeneity, DerSimonian-Laird random-effects or fixed-effects models were used for meta-analyses. Geographical variability in rotavirus burden within countries in sub-Saharan Africa is substantial, and most countries lack information on rotavirus epidemiology. We estimated that annual mortality for this region was 243.3 (95% CI 187.6-301.7) deaths per 100,000 under 5 years (ie, a total of 300,000 children die of rotavirus infection in this region each year). The most common G type detected was G1 (34.9%), followed by G2 (9.1%), and G3 (8.6%). The most common P types detected were P[8] (35.5%) and P[6] (27.5%). Accurate information should be collected from surveillance based on standardised methods in these countries to obtain comparable data on the burden of disease and the circulating strains to assess the potential impact of vaccine introduction

Shallow Ultraviolet Transits of WD 1145+017

WD 1145+017 is a unique white dwarf system that has a heavily polluted atmosphere, an infrared excess from a dust disk, numerous broad absorption lines from circumstellar gas, and changing transit features, likely from fragments of an actively disintegrating asteroid. Here, we present results from a large photometric and spectroscopic campaign with Hubble, Keck , VLT, Spitzer, and many other smaller telescopes from 2015 to 2018. Somewhat surprisingly, but consistent with previous observations in the u' band, the UV transit depths are always shallower than those in the optical. We develop a model that can quantitatively explain the observed "bluing" and the main findings are: I. the transiting objects, circumstellar gas, and white dwarf are all aligned along our line of sight; II. the transiting object is blocking a larger fraction of the circumstellar gas than of the white dwarf itself. Because most circumstellar lines are concentrated in the UV, the UV flux appears to be less blocked compared to the optical during a transit, leading to a shallower UV transit. This scenario is further supported by the strong anti-correlation between optical transit depth and circumstellar line strength. We have yet to detect any wavelength-dependent transits caused by the transiting material around WD 1145+017.Comment: 16 pages, 11 figures, 6 tables, ApJ, in pres

Surgical Management of Fistulating Perianal Crohn's Disease - A UK Survey.

AIM: Around one-third of patients with Crohn's disease are affected by Crohn's fistula-in-ano (pCD). It typically follows a chronic course and patients undergo long-term medical and surgical therapy. We set out to describe current surgical practice in the management of pCD in the UK. METHODS: A survey of surgical management of pCD was designed by an expert group of colorectal surgeons and gastroenterologists. This assessed acute, elective, multidisciplinary and definitive surgical management. A pilot of the questionnaire was undertaken at the Digestive Disease Federation 2015 meeting. The survey was refined and distributed nationally through the trainee collaborative networks. RESULTS: National rollout obtained responses from 133 surgeons of 179 approached (response rate 74.3%). At first operation, 32% surgeons would always consider drainage of sepsis and 31.1% would place a draining seton. At first elective operation, 66.6% would routinely insert of draining seton, and 84.4% would avoid cutting seton. The IBD multidisciplinary team was available to 87.6% respondents, although only 25.1% routinely discussed pCD patients. Anti-TNF-α therapy was routinely considered by 64.2%, although 44.2% left medical management to gastroenterology. Common definitive procedures were removal of seton only (70.7%), fistulotomy (57.1%), advancement flap (38.9%), fistula plug (36.4%) and ligation of intersphincteric track (LIFT) procedure (31.8%). Indications for diverting stoma or proctectomy were intractable sepsis, incontinence, and poor quality of life. DISCUSSION: This survey has demonstrated areas of common practice, but has also highlighted divergent practice including choices of definitive surgery and multimodal management. Practical guidelines are required to support colorectal surgeons in the UK. This article is protected by copyright. All rights reserved

Raman spectroscopic evidence of tissue restructuring in heat-induced tissue fusion

Heat-induced tissue fusion via radio-frequency (RF) energy has gained wide acceptance clinically and here we present the first optical-Raman-spectroscopy study on tissue fusion samples in vitro. This study provides direct insights into tissue constituent and structural changes on the molecular level, exposing spectroscopic evidence for the loss of distinct collagen fibre rich tissue layers as well as the denaturing and restructuring of collagen crosslinks post RF fusion. These findings open the door for more advanced optical feedback-control methods and characterization during heat-induced tissue fusion, which will lead to new clinical applications of this promising technology. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Cancellous bone and theropod dinosaur locomotion. Part II—a new approach to inferring posture and locomotor biomechanics in extinct tetrapod vertebrates

This paper is the second of a three-part series that investigates the architecture of cancellous bone in the main hindlimb bones of theropod dinosaurs, and uses cancellous bone architectural patterns to infer locomotor biomechanics in extinct non-avian species. Cancellous bone is widely known to be highly sensitive to its mechanical environment, and therefore has the potential to provide insight into locomotor biomechanics in extinct tetrapod vertebrates such as dinosaurs. Here in Part II, a new biomechanical modelling approach is outlined, one which mechanistically links cancellous bone architectural patterns with three-dimensional musculoskeletal and finite element modelling of the hindlimb. In particular, the architecture of cancellous bone is used to derive a single ‘characteristic posture’ for a given species—one in which bone continuum-level principal stresses best align with cancellous bone fabric—and thereby clarify hindlimb locomotor biomechanics. The quasi-static approach was validated for an extant theropod, the chicken, and is shown to provide a good estimate of limb posture at around mid-stance. It also provides reasonable predictions of bone loading mechanics, especially for the proximal hindlimb, and also provides a broadly accurate assessment of muscle recruitment insofar as limb stabilization is concerned. In addition to being useful for better understanding locomotor biomechanics in extant species, the approach hence provides a new avenue by which to analyse, test and refine palaeobiomechanical hypotheses, not just for extinct theropods, but potentially many other extinct tetrapod groups as well

The superhydrophobicity of polymer surfaces: Recent developments

Superhydrophobicity is the extreme water repellence of highly textured surfaces. The field of superhydrophobicity research has reached a stage where huge numbers of candidate treatments have been proposed and jumps have been made in theoretically describing them. There now seems to be a move to more practical concerns and to considering the demands of individual applications instead of more general cases. With these developments, polymeric surfaces with their huge variety of properties have come to the fore and are fast becoming the material of choice for designing, developing, and producing superhydrophobic surfaces. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1203–1217, 201

Fighting viral infections and virus-driven tumors with cytotoxic CD4+ T cells

CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors

Efficacy of EGFR Inhibition Is Modulated by Model, Sex, Genetic Background and Diet: Implications for Preclinical Cancer Prevention and Therapy Trials

Molecule-targeted therapies are being widely developed and deployed, but they are frequently less effective in clinical trials than predicted based upon preclinical studies. Frequently, only a single model or genetic background is utilized using diets that are not relevant to that consumed by most cancer patients, which may contribute to the lack of predictability of many preclinical therapeutic studies. Inhibition of epidermal growth factor receptor (EGFR) in colorectal cancer was used to investigate potential causes for low predictive values of many preclinical studies. The efficacy of the small molecule EGFR inhibitor AG1478 was evaluated using two mouse models, ApcMin/+ and azoxymethane (AOM), both sexes on three genetic backgrounds, C57BL/6J (B6) and A/J (A) inbred strains and AB6F1 hybrids, and two diets, standard chow (STD) or Western-style diet (WD). AG1478 has significant anti-tumor activity in the B6-ApcMin/+ model with STD but only moderately on the WD and in the AOM model on an A background with a WD but not STD. On the F1 hybrid background AG1478 is effective in the ApcMin/+ model with either STD or WD, but has only moderate efficacy in the AOM model with either diet. Sex differences were also observed. Unexpectedly, the level of liver EGFR phosphorylation inhibition by AG1478 was not positively correlated with inhibition of tumor growth in the AOM model. Model-dependent interactions between genetic background and diet can dramatically impact preclinical results, and indicate that low predictive values of preclinical studies can be attributed to study designs that do not account for the heterogeneous patient population or the diets they consume. Better-designed preclinical studies should lead to more accurate predictions of therapeutic response in the clinic

The Absence of NOD1 Enhances Killing of Aspergillus fumigatus Through Modulation of Dectin-1 Expression

One of the major life-threatening infections for which severely immunocompromised patients are at risk is invasive aspergillosis (IA). Despite the current treatment options, the increasing antifungal resistance and poor outcome highlight the need for novel therapeutic strategies to improve outcome of patients with IA. In the current study, we investigated whether and how the intracellular pattern recognition receptor NOD1 is involved in host defense against Aspergillus fumigatus. When exploring the role of NOD1 in an experimental mouse model, we found that Nod1(-/-) mice were protected against IA and demonstrated reduced fungal outgrowth in the lungs. We found that macrophages derived from bone marrow of Nod1(-/-) mice were more efficiently inducing reactive oxygen species and cytokines in response to Aspergillus. Most strikingly, these cells were highly potent in killing A. fumigatus compared with wild-type cells. In line, human macrophages in which NOD1 was silenced demonstrated augmented Aspergillus killing and NOD1 stimulation decreased fungal killing. The differentially altered killing capacity of NOD1 silencing versus NOD1 activation was associated with alterations in dectin-1 expression, with activation of NOD1 reducing dectin-1 expression. Furthermore, we were able to demonstrate that Nod1(-/-) mice have elevated dectin-1 expression in the lung and bone marrow, and silencing of NOD1 gene expression in human macrophages increases dectin-1 expression. The enhanced dectin-1 expression may be the mechanism of enhanced fungal killing of Nod1(-/-) cells and human cells in which NOD1 was silenced, since blockade of dectin-1 reversed the augmented killing in these cells. Collectively, our data demonstrate that NOD1 receptor plays an inhibitory role in the host defense against Aspergillus. This provides a rationale to develop novel immunotherapeutic strategies for treatment of aspergillosis that target the NOD1 receptor, to enhance the efficiency of host immune cells to clear the infection by increasing fungal kilMG was supported by the Erasmus lifelong learning program. FV was supported by the E-rare project EURO-CMC. TK was supported by the National Institutes of Health [grant numbers AI101935, AI124346, AR056296, and CA163507]. AC was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014).info:eu-repo/semantics/publishedVersio