TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells.
NOD2, a member of the NOD1/Apaf-1 family, was recently identified as the first susceptibility gene for Crohn's disease. The aim of this report was to describe the regulation and functional significance of NOD2 expression in intestinal epithelial cells. Expression of NOD2 messenger RNA was determined by reverse-transcription polymerase chain reaction (RT-PCR); NOD2 protein was detected by Western blot. Promoter activity was assessed by reporter gene assays and DNA-binding of NF-kappaB by electrophoretic mobility shift assays. IL-8 production was investigated by RT-PCR and enzyme-linked immunosorbent assay. TNF-alpha induced an up-regulation of NOD2 in epithelial cell lines (HT-29, SW620, SW948, HeLa S3) and in primary colonic epithelial cells. A synergism was seen by cotreatment with IFN-gamma. Two NF-kappaB binding sites were identified in the promoter. Deletion of either site or overexpression of dominant negative IkappaBalpha led to reduced levels of TNF-alpha/IFN-gamma-stimulated reporter gene activity. The identified kappaB3 site was bound by NF-kappaB as determined by gelshift assays. Elevated amounts of NOD2 protein were also found in colonic epithelial cells from patients with IBD. LPS induced high levels of IL-8 production in SW620 cells overexpressing NOD2. TNF-alpha(/IFN-gamma) treatment up-regulates the expression of the NOD2 gene in intestinal epithelial cells and subsequently increases their LPS susceptibility. Together with the mutation-derived truncation and functional change of the NOD2 protein, this could be part of the complex pathophysiology of barrier disruption as it is observed in inflammatory bowel diseases.


Bait station devices can improve mass trapping performance for the control of the Mediterranean fruit fly.
The use of traps and other attract-and-kill devices in pest management strategies to reduce Mediterranean fruit fly populations has proved to be efficient. Nevertheless, many farmers are concerned about the effect of these devices on the trees where they are hung. Direct field observations have revealed that fruit damage is higher in trees with traps than in trees without them. This work evaluates the efficacy of different types of attract-and-kill device to protect fruit of the single tree on which the device is placed. Results suggested that trees with traps had at least the same fruit damage than trees without them. When traps were baited with protein hydrolysate, fruit damage was even higher than in trees without traps. However, fruit damage was significantly diminished when efficient bait station devices were used. Although mass trapping is able to control fruit fly populations as a control method, trees with some types of trap and bait are more susceptible to fly puncture. However, bait station devices reduce fruit damage in the single trees where they are hung. Bait stations are more efficient in fruit protection because fruit flies are affected as soon as they contact the device. Some recommendations for the use of the different attract-and-kill devices are discussed.


The project nurse and pressure-relieving equipment.
This article describes the work of a project management nurse in improving accessibility and appropriate use of pressure-relieving equipment in an integrated (acute and community) trust. It examines key issues for future service development in the management and appropriate use of pressure-relieving equipment. The importance of education in maintaining the accuracy and process of recording pressure damage at ward level is also highlighted. One recommendation is that employing a pressure equipment assistant might improve the control and management of pressure equipment availability.


Reducing Three Infections Across Cardiac Surgery Programs: A Multisite Cross-Unit Collaboration.
Using a pre-post design, this study examined the impact of a multifaceted program to simultaneously improve 3 health care-associated infections and patient safety culture throughout the cardiac surgery service line in 11 hospitals. Interventions included the Comprehensive Unit-based Safety Program to improve safety culture and evidence-based bundles to prevent central line-associated bloodstream infection (CLABSI), surgical site infection (SSI), and ventilator-associated pneumonia (VAP). CLABSIs and SSIs showed a downward trend over 2 years, then the rates returned to levels similar to baseline in the third year. VAP rate changes were difficult to interpret because of the VAP definition change. Patient safety culture domain "hospital management support" showed significant improvement, but feedback and communication about errors and staffing declined. Simultaneous implementation of multiple interventions across units is challenging. The findings highlight the importance of sustainment efforts and suggest future work should anticipate both positive and negative change in safety culture dimensions.


Pain self-management in HIV-infected individuals with chronic pain: a qualitative study.
Chronic pain in individuals with HIV is a common, impairing condition. Behavioral interventions for chronic pain specifically tailored to this population have yet to be developed. We assert that understanding self-management strategies already used by persons living with these conditions is an essential first step, and is the objective of this investigation. We conducted a thematic analysis of qualitative data from 25 in-depth interviews with individuals with HIV and chronic pain. The primary pain self-management strategies articulated by participants were: physical activity; cognitive and spiritual strategies; spending time with family and friends and social support; avoidance of physical/social activity; medication-centric pain management; and substance use. Some of these strategies may be viewed as beneficial and overlap with known HIV self-management strategies (cognitive strategies), whereas others may have negative health consequences (substance use). Interventions that incorporate healthy self-management strategies may be particularly effective in improving both HIV and pain outcomes.


Cellular and Molecular Connections Between Bone Fracture Healing and Exosomes.
Fracture healing is a multifaceted process that requires various phases and intercellular interactions. In recent years, investigations have been conducted to assess the feasibility of utilizing exosomes, small extracellular vesicles (EVs), to enhance and accelerate the healing process. Exosomes serve as a cargo transport platform, facilitating intercellular communication, promoting the presentation of antigens to dendritic cells, and stimulating angiogenesis. Exosomes have a special structure that gives them a special function, especially in the healing process of bone injuries. This article provides an overview of cellular and molecular processes associated with bone fracture healing, as well as a survey of existing exosome research in this context. We also discuss the potential use of exosomes in fracture healing, as well as the obstacles that must be overcome to make this a viable clinical practice.


Biomechanical comparison of anterior lumbar interbody fusion: stand-alone interbody cage versus interbody cage with pedicle screw fixation -- a finite element analysis.
Anterior lumbar interbody fusion (ALIF) followed by pedicle screw fixation (PSF) is used to restore the height of the intervertebral disc and provide stability. Recently, stand-alone interbody cage with anterior fixation has been introduced, which eliminates the need for posterior surgery. We compared the biomechanics of the stand-alone interbody cage to that of the interbody cage with additional PSF in ALIF. A three-dimensional, non-linear finite element model (FEM) of the L2-5 segment was modified to simulate ALIF in L3-4. The models were tested under the following conditions: (1) intact spine, (2) destabilized spine, (3) with the interbody cage alone (type 1), (4) with the stand-alone cage with anterior fixation (SynFix-LR®; type 2), and (5) with type 1 in addition to PSF (type 3). Range of motion (ROM) and the stiffness of the operated level, ROM of the adjacent segments, load sharing distribution, facet load, and vertebral body stress were quantified with external loading. The implanted models had decreased ROM and increased stiffness compared to those of the destabilized spine. The type 2 had differences in ROM limitation of 8%, 10%, 4%, and 6% in flexion, extension, axial rotation, and lateral bending, respectively, compared to those of type 3. Type 2 had decreased ROM of the upper and lower adjacent segments by 3-11% and 3-6%, respectively, compared to those of type 3. The greatest reduction in facet load at the operated level was observed in type 3 (71%), followed by type 2 (31%) and type 1 (23%). An increase in facet load at the adjacent level was highest in type 3, followed by type 2 and type 1. The distribution of load sharing in type 2 (anterior:posterior, 95:5) was similar to that of the intact spine (89:11), while type 3 migrated posterior (75:25) to the normal. Type 2 reduced about 15% of the stress on the lower vertebral endplate compared to that in type 1. The stress of type 2 increased two-fold compared to the stress of type 3, especially in extension. The stand-alone interbody cage can provide sufficient stability, reduce stress in adjacent levels, and share the loading distribution in a manner similar to an intact spine.


Dietary medium-chain fatty acid and Bacillus in combination alleviate weaning stress of piglets by regulating intestinal microbiota and barrier function.
The present study evaluated the effects of dietary medium-chain fatty acid (MCFA) and Bacillus on growth performance, nutrient digestibility, antioxidant capacity, colonic fermentation, and microbiota of weaning piglets. A total of 400 weaned piglets were randomly divided into 4 treatments, with 10 replicates per treatment and 10 pigs per replicate. The treatment included: basal diet (control, CON), basal diet with 0.588 g/kg MCFA (MCF), basal diet with 1.3 × 109 CFU/kg Bacillus (BAC), and basal diet with 0.588 g/kg MCFA and 1.3 × 109 CFU/kg Bacillus (SYN). Compared with CON group, the average daily gain of MCF and SYN in the early (1 to 9 d) and whole stage (1 to 36 d) of trail were improved (P < 0.05), the feed to gain ratio of MCF in later (10 to 36 d) and whole stage of trial were decreased (P < 0.05), and the diarrhea rate of SYN in the early stage (1 to 9 d) of trial decreased (P < 0.05). The digestibility of dry matter, ether extract, acid detergent fiber digestibility of MCF were decreased (P < 0.05) compared with CON. The serum d-lactic acid in MCF, BAC, and SYN were lower (P < 0.05) compared with CON group. Compared with CON group, the contents of total antioxidant capacity, superoxide dismutase, and glutathione peroxidase were greater (P < 0.05), whereas the content of malondialdehyde and the contents of colonic isobutyrate and isovalerate were lower (P < 0.05) in MCF. The microbial Shannon and Simpson diversity was lower in MCF (P < 0.05) than that in BAC and SYN. The relative abundance of Prevotella was greater (P < 0.05), whereas the Treponema and Oscillibacter were lower (P < 0.05) in MCF than that in BAC and SYN. In addition, the metabolic pathways of bacteria such as pentose phosphate pathway, adenosine nucleotides degradation II were enhanced (P < 0.05), whereas the pathways such as incomplete reductive TCA cycle, and TCA cycle IV (2-oxoglutarate decarboxylase) were decreased (P < 0.05) in MCF compared with BAC. The results indicated that dietary MCFA and Bacillus in combination improved the intestinal barrier function of piglets by changing the intestinal microbiota and its metabolic function, and finally alleviated the diarrhea rate in early weaning stage and improved growth performance in whole trial period. In addition, MCFA was effective in improving feed efficiency and antioxidant capacity of piglets.


Novel cardiac nuclear magnetic resonance method for noninvasive assessment of myocardial fibrosis in hemodialysis patients.
Left ventricular hypertrophy and myocardial fibrosis frequently occur in patients with end-stage renal disease receiving hemodialysis therapy and are associated with poor prognosis. Native T1 mapping is a novel cardiac magnetic resonance imaging technique that measures native myocardial T1 relaxation, a surrogate of myocardial fibrosis. Here we compared global and segmental native myocardial T1 time and global longitudinal, circumferential and segmental strain, and cardiac function of 35 hemodialysis patients and 22 control individuals. The median native global T1 time was significantly higher in the hemodialysis than the control group (1270 vs. 1085 ms), with the septal regions of hemodialysis patients having significantly higher median T1 times than nonseptal regions (1293 vs. 1252 ms). The mean peak global circumferential strain and global longitudinal strain were both significantly reduced in hemodialysis patients compared with controls (-18.3 vs. -21.7 and -16.1 vs. -20.4, respectively). Systolic strain was also significantly reduced in the septum compared with the nonseptal myocardium in hemodialysis patients (-16.2 vs. -21.9) but not in control subjects. Global circumferential strain and longitudinal strain significantly correlated with global native T1 values (r = 0.41 and 0.55, respectively), and the septal native T1 significantly correlated with the septal systolic strain (r = 0.46). Thus, myocardial fibrosis may be assessed noninvasively with native T1 mapping; the interventricular septum appears to be particularly prone to the development of fibrosis in hemodialysis patients.


[Modelling of the 3-dimensional structure of the epithelia, constructed of bi-, tri and tetracellular modules].
A new approach for studying 3-dimensional histoarchitectonics of cellular layers is suggested. It is based on (1) development of theoretical concepts on module structure of tissues; (2) working out topological and geometrical models of tissue structure and; (3) their experimental testing using this approach. Spatial organization of certain stratified and pseudostratified epithelia was analysed and it was shown that their topology may be principally calculated. Such previously unknown characteristics of epithelia as translation symmetry and structure stoichiometry were described. This approach was shown to add to concept system of histology, reveal regularities of tissue spatial organisation and prognostic factors for their developmental changes. Cellular layers were shown to consist of a relatively small number of standard fragments (slices)--alone and arranged in different combinations thus providing a certain quantity of types of spatial organisations that is amenable to calculation.


Calibration of colloidal probes with atomic force microscopy for micromechanical assessment.
Mechanical assessment of biological materials and tissue-engineered scaffolds is increasingly focusing at lower length scale levels. Amongst other techniques, atomic force microscopy (AFM) has gained popularity as an instrument to interrogate material properties, such as the indentation modulus, at the microscale via cantilever-based indentation tests equipped with colloidal probes. Current analysis approaches of the indentation modulus from such tests require the size and shape of the colloidal probe as well as the spring constant of the cantilever. To make this technique reproducible, there still exist the challenge of proper calibration and validation of such mechanical assessment. Here, we present a method to (a) fabricate and characterize cantilevers with colloidal probes and (b) provide a guide for estimating the spring constant and the sphere diameter that should be used for a given sample to achieve the highest possible measurement sensitivity. We validated our method by testing agarose samples with indentation moduli ranging over three orders of magnitude via AFM and compared these results with bulk compression tests. Our results show that quantitative measurements of indentation modulus is achieved over three orders of magnitude ranging from 1 kPa to 1000 kPa via AFM cantilever-based microindentation experiments. Therefore, our approach could be used for quantitative micromechanical measurements without the need to perform further validation via bulk compression experiments.


Synthesis and evaluation of solanesol derivatives as novel potent synergistic agents.
Novel solanesylpiperazinotriamines as well as their N-aryl-substituted analogs were synthesized starting from solanesol through a multistep procedure. Their structures were confirmed by IR, (1)H NMR, MS, and elemental analysis. The preliminary results indicated that these novel derivatives were preferentially toxic against tumor cells, and at non-cytotoxic concentration, the synergistic effect of solanesyltriamines (3a and 3c) was even superior to that of N,N'-bis(3,4-dimethoxybenzyl)-N-solanesylethylenediamine. Interestingly, the cytotoxicity of solanesylpiperazinotriamine derivatives was markedly enhanced when conjugating with aryl pharmacophores (7-9).


Modifiable factors associated with weight regain after bariatric surgery: a scoping review.
Background: Although bariatric surgery is the most effective treatment for severe obesity, weight regain may still occur. While non-modifiable factors associated with weight regain have been explored, modifiable factors responsible for weight regain are understudied. This scoping review aimed to identify modifiable behaviors associated with weight regain after bariatric surgery. Methods: A systematic search was conducted in Medline, Google Scholar, Cochrane, National Collaborating Centre for Methods and Tools (NCCMT) and Practice-based Evidence in Nutrition (PEN) which included articles published between January 1990 and February 2 2017, for studies examining "weight regain" after bariatric surgery. A total of 293 citations were retrieved. Eligible articles must have examined modifiable factors and addressed weight regain, or a long-term post-operative phase in which weight regain may occur. After removing duplicates, 22 studies were included for thematic analysis. Results: Key modifiable factors associated with weight regain were identified and categorized under the following themes: poor dietary adherence (e.g. excessive calorie, carbohydrate, and alcohol intake), maladaptive eating behaviors (e.g. grazing, binging), lack of on-going follow-up with the bariatric team and insufficient physical activity. Conclusions: Health professionals and self-monitoring tools for patients who have undergone bariatric surgery may benefit from these findings to direct their education and interventions to target behavior change.


The Australian Medical Schools Assessment Collaboration: benchmarking the preclinical performance of medical students.
To report the level of participation of medical schools in the Australian Medical Schools Assessment Collaboration (AMSAC); and to measure differences in student performance related to medical school characteristics and implementation methods. Retrospective analysis of data using the Rasch statistical model to correct for missing data and variability in item difficulty. Linear model analysis of variance was used to assess differences in student performance. 6401 preclinical students from 13 medical schools that participated in AMSAC from 2011 to 2013. Rasch estimates of preclinical basic and clinical science knowledge. Representation of Australian medical schools and students in AMSAC more than doubled between 2009 and 2013. In 2013 it included 12 of 19 medical schools and 68% of medical students. Graduate-entry students scored higher than students entering straight from school. Students at large schools scored higher than students at small schools. Although the significance level was high (P < 0.001), the main effect sizes were small (4.5% and 2.3%, respectively). The time allowed per multiple choice question was not significantly associated with student performance. The effect on performance of multiple assessments compared with the test items as part of a single end-of-year examination was negligible. The variables investigated explain only 12% of the total variation in student performance. An increasing number of medical schools are participating in AMSAC to monitor student performance in preclinical sciences against an external benchmark. Medical school characteristics account for only a small part of overall variation in student performance. Student performance was not affected by the different methods of administering test items.


Differential regulation of estrogen receptor α expression in breast cancer cells by metastasis-associated protein 1.
Metastasis-associated protein 1 (MTA1) is a component of the nucleosome remodeling and histone deacetylase (HDAC) complex, which plays an important role in progression of breast cancer. Although MTA1 is known as a repressor of the transactivation function of estrogen receptor α (ERα), its involvement in the epigenetic control of transcription of the ERα gene ESR1 has not been studied. Here, we show that silencing of MTA1 reduced the level of expression of ERα in ERα-positive cells but increased it in ERα-negative cells. In both MCF7 and MDA-MB-231, MTA1 was recruited to the region +146 to +461 bp downstream of the transcription start site of ESR1 (ERpro315). Proteomics analysis of the MTA1 complex that was pulled down by an oligonucleotide encoding ERpro315 revealed that the transcription factor AP-2γ (TFAP2C) and the IFN-γ-inducible protein 16 (IFI16) were components of the complex. Interestingly, in MCF7, TFAP2C activated the reporter encoding ERpro315 and the level of ERα mRNA. By contrast, in MDA-MB-231, IFI16 repressed the promoter activity and silencing of MTA1 increased expression of ERα. Importantly, class II HDACs are involved in the MTA1-mediated differential regulation of ERα. Finally, an MDA-MB-231-derived cell line that stably expressed shIFI16 or shMTA1 was more susceptible to tamoxifen-induced growth inhibition in in vitro and in vivo experiments. Taken together, our findings suggest that the MTA1-TFAP2C or the MTA1-IFI16 complex may contribute to the epigenetic regulation of ESR1 expression in breast cancer and may determine the chemosensitivity of tumors to tamoxifen therapy in patients with breast cancer.


Experience with the objective structured examination as a tool for students' assessment in the Department of Community Medicine and Primary Health Care in a university [corrected] in Western Saudi Arabia.
The objectives of this study were to 1. assess the knowledge and attitude of the 5th year female medical students towards the objective structured examination in general and in Community Medicine in particular prior to the exam, 2. Detect any change in students' knowledge and attitude after passing the exam, 3. Identify the students' evaluation for future objective structured examination in Community Medicine and Primary Health Care and 4. Compare the students' performance in the objective structured examination in Community Medicine and Primary Health Care to the results of multiple choice questions evaluation in the department. There were 2 data sets, the first was collected by self-administered pre and post-objective structured examination questionnaires from all female medical students in the 5th year during the academic year 1996-1997 and the 2nd was copied from the students' results for objective structured examination and multiple choice questions in the department of Community Medicine and Primary Health Care during same academic year. All the 34 5th year female medical students were enrolled in the study. Most of them reported that they did not receive enough information prior to the objective structured examination and most of their knowledge came from side chats with friends or staff members which was confirmed by their weak knowledge and negative attitude towards the objective structured examination prior to the exam. After setting the objective structured examination, students' knowledge and attitude towards objective structured examination markedly improved and the majority displayed its advantage as an assessment tool and were convinced of its suitability for medical practice in general and community medicine in particular. Most students believed that objective structured examination in Community Medicine and Primary Health Care met their expectations and recommended it for the coming years. Also, students stated the negative and positive aspects that should be considered for future assessments. Moreover, the multiple choice questions were nearly similar and there was a significant correlation between both scores. The 5th year female medical students did not receive enough information and training on the objective structured examination which influenced their attitude prior to the exam. However, most of them showed a positive attitude after the experience and their marks in the objective structured examination were comparable to their marks in the multiple choice questions. The objective structured examination is a popular method of assessment in medical practice worldwide. The decision to discontinue its use after only one year did not allow space of time for evaluation of its appropriateness as an assessment tool. More research is recommended to study the main causes that lead to disregarding this type of medical assessment in the College of Medicine at King Abdulaziz University.


Clinical decision support systems in community pharmacies: a scoping review.
Clinical decision support systems (CDSS) were implemented in community pharmacies over 40 years ago. However, unlike CDSS studies in other health settings, few studies have been undertaken to evaluate and improve their use in community pharmacies, where billions of prescriptions are filled every year. The aim of this scoping review is to summarize what research has been done surrounding CDSS in community pharmacies and call for rigorous research in this area. Six databases were searched using a combination of controlled vocabulary and keywords relating to community pharmacy and CDSS. After deduplicating the initial search results, 2 independent reviewers conducted title/abstract screening and full-text review. Then, the selected studies were synthesized in terms of investigational/clinical focuses. The selected 21 studies investigated the perception of and response to CDSS alerts (n = 7), the impact of CDSS alerts (n = 7), and drug-drug interaction (DDI) alerts (n = 8). Three causes of the failures to prevent DDIs of clinical importance have been noted: the perception of and response to a high volume of DDI alerts, a suboptimal performance of CDSS, and a dearth of sociotechnical considerations for managing workload and workflow. Additionally, 7 studies emphasized the importance of utilizing CDSS for a specific clinical focus, ie, antibiotics, diabetes, opioids, and vaccinations. Despite the range of topics dealt in the last 30 years, this scoping review confirms that research on CDSS in community pharmacies is limited and disjointed, lacking a comprehensive approach to highlight areas for improvement and ways to optimize CDSS utilization.


Secondary enuresis: post-traumatic stress disorder in children after car accidents.
In our experience, secondary enuresis nocturna is a common complaint among children after a motor vehicle accident. However, as these children are often brought for examination as part of an insurance compensation claim, this complaint is not always reliable. To describe a series of children in whom secondary enuresis occurred after a motor vehicle accident. Five children were brought to our clinic for evaluation of secondary nocturnal enuresis. Review of past history revealed a car accident preceding the onset of the enuresis. All but one had additional behavioral symptoms typical of post-traumatic stress disorder. Four children had evidence of head trauma, and one had psychological but no physical trauma. Nocturnal enuresis can occur after a motor vehicle accident due either to purely psychological trauma or organic head trauma. While nocturnal enuresis is generally attributed to organic causes, psychological mechanisms also play a significant role.


[Naevus pigmentosus and melanoma].
Clinical observations and histological findings support the relationship between pigmented naevi and melanoma. The author describes the morphological characteristics of congenital, acquired and atypical naevi in relation to the appearance of melanoma. On the basis of clinical observations, in harmony with other investigators, the author advises patients to perform self examination and to undergo regular survey of numerous atypical naevi by a dermatologist. In fact, any of the atypical pigmented naevi present in high number may be a precursor lesion. Patients with such lesions are at higher risk of melanoma development.


Advancing Exercise Science for Better Health Outcomes Across the Spectrum of Chronic Kidney Disease.
Despite over 30 years of evidence for improvements in physical function, physical fitness, and health-related quality of life with exercise training in individuals with chronic kidney disease, access to dedicated exercise training programs remains outside the realm of standard of care for most kidney care programs. In this review, we explore possible reasons for this by comparing approaches in other chronic diseases where exercise rehabilitation has become the standard of care, identifying enablers and factors that need to be addressed for continued growth in this area, and discussing knowledge gaps for future research. For exercise rehabilitation to be relevant to all stakeholders and become a sustainable component of kidney care, a focus on the effect of exercise on clinically relevant outcomes that are prioritized by individuals living with kidney disease, use of evidence-based implementation strategies for diverse settings and populations, and approaching exercise as a medical therapy are required.


Contrasting effects of habitat loss and fragmentation on coral-associated reef fishes.
Disturbance can result in the fragmentation and/or loss of suitable habitat, both of which can have important consequences for survival, species interactions, and resulting patterns of local diversity. However, effects of habitat loss and fragmentation are typically confounded during disturbance events, and previous attempts to determine their relative significance have proved ineffective. Here we experimentally manipulated live coral habitats to examine the potential independent and interactive effects of habitat loss and fragmentation on survival, abundance, and species richness of recruitment-stage, coral-associated reef fishes. Loss of 75% of live coral from experimental reefs resulted in low survival of a coral-associated damselfish and low abundance and richness of other recruits 16 weeks after habitat manipulations. In contrast, fragmentation had positive effects on damselfish survival and resulted in greater abundance and species richness of other recruits. We hypothesize that spacing of habitat through fragmentation weakens competition within and among species. Comparison of effect sizes over the course of the study period revealed that, in the first six weeks following habitat manipulations, the positive effects of fragmentation were at least four times stronger than the effects of habitat loss. This initial positive effect of fragmentation attenuated considerably after 16 weeks, whereas the negative effects of habitat loss increased in strength over time. There was little indication that the amount of habitat influenced the magnitude of the habitat fragmentation effect. Numerous studies have reported dramatic declines in coral reef fish abundance and diversity in response to disturbances that cause the loss and fragmentation of coral habitats. Our results suggest that these declines occur as a result of habitat loss, not habitat fragmentation. Positive fragmentation effects may actually buffer against the negative effects of habitat loss and contribute to the resistance of reef fish populations to declines in coral cover.


Self-assembled PCBM bilayers on graphene and HOPG examined by AFM and STM.
In this work we report fabrication and characterization of phenyl-C61-butyric acid methyl ester (PCBM) bilayer structures on graphene and highly oriented pyrolytic graphite (HOPG). Through careful control of the PCBM solution concentration (from 0.1 to 2 mg ml-1) and the deposition conditions, we demonstrate that PCBM molecules self-assemble into bilayer structures on graphene and HOPG substrates. Interestingly, the PCBM bilayers are formed with two distinct heights on HOPG, but only one unique representative height on graphene. At elevated annealing temperatures, edge diffusion allows neighboring vacancies to merge into a more ordered structure. This is, to the best of our knowledge, the first experimental realization of PCBM bilayer structures on graphene. This work could provide valuable insight into fabrication of new hybrid, ordered structures for applications to organic solar cells.


Single-Bit All-Digital Frequency Synthesis Using Homodyne Sigma-Delta Modulation.
All-digital frequency synthesis using bandpass sigma-delta modulation to achieve spectrally clean single-bit output is presented and mathematically analyzed resulting in a complete model to predict the stability and output spectrum. The quadrature homodyne filter architecture is introduced resulting in efficient implementations of carrier-frequency-centered bandpass filters for the modulator. A multiplierless version of the quadrature homodyne filter architecture is also introduced to reduce complexity while maintaining a clean in-band spectrum. MATLAB and SIMULINK simulation results present the potential capabilities of the synthesizer architectures and validate the accuracy of the developed theoretical framework.


Patterns of gene expression associated with BMP-2-induced osteoblast and adipocyte differentiation of mesenchymal progenitor cell 3T3-F442A.
The pluripotent mesenchymal stem cells give rise to osteoblasts, adipocytes, chondrocytes, and myoblasts. The differentiation of these stem cells into each of the mature functional cells may be controlled by a distinctive master gene(s) and is associated with temporal and spatial expression of diverse genes. Identification of genes that are expressed during the differentiation of the mesenchymal cells to osteoblasts is, therefore, important to obtain insights into the molecular mechanisms of osteogenesis. The murine undifferentiated mesenchymal cell 3T3-F442A, when treated with the bone morphogenetic protein 2 (BMP-2), a well-characterized inducer of mesenchymal cell differentiation, exhibited both osteoblastic and adipocytic differentiation. Using the SAGE (serial analysis of gene expression) technique, which has been shown to enable quantitative analysis of large numbers of genes in a simple and quick manner, we obtained 1600 sequence tags representing 2107 individual nucleotide sequences from control and BMP-2-treated 3T3-F442A cells, respectively. By comparing the frequency of tag occurrence, we found profiles of up- or downregulated genes associated with osteoblast or adipocyte phenotype such as type I collagen, osteonectin and OSF-2, or C/EBPbeta, aP2, fatty acid synthase, and lipoprotein lipase, respectively, in BMP-2-treated 3T3-F442A cells. Our data show that BMP-2 induces not only osteoblastic but also adipocytic differentiation in the 3T3-F442A cells. They also show that the 3T3-F442A cells have bipotentials of differentiating toward osteoblasts and adipocytes. The results, therefore, might explain the inverse correlation between trabecular bone volume and fat volume in the bone marrow cavity. The results also suggest that the SAGE may be a useful technique that allows us a fast and efficient way to generate global and local views of gene expression associated with cellular differentiation of the mesenchymal stem cells.


Alternative treatments for atopic dermatitis: a selected review.
Atopic dermatitis (AD) is a chronic itchy, inflammatory skin disease that is extremely difficult to treat. Effective therapeutic agents are limited in number, and may have long-term toxic side-effects. Frustrated by these realities, many patients stop seeking help from conventional physicians and turn to alternative medical approaches. These can include so-called natural products, herbal products and over-the-counter (OTC) treatments. Herbs and medications share a common history, as most of our well-known medications were derived from plants. However, herbal remedies are largely unregulated. Many may have scientific merit and clinical benefit, but they are still scientifically invalid and inadequately monitored. Dermatologists need information about the effects of herbal remedies in order to better serve their patients.


A fuzzy controller with supervised learning assisted reinforcement learning algorithm for obstacle avoidance.
Fuzzy logic systems are promising for efficient obstacle avoidance. However, it is difficult to maintain the correctness, consistency, and completeness of a fuzzy rule base constructed and tuned by a human expert. A reinforcement learning method is capable of learning the fuzzy rules automatically. However, it incurs a heavy learning phase and may result in an insufficiently learned rule base due to the curse of dimensionality. In this paper, we propose a neural fuzzy system with mixed coarse learning and fine learning phases. In the first phase, a supervised learning method is used to determine the membership functions for input and output variables simultaneously. After sufficient training, fine learning is applied which employs reinforcement learning algorithm to fine-tune the membership functions for output variables. For sufficient learning, a new learning method using a modification of Sutton and Barto's model is proposed to strengthen the exploration. Through this two-step tuning approach, the mobile robot is able to perform collision-free navigation. To deal with the difficulty of acquiring a large amount of training data with high consistency for supervised learning, we develop a virtual environment (VE) simulator, which is able to provide desktop virtual environment (DVE) and immersive virtual environment (IVE) visualization. Through operating a mobile robot in the virtual environment (DVE/IVE) by a skilled human operator, training data are readily obtained and used to train the neural fuzzy system.


Pancreatic hormonal and metabolic responses in overfed ducks.
When overfed at their maximum (intensive overfeeding) or at only 80% (moderate overfeeding) of food intake capacity, Mule ducks developed strong liver steatosis, whereas Pekin ducks showed very marked extrahepatic fattening. During overfeeding, evolution of plasma glucose and triacylglycerol concentrations suggested a very strong increase in the hepatic lipogenesis as well as genotype- and diet-independent lipoprotein secretion. In contrast, lipoprotein-lipase activity was dependent on alimentary status (the intensive overfeeding induces the highest activities), and Pekin ducks showed higher lipoprotein-lipase activity than Mule ducks, which could favor extrahepatic fattening to the detriment of hepatic steatosis. In Pekin ducks, plasma pancreatic hormone concentrations are related to diet levels and blood sugar. With similar food intake, Mule ducks (moderately overfed) showed global blood insulin lower than that of Pekin ducks (intensively overfed) despite similar blood sugar levels, suggesting a trend towards reduced pancreas response to glucose in Mule ducks. This may result from their lower lipoprotein-lipase activity as previously shown in these two ducks overfed at only 60% of their maximal food intake capacity (unpublished results). These results suggest that high plasma insulin concentrations may be necessary to induce an optimum lipoprotein-lipase activity in overfed ducks.


Identification of separate bombesin and substance P receptors on isolated muscle cells from canine gallbladder.
Smooth muscle cells were isolated from the dog gallbladder and used to examine whether bombesin-14 and substance P cause direct contraction and whether this effect is mediated by the same or different receptors. Both peptides caused concentration-dependent contraction that was inhibited by two substance P derivatives, [D-Pro2,D-Trp7,9]SP ([PTT]SP) and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP ([APTTL]SP). In nonmuscle cells, these substance P derivatives exhibit preferential antagonism of responses to substance P and bombesin, respectively; accordingly, these properties were used to demonstrate the presence of separate bombesin and substance P receptors. Estimates of the apparent Ki showed that [PTT]SP was 40 times more potent than [APTTL]SP as an antagonist of the response to substance P, whereas [APTTL]SP was 85 times more potent than [PTT]SP as an antagonist of the response to bombesin-14. Estimates of median inhibitory concentration obtained from inhibition curves for the effect of various concentrations of each antagonist on the responses to substance P and bombesin-14 confirmed that [PTT]SP was a preferential antagonist of the response to substance P and [APTTL]SP, a preferential antagonist of the response to bombesin-14. The results demonstrate the presence of separate bombesin and substance P receptors mediating contraction of smooth muscle cells of the dog gallbladder.


Fructose 2,6-bisphosphate in rat skeletal muscle during contraction.
Fructose 2,6-bisphosphate and several glycolytic intermediates were measured in two rat muscles, extensor digitorum longus and gastrocnemius, which were electrically stimulated in situ. Both the duration and the frequency of stimulation were varied to obtain different rates of glycolysis. There was no relationship between fructose 2,6-bisphosphate content and the increase in tissue lactate in contracting muscle. However, in gastrocnemius stimulated at low frequencies (less than or equal to 5 Hz), there was a 2-fold increase in fructose 2,6-bisphosphate at 10s, followed by a return to basal values, whereas lactate increased only after 1 min of contraction. The concentrations of hexose 6-phosphates, fructose 1,6-bisphosphate and triose phosphates were all increased during the 3 min stimulation. During tetanus (frequencies greater than or equal to 10 Hz) fructose 2,6-bisphosphate was not increased, whereas glycolysis was maximally stimulated and resulted in an accumulation of tissue lactate, mostly from glycogen. The concentrations of hexose 6-phosphate increased continuously during the 1 min tetanus, whereas fructose 1,6-bisphosphate was increased at 10s and then decreased progressively. It therefore appears that fructose 2,6-bisphosphate does not play a role in the stimulation of glycolysis during tetanus; it may, however, be involved in the control of glycolysis when the muscles are stimulated at low frequencies for short periods of time.


White sponge nevus of the tongue.
To my knowledge, this is the fifth case of white sponge nevus of the tongue to be reported. This lesion is probably much more common than has been reported in the past. The disorder is benign and almost always asymptomatic. The recognition of this disorder is important in that it must be differentiated from other congenital or familial disorders of more widespread clinical significance. It is important for any physician, and especially for dermatologists, to do a thorough examination of the oral mucous membranes as a part of any physical examination.


[Aggressive surgical approach in pancreatic cancer--is it justified?].
Resection presents the only possible cure for pancreatic cancer. An aggressive surgical approach may extend the limits of resection and offer cure for more patients. 37 women and 28 men, mean age 67 years (range 33-84) with focal lesions underwent pancreatic resection (1993-1999). Cancer of the pancreatic head was found in 45, in the ampulla in 4 and in the body or tail in 16. There was a tumor larger than 5 cm in 9, vascular involvement in 8, and a combination of both in 6. All were evaluated prior to exploration by standard imaging techniques and 44 by laparoscopic ultrasound. 42 underwent pancreatico-duodenectomy, 16 distal subtotal pancreatectomy and 3 local excision of an ampullary tumor. Benign lesions were found in 8 (focal pancreatitis in 4 and a serous cystic lesion in 4). Curative resection (microscopically negative margins, negative lymph nodes) was achieved in 44. 2 died 1-2 months after operation of septic complications (2% operative mortality). The most frequent complication (in 8) was pancreatic fistula. Additional complications included anastomotic-line bleeding (3), intra-abdominal abscess (2), and 1 developed portal vein thrombosis (treated surgically). 1- and 2-year survival in those after curative pancreatic resection was 81% and 55% respectively. 2-year survival in those after palliative resection (positive resection margins or positive lymph nodes) was 50% and 11%, respectively. After proper selection of those in whom it is possible to perform curative resection, regardless of size or vascular involvement, an aggressive surgical approach is justified.


One-step extraction of subcellular proteins from eukaryotic cells.
Conventional biochemical analysis mainly focuses on the expression level of cellular proteins from entire cells. However, it has been increasingly acknowledged that the subcellular location of proteins often carries important information. Analysis of subcellular proteins conventionally requires subcellular fractionation which involves two steps: cell lysis to release proteins and high-speed centrifugation to separate the homogenate. Such approach requires bulky and expensive equipment and is not compatible with processing scarce cell samples of limited volume. In this study, we apply microfluidic flow-through electroporation to breach cell membranes and extract cytosolic proteins selectively in a single step. We demonstrate that this approach allows monitoring the translocation of the transcription factor NF-kappaB from the cytosol to the nucleus without the need of subcellular fractionation. Our technique is compatible with the processing of samples of various sizes and provides a simple and universal tool for bioanalytical analysis and spatial proteomics.


Allergen-induced increases in IL-5 receptor alpha-subunit expression on bone marrow-derived CD34+ cells from asthmatic subjects. A novel marker of progenitor cell commitment towards eosinophilic differentiation.
We have proposed previously that hemopoietic myeloid progenitors contribute to the ongoing recruitment of proinflammatory cells, namely eosinophils, to sites of allergen challenge in allergic diseases such as asthma. In this study, we investigated the involvement of bone marrow-derived progenitors in the development of allergen-induced pulmonary inflammation in mild asthmatic subjects. By flow cytometry, we enumerated the level of expression of CD34, a hemopoietic progenitor cell marker, on bone marrow aspirates taken before and 24 h after allergen challenge. In addition, the coexpression of the alpha-subunits of IL-3 receptor (IL-3R) and IL-5 receptor (IL-5R) on CD34+ cells was investigated. After allergen-challenge, although no significant change in total BM CD34+ cell numbers was observed, a significant increase in the proportion of CD34+ cells expressing IL-5R alpha, but not IL-3R alpha, was detected in the 24-h post-allergen, compared with the pre-allergen bone marrow. This was associated with a significant blood and sputum eosinophilia and increased methacholine airway responsiveness, 24 h post-allergen. Using simultaneous in situ hybridization and immunocytochemistry, we colocalized the expression of messenger RNA for membrane-bound IL-5R alpha to CD34+ cells. In summary, our data suggest that increased expression of IL-5R alpha on CD34+ cells favors eosinophilopoiesis and may thus contribute to the subsequent development of blood and tissue eosinophilia, a hallmark of allergic inflammation.


Developing a national certification pathway for genetic counselors in Sweden-a short report.
There is no Master's level education for genetic counseling in Sweden, meaning that genetic counselor professionals have very different backgrounds. Hence, there is a need to harmonize the quality of genetic counseling and introduce standards for practice. The Swedish Society for Genetic Counselors and the Swedish Society of Medical Genetics and Genomics collaborated to determine professional requirements and a career pathway, defining three vocational levels within the genetic counselor profession. We report here an individual educational pathway leading up to eligibility for certification as a genetic counselor in Sweden.


LBERT: Lexically aware Transformer-based Bidirectional Encoder Representation model for learning universal bio-entity relations.
Natural Language Processing techniques are constantly being advanced to accommodate the influx of data as well as to provide exhaustive and structured knowledge dissemination. Within the biomedical domain, relation detection between bio-entities known as the Bio-Entity Relation Extraction (BRE) task has a critical function in knowledge structuring. Although recent advances in deep learning-based biomedical domain embedding have improved BRE predictive analytics, these works are often task selective or use external knowledge-based pre-/post-processing. In addition, deep learning-based models do not account for local syntactic contexts, which have improved data representation in many kernel classifier-based models. In this study, we propose a universal BRE model, i.e. LBERT, which is a Lexically aware Transformer-based Bidirectional Encoder Representation model, and which explores both local and global contexts representations for sentence-level classification tasks. This article presents one of the most exhaustive BRE studies ever conducted over five different bio-entity relation types. Our model outperforms state-of-the-art deep learning models in protein-protein interaction (PPI), drug-drug interaction and protein-bio-entity relation classification tasks by 0.02%, 11.2% and 41.4%, respectively. LBERT representations show a statistically significant improvement over BioBERT in detecting true bio-entity relation for large corpora like PPI. Our ablation studies clearly indicate the contribution of the lexical features and distance-adjusted attention in improving prediction performance by learning additional local semantic context along with bi-directionally learned global context. Github. https://github.com/warikoone/LBERT. Supplementary data are available at Bioinformatics online.


BAG1 is a protective factor for sporadic frontotemporal lobar degeneration but not for Alzheimer's disease.
BCL2-associated athanogene 1 (BAG1) is an anti-apoptotic factor that interacts with tau and regulates its proteasomal degradation. A significant increase of the BAG-1M isoform was found in Alzheimer's disease (AD) brains, and the protein co-localized with tau and amyloid. We carried out an association study of BAG1 in a population of 291 patients clinically diagnosed with frontotemporal lobar degeneration (FTLD), none of whom was a carrier of mutations in progranulin or microtubule associated protein tau genes and 374 with AD as compared with 314 age- and gender-matched controls. In addition, another candidate named Chromatin-modifying protein 5 (CHMP5) and located in the same linkage disequilibrium block, has been included in this study. The distribution of the two single nucleotide polymorphism (SNPs), rs844239 in CHMP5 and rs706118 in BAG1, covering 100% gene variability, were determined. A statistically significant decreased allelic frequency of the BAG-1 rs706118 SNP was observed in patients with FTLD as compared with controls (16.7 versus 23.9%; p = 0.007, OR: 0.35, CI: 0.25-0.50), whereas allelic frequency of the SNP in patients with AD was similar to controls (24.3%, p > 0.05). Conversely, no significant association was found as regards CHMP5 rs844239. Stratifying according to gender, no differences were observed. BAG-1 rs706118 SNP likely acts as protective factor for sporadic FTLD, but not for AD, suggesting its specific role in a pathogenic event in FTLD. Nevertheless, a replication study would be needed to confirm these preliminary results.


Targeting of MAPK-associated molecules identifies SON as a prime target to attenuate the proliferation and tumorigenicity of pancreatic cancer cells.
Pancreatic cancer is characterized by constitutive activation of mitogen-activated protein kinase (MAPK). Activation of MAPK is associated with the upregulation of genes implicated in the proliferation and survival of pancreatic cancer cells. We hypothesized that knockdown of these MAPK-associated molecules could produce notable anticancer phenotypes. A RNA interference-mediated knockdown screening of 78 MAPK-associated molecules previously identified was performed to find molecules specifically associated with proliferation of pancreatic cancer cells in vitro. Expression of an identified molecule in pancreatic cancer tissues was examined by immunohistochemistry. In vivo tumorigenicity of cancer cells with stable knockdown of the molecule was assayed by using xenograft models. Flow cytometry and live cell imaging were employed to assess an association of the molecule with cell cycle. The knockdown screening revealed that knockdown of SON, the gene encoding SON, which is a large serine/arginine-rich protein involved in RNA processing, substantially suppressed pancreatic cancer cell proliferation and survival in vitro and tumorigenicity in vivo. SON expression was higher in ductal adenocarcinomas than in cells of normal ducts and precursor lesions in pancreatic cancer tissues. Knockdown of SON induced G2/M arrest and apoptosis in cultured cancer cells. The suppressive effect of SON knockdown on proliferation was less pronounced in cultured normal duct epithelial cells. SON formed nuclear speckles in the interphase of the cell cycle and dispersed in the cytoplasm during mitosis. Live cell imaging showed that SON diffusely dispersed in the early mitotic phase, accumulated in some foci in the cytoplasm in the late mitotic phase, and gradually reassembled into speckles after mitosis. These results indicate that SON plays a critical role in the proliferation, survival, and tumorigenicity of pancreatic cancer cells, suggesting that SON is a novel therapeutic molecular target for pancreatic cancer.


Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis.
The Wells clinical decision rule (CDR) and D-dimer tests can be used to exclude pulmonary embolism (PE). We performed a meta-analysis to determine the negative predictive value (NPV) of an "unlikely" CDR (<or=4 points) combined with a normal D-dimer test and the safety of withholding anti-coagulants based on these criteria. Prospective studies that withheld anti-coagulant treatment from patients with clinically suspected PE and an "unlikely" CDR in combination with a normal D-dimer concentration without performing further tests were searched for in Medline, Cochrane and Embase. Primary endpoints were the recurrence rate of venous thromboembolism (VTE) and PE-related mortality during 3-months follow-up. Four studies including 1660 consecutive patients were identified. The pooled incidence of VTE after initial exclusion of acute PE based on an "unlikely" CDR and normal D-dimer was 0.34% (95%CI 0.036-0.96%), resulting in a NPV of 99.7% (95%CI: 99.0-99.9%, random effects-model). The risk for PE related mortality was very low: 1/1660 patients had fatal PE (0.06%, 95%CI 0.0017-0.46%). Acute PE can be safely excluded in patients with clinically suspected acute PE who have an "unlikely" probability and a negative D-dimer test and anticoagulant treatment can be withheld. There is no need for additional radiological tests in these patients to rule out PE.


COVID-19 Vaccine Literacy of Family Carers for Their Older Parents in Japan.
In super-ageing Japan, COVID-19 vaccinations were starting to reach older people as of June 2021, which raises the issue of vaccine literacy. This study focuses on family members who work and also care for their older parents, as they are at risk of COVID-19 and also risk transmitting COVID-19 to the parents they care for and potentially influencing their parents' vaccine uptake. Such family carers are central to the approach in Japan to achieving a sustainable and resilient society in response to ageing. Contrasting family carers' COVID-19 vaccine literacy with their overall health literacy provides insights into their preparedness for COVID-19 vaccinations. The purpose of this study is to understand how vaccine literacy, compared to health literacy, varies across family carers and the sources of information they use. Through a cross-sectional online survey, family carers' vaccine literacy, health literacy and their sources of information, including mass media, social media, health and care professionals, family, colleagues, friends, and others, were assessed. The participants' (n = 292) mean age was 53, with 44% women, and an average of 8.3 h per week caring for their parents. Notwithstanding the increased risks from COVID-19 with age, COVID-19 vaccine literacy relative to health literacy for older family carers is lower on average, higher with increased provision of care, and more variable, resulting in a substantial proportion of older family carers with relatively low vaccine literacy. At this stage of vaccine rollout in Japan, family carers' sources of information to inform COVID-19 vaccine literacy is distinct, including more national and local mass media versus less health and care professionals and informal networks, which indicates the importance of tailored health communication strategies to enhance vaccine literacy.


Physician-older patient communication during the transition from independence to dependence.
This article reviews recent research regarding the communication between physicians and their older patients who are passing from independence to dependence. Major findings from these studies are summarized with a discussion of how the context of the medical encounter, the physical, cognitive and language changes related to age, the amount of time permitted for a medical encounter, the managed care environment, and the presence of a companion can affect competent communication between a physician and an older adult. The article concludes with a comment about the need to educate current and future physicians on the complexity of communicating effectively with older patients.


Clinical effects of strontium ranelate in women with postmenopausal osteoporosis.
Postmenopausal osteoporosis has long-term physical, psychological, and social consequences with a major impact on patients' daily life. Treatment for such a chronic disease needs to be clinically effective and well tolerated, and should ultimately result in a beneficial effect on quality of life. The antifracture efficacy of strontium ranelate, 2 g/day orally, an agent that appears to have dissociation effects on resorption and formation, has been assessed in two large, randomized, double-blind, placebo-controlled clinical studies: the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial and the TReatment Of Peripheral Osteoporosis Study (TROPOS), including more than 6,700 postmenopausal women. Pending the results of TROPOS, a 3-year analysis of SOTI results shows that strontium ranelate significantly reduces new vertebral and clinical vertebral fracture incidence in postmenopausal osteoporotic women. This significant reduction in the risk of clinical and new vertebral fractures has been demonstrated as early as after 1 year of treatment (RR = 0.48, p = 0.003; and RR = 0.51, p < 0.001, respectively) and is maintained over 3 years (RR = 0.62, p < 0.001; and RR = 0.59, p < 0.001, respectively). This is accompanied by decreased back pain and body height loss in the strontium ranelate group compared with the placebo group. As strontium ranelate appears to improve clinical signs and is, furthermore, well tolerated especially in the upper gastrointestinal region, this treatment is expected to result in an improved health-related quality of life (HRQoL). Strontium ranelate thus offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal women with vertebral osteoporotic fractures.


Adolescents' Experiences of Staying Overnight at Family-Centered Pediatric Wards.
Sleep is essential for health and recovery. Hospital stays may affect adolescents' sleep quality negatively as routines in the ward are not adapted for adolescents' developmental status or sleep habits. The aims with this study were to (a) explore and describe how adolescents experience sleep in the family-centered pediatric ward, (b) explore and describe how adolescents experience the presence or absence of a parent during the hospital stay, and (c) identify circumstances that the adolescents describe as influential of their sleep in the pediatric wards. This is a qualitative interview study employing thematic analysis with an inductive and exploratory approach. Sixteen adolescents aged between 13 and 17 years participated in the study. Three themes were found: the importance of good sleep, safety as a prerequisite for sleep in hospital, and circumstances influencing adolescents' sleep in hospital. The adolescents described their sleep at the pediatric ward positively, but mentioned disturbing factors associated with pain, nightly check-ups, noises, and inactivity. Parental presence was perceived as very positive both during the night and the day.


Regulation and function of triacylglycerol lipases in cellular metabolism.
The ability to store energy in the form of energy-dense TAG (triacylglycerol) and to mobilize these stores rapidly during times of low carbohydrate availability (fasting or famine) or during heightened metabolic demand (exercise or cold-stress) is a highly conserved process essential for survival. Today, in the presence of nutrient excess and sedentary lifestyles, the regulation of this pathway is viewed as an important therapeutic target for disease prevention, as elevated circulating fatty acids in obesity contribute to many aspects of the metabolic syndrome including hepatic steatosis, atherosclerosis and insulin resistance. In the present review, we discuss the metabolic regulation and function of TAG lipases with a focus on HSL (hormone-sensitive lipase), ATGL (adipose triacylglycerol lipase) and newly identified members of the lipolytic proteome.


Combination Therapy With Charged Particles and Molecular Targeting: A Promising Avenue to Overcome Radioresistance.
Radiotherapy plays a central role in the treatment of cancer patients. Over the past decades, remarkable technological progress has been made in the field of conventional radiotherapy. In addition, the use of charged particles (e.g., protons and carbon ions) makes it possible to further improve dose deposition to the tumor, while sparing the surrounding healthy tissues. Despite these improvements, radioresistance and tumor recurrence are still observed. Although the mechanisms underlying resistance to conventional radiotherapy are well-studied, scientific evidence on the impact of charged particle therapy on cancer cell radioresistance is restricted. The purpose of this review is to discuss the potential role that charged particles could play to overcome radioresistance. This review will focus on hypoxia, cancer stem cells, and specific signaling pathways of EGFR, NFκB, and Hedgehog as well as DNA damage signaling involving PARP, as mechanisms of radioresistance for which pharmacological targets have been identified. Finally, new lines of future research will be proposed, with a focus on novel molecular inhibitors that could be used in combination with charged particle therapy as a novel treatment option for radioresistant tumors.


Photon energy lifter.
We propose a time-dependent, spatially periodic photonic structure which is able to shift the carrier frequency of an optical pulse which propagates through it. Taking advantage of the slow group velocity of light in periodic photonic structures, the wavelength conversion process can be performed with an efficiency close to 1 and without affecting the shape and the coherence of the pulse. Quantitative Finite Difference Time Domain simulations are performed for realistic systems with optical parameters of conventional silicon technology.


Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis. A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis.
Neutrophil migration into the airspaces of the lung is thought to contribute to the alveolar damage and subsequent fibrosis in idiopathic pulmonary fibrosis (IPF). Interleukin 8 (IL-8), a monocyte- and macrophage-derived cytokine, displays potent chemotactic and activating properties towards neutrophils and thus may contribute to the pathogenesis of IPF. The objective of this investigation was to quantify the spontaneous expression of IL-8 transcripts by alveolar macrophages from normal healthy volunteers and individuals with IPF. A quantitative assay employing reverse transcription of mRNA and the polymerase chain reaction was utilized. The level of IL-8 mRNA in alveolar macrophages was found to be significantly elevated in individuals with lone IPF or with lung fibrosis associated with connective tissue disorders compared to normal healthy controls. Moreover, the level of IL-8 mRNA in the 23 individuals with IPF correlated with the number of neutrophils per milliliter in their bronchoalveolar lavage (BAL) and with the degree of disease severity. In addition, the level of IL-8 protein in BAL was found to reflect the pattern of IL-8 mRNA expression by alveolar macrophages. These data suggest that IL-8 derived from alveolar macrophages may significantly contribute to neutrophil involvement in the pathogenesis of IPF.


Bosminopsis deitersi (Crustacea: Cladocera) as an ancient species group: a revision.
Water fleas (Crustacea: Cladocera) of the Family Bosminidae have been studied since the founding of paleolimnology and freshwater ecology. However, one species, Bosminopsis deitersi, stands out for its exceptional multicontinental range and broad ecological requirements. Here we use an integrated morphological and multilocus genetic approach to address the species problem in B. deitersi. We analyzed 32 populations of B. deitersi s. lat. Two nuclear and two mitochondrial loci were used to carry out the bGMYC, mPTP and STACEY algorithms for species delimitation. Detailed morphological study was also carried out across continents. The evidence indicated a widely distributed cryptic species in the Old World (Bosminopsis zernowi) that is genetically divergent from B. deitersi s.str. We revised the taxonomy and redescribed the species in this complex. Our sampling indicated that B. zernowi had weak genetic differentiation across its range. A molecular clock and biogeographic analysis with fossil calibrations suggested a Mesozoic origin for the Bosminopsis deitersi group. Our evidence rejects the single species hypothesis for B. deitersi and is consistent with an ancient species group (potentially Mesozoic) that shows marked morphological conservation. The family Bosminidae, then, has examples of both rapid morphological evolution (Holocene Bosmina), and morphological stasis (Bosminopsis).


The neuroprotective effects of rituximab in rat spinal cord injury model: an immunohistochemical study.
In the present study, we investigate the neuroprotective effects of rituximab, a monoclonal antibody directed towards B cell mediated humoral immunity, on a rat spinal cord injury (SCI) model with immunohistochemical methods. Twenty-four rats were used for the study. Rats were divided as control, SCI, and rituximab-treated SCI groups. Intraperitoneal rituximab administration was performed on days 0, 3 and 5 in the third group. Rats were sacrificed 7 days after trauma. Antibodies against IL-1β, IL-6, TNF-α and CD20 were studied with the ELISA method together with electron microscopic analysis. It was found that rituximab suppressed oligodendrocytes at the phagocytic stage but was still inefficient for the regenerative phase. TNF-α expression was markedly increased in rats subjected to SCI and suppressed after rituximab treatment. Decreased CD20 expression was another prominent finding in rats under rituximab therapy. However, expressions of IL-1β and IL-6 were both increased in glial cells without significant change after rituximab administration. TNF-α expression was augmented at the level of SCI both in neuronal and glial cells, particularly in oligodendrocytes. All were suppressed after rituximab administration and rituximab reduced CD20 expression both in neuronal and supportive glial cells which may be related to neural healing.


English language and language-free detection of spatial processing disorders in Aboriginal and Torres Strait Islander children.
The aim of this study was to compare speech reception thresholds in noise measured with the Listening in Spatialised Noise - Universal test (LiSN-U; which requires no English knowledge) with those measured from the relevant conditions of the LiSN - Sentences test (LiSN-S; a test requiring knowledge of English) in Aboriginal and Torres Strait Islander children. A second aim was to compare the ability of the two tests to detect spatial processing disorder. Participants completed audiometry, the LiSN-S, and the LiSN-U. 90 Aboriginal and Torres Strait Islander children aged six to 14 years tested in a school setting. Strong correlations were found between speech reception thresholds in noise for the two tests. A moderate correlation was found between the difference scores that each test uses to detect spatial processing disorder. Consistent diagnoses of whether a child had spatial processing disorder or not on both tests were found for 72% of children. The moderate-to-strong relationships and agreement between diagnoses found for the LiSN-S and LiSN-U show promise for the LiSN-U being used as a tool to investigate spatial processing disorder in children, without requiring the test to use a language familiar to the children being tested.


Tail-suspended mice lacking calponin H1 experience decreased bone loss.
Calponin h1 (CNh1) is an actin-binding protein originally isolated from vascular smooth muscle and has been reported to suppress bone formation. We are therefore curious how CNh1 is involved in bone loss that is caused by space flight in microgravity. We assessed the effects of tail suspension (TS) in C57BL/6J wild (CN+/+) and CNh1-deleted (CN-/-) mice to elucidate the role of CNh1 in bone loss under weightless conditions. Bone mineral density (BMD) of tibiae was measured by single energy X-ray absorptiometry, and bone volume fraction (BV/TV), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were measured by bone histomorphometry. BMD, BV/TV, MAR, and BFR/BS were lower in CN+/+ mice with TS than in those without. In the CN-/- group, however, the decrease in each of these parameters by TS was ameliorated. Decreases in serum osteocalcin levels by TS in CN+/+ mice were attenuated in CN-/- mice. Furthermore, urinary deoxypyridinolin (DPD), an indicator of bone resorption, was increased in CN+/+ mice following TS, but not in CN-/- mice. In transfection experiments, the degree of induction of bone formation markers, alkaline phosphatase (ALP) activity and bone morphogenetic protein (BMP)-4 mRNA expression, under stimulation with BMP-2, was lower in MC3T3-E1 mouse osteoblast-like cells expressing CNh1 than that in mock transfected cells. Notably, the BMP-2-induced ALP activity was decreased by CNh1 expression, which was partially rescued by treatment with the Rho kinase inhibitor Y27632. Taken together, these results indicate that CNh1 is responsible for weightlessness-induced bone loss in part through Rho signaling pathway.


Factors that influence the decision to be an organ donor: a systematic review of the qualitative literature.
Transplantation is the treatment of choice for organ failure, but a worldwide shortage of suitable organs exists. We conducted a systematic review of qualitative studies that explored community attitudes towards living and deceased solid organ donation to inform strategies to improve organ donation rates. Medline, Embase, PsycINFO and EconLIT were searched. Qualitative studies that explored community attitudes towards living and deceased solid organ donation were included. A thematic synthesis of the results and conclusions reported by primary authors was performed. Eighteen studies involving 1019 participants were identified. Eight themes emerged. The decision to be an organ donor was influenced by (i) relational ties; (ii) religious beliefs; (iii) cultural influences; (iv) family influences; (v) body integrity; (vi) previous interactions with the health care system-medical mistrust, validity of brain death and fear of early organ retrieval; (vii) the individual's knowledge about the organ donation process and (viii) major reservations about the process of donation, even in those who support organ donation. This review of qualitative studies highlights that seemingly intractable factors, such as religion and culture, are often tied in with more complex issues such as a distrust of the medical system, misunderstandings about religious stances and ignorance about the donation process. Intervention that could be considered includes culturally appropriate strategies to engage minority groups, especially through religious or cultural leaders, and more comprehensively available information about the donation process and its positive outcomes.


[Medical empiricism from one myth to another. A critical reading of Foucault's Birth of Clinic].
The new history of the clinic, developed mainly after the publication of Othmar Keel's L'avènement de la médecine clinique moderne en Europe, 1750-1815 in 2001, invites the scholars to turn upside down the chronology adopted by Michel Foucault in his classic Birth of the Clinic. This paper investigates the philosophical consequences of this chronological displacement, showing that the medical empiricism of the clinic cannot have the characteristics attributed by Foucault. If the myth of the purity of such empiricism cannot be taken seriously anymore thanks to Foucault, is has been substituted by the myth of the creation of the clinic on the basis of enlightened empiricism. The clinic is, however, older than empiricism à la Condillac. It refers to an earlier medical empiricism developed in the 17th century which in its turn allowed for Condillac's philosophy. The clinic had in fact to choose between an elder medical empiricism and a new chemical empirism that appeared in the late 17th century. But the clinic was not a creation of the Enlightenment.


Activin-like kinase 2 functions in peri-implantation uterine signaling in mice and humans.
Implantation of a blastocyst in the uterus is a multistep process tightly controlled by an intricate regulatory network of interconnected ovarian, uterine, and embryonic factors. Bone morphogenetic protein (BMP) ligands and receptors are expressed in the uterus of pregnant mice, and BMP2 has been shown to be a key regulator of implantation. In this study, we investigated the roles of the BMP type 1 receptor, activin-like kinase 2 (ALK2), during mouse pregnancy by producing mice carrying a conditional ablation of Alk2 in the uterus (Alk2 cKO mice). In the absence of ALK2, embryos demonstrate delayed invasion into the uterine epithelium and stroma, and upon implantation, stromal cells fail to undergo uterine decidualization, resulting in sterility. Mechanistically, microarray analysis revealed that CCAAT/enhancer-binding protein β (Cebpb) expression is suppressed during decidualization in Alk2 cKO females. These findings and the similar phenotypes of Cebpb cKO and Alk2 cKO mice lead to the hypothesis that BMPs act upstream of CEBPB in the stroma to regulate decidualization. To test this hypothesis, we knocked down ALK2 in human uterine stromal cells (hESC) and discovered that ablation of ALK2 alters hESC decidualization and suppresses CEBPB mRNA and protein levels. Chromatin immunoprecipitation (ChIP) analysis of decidualizing hESC confirmed that BMP signaling proteins, SMAD1/5, directly regulate expression of CEBPB by binding a distinct regulatory sequence in the 3' UTR of this gene; CEBPB, in turn, regulates the expression of progesterone receptor (PGR). Our work clarifies the conserved mechanisms through which BMPs regulate peri-implantation in rodents and primates and, for the first time, uncovers a linear pathway of BMP signaling through ALK2 to regulate CEBPB and, subsequently, PGR during decidualization.


Heavy LIFting: tumor promotion and radioresistance in NPC.
The epithelial-derived nasopharyngeal carcinoma (NPC) is a rare tumor in most of the world; however, it is common in southern China, northern Africa, and Alaska. NPC is often left undiagnosed and untreated until a late stage of disease. Furthermore, while radiation therapy is effective against this tumor, local recurrence due to radioresistance is an important clinical problem. In this issue, Liu et al. report on their identification of the IL-6 family cytokine leukemia inhibitory factor (LIF) as a serum predictor of local NPC recurrence following radiation therapy. The authors developed this initial finding to discover a role for the LIF/LIFR/mTORC1 signaling axis in NPC tumor cell growth as well as radioresistance.


Inhibition of lactate dehydrogenase C4 (LDH-C4) blocks capacitation of mouse sperm in vitro.
Lactate dehydrogenase C4 (LDH-C4) is a tissue-specific enzyme in the mammalian testis and the only lactate dehydrogenase isozyme of sperm. Inhibitors of LDH activity were used to determine whether this enzyme plays a role in sperm capacitation, the acrosome reaction and/or fertilization. Oxamate or its derivative was used to inhibit sperm LDH activity in a medium promoting capacitation. Complete inhibition of LDH activity blocked capacitation. This effect could be reversed partially by the addition of dbcAMP or pentoxifylline to the culture medium. Western blotting showed that oxamate and N-isopropyl oxamate inhibited the tyrosine phosphorylation of proteins during the sperm capacitation process. Presumably, glycolysis is the primary energy pathway for sperm metabolism. The oxidation of reduced NAD with the conversion of pyruvate to lactate by LDH provides ATP necessary for protein kinase A (PKA) activity. Our data indicate that LDH-C4 plays an important metabolic role in sperm capacitation.


Sepsis Mortality in Critical Care and Prior Statin Therapy: A Retrospective Cohort Study in Central Argentina.
Sepsis is a major public health problem, frequent, costly, and often fatal. Despite of improvements in supportive treatments the incidence of sepsis and the number of deaths related to sepsis is increasing. Statins have been recently proposed as adjuvants in the treatment of sepsis, but its effects on mortality show conflicting results worldwide. The purpose of this study was to describe the clinical outcome of patients diagnosed with sepsis in a university-affiliated hospital in central Argentina and to evaluate it in relation to a group of septic patients with previous use of statins before the onset of sepsis. The present study was conducted as an observational retrospective research from April 2010 to December 2014 with patients over 18 years of age which were assigned to statins or control groups. Out of 2906 patients, 231 matched study and diagnostic criteria for sepsis and among them 33 (14.3%) belonged to the group of statins. The mean age was 64.2 ± 14.3 years. The severity of sepsis on admission was as follows: Sepsis, n=147 (63.6%), Severe sepsis, n=26 (11.3%) and Septic shock, n=58 (25.1%). The mean length of stay in Intensive Care Unit (ICU) was10.8 ± 9.6 days and 21.2 ± 17 days in general hospital ward settings, without differences between groups of statin users and controls, p=0.873 and p=0.766, respectively. The in-hospital mortality rate was 31.2% (n=72). Previous statin use did not affect in-hospital or 30-day mortality (OR 0.978; 95% CI 0.339 to 2.274; p=0.789). Creatinine levels on days 3 and 14 were substantially higher in statins group (1.80 ±1.39 vs. 1.45 ± 1.47 mg/dl) (p=0.010) and (1.42 ± 1.14 vs. 1.09 ± 1.05 mg/dl) (p=0.009), respectively. Prior use of statins did not reduce in-hospital or 30-day mortality in septic patients and it may be associated with impaired renal function in this group of Argentinian participants.


Unexpected high genetic diversity in small populations suggests maintenance by associative overdominance.
The effective population size (Ne ) is a central factor in determining maintenance of genetic variation. The neutral theory predicts that loss of variation depends on Ne , with less genetic drift in larger populations. We monitored genetic drift in 42 Drosophila melanogaster populations of different adult census population sizes (10, 50 or 500) using pooled RAD sequencing. In small populations, variation was lost at a substantially lower rate than expected. This observation was consistent across two ecological relevant thermal regimes, one stable and one with a stressful increase in temperature across generations. Estimated ratios between Ne and adult census size were consistently higher in small than in larger populations. The finding provides evidence for a slower than expected loss of genetic diversity and consequently a higher than expected long-term evolutionary potential in small fragmented populations. More genetic diversity was retained in areas of low recombination, suggesting that associative overdominance, driven by disfavoured homozygosity of recessive deleterious alleles, is responsible for the maintenance of genetic diversity in smaller populations. Consistent with this hypothesis, the X-chromosome, which is largely free of recessive deleterious alleles due to hemizygosity in males, fits neutral expectations even in small populations. Our experiments provide experimental answers to a range of unexpected patterns in natural populations, ranging from variable diversity on X-chromosomes and autosomes to surprisingly high levels of nucleotide diversity in small populations.


Cell cycle inhibitory protein p27 in esophageal squamous cell carcinoma.
p27 protein is one of the cdk inhibitors which regulates the progression from G1 to S phase of the cell cycle. Reduced expression of p27 protein has been reported to be correlated with poor clinical outcome in patients with various cancers. We performed immunohistochemistry of both p27 and Ki67 in 136 cases of resected human esophageal squamous cell carcinoma, and evaluated the association between p27 immunoreactivity and clinicopathological features including clinical outcome in these patients. We also examined the correlation between labeling index or the percentage of positive tumor cells for p27 and Ki67 in serial tissue sections in these cases. Cases with invasion of the muscularis propria or adventitia had significantly (p < 0.05) higher p27 LI (65.0 +/- 23.7) than those with invasion limited to mucosa or submucosa and those with carcinoma in situ (58.9 +/- 18.3). There were no significant correlations between p27 and other clinicopathological factors such as sex, age, tumor size, differentiation type, nodal status and histological stage. The cases with p27 LI below 40% tended to have a worse prognosis than those with p27 LI above 40%. There was no significant correlation between Ki67 and p27 LIs. Reduced expression of p27 may be correlated with the biological behavior of esophageal squamous cell carcinoma and may play an important role in the early stages of cancer.


Ankle foot orthoses in cerebral palsy: Effects of ankle stiffness on trunk kinematics, gait stability and energy cost of walking.
In children with cerebral palsy (CP), rigid ventral shell ankle-foot orthoses (vAFOs) are often prescribed to reduce excessive knee flexion in stance and lower the energy cost of walking (ECW). However, how vAFOs affect ECW is a complex issue, as vAFOs may have an impact on lower limb biomechanics, upper body movements, and balance. Besides, the vAFO's biomechanical effect have been shown to be dependent on its stiffness around the ankle joint. We examined whether vAFO stiffness influences trunk movements and gait stability in CP, and whether there is a relationship between these factors and ECW. Fifteen children with spastic CP were prescribed vAFOs. Stiffness was varied into a rigid, stiff and flexible configuration. At baseline (shoes-only) and for each vAFO stiffness configuration, 3D-gait analyses and ECW-tests were performed. From the gait analyses, we derived trunk tilt, lateroflexion, and rotation range of motion (RoM) and the mediolateral and anteroposterior Margins of Stability (MoS) and their variability as measures of gait stability. With the ECW-test we determined the netEC. We found that wearing vAFOs significantly increased trunk lateroflexion (Wald χ2 = 33.7, p < 0.001), rotation RoM (Wald χ2 = 20.5, p < 0.001) and mediolateral gait instability (Wald χ2 = 10.4, p = 0.016). The extent of these effects partly depended on the stiffness of the vAFO. Significant relations between trunk movements, gait stability and ECW were found r = 0.57-0.81, p < 0.05), which indicates that trunk movements and gait stability should be taken into account when prescribing vAFOs to improve gait in children with CP walking with excessive knee flexion.


The adverse events and hemodynamic effects of adenosine-based cardiac MRI.
We wanted to prospectively assess the adverse events and hemodynamic effects associated with an intravenous adenosine infusion in patients with suspected or known coronary artery disease and who were undergoing cardiac MRI. One hundred and sixty-eight patients (64 ± 9 years) received adenosine (140 µg/kg/min) during cardiac MRI. Before and during the administration, the heart rate, systemic blood pressure, and oxygen saturation were monitored using a MRI-compatible system. We documented any signs and symptoms of potential adverse events. In total, 47 out of 168 patients (28%) experienced adverse effects, which were mostly mild or moderate. In 13 patients (8%), the adenosine infusion was discontinued due to intolerable dyspnea or chest pain. No high grade atrioventricular block, bronchospasm or other life-threatening adverse events occurred. The hemodynamic measurements showed a significant increase in the heart rate during adenosine infusion (69.3 ± 11.7 versus 82.4 ± 13.0 beats/min, respectively; p < 0.001). A significant but clinically irrelevant increase in oxygen saturation occurred during adenosine infusion (96 ± 1.9% versus 97 ± 1.3%, respectively; p < 0.001). The blood pressure did not significantly change during adenosine infusion (systolic: 142.8 ± 24.0 versus 140.9 ± 25.7 mmHg; diastolic: 80.2 ± 12.5 mmHg versus 78.9 ± 15.6, respectively). This study confirms the safety of adenosine infusion during cardiac MRI. A considerable proportion of all patients will experience minor adverse effects and some patients will not tolerate adenosine infusion. However, all adverse events can be successfully managed by a radiologist. The increased heart rate during adenosine infusion highlights the need to individually adjust the settings according to the patient, e.g., the number of slices of myocardial perfusion imaging.


Social determinants of stage IV anal cancer and the impact of pelvic radiotherapy in the metastatic setting.
Anal cancer is a relatively rare malignancy, and a minority of patients present with metastatic disease in the United States. The National Cancer Database (NCDB) was used to identify factors associated with metastatic disease at presentation and evaluate the role of pelvic radiotherapy in these patients. The NCDB was queried for patients with squamous cell cancer of the anus diagnosed between 2004 and 2013. Patients were stratified by clinical stage at diagnosis, and a binary logistic regression model was created to identify factors associated with metastatic disease at diagnosis. A secondary metastatic cohort was generated and a multivariable Cox proportional hazards model was created to identify factors associated with improved survival. To validate findings, propensity-score matching was performed to generate a 1:1 paired dataset stratified by receipt of pelvic radiotherapy. The primary analysis cohort consisted of 28,500 patients. Facility location, male gender, and lack of insurance were confirmed as independent risk factors for metastatic disease. The metastatic cohort consisted of 1264 patients. Multivariable analysis confirmed female sex, possession of a private or Medicare insurance plan, pelvic radiotherapy, and chemotherapy as independent predictors of improved survival. A propensity-score matched cohort of 730 patients was generated. The median survival was 17.6 months in patients who received radiotherapy versus 14.5 months in those who did not (P < 0.01). In this cohort, male gender and lack of insurance were associated with metastatic disease at presentation. Furthermore, a significant benefit was associated with the use of pelvic radiotherapy. Future prospective research is warranted to confirm these findings.


J.G. Crowther's War: Institutional strife at the BBC and British Council.
Science writer, historian and administrator J.G. Crowther (1899-1983) had an uneasy relationship with the BBC during the 1920s and 1930s, and was regarded with suspicion by the British security services because of his left politics. Nevertheless the Second World War saw him working for 'establishment' institutions. He was closely associated with the BBC's Overseas Service and employed by the British Council's Science Committee. Both organizations found Crowther useful because of his wide, international knowledge of science and scientists. Crowther's political views, and his international aspirations for the British Council's Science Committee, increasingly embroiled him in an institutional conflict with the Royal Society and with its president, Sir Henry Dale, who was also chairman of the British Council's Science Committee. The conflict centred on the management of international scientific relations, a matter close Crowther's heart, and to Dale's. Dale considered that the formal conduct of international scientific relations was the Royal Society's business rather than the British Council's. Crowther disagreed, and eventually resigned from the British Council Science Committee in 1946. The article expands knowledge of Crowther by drawing on archival documents to elucidate a side of his career that is only lightly touched on in his memoirs. It shows that 'Crowther's war' was also an institutional war between the Science Committee of the British Council and the Royal Society. Crowther's unhappy experience of interference by the Royal Society plausibly accounts for a retreat from his pre-war view that institutional science should plan and manage BBC science broadcasts.


Agriculture in Africa - Telling myths from facts: A synthesis.
Stylized facts drive research agendas and policy debates. Yet robust stylized facts are hard to come by, and when available, often outdated. The 12 papers in this Special Issue revisit conventional wisdom on African agriculture and its farmers' livelihoods using nationally representative surveys from the Living Standards Measurement Study-Integrated Surveys on Agriculture Initiative in six African countries. At times they simply confirm our common understanding of the topic. But they also throw up a number of surprises, redirecting policy debates while fine-tuning others. Overall, the project calls for more attention to checking and updating our common wisdom. This requires nationally representative data, and sufficient incentives among researchers and policymakers alike. Without well-grounded stylized facts, they can easily be profoundly misguided.


Induction of caspase-11 by aspartyl proteinases of Candida albicans and implication in promoting inflammatory response.
We recently demonstrated that the secreted aspartyl proteinases (Saps), Sap2 and Sap6, of Candida albicans have the potential to induce the canonical activation of the NLRP3 inflammasome, leading to the secretion of interleukin-1β (IL-1β) and IL-18 via caspase-1 activation. We also observed that the activation of caspase-1 is partially independent from the NLRP3 activation pathway. In this study, we examined whether Sap2 and Sap6 are also able to activate the noncanonical inflammasome pathway in murine macrophages. Our data show that both Sap2 and Sap6 can activate caspase-11 through type I interferon (IFN) production. Caspase-11 cooperates to activate caspase-1, with a subsequent increase of IL-1β secretion. Endocytosis and internalization of Saps are required for the induction of type I IFN production, which is essential for induction of noncanonical inflammasome activation. Our study indicates a sophisticated interplay between caspase-1 and caspase-11 that connects the canonical and noncanonical pathways of inflammasome activation in response to C. albicans Saps.


Molecular genotyping of Candida species with special respect to Candida (Torulopsis) glabrata strains by arbitrarily primed PCR.
A set of 46 epidemiologically related or unrelated Candida (Torulopsis) glabrata isolates from four different medical centres in Germany and Hungary, and the type strain of this species, were genetically typed by arbitrarily primed PCR (AP-PCR). The resulting band patterns of C. glabrata strains were compared with those of other species of the genus Candida including C. albicans, C. guilliermondii, C. kefyr, C. parapsilosis, C. tropicalis and C. krusei. After preliminary trials of various reaction parameters and control experiments to test the reproducibility of this method, it was found that consistently reproducible amplification patterns were obtained only when rigorously optimised and standardised reaction conditions were employed. Discriminatory abilities were studied with 29 generated 10-mer oligonucleotides of different G+C content. Typing of clinical isolates with the optimised AP-PCR protocol was then performed with the primer 50-1, with a G+C content of 50%. Sufficiently discriminatory polymorphisms were observed among the band patterns of the Candida species included. The gel electrophoresis patterns of each species showed an adequate similarity. Variations in minor bands were characteristic for comparison at the isolate level. Only three AP-PCR genotypes were identified among the clinical isolates of C. glabrata tested. Two of these genotypes were closely related and appeared to be widespread within German and Hungarian isolates. The third genotype of C. glabrata showed a distinct band pattern. With optimised, validated and standardised assay conditions, the feasibility, sensitivity and rapidity of AP-PCR may offer a discriminatory method for genotyping of yeasts in epidemiological studies, as well as in the control of nosocomial infections.


Clinical outcomes of laparoscopic and endoscopic cooperative surgery for submucosal tumors on the esophagogastric junction: a retrospective single-center analysis.
Laparoscopic and endoscopic cooperative surgery (LECS) technique for gastric submucosal tumor (SMT) has developed, but treatment of SMT on the esophagogastric junction (EGJ) remains technically difficult because excessive resection may result in postoperative transformation of the EGJ and cause stenosis, and intervention to lower esophageal sphincter may result in gastroesophageal reflux. The study aim was to evaluate the feasibility and safety of LECS for SMT on the EGJ. Between September 2012 and December 2018, LECS was performed for 21 patients with SMTs on the EGJ. Fundoplication was performed after LECS according to the intraoperative findings for each case. The patients' backgrounds, operative outcomes, and follow-up data, including endoscopic findings of gastroesophageal reflux disease (GERD) and proton pomp inhibitor (PPI) use, were reviewed. In all 21 cases, LECS was completed with a mean operation time of 225 min, and a mean blood loss of 8.8 mL. All patients were alive without recurrence within the mean follow-up period of 30.5 months. Both GERD and PPI use tended to be less frequent when fundoplication was performed, although these differences were not statistically significant. (7.7% vs. 37.5%; P = 0.091, 23.1% vs. 50.0%; P = 0.204, respectively). We demonstrated the feasibility and safety of LECS for SMTs even on the EGJ. Fundoplication after LECS may be an approach for the prevention of postoperative reflux esophagitis. Future research is warranted to validate the efficacy of the addition of fundoplication.