Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10.
Pulmonary fibrosis is an enigmatic and devastating disease with few treatment options, now thought to result from abnormal wound healing in the lung in response to injury. We have previously noted a role for the chemokine interferon gamma-inducible protein of 10 kD (IP-10)/CXC chemokine ligand 10 in the regulation of cutaneous wound healing, and consequently investigated whether IP-10 regulates pulmonary fibrosis. We found that IP-10 is highly expressed in a mouse model of pulmonary fibrosis induced by bleomycin. IP-10-deficient mice exhibited increased pulmonary fibrosis after administration of bleomycin, suggesting that IP-10 limits the development of fibrosis in this model. Substantial fibroblast chemoattractant and proliferative activities were generated in the lung after bleomycin exposure. IP-10 significantly inhibited fibroblast responses to the chemotactic, but not the proliferative activity generated, suggesting that IP-10 may attenuate fibroblast accumulation in bleomycin-induced pulmonary fibrosis by limiting fibroblast migration. Consistent with this inhibitory activity of IP-10 on fibroblast migration, fibroblast accumulation in the lung after bleomycin exposure was dramatically increased in IP-10-deficient mice compared with wild-type mice. Conversely, transgenic mice overexpressing IP-10 were protected from mortality after bleomycin exposure, and demonstrated decreased fibroblast accumulation in the lung after challenge compared with wild-type mice. Our findings suggest that interruption of fibroblast recruitment may represent a novel therapeutic strategy for pulmonary fibrosis, which could have applicability to a wide range of fibrotic illnesses.


Effects of alcohol and blood alcohol concentration limb on sexual risk-taking intentions.
Although there have been numerous investigations of alcohol's relationship to sexual risk taking, the vast majority of these studies have not examined whether the biphasic nature of alcohol intoxication differentially influences risky sexual decisions. Thus, a laboratory study was conducted to investigate the effects of alcohol consumption and blood alcohol concentration (BAC) limb on sexual risk-taking intentions. Participants (N = 150; 51.3% male) were randomly assigned to consume alcoholic drinks (target peak BAC = .08%) or nonalcoholic drinks and then completed a hypothetical sexual risk assessment involving an opposite-gender new partner while on either the ascending BAC limb or descending BAC limb. Alcohol intoxication resulted in increased sexual risk-taking intentions indirectly through its influence on perceived intoxication and, subsequently, sexual arousal. An interaction of beverage condition and BAC limb condition indicated that alcohol's effects on perceived intoxication varied significantly by limb, with those on the ascending limb reporting greater perceived intoxication than those on the descending limb. Findings suggest that future research and prevention efforts would be better informed through a more comprehensive consideration of BAC limb effects on sexual risk behaviors. Moreover, results indicate that prevention programs should address in-the-moment states, such as perceived intoxication and sexual arousal, in interventions targeting risky sexual decision-making processes.


Evaluation and application of potential schistosome-associated morbidity markers within large-scale mass chemotherapy programmes.
A primary objective of schistosomiasis control programmes is to achieve, and hence also demonstrate, a quantifiable reduction in schistosome-associated morbidity as a consequence of chemotherapeutic intervention. Inherent within such an objective, it is necessary to define and validate direct and indirect indicators of schistosome-related morbidity. However, to define and thereby document such morbidity, and its reduction following treatment, may not be straightforward, particularly for intestinal schistosomiasis-induced morbidity, which is often not apparent in all but the most severe or chronic cases. Within all 'Schistosomiasis Control Initiative' activities, across selected sub-Saharan African countries since 2002, a range of standard and novel potential morbidity markers have been monitored and evaluated. Parasitological intensity measures, combined with haemoglobin/anaemia counts and ultrasonography, proved valuable schistosomiasis-related morbidity indicators, being both logistically practical and informative. Additional measures tested, such as albumin excretion profiles, were promising, and are subject to ongoing research, whilst some measures, such as distended stomach/umbilical circumference, anthropometrics and health questionnaires proved less reliable. These results serve to both illustrate the success of current control activities in reducing schistosome-induced morbidity, and to highlight key tools and techniques for continued application within ongoing and future mass drug administration programmes.


The New Forest Suicide Prevention Initiative (NFSPI).
A retrospective suicide study revealed that the Forestry Commission car parks in the New Forest in southern England were a previously unrecognized magnet for nonlocal suicides, attracting as high a proportion of "visitors" (35/43 in 1993-97) as among suicides who jumped from the cliffs at the infamous Beachy Head (39/48 in 1993-97). Over 95% of the car park suicides died from car exhaust gas poisoning. A multiagency initiative aimed to reduce the number of suicides in the 140 New Forest car parks where restricting access was impossible, and environmental issues paramount. Signs displaying the Samaritans' national telephone number were erected in the 26 car parks in which 50% of the car park suicides had occurred. Numbers, location, and residence of all car park deaths were monitored for 3 years. Corresponding changes in other forest registration districts were also monitored. During the 3-year intervention period the number of car park suicides fell significantly from 10/year, 1988-1997, to 3.3/year. The average annual total number of suicides in the New Forest registration district also decreased. No significant changes were found in comparable forest districts. The number of suicides in the New Forest car parks remained low during the 2 years following the evaluation.


IF1, a natural inhibitor of mitochondrial ATP synthase, is not essential for the normal growth and breeding of mice.
IF1 is an endogenous inhibitor protein of mitochondrial ATP synthase. It is evolutionarily conserved throughout all eukaryotes and it has been proposed to play crucial roles in prevention of the wasteful reverse reaction of ATP synthase, in the metabolic shift from oxidative phosphorylation to glycolysis, in the suppression of ROS (reactive oxygen species) generation, in mitochondria morphology and in haem biosynthesis in mitochondria, which leads to anaemia. Here, we report the phenotype of a mouse strain in which IF1 gene was destroyed. Unexpectedly, individuals of this IF1-KO (knockout) mouse strain grew and bred without defect. The general behaviours, blood test results and responses to starvation of the IF1-KO mice were apparently normal. There were no abnormalities in the tissue anatomy or the autophagy. Mitochondria of the IF1-KO mice were normal in morphology, in the content of ATP synthase molecules and in ATP synthesis activity. Thus, IF1 is not an essential protein for mice despite its ubiquitous presence in eukaryotes.


Inhibition of airway liquid secretion and its effect on the physical properties of airway mucus.
The combination of both Cl- and HCO3- secretion inhibitors causes an accumulation of mucins within the submucosal gland ducts of acetylcholine (ACh)-treated bronchi [S. K. Inglis, M. R. Corboz, A. E. Taylor, and S. T. Ballard. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L372-L377, 1997], suggesting indirectly that these agents block airway gland liquid secretion. The present study tested the hypotheses that ACh-stimulated liquid secretion is driven by Cl- and HCO3- secretion and that inhibition of this process leads to secretion of a dehydrated mucus with altered rheological properties. Excised distal bronchi from pigs were pretreated with either a combination of Cl- and HCO3- secretion inhibitors (bumetanide, acetazolamide, dimethylamiloride, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid) or the dimethyl sulfoxide vehicle and were then treated with ACh to induce secretion. The rate of mucus liquid secretion was substantially reduced when the airways were pretreated with the anion secretion inhibitors. Mucus liquid from inhibitor-pretreated airways contained almost threefold more nonvolatile solids than the control liquid. Rheological analysis revealed that mucus liquid from inhibitor-pretreated airways expressed a significantly greater log G* (rigidity factor), whereas tangent delta (recoil factor) was significantly reduced. These results suggest that 1) ACh-induced liquid secretion in bronchi is driven by both Cl- and HCO3- secretion and 2) inhibition of ACh-induced liquid secretion results in the secretion of mucus with a reduced water content and altered rheological properties.


The XPA-binding domain of ERCC1 is required for nucleotide excision repair but not other DNA repair pathways.
The endonuclease ERCC1-XPF incises the damaged strand of DNA 5' to a lesion during nucleotide excision repair (NER) and has additional, poorly characterized functions in interstrand cross-link repair, double-strand break repair, and homologous recombination. XPA, another key factor in NER, interacts with ERCC1 and recruits it to sites of damage. We identified ERCC1 residues that are critical for the interaction with XPA and assessed their importance for NER in vitro and in vivo. Mutation of two conserved residues (Asn-110 and Tyr-145) located in the XPA-binding site of ERCC1 dramatically affected NER but not nuclease activity on model DNA substrates. In ERCC1-deficient cells expressing ERCC1(N110A/Y145A), the nuclease was not recruited to sites of UV damage. The repair of UV-induced (6-4)photoproducts was severely impaired in these cells, and they were hypersensitive to UV irradiation. Remarkably, the ERCC1(N110A/Y145A) protein rescues the sensitivity of ERCC1-deficient cells to cross-linking agents. Our studies suggest that ERCC1-XPF engages in different repair pathways through specific protein-protein interactions and that these functions can be separated through the selective disruption of these interactions. We discuss the impact of these findings for understanding how ERCC1 contributes to resistance of tumor cells to therapeutic agents such as cisplatin.


Benign cerebellar astrocytomas of childhood.
Benign cerebellar astrocytomas of childhood are potentially surgically curable lesions. Histologically, these neoplasms can be divided into pilocytic and diffuse astrocytomas. Whether there is a difference in the recurrence rate between these two tumor types after a surgical resection is not clear. In addition, the role of immediate postoperative imaging in predicting a recurrence has not been established. To answer these questions, we have reviewed the charts of 23 patients with benign cerebellar astrocytomas treated at Childrens Hospital of Los Angeles over a 10-year period (1977-1987). Of the 23 tumors, 15 were pilocytic and 8 were diffuse. All patients underwent an attempted gross total surgical removal of the tumor, and all patients had a postoperative computed tomographic (CT) scan with and without intravenously administered contrast material performed within 72 hours of the operation. Based on the postoperative CT scan, 12 patients had residual tumors. Seven of the subtotally resected tumors were pilocytic (7 of 15), and 5 were diffuse (5 of 8). Interestingly, the surgeon believed that a gross total resection had been obtained in 9 of these patients. There have been 4 recurrences in these 23 patients, with a mean follow-up of 4.9 years. All recurrences were in patients with subtotal resections. Of the 11 patients with a total resection of the tumor, 7 developed a small rim of enhancement on subsequent scans an average of 5 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)


Humor and death: a qualitative study of The New Yorker cartoons (1986-2006).
American's experiences with dying and death have changed throughout the course of our history. As an agrarian society death, was seen first-hand on, often, a daily basis. Industrialization brought with it removal of the dying process to the hospital and burial became the responsibility of the undertaker. This separation of dying and death from society resulted in not only a physical barrier but a psychological one as well. Technology in health care once again raised issues of the dying process by asking people to make decisions about their health care in the realm of resuscitation, respirators, and the use of artificial food and fluids.One way that Americans have been known handle the difficult times in their lives is through humor. When it becomes difficult to cope, tears and laughter are both cathartic. This study analyzes cartoons from The New Yorker in an effort to categorize contemporary notions of death as well as establish the correlation between societal events related to dying and death and the overall percent of death-related cartoons in this media.


[Parameters of lipid metabolism during perimenopause and thyroid pathology].
A total of 210 perimenopausal women were examined. Lipid status was evaluated in groups of patients differing by thyroid function and characteristics of the perimenopausal period. Case histories were analyzed using a universal information chart. Serum levels of T3, T4, TTH, LH, FSH, PRL, E2, and progesterone were radioimmunoassayed. Blood lipid spectrum was evaluated on a Kone device (Finland) by special standard methods. High levels of cholesterol and triglycerides, a tendency to an increase in CH-LDL and CH-VLDL, a decrease in CH-HDL, and a high atherogenicity coefficient were detected in women with endemic goiter and hypothyrosis in comparison with perimenopausal women without thyroid disease. The highest levels of cholesterol, triglycerides, CH-LDL, and atherogenicity coefficient were detected in women with endemic goiter and climacteric syndrome, which suggests that hypothyrosis in the presence of climacteric syndrome aggravates disordered lipid metabolism.


Complete mapping of substrate translocation highlights the role of LeuT N-terminal segment in regulating transport cycle.
Neurotransmitter: sodium symporters (NSSs) regulate neuronal signal transmission by clearing excess neurotransmitters from the synapse, assisted by the co-transport of sodium ions. Extensive structural data have been collected in recent years for several members of the NSS family, which opened the way to structure-based studies for a mechanistic understanding of substrate transport. Leucine transporter (LeuT), a bacterial orthologue, has been broadly adopted as a prototype in these studies. This goal has been elusive, however, due to the complex interplay of global and local events as well as missing structural data on LeuT N-terminal segment. We provide here for the first time a comprehensive description of the molecular events leading to substrate/Na+ release to the postsynaptic cell, including the structure and dynamics of the N-terminal segment using a combination of molecular simulations. Substrate and Na+-release follows an influx of water molecules into the substrate/Na+-binding pocket accompanied by concerted rearrangements of transmembrane helices. A redistribution of salt bridges and cation-π interactions at the N-terminal segment prompts substrate release. Significantly, substrate release is followed by the closure of the intracellular gate and a global reconfiguration back to outward-facing state to resume the transport cycle. Two minimally hydrated intermediates, not structurally resolved to date, are identified: one, substrate-bound, stabilized during the passage from outward- to inward-facing state (holo-occluded), and another, substrate-free, along the reverse transition (apo-occluded).


Frequency-Selective Computed Tomography: Applications During Periodic Thoracic Motion.
We seek to use computed tomography (CT) to characterize regional lung parenchymal deformation during high-frequency and multi-frequency oscillatory ventilation. Periodic motion of thoracic structures results in artifacts of CT images obtained by standard reconstruction algorithms, especially for frequencies exceeding that of the X-ray source rotation. In this paper, we propose an acquisition and reconstruction technique for high-resolution imaging of the thorax during periodic motion. Our technique relies on phase-binning projections according to the frequency of subject motion relative to the scanner rotation, prior to volumetric reconstruction. The mathematical theory and limitations of the proposed technique are presented, and then validated in a simulated phantom as well as a living porcine subject during oscillatory ventilation. The 4-D image sequences obtained using this frequency-selective reconstruction technique yielded high-spatio-temporal resolution of the thorax during periodic motion. We conclude that the frequency-based selection of CT projections is ideal for characterizing dynamic deformations of thoracic structures that are ordinarily obscured by motion artifact using conventional reconstruction techniques.


Neanderthal medics? Evidence for food, cooking, and medicinal plants entrapped in dental calculus.
Neanderthals disappeared sometime between 30,000 and 24,000 years ago. Until recently, Neanderthals were understood to have been predominantly meat-eaters; however, a growing body of evidence suggests their diet also included plants. We present the results of a study, in which sequential thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) and pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) were combined with morphological analysis of plant microfossils, to identify material entrapped in dental calculus from five Neanderthal individuals from the north Spanish site of El Sidrón. Our results provide the first molecular evidence for inhalation of wood-fire smoke and bitumen or oil shale and ingestion of a range of cooked plant foods. We also offer the first evidence for the use of medicinal plants by a Neanderthal individual. The varied use of plants that we have identified suggests that the Neanderthal occupants of El Sidrón had a sophisticated knowledge of their natural surroundings which included the ability to select and use certain plants.


A 16.7 kb deletion in Sipa1l3 is associated with juvenile cataract in mice.
Congenital or juvenile cataract is a disease condition in which opacification of the lenses is present at birth or manifests early in life. It has been attributed to different monogenic factors with a high degree of heterogeneity and is often studied using mouse models. A spontaneous mutation was identified in a mouse line selected for heat loss that influenced lens formation and resulted in juvenile cataracts in mice homozygous for the recessive allele. Genetic dissection of this selection line by combining high-density genotypes and homozygosity mapping uncovered a 906 kb fragment on MMU7 encompassing 21 SNPs split into two groups of consecutive, homozygous segments specific to the cataract phenotype. Haplotype analysis revealed a 197.5 kb segment unique to cataract-affected mice that included a single known transcript consisting of the first 14 exons of Sipa1l3. In this region, we discovered a deletion of 1114 bp at the mRNA level, spanning four coding exons, predicted to produce a truncated Sipa1l3 protein lacking a portion of a Rap-GAP domain and two other potentially vital domains. At the genome level, the deletion consisted of 16,733 bp. Genotyping across different samples confirmed that only affected mice were homozygous for the deletion and normal mice were either heterozygous or homozygous for the wild-type allele. Further studies will be required to determine the impact of the truncated Sipa1l3 domains on eye development.


Registration of translated and rotated images using finite fourier transforms.
A well-known method for image registration is based on a conventional correlation between phase-only, or whitened, versions of the two images to be realigned. The method, covering rigid translational movements, is characterized by an outstanding robustness against correlated noise and disturbances, such as those encountered with nonuniform, time varying illumination. This correspondence discusses an extension of the method to cover both translational and rotational movements.


Proliferation and polarity in breast cancer: untying the Gordian knot.
Epithelial cancers are associated with genomic instability and alterations in signaling pathways that affect proliferation, apoptosis, and integrity of tissue structure. Overexpression of a number of oncogenic protein kinases has been shown to malignantly transform cells in culture and to cause tumors in vivo, but the interconnected signaling events induced by transformation still awaits detailed dissection. We propose that the network of cellular signaling pathways can be classified into functionally distinct branches, and that these pathways are rewired in transformed cells and tissues after they lose tissue-specific architecture to favor tumor expansion and invasion. Using three-dimensional (3D) culture systems, we recently demonstrated that polarity and proliferation of human mammary epithelial cancer cells were separable consequences of signaling pathways downstream of PI3 kinase. These, and results from a number of other laboratories are beginning to provide insight into how different signaling pathways may become interconnected in normal tissues to allow homeostasis, and how they are disrupted during malignant progression.


Induction of matrix metalloproteinase-13 gene expression by TNF-alpha is mediated by MAP kinases, AP-1, and NF-kappaB transcription factors in articular chondrocytes.
Tumor necrosis factor alpha (TNF-alpha), a major proinflammatory cytokine, induces arthritic joint inflammation and resorption of cartilage by matrix metalloproteinase-13 (MMP-13). RNA for MMP-13 is increased in human arthritic femoral cartilage. Mechanisms of this induction were investigated by pretreating primary human osteoarthritic (OA) femoral head chondrocytes or chondrosarcoma cells with the potential inhibitors of TNF-alpha signal transduction and downstream target transcription factors followed by stimulation with TNF-alpha and analysis of MMP-13 RNA/protein. TNF-alpha rapidly activated phosphorylation of extracellular signal-regulated kinases (ERKs), p38, and c-jun N-terminal kinase (JNK) mitogen-activated protein (MAP) kinases in human chondrocytes. Inhibitors of ERK (U0126, PD98059, and ERK1/2 antisense phosphorothioate oligonucleotide), JNK (SB203580, SP600125, and curcumin), and p38 (SB203580 and SB202190) pathways down-regulated the TNF-stimulated expression of MMP-13. Inhibitors of the transcription factors AP-1 (nordihydroguaiaretic acid, NDGA) and NF-kappaB (curcumin, proteasome inhibitors, and Bay-11-7085) suppressed TNF-alpha-induced MMP-13 expression in primary chondrocytes and SW1353 cells. These results suggest that induction of the MMP-13 gene by TNF-alpha is mediated by ERK, p38, and JNK MAP kinases as well as AP-1 and NF-kappaB transcription factors. Blockade of TNF-alpha signaling and its target transcription factors by the approaches tested here may be beneficial for reducing cartilage breakdown by MMP-13 in arthritis.


Optimal Join Algorithms Meet Top-k.
Top-k queries have been studied intensively in the database community and they are an important means to reduce query cost when only the "best" or "most interesting" results are needed instead of the full output. While some optimality results exist, e.g., the famous Threshold Algorithm, they hold only in a fairly limited model of computation that does not account for the cost incurred by large intermediate results and hence is not aligned with typical database-optimizer cost models. On the other hand, the idea of avoiding large intermediate results is arguably the main goal of recent work on optimal join algorithms, which uses the standard RAM model of computation to determine algorithm complexity. This research has created a lot of excitement due to its promise of reducing the time complexity of join queries with cycles, but it has mostly focused on full-output computation. We argue that the two areas can and should be studied from a unified point of view in order to achieve optimality in the common model of computation for a very general class of top-k-style join queries. This tutorial has two main objectives. First, we will explore and contrast the main assumptions, concepts, and algorithmic achievements of the two research areas. Second, we will cover recent, as well as some older, approaches that emerged at the intersection to support efficient ranked enumeration of join-query results. These are related to classic work on k-shortest path algorithms and more general optimization problems, some of which dates back to the 1950s. We demonstrate that this line of research warrants renewed attention in the challenging context of ranked enumeration for general join queries.


[Features of methodology for the formation of standard operational procedure in the practice of bureau of forensic medical expertise].
To analyze and summarize data on formation and implementation in practice of standard operational procedures for developing algorithm to improve the quality management system of bureau of forensic medical expertise. Normative legal documents regulating principles of standardization in healthcare were studied. Literature was analyzed in PubMed, Google Scholar, eLIBRARY search engines in English and Russian languages on the issues of development and implementation of standard operational procedures in practice. Data on using standard operational procedures as a standardization element in medical practice have been analyzed and generalized. Specific proposals for developing system of standard operational procedures, based on general principles for the creation of such documents, in forensic medical expert institutions have been proposed. Suggested recommendations can be used in practice to develop new common standard operational procedures.


In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.
The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard.


A review on robotic fish enabled by ionic polymer-metal composite artificial muscles.
A novel actuating material, which is lightweight, soft, and capable of generating large flapping motion under electrical stimuli, is highly desirable to build energy-efficient and maneuverable bio-inspired underwater robots. Ionic polymer-metal composites are important category of electroactive polymers, since they can generate large bending motions under low actuation voltages. IPMCs are ideal artificial muscles for small-scale and bio-inspired robots. This paper takes a system perspective to review the recent work on IPMC-enabled underwater robots, from modeling, fabrication, and bio-inspired design perspectives. First, a physics-based and control-oriented model of IPMC actuator will be reviewed. Second, a bio-inspired robotic fish propelled by IPMC caudal fin will be presented and a steady-state speed model of the fish will be demonstrated. Third, a novel fabrication process for 3D actuating membrane will be introduced and a bio-inspired robotic manta ray propelled by two IPMC pectoral fins will be demonstrated. Fourth, a 2D maneuverable robotic fish propelled by multiple IPMC fin will be presented. Last, advantages and challenges of using IPMC artificial muscles in bio-inspired robots will be concluded.


Atraumatic osteonecrosis of the knee.
The purposes of this study were to define the clinical, demographic, and radiographic patterns of atraumatic osteonecrosis of the distal part of the femur and the proximal part of the tibia at presentation and to report the outcome of treatment of this condition. Two hundred and forty-eight knees in 136 patients who were younger than the age of fifty-five years were treated at our institution between July 1, 1974, and September 15, 1998, for atraumatic osteonecrosis of the distal part of the femur or the proximal part of the tibia, or both. Demographic and radiographic features were characterized. The results of nonoperative treatment, core decompression, arthroscopic debridement, and total knee arthroplasty were evaluated. There were 106 female patients and thirty male patients, and their mean age was thirty-six years (range, fifteen to fifty-four years) at the time of diagnosis. One hundred and one patients (74 percent) had involvement of other large joints, with eighteen (13 percent) presenting initially with knee symptoms. One hundred and one patients (74 percent) had a disease that affected the immune system; sixty-seven of them had systemic lupus erythematosus. One hundred and twenty-three patients (90 percent) had a history of corticosteroid use. Technetium-99m bone-scanning missed lesions in sixteen (29 percent) of fifty-six knees. Eight (20 percent) of forty-one initially symptomatic knees treated nonoperatively had a successful clinical outcome (a Knee Society score of at least 80 points and no additional surgery) at a mean of eight years. The knees that remained severely symptomatic for three months were treated with either core decompression (ninety-one knees) or total knee arthroplasty (seven knees). Seventy-two (79 percent) of the ninety-one knees treated with core decompression had a good or excellent clinical outcome at a mean of seven years. Efforts to avoid total knee arthroplasty with repeat core decompression or arthroscopic debridement led to a successful outcome in fifteen (60 percent) of twenty-five knees. Thirty-four (71 percent) of forty-eight knees treated with total knee arthroplasty had a successful clinical outcome at a mean of nine years. Atraumatic osteonecrosis of the knee predominantly affects women, and in our study it was associated with corticosteroid use in 90 percent of the patients. Evaluation should include standard radiographic and magnetic resonance imaging of all symptomatic joints. Prognosis was negatively related to large juxta-articular lesions. Nonoperative treatment should be reserved for asymptomatic knees only. Core decompression was successful (a Knee Society score of at least 80 points and no additional surgery) in 79 percent of the knees in which the disease was in an early stage. Total knee arthroplasty was successful in only 71 percent of the knees.


Coronary artery disease surveillance among childhood, adolescent and young adult cancer survivors: A systematic review and recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.
Coronary artery disease (CAD) is a concerning late outcome for cancer survivors. However, uniform surveillance guidelines are lacking. To harmonise international recommendations for CAD surveillance for survivors of childhood, adolescent and young adult (CAYA) cancers. A systematic literature review was performed and evidence graded using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Eligibility included English language studies, a minimum of 20 off-therapy cancer survivors assessed for CAD, and 75% diagnosed prior to age 35 years. All study designs were included, and a multidisciplinary guideline panel formulated and graded recommendations. 32 of 522 identified articles met eligibility criteria. The prevalence of CAD ranged from 0 to 72% and was significantly increased compared to control populations. The risk of CAD was increased among survivors who received radiotherapy exposing the heart, especially at doses ≥15 Gy (moderate-quality evidence). The guideline panel agreed that healthcare providers and CAYA cancer survivors treated with radiotherapy exposing the heart should be counselled about the increased risk for premature CAD. While the evidence is insufficient to support primary screening, monitoring and early management of modifiable cardiovascular risk factors are recommended. Initiation and frequency of surveillance should be based on the intensity of treatment exposures, family history, and presence of co-morbidities but at least by age 40 years and at a minimum of every 5 years. All were strong recommendations. These systematically assessed and harmonised recommendations for CAD surveillance will inform care and guide research concerning this critical outcome for CAYA cancer survivors.


Prognostic factors for splenectomy response in adult idiopathic thrombocytopenic purpura.
The prognostic factors for splenectomy response were evaluated in 40 adult patients with idiopathic thrombocytopenic purpura (ITP). We defined the corticosteroid response on the basis of the platelet count after seven to ten days of therapy, rather than at some time after discontinuing corticosteroid agents, as previously reported in the literature. Initial corticosteroid response was statistically significant in predicting splenectomy response; age and sex were marginally significant; duration of symptoms and spleen weight were not predictive. Of 30 patients with a minor or complete response to corticosteroids, 28 (93%) responded to splenectomy; of ten patients unresponsive to corticosteroids only four (40%) responded to splenectomy (P less than .001). Eighty-two percent of the patients in the complete responder group are projected to be continually relapse-free at 96 months. Only one of the patients in this group died; the nonresponders to splenectomy had a median survival of only ten months.


Effects of ceranib-2 on cell survival and TNF-alpha in colon cancer cell line.
The aim of this study was to investigate the effects of a novel anti-cancer drug, ceranib-2, which targets the acid ceramidase, in human colon cancer cell line. The cell lines were treated with 50 µM of ceranib-2. Relative mRNA expression of TNF-alpha, TNF-R1 and ASAH were assessed by quantitative RT-PCR. Ceranib-2 reduced cell viability in a dose-dependent manner and the apoptotic values of cells following treatment with the dose of 50 µM were reduced significantly both at 24 h and 48 h compared to the control cells (p < 0.001). TNF-alpha receptor 1 (TNF-R1) mRNA levels were reduced significantly in the cell lines treated with both 25 µM and 50 µM of ceranib-2 for 24 h compared to the control cells (p < 0.05), whereas the difference between the treatment and the control cell lines diminished at 48 h. The human acid ceramidase gene (ASAH) mRNA levels were significantly higher in the cell lines treated with 50 µM of ceranib-2 for 48 h than in the other cell lines (p < 0.001). The study shows that ceranib-2 increased apoptosis by inducing ASAH expression and reduced TNF-R1 expression in human colon cancer cell lines in a dose and time-dependent manner (Fig. 3, Ref. 17).


Comparison of the Effect of Fluoride Varnish, Chlorhexidine Varnish and Casein Phosphopeptide- Amorphous Calcium Phosphate (CPP-ACP) Varnish on Salivary Streptococcus mutans Level: A Six Month Clinical Study.
Dental caries is the most widespread disease which has a multi factorial origin. Streptococcus mutans is considered to be the chief pathogen in its development. Different varnishes are available which can be used for the prevention of the carious process. To compare the effect of fluoride varnish, chlorhexidine varnish and fluoride varnish containing Casein Phosphopeptide - Amorphous Calcium Phosphate (CPP-ACP) on salivary Streptococcusmutans count in children with mixed dentition over a period of six months. Seventy two children of age 6-12 years with mixed dentition were selected fulfilling inclusion and exclusion criteria and divided into three groups: Group I- Fluoride varnish group; Group II- Chlorhexidine varnish group; Group III- MI varnish (fluoride varnish containing CPP-ACP) group. After thorough oral prophylaxis and restorative treatment the varnishes were applied to the teeth once a week for four consecutive weeks in the respective groups. Salivary Streptococcus mutans count (CFU/ml of saliva) was estimated at baseline, 1 month, 3 months and 6 months after varnish application. Bonferroni post-hoc test and paired t-test for inter group and intra group comparison was used in the study. A statistically significant reduction in salivary S. mutans colony count was seen with all three groups at all the different time intervals. Maximum reduction was noted in chlorhexidine varnish group at all the intervals after varnish application. Prevention of dental caries plays a vital role in paediatric dental practice. The use of dental varnish has proved to be effective in reducing the dental caries. Chlorhexidine varnish was found to show maximum reduction in salivary S. mutans count for six month period, when compared to MI varnish and fluoride varnish. Thus, chlorhexidine varnish can be used as potent caries inhibiting agent and promote good oral health.


[Responsibilities of oral health technician in the family health strategy in Minas Gerais, Brazil].
The scope of this article is to analyze the self-reporting of duties performed by the Oral Health Technicians in the State of Minas Gerais. A cross-sectional descriptive study was conducted through telephone interviews, with a representative sample of 231 workers. The descriptive analysis involved the calculation of proportions. It was found that 71.6% (95% CI, 64.4 to 77.5) performed coronal polishing, 63.2% (95% CI, 56.1 to 69.7) carried out scaling of dental calculus and 14.7% (95% CI, 10.3 to 15.4) inserted restorative materials. Regarding preventive/collective actions, 100% (95% CI, 97.6 to 100.0) participated in educational activities, 99% (95% CI, 96.1 to 99.8) demonstrated oral hygiene techniques, 96.6% (95% CI, 92.7 to 98.4) administrated topical fluoride, 77.9% (95% CI, 71.5 to 83.3) made home visits, and 96.6 % (95% CI, 92.7 to 98.4) performed collective actions, especially in schools. Oral Health Technicians have spent their more time on preventive/collective activities than on individual clinical care.


Social network composition and sexual risk-taking among gay and bisexual men in Atlanta, GA.
Social network composition is known to effect patterns of reported sexual risk-taking among men who have sex with men (MSM); however, consensus as to the directionality and size of these effects is lacking. We examined the relationships between novel aspects of social network composition and sexual risk-taking using a cross-sectional survey of 870 MSM. Social network composition was found to have mixed effects on reported sexual risk-taking: reporting proportionally more lesbian, gay, or bisexual (LGB)-identified friends and reporting friends who were on average significantly older than the respondent were both associated with reporting increased sexual risk, while reporting proportionally more LGB-identified friends in relationships and reporting a social network proportionally more aware of the respondent's homosexuality/bisexuality were both associated with reporting decreased sexual risk. The support structures created by differing social network compositions-and particularly the presence of LGB couples-may be a potential area for targeting sexual risk-reduction interventions for MSM.


Histone hyperacetylation is associated with amelioration of experimental colitis in mice.
Inhibitors of histone deacetylases (HDAC) are being studied for their antiproliferative effects in preclinical cancer trials. Recent studies suggest an anti-inflammatory role for this class of compounds. Because inflammatory bowel disease is associated with an increased risk of malignancies, agents with antiproliferative and anti-inflammatory properties would be of therapeutic interest. HDAC inhibitors from various classes were selected and evaluated for their in vitro capacity to suppress cytokine production and to induce apoptosis and histone acetylation. Valproic acid (VPA) and suberyolanilide hydroxamic acid (SAHA) were chosen for further studies in dextran sulfate sodium- and trinitrobenzene sulfonic acid-induced colitis in mice. In vitro, inhibition of HDAC resulted in a dose-dependent suppression of cytokine synthesis and apoptosis induction requiring higher concentrations of HDAC inhibitors for apoptosis induction compared with cytokine inhibition. Oral administration of either VPA or SAHA reduced disease severity in dextran sulfate sodium-induced colitis. The macroscopic and histologic reduction of disease severity was associated with a marked suppression of colonic proinflammatory cytokines. In parallel to the beneficial effect observed, a dose-dependent increase in histone 3 acetylation at the site of inflammation was shown under VPA treatment. Furthermore, SAHA as well as VPA treatment resulted in amelioration of trinitrobenzene sulfonic acid-induced colitis, which was associated with an increase of apoptosis of lamina propria lymphocytes. Inhibitors of HDAC reveal strong protective effects in different models of experimental colitis by inducing apoptosis and suppressing proinflammatory cytokines, thereby representing a promising class of compounds for clinical studies in human inflammatory bowel disease.


Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential.
The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide, an FDA-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as SARS-CoV, MERS-CoV, ZIKV, HCV, and human adenovirus, indicating its potential as an antiviral agent. In this brief review, we summarize the broad antiviral activity of niclosamide and highlight its potential clinical use in the treatment of COVID-19.


Does preoperative American Society of Anesthesiologists score relate to complications after total shoulder arthroplasty?
For hip and knee arthroplasties, an American Society of Anesthesiologists (ASA) score greater than 2 is associated with an increased risk of medical and surgical complications. No study, to our knowledge, has evaluated this relationship for total shoulder arthroplasty (TSA) or reverse total shoulder arthroplasty (reverse TSA). We aimed to assess the relationship between the ASA score and (1) surgical complications, (2) medical complications, and (3) hospitalization length after TSA, reverse TSA, and revision arthroplasty. We retrospectively analyzed all patients who had undergone TSAs, reverse TSAs, or revision arthroplasties by the senior author (EGM) from November 1999 through July 2011 who had at least 6 months' followup. Of the 485 procedures, 452 (93.2%) met the inclusion criteria. Data were collected on patient demographics, comorbidities, hospitalization length, and short-term (≤ 6 months) medical and surgical complications. Logistic regression analysis modeled the risk of having postoperative complications develop as a function of the ASA score. Patients with an ASA score greater than 2 had a greater risk of having a surgical complication develop (p < 0.001; OR, 2.27; 95% CI, 1.36-3.70) and three times the risk of prosthesis failure (ie, component dislocation, component loosening, and hardware failure) (p < 0.001; OR, 3.23; 95% CI, 1.54-6.67). Higher ASA scores were associated with prolonged length of hospitalization (effect size 0.46, p < 0.001), but not medical complications. ASA score is associated with surgical, but not medical, complications after TSA and reverse TSA. The ASA score could be used for risk assessment and preoperative counseling. Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.


Can mutual health organisations influence the quality and the affordability of healthcare provision? The case of the Democratic Republic of Congo.
In their mission to achieve better access to quality healthcare services, mutual health organisations (MHOs) are not limited to providing health insurance. As democratically controlled member organisations, MHOs aim to make people's voices heard. At national level, they seek involvement in the design of social protection policies; at local level, they seek to improve responsiveness of healthcare services to members' needs and expectations. In this qualitative study, we investigated whether MHOs in the Democratic Republic of Congo (DRC) succeed in defending members' rights by improving healthcare quality while minimising expenses. The data originate from an earlier in-depth investigation conducted in the DRC in 2016 of the performance of 13 MHOs. We re-analysed this existing dataset and more specifically investigated actions that the MHOs undertook to improve quality and affordability of healthcare provision for their members, using a framework for analysis based on Hirschman's exit-voice theory. This framework distinguishes four mechanisms for MHO members to use in influencing providers: (1) 'exit' or 'voting with the feet'; (2) 'co-producing a long voice route' or imposing rules through strategic purchasing; (3) 'guarding over the long voice route of accountability' or pressuring authorities to regulate and enforce regulations; and (4) 'strengthening the short voice route' by transforming the power imbalance at the provider-patient interface. All studied MHOs used these four mechanisms to improve healthcare provision. Most healthcare providers, however, did not recognise their authority to do so. In the DRC, controlling quality and affordability of healthcare is firmly seen as a role for the health authorities, but the authorities only marginally take up this role. Under current circumstances, the power of MHOs in the DRC to enhance quality and affordability of healthcare is weak. On their own, mutual health organisations in the DRC do not have sufficient power to influence the practices of healthcare providers. Greater responsiveness of the health services to MHO members requires cooperation of all actors involved in healthcare delivery to create an enabling environment where voices defending people's rights are heard.


DNA metabarcoding focused on difficult-to-culture protists: An effective approach to clarify biological interactions.
DNA metabarcoding on a single organism is a promising approach to clarify the biological interactions (e.g., predator-prey relationships and symbiosis, including parasitism) of difficult-to-culture protists. To evaluate the effectiveness of this method, Radiolaria and Phaeodaria, which are ecologically important protistan groups, were chosen as target taxa. DNA metabarcoding on a single organism focused on the V9 region of the 18S rRNA gene revealed potential symbionts, parasites and food sources of Radiolaria and Phaeodaria. Previously reported hosts and symbionts (parasites) were detected, and newly recognized combinations were also identified. The contained organisms largely differed between Radiolaria and Phaeodaria. In Radiolaria, members of the same order tended to contain similar organisms, and the taxonomic composition of possible symbionts, parasites, and food sources was fixed at the species level. Members of the same phaeodarian family, however, did not contain similar organisms, and body part (i.e., the central capsule or the phaeodium) was the most important factor that divided the taxonomic composition of detected organisms, implying that the selection of appropriate body part is important when trying to ascertain contained organisms, even for unicellular zooplankton. Our results show that DNA metabarcoding on a single organism is effective in revealing the biological interactions of difficult-to-culture protists.


Inactivation of urease by 1,4-benzoquinone: chemistry at the protein surface.
The high activity of urease, a Ni(ii) enzyme, has several adverse effects on human health and agriculture, and its modulation needs the use of inhibitors. 1,4-Benzoquinone (BQ) irreversibly inactivates Sporosarcina pasteurii urease (SPU), with first order kinetics for both the inhibitor and the enzyme. This reaction is stoichiometrically quenched in the presence of sulphite. The 2.07 Å crystal structure of SPU bound to BQ shows the presence of a 1,4-hydroquinone moiety covalently bound to the thiol group of αCys322, a key residue found on the mobile flap regulating the substrate access to the active site. The 1.75 Å crystal structure obtained when sulphite is added to a solution of SPU previously incubated with BQ shows the presence of a 2,5-dihydroxy-benzenesulphonate moiety bound to the αCys322 thiol group. These data reveal how the active site cysteine reacts with a prototypical BQ moiety, found in a large number of natural substances potentially suitable to control the urease activity.


Bacillus thuringiensis Cry1Da_7 and Cry1B.868 Protein Interactions with Novel Receptors Allow Control of Resistant Fall Armyworms, Spodoptera frugiperda (J.E. Smith).
Two new modified Bacillus thuringiensis (Bt) proteins, Cry1Da_7 and Cry1B.868, with activity against fall armyworms (FAW), Spodoptera frugiperda (J.E. Smith), were evaluated for their potential to bind new insect receptors compared to proteins currently deployed as plant-incorporated protectants (PIPs) in row crops. Results from resistant insect bioassays, disabled insecticidal protein (DIP) bioassays, and cell-based assays using insect cells expressing individual receptors demonstrate that receptor utilizations of the newly modified Cry1Da_7 and Cry1B.868 proteins are distinct from each other and from those of commercially available Bt proteins such as Cry1F, Cry1A.105, Cry2Ab, and Vip3A. Accordingly, these two proteins target different insect proteins in FAW midgut cells and when pyramided together should provide durability in the field against this economically important pest.IMPORTANCE There is increased concern with the development of resistance to insecticidal proteins currently expressed in crop plants, especially against high-resistance-risk pests such as fall armyworm (FAW), Spodoptera frugiperda, a maize pest that already has developed resistance to Bacillus thuringiensis (Bt) proteins such as Cry1F. Lepidopteran-specific proteins that bind new insect receptors will be critical in managing current Cry1F-resistant FAW and delaying future resistance development. Results from resistant insect assays, disabled insecticidal protein (DIP) bioassays, and cell-based assays using insect cells expressing individual receptors demonstrate that target receptors of the Cry1Da_7 and Cry1B.868 proteins are different from each other and from those of commercially available Bt proteins such as Cry1F, Cry1A.105, Cry2Ab, and Vip3A. Therefore, pyramiding these two new proteins in maize will provide durable control of this economically important pest in production agriculture.


Advanced Flame Spray Pyrolysis (FSP) Technologies for Engineering Multifunctional Nanostructures and Nanodevices.
Flame spray pyrolysis (FSP) is an industrially scalable technology that enables the engineering of a wide range of metal-based nanomaterials with tailored properties nanoparticles. In the present review, we discuss the recent state-of-the-art advances in FSP technology with regard to nanostructure engineering as well as the FSP reactor setup designs. The challenges of in situ incorporation of nanoparticles into complex functional arrays are reviewed, underscoring FSP's transformative potential in next-generation nanodevice fabrication. Key areas of focus include the integration of FSP into the technology readiness level (TRL) for nanomaterials production, the FSP process design, and recent advancements in nanodevice development. With a comprehensive overview of engineering methodologies such as the oxygen-deficient process, double-nozzle configuration, and in situ coatings deposition, this review charts the trajectory of FSP from its foundational roots to its contemporary applications in intricate nanostructure and nanodevice synthesis.


Protective effects of fucoidan against ethanol-induced liver injury through maintaining mitochondrial function and mitophagy balance in rats.
For alcoholic liver disease (ALD), mitophagy has been reported as a promising therapeutic strategy to alleviate the hepatic lesion elicited by ethanol. This study was conducted to investigate the regulatory effects of fucoidan on mitophagy induced by chronic ethanol administration in rats. Here, 20 male rats in each group were treated with fucoidan (150 and 300 mg per kg body weight) by gavage once daily. Up to 56% liquor (7 to 9 mL per kg body weight) was orally administered 1 h after the fucoidan treatment for 20 weeks. The results showed that chronic ethanol consumption elevated the levels of hepatic enzymes (ALT, AST, and GGT) and triglyceride (TG) contents, with liver antioxidant enzymes being decreased and lipid peroxidation products increased and thus initiating the mitochondria-induced endogenous apoptotic pathway. Furthermore, ethanol-induced excessive oxidative stress inhibited the function of mitochondria and promoted damaged mitochondria accumulation which stimulated the PTEN-induced putative kinase 1 (PINK1) and Parkin associated mitophagic pathway in the liver. In contrast, the fucoidan pretreatment alleviated ethanol-induced histopathological changes, disorders of lipid metabolism, and oxidative damage with mitophagy related proteins and mitochondrial dynamics-related proteins namely mitochondrial E3 ubiquitin ligase 1 (Mul1), mitofusin2 (Mfn2) and dynamin-related protein 1 (Drp1) being restored to a normal level. In summary, our findings suggest that fucoidan pretreatment protects against ethanol-induced damaged mitochondria accumulation and over-activated mitophagy, which plays a pivotal role in maintaining mitochondrial homeostasis and ensuring mitochondrial quality.


Variability of arginine content and yield components in Valencia peanut germplasm.
Peanut seeds are rich in arginine, an amino acid that has several positive effects on human health. Establishing the genetic variability of arginine content in peanut will be useful for breeding programs that have high arginine as one of their goals. The objective of this study was to evaluate the variation of arginine content, pods/plant, seeds/pod, seed weight, and yield in Valencia peanut germplasm. One hundred and thirty peanut genotypes were grown under field condition for two years. A randomized complete block design with three replications was used for this study. Arginine content was analyzed in peanut seeds at harvest using spectrophotometry. Yield and yield components were recorded for each genotype. Significant differences in arginine content and yield components were found in the tested Valencia peanut germplasm. Arginine content ranged from 8.68-23.35 μg/g seed. Kremena was the best overall genotype of high arginine content, number of pods/plant, 100 seed weight and pod yield.


From College Graduate to Physician: Professional Identity Formation.
This article was migrated. The article was marked as recommended. A newly matriculated medical student must transition from college student to physician in four short years. The call has been made to help students in this transition. There is little data on how this can occur and how the system of medical education can guide students. We set out to describe and understand medical students' process of professional identity formation (PIF) longitudinally from first-year to fourth-year students. Using a qualitative thematic analysis of 58 survey responses from the anatomy dissection laboratory (1st and 2nd year students), 78 clerkship reflective practice essays (3rd year students), and 26 survey responses to a realistic field exercise (4th year students) we developed a grounded theory: We found four developmental/transformational stages (Building, Becoming, Bridging, and Being) in PIF of a physician with the end result that the physician is confident, resilient, and embraces his/her identity. Additionally, there were three longitudinal supports identified that faculty provide: promoting self-reflection, promoting mastery of difficult tasks, and being available. Successful transition is tied to transformational experiences that with the faculty support propel the student toward PIF. These findings serve as a framework for medical educators to develop a curriculum that supports positive PIF in medical students.


Automatic Localization of the Scleral Spur Using Deep Learning and Ultrasound Biomicroscopy.
The purpose of this study was to develop a convolutional neural network (CNN) for automated localization of the scleral spur in ultrasound biomicroscopy (UBM) images of open-angle eyes. UBM images were acquired, and one glaucoma specialist provided reference coordinates of scleral spur locations in all images. A CNN model based on the EfficientNetB3 architecture was developed to detect the scleral spur in each image. The prediction errors and Euclidean distance were used to evaluate localization performance of the CNN model. Trabecular-iris angle 500 (TIA500) and angle-opening distance 500 (AOD500) were measured and analyzed using the scleral spur locations provided by the specialist and predicted by the CNN model. The CNN was developed using a training dataset of 2328 images and tested using an independent dataset of 258 images. The mean absolute prediction errors of CNN model were 48.06 ± 45.40 µm for X-coordinates and 30.84 ± 27.03 µm for Y-coordinates. The mean absolute intraobserver variability was 47.80 ± 44.45 µm for X-coordinates and 29.50 ± 25.77 µm for Y-coordinates. The mean Euclidean distance of the CNN was 60.41 ± 49.02 µm and the intraobserver mean Euclidean distance was 59.78 ± 47.12 µm. The mean absolute error in TIA500 was 1.26 ± 1.38 degrees for all test images and in AOD500 was 0.039 ± 0.051 mm. A CNN can detect the scleral spur on UBM images of open-angle eyes with performance similar to that of a glaucoma specialist. Deep learning algorithms for automating scleral spur localization would facilitate the quantitative assessment of the opening of the angle and the risk in angle closure.


Minimizing the exposure of airborne pathogens by upper-room ultraviolet germicidal irradiation: an experimental and numerical study.
There has been increasing interest in the use of upper-room ultraviolet germicidal irradiation (UVGI) because of its proven effectiveness in disinfecting airborne pathogens. An improved drift flux mathematical model is developed for optimizing the design of indoor upper-room UVGI systems by predicting the distribution and inactivation of bioaerosols in a ventilation room equipped with a UVGI system. The model takes into account several bacteria removal mechanisms such as convection, turbulent diffusion, deposition and UV inactivation. Before applying the model, the natural die-off rate and susceptibility constants of bioaerosols were measured experimentally. Two bacteria aerosols, Escherichia coli and Serratia marcescens, were tested for this purpose. It was found out that the general decay trend of the bioaerosol concentration predicted by the numerical model agrees well with the experimental measurements. The modelling results agree better with experimental observations for the case when the UVGI inactivation mechanism dominates at the upper-room region than for the case without UVGI. The numerical results also illustrate that the spatial distribution of airborne bacteria was influenced by both air-flow pattern and irradiance distribution. In addition to predicting the local variation of concentration, the model assesses the overall performance of an upper-room UVGI system. This model has great potential for optimizing the design of indoor an upper-room UVGI systems.


All Children Thrive: Integration of Nutrition and Early Childhood Development.
Building on the successes of child survival, we review the evidence needed to ensure both that children who survive also thrive and that recommendations promote equity, with no child left behind. To illustrate the critical roles played by nutrition and child development, we revise the Conceptual Framework for the Causes of Malnutrition and Death and the Nurturing Care Framework to create the Conceptual Framework of All Children Surviving and Thriving. The revised framework highlights the goals of child growth and development, supported by health, nutrition, learning, responsive caregiving, and security and safety. We review the challenges posed by undernutrition, stunting, micronutrient deficiencies, overweight, and children not reaching their developmental potential. Although integrated nutrition-childhood development interventions have shown promising effects, most have not been implemented at scale. Implementation science that investigates how and why integrated interventions work in real life, along with the acceptability, feasibility, cost, coverage, and sustainability of the interventions, is needed to ensure equity for all children thriving.


Monozygotic Twins Discordant for Trisomy 13: A Case of Trisomic Rescue Supporting the Continued Need for First-Trimester Ultrasound.
Monozygotic twins with discordant karyotypes for trisomy 13 are rare. We report a case of a spontaneously conceived pregnancy who presented with first-trimester ultrasound finding of umbilical cord cyst and increased nuchal translucency in Twin A and no abnormalities in Twin B. Amniocentesis revealed 47,XY,+13 karyotype in Twin A and 46,XY karyotype in Twin B. Selective fetal reduction was performed for Twin A. Twin B was delivered at 32 weeks gestation with normal phenotype. Peripheral blood karyotype revealed 15% mosaicism for trisomy 13 and skin fibroblast revealed 46,XY karyotype. The surviving twin will be monitored for potential complication of uniparental disomy 13 and mosaic trisomy 13. This case reinforces the need for early ultrasound and nuchal translucency measurements, especially in twin gestations.


[Postoperative pancreatic fistulas: clinical study of a series of 114 consecutive cephalic duodeno-pancreatectomies].
The present study explores the incidence, the predisposing factors and the consequences of pancreatic fistulae in a series of 114 consecutive, non selected, pancreatico-duodenal resections performed during the period January 1967-December 1982 for malignant and benign diseases of the (peri)ampullary region and the head of the pancreas. Overall hospital mortality reached 10.8% (12/114 pat.). The most common surgical complication was pancreatic fistula (17 pat.-14.9%) responsible for half of the postoperative fatal outcomes. The incidence of the pancreatic fistula is significantly influenced by a patient age of over 65 years, a preoperative serum bilirubin level exceeding 6 mg %, urgent degree of the intervention, presence of a renal insufficiency and last but not least by the poor quality of the pancreatic remnant. As surgical treatment of this complication is compromised by a high mortality (40% - 4/10 pat.), surgery should be reserved to hemorrhagic or persistent local or systemic, septic complications. Therefore more attention should be given to the prevention of this complication by a careful patient selection, based on evaluation of the different mentioned risk factors and by an adequate technique based on a separation of the different anastomoses by the greater omentum and the transverse mesocolon.


Deposition of SiO2 films with high laser damage thresholds by ion-assisted electron-beam evaporation.
SiO(2) thin films (approximately 100 nm thick) with transmittivity and a laser damage threshold nearly equal to those of bulk material are deposited on silica substrates by the technique of ion-assisted electron-beam evaporation. The influence of film packing density on the laser damage threshold is investigated by the technique of photoacoustic probe beam deflection. It is shown that films with lower packing density may have a higher laser damage threshold and as a consequence better heat dissipation.


Young Transgender Women Survivors of Intimate Partner Violence: A Latent Class Analysis of Protective Processes.
Research is critically needed to understand protective processes that may lessen the impact of intimate partner violence (IPV) on negative outcomes for transgender individuals. The current study utilized a latent class analysis to identify combinations of protective processes (i.e., collective self-esteem and social support) in relation to internalizing mental health symptoms among young transgender women (YTW) survivors of IPV. Data from Project LifeSkills (2012-2015), a multisite trial for HIV sexual risk reduction intervention, were used for the present study. A subsample of 78 YTW (ages 16 to 29) who were IPV survivors (i.e., indicated lifetime IPV) were included in the analyses. Participants completed measures of general social support, perceived social support from their mother and friends, and collective self-esteem, as well as mental health symptoms. Three latent classes emerged: 1) YTW who perceived high levels of social support and collective self-esteem (48%), 2) YTW who perceived low levels of collective self-esteem, but average to high levels of social support from mother and friends (23%), and 3) YTW who perceived low levels of collective self-esteem and low to average levels of social support from mother and friends (29%). YTW in the overall low class had significantly higher levels of depressive, anxiety, and somatization symptoms, compared to the other two classes. These findings highlight how low levels of social support and collective self-esteem can place YTW survivors of IPV at significant risk for experiencing negative internalizing mental health symptoms.


Progesterone modulation of osteopontin gene expression in the ovine uterus.
Osteopontin (OPN) is an acidic phosphorylated glycoprotein component of the extracellular matrix that binds to integrins at the cell surface to promote cell-cell attachment and cell spreading. This matrix constituent is a ligand that could potentially bind integrins on trophectoderm and endometrium to facilitate superficial implantation and placentation. OPN mRNA increases in the endometrial glandular epithelium (GE) of early-pregnant ewes, and OPN protein is secreted into the uterine lumen. Therefore, progesterone and/or interferon-tau (IFNtau) may regulate OPN expression in the uterine GE. Cyclic ewes were ovariectomized and fitted with intrauterine (i. u.) catheters on Day 5 and treated daily with steroids (i.m.) and protein (i.u.) as follows: 1) progesterone (P, Days 5-24) and control serum proteins (CX, Days 11-24); 2) P and ZK 136.317 (ZK; progesterone receptor [PR] antagonist, Days 11-24) and CX proteins; 3) P and recombinant ovine IFNtau (roIFNtau, Days 11-24); or 4) P and ZK and roIFNtau. All ewes were hysterectomized on Day 25. Progesterone induced the expression of endometrial OPN mRNA in the GE and increased secretion of a 45-kDa OPN protein from endometrial explants maintained in culture for 24 h. Administration of ZK ablated progesterone effects. Intrauterine infusion of roIFNtau did not affect OPN gene expression or secretion in any of the steroid treatments. Interestingly, OPN mRNA-positive GE cells lacked detectable PR expression, although PR were detected in the stroma. Results indicate that progesterone regulates OPN expression in GE through a complex mechanism that includes PR down-regulation, and we suggest the possible involvement of a progesterone-induced stromal cell-derived growth factor(s) that acts as a progestamedin.


The regulation of the expression of inducible nitric oxide synthase by Src-family tyrosine kinases mediated through MyD88-independent signaling pathways of Toll-like receptor 4.
Bacterial lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4) leading to the expression of inflammatory gene products. Src-family tyrosine kinases (STKs) are known to be activated by LPS in monocytes/macrophages. Therefore, we determined the role of STKs in TLR4 signaling pathways and target gene expression in macrophages. The activation of NFkappaB, and p38 MAPK, and the expression of inducible nitric oxide synthase (iNOS) induced by LPS were not affected in macrophages deficient in three STKs (Lyn, Hck, and Fgr). These results suggest that the deletion of the three STKs among possibly nine STKs is not sufficient to abolish total activity of STKs possibly due to the functional redundancy of other STKs present in macrophages. However, two structurally unrelated pan-inhibitors of STKs, PP1 and SU6656, suppressed LPS-induced iNOS expression in MyD88-knockout as well as wild-type macrophages. The suppression of iNOS expression by the inhibitors was correlated with the downregulation of IFNbeta (a MyD88-independent gene) expression and subsequent decrease in STAT1 phosphorylation. Moreover, PP1 suppressed the expression of IFNbeta and iNOS induced by TRIF, a MyD88-independent adaptor of TLR4. PP1 suppressed STAT1 phosphorylation induced by LPS, but not by IFNbeta suggesting that STKs are involved in the primary downstream signaling pathways of TLR4, but not the secondary signaling pathways downstream of IFNbeta receptor. Together, these results demonstrate that STKs play a positive regulatory role in TLR4-mediated iNOS expression in a MyD88-independent (TRIF-dependent) manner. These results provide new insight in understanding the role of STKs in TLR4 signaling pathways and inflammatory target gene expression.


Exacerbations and time spent outdoors in chronic obstructive pulmonary disease.
Patients with chronic obstructive pulmonary disease have a progressive reduction in activity, although its time scale and the contribution of exacerbations are unknown. A rolling cohort of 147 patients (101 male; mean age, 88.5 years; and forced expiratory volume in 1 second as percent predicted, 38.4%) were monitored for a median of 1,044 days (interquartile range, 685 to 1,779) over an 8-year period starting in March 1996. Patients recorded any increase in daily respiratory symptoms and time spent outside their home. They completed the St. George's Respiratory Questionnaire yearly. They experienced 1,465 exacerbations and time outdoors decreased by -0.16 hours/day per year (p < 0.001). This decline was faster in frequent exacerbators (p = 0.011). Before exacerbation, the patients stayed indoors all day for 2.1 days/week (on any day 34.1% were at home), but for 5 weeks postexacerbation they spent 2.5 days/week at home (p < 0.001) (44.4% remaining at home at onset; p = 0.021). St. George's total, activity, and impact scores were independently associated with time outdoors (p < 0.005), but not with symptom score. In conclusion, time spent outside the home declines over time and acutely at exacerbation. Patients with frequent exacerbations are more likely to become housebound and need targeting in rehabilitation programs.


Optical properties of graphene nanoribbons encapsulated in single-walled carbon nanotubes.
We report the photoluminescence (PL) from graphene nanoribbons (GNRs) encapsulated in single-walled carbon nanotubes (SWCNTs). New PL spectral features originating from GNRs have been detected in the visible spectral range. PL peaks from GNRs have resonant character, and their positions depend on the ribbon geometrical structure in accordance with the theoretical predictions. GNRs were synthesized using confined polymerization and fusion of coronene molecules. GNR@SWCNTs material demonstrates a bright photoluminescence both in infrared (IR) and visible regions. The photoluminescence excitation mapping in the near-IR spectral range has revealed the geometry-dependent shifts of the SWCNT peaks (up to 11 meV in excitation and emission) after the process of polymerization of coronene molecules inside the nanotubes. This behavior has been attributed to the strain of SWCNTs induced by insertion of the coronene molecules.


Climate change and body size shift in Mediterranean bivalve assemblages: unexpected role of biological invasions.
Body size is a synthetic functional trait determining many key ecosystem properties. Reduction in average body size has been suggested as one of the universal responses to global warming in aquatic ecosystems. Climate change, however, coincides with human-enhanced dispersal of alien species and can facilitate their establishment. We address effects of species introductions on the size structure of recipient communities using data on Red Sea bivalves entering the Mediterranean Sea through the Suez Canal. We show that the invasion leads to increase in median body size of the Mediterranean assemblage. Alien species are significantly larger than native Mediterranean bivalves, even though they represent a random subset of the Red Sea species with respect to body size. The observed patterns result primarily from the differences in the taxonomic composition and body-size distributions of the source and recipient species pools. In contrast to the expectations based on the general temperature-size relationships in marine ectotherms, continued warming of the Mediterranean Sea indirectly leads to an increase in the proportion of large-bodied species in bivalve assemblages by accelerating the entry and spread of tropical aliens. These results underscore complex interactions between changing climate and species invasions in driving functional shifts in marine ecosystems.


Preparation and characterization of adefovir dipivoxil-stearic acid cocrystal with enhanced physicochemical properties.
The objectives of this study were to prepare cocrystal composed of adefovir dipivoxil (AD) and stearic acid (SA) and to investigate the enhanced properties of the cocrystal. The cocrystal was prepared by antisolvent precipitation and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). The enhanced properties were evaluated by dissolution testing, permeability studies, and powder rheology analysis. The AD raw material has a cuboid-like crystal and the cocrystal has a needle shape. In the FT-IR study, there were bathochromic shifts caused by the hydrogen bonding. The melting point of the cocrystal was 52.9 °C, which was lower than that of AD. The XRPD pattern also had distinct differences, supporting the formation of a new crystalline form. The cocrystal showed changes in the lattice energy and the solvation strength, which caused an enhanced dissolution. The permeability was increased due to the SA, which acts as a P-gp inhibitor. The tabletability was enhanced due to the altered crystal habit. In conclusion, cocrystal containing AD and SA was successfully prepared, presenting advantages such as enhanced solubility, tabletability, and permeability. The use of the cocrystal is a desirable approach for the improved physicochemical properties.


Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review.
Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications. We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age. 73 studies were included. Many studies had methodological limitations or were poorly reported. Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring. Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation. There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required.


Identification of "BRAF-Positive" Cases Based on Whole-Slide Image Analysis.
A key requirement for precision medicine is the accurate identification of patients that would respond to a specific treatment or those that represent a high-risk group, and a plethora of molecular biomarkers have been proposed for this purpose during the last decade. Their application in clinical settings, however, is not always straightforward due to relatively high costs of some tests, limited availability of the biological material and time, and procedural constraints. Hence, there is an increasing interest in constructing tissue-based surrogate biomarkers that could be applied with minimal overhead directly to histopathology images and which could be used for guiding the selection of eventual further molecular tests. In the context of colorectal cancer, we present a method for constructing a surrogate biomarker that is able to predict with high accuracy whether a sample belongs to the "BRAF-positive" group, a high-risk group comprising V600E BRAF mutants and BRAF-mutant-like tumors. Our model is trained to mimic the predictions of a 64-gene signature, the current definition of BRAF-positive group, thus effectively identifying histopathology image features that can be linked to a molecular score. Since the only required input is the routine histopathology image, the model can easily be integrated in the diagnostic workflow.


Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension.
This perspective highlights advances in the understanding of the role of cellular metabolism in the pathogenesis of pulmonary hypertension. Insights gained in the past 20 years have revealed several similarities between the cellular processes underlying the pulmonary vascular remodeling in pulmonary hypertension and those seen in cancer processes. In line with these insights, there is increasing recognition that abnormal cellular metabolism, notably of aerobic glycolysis (the "Warburg effect"), the potential involvement of hypoxia-inducible factor in this process, and alterations in mitochondrial function, are key elements in the pathogenesis of this disease. The glycolytic shift may underlie the resistance to apoptosis and increased vascular cell proliferation, which are hallmarks of pulmonary hypertension. These investigations have led to novel approaches in the diagnosis and therapy of pulmonary hypertension.


Comparison of similarity-based tests and pooling strategies for rare variants.
As several rare genomic variants have been shown to affect common phenotypes, rare variants association analysis has received considerable attention. Several efficient association tests using genotype and phenotype similarity measures have been proposed in the literature. The major advantages of similarity-based tests are their ability to accommodate multiple types of DNA variations within one association test, and to account for the possible interaction within a region. However, not much work has been done to compare the performance of similarity-based tests on rare variants association scenarios, especially when applied with different rare variants pooling strategies. Based on the population genetics simulations and analysis of a publicly-available sequencing data set, we compared the performance of four similarity-based tests and two rare variants pooling strategies. We showed that weighting approach outperforms collapsing under the presence of strong effect from rare variants and under the presence of moderate effect from common variants, whereas collapsing of rare variants is preferable when common variants possess a strong effect. We also demonstrated that the difference in statistical power between the two pooling strategies may be substantial. The results also highlighted consistently high power of two similarity-based approaches when applied with an appropriate pooling strategy. Population genetics simulations and sequencing data set analysis showed high power of two similarity-based tests and a substantial difference in power between the two pooling strategies.


Development of myocardial constructs using modulus-matched acrylated polypropylene glycol triol substrate and different nonmyocyte cell populations.
Tissue engineering approaches are currently being investigated for the restoration of myocardial function in heart failure patients, most commonly by combining cells with a substrate to form myocardial-like constructs (MCs). The final properties of these constructs are dependant on the characteristics of both the substrate and the cells used for fabrication. To create a construct with the appropriate mechanical properties required for any future therapeutic, we tailored an acrylated polypropylene glycol triol (aPPGT) substrate to the elastic modulus of heart tissue and then investigated the fabrication of MCs. We first assessed the aPPGT substrate alone in vivo, both under normal conditions and in an infarct model in mice, and found that there was a mild foreign body response with good integration of the substrate into the epicardial surface in mice hearts. We next studied the fabrication and properties of MCs by culturing mouse embryonic cardiomyocytes on the aPPGT substrate. To achieve myocardial-like concentrically contractile constructs, cocultures with supportive stromal cells were found to be essential and both mouse heart-derived stromal cells or bone-derived mouse mesenchymal stromal progenitor cells (mMSCs) could be used. These different stromal cell types produced MCs with different properties. The average beating rate of the constructs formed from mouse heart-derived stromal cells was significantly higher those constructs formed using mMSCs. Conversely, the constructs formed using mMSCs had reduced fibrotic extracellular matrix secretion and increased hepatocyte growth factor expression. Both of these mMSC construct properties may enhance integration and therapeutic efficacy of the construct postimplantation on the surface of the infarcted heart. This study thus demonstrates the formation of MCs using mechanically tailored aPPGT substrate and also demonstrates the effects of different stromal cell populations have on the properties of the resultant MCs, both of which are critical for future applications of tissue engineering in heart failure patients.


Adolescents' intergenerational narratives across cultures.
Adolescents' intergenerational narratives-the stories they tell about their mothers' and fathers' early experiences-are an important component of their identities (Fivush & Merrill, 2016; Merrill & Fivush, 2016). This study explored adolescents' intergenerational narratives across cultures. Adolescents aged 12 to 21 from 3 cultural groups in New Zealand (Chinese: n = 88; Māori: n = 91; European: n = 91) narrated stories about their mothers' and fathers' childhood experiences. In these narratives, New Zealand Chinese and Māori adolescents included more identity connections (statements linking their own identities to their parents' experiences) than did New Zealand European adolescents, and New Zealand Chinese adolescents' intergenerational narratives were more coherent than were New Zealand European and Māori adolescents' narratives. New Zealand Chinese and Māori adolescents were also more likely to report didactic reasons for their mothers' telling of the narratives, whereas New Zealand European adolescents were more likely to report reasons of sharing family history. Across cultures, but only in their mother narratives, adolescent girls included more references to subjective perspectives (emotions, evaluations, and cognitions) than did adolescent boys. Older adolescents also used more subjective perspective terms than younger adolescents. These findings suggest that intergenerational narratives serve different functions when adolescents across cultures explore their identities. These narratives may be especially important for adolescents growing up in cultures with an interdependent orientation. (PsycINFO Database Record


The effect of iconicity of visual displays on statistical reasoning: evidence in favor of the null hypothesis.
Knowing which properties of visual displays facilitate statistical reasoning bears practical and theoretical implications. Therefore, we studied the effect of one property of visual diplays - iconicity (i.e., the resemblance of a visual sign to its referent) - on Bayesian reasoning. Two main accounts of statistical reasoning predict different effect of iconicity on Bayesian reasoning. The ecological-rationality account predicts a positive iconicity effect, because more highly iconic signs resemble more individuated objects, which tap better into an evolutionary-designed frequency-coding mechanism that, in turn, facilitates Bayesian reasoning. The nested-sets account predicts a null iconicity effect, because iconicity does not affect the salience of a nested-sets structure-the factor facilitating Bayesian reasoning processed by a general reasoning mechanism. In two well-powered experiments (N = 577), we found no support for a positive iconicity effect across different iconicity levels that were manipulated in different visual displays (meta-analytical overall effect: log OR = -0.13, 95% CI [-0.53, 0.28]). A Bayes factor analysis provided strong evidence in favor of the null hypothesis-the null iconicity effect. Thus, these findings corroborate the nested-sets rather than the ecological-rationality account of statistical reasoning.


Simple thermodynamic model of unassisted proton shuttle uncoupling and prediction of activity from calculated speciation, lipophilicity, and molecular geometry.
A mechanistic model of uncoupling of oxidative phosphorylation by lipophilic weak acids (i.e. proton shuttles) was developed for the purposes of predicting the relative activity of xenobiotics of widely varying structure and of guiding the design of optimized derivatives. The model is based on thermodynamic premises not formulated elsewhere that allow for the calculation of steady-state conditions and of rate of energy dissipation on the basis of acid-dissociation and permeability behavior, the later estimated from partitioning behavior and geometric considerations. Moreover, permeability of either the neutral or of the ionized species is proposed to be effectively enhanced under conditions of asymmetrical molecular distribution. Finally, special considerations were developed to accommodate multi-protic compounds. The comparison of predicted to measured activity for a diverse testset of 48 compounds of natural origin spanning a wide range of activity yielded a Spearman's rho of 0.90. The model was used to tentatively identify several novel proton shuttles, as well as to elucidate core structures particularly conducive to proton shuttle activity from which optimized derivatives can be designed. Principles of design were formulated and examples of derivatives projected to be active at concentrations on the order of 10(-7)M are proposed. Among these are di-protic compounds predicted to shuttle two protons per cycle iteration and proposed to maximally exploit the proton shuttle mechanism. This work promotes the design of highly active, yet easily-metabolized uncouplers for therapeutic applications, namely the indirect activation of AMP-kinase, as well as for various industrial applications where low persistence is desirable.


Whole-grain dietary recommendations: the need for a unified global approach.
Increased whole-grain (WG) consumption reduces the risk of CVD, type 2 diabetes and some cancers, is related to reduced body weight and weight gain and is related to improved intestinal health. Definitions of 'WG' and 'WG food' are proposed and used in some countries but are not consistent. Many countries promote WG consumption, but the emphasis given and the messages used vary. We surveyed dietary recommendations of fifty-three countries for mentions of WG to assess the extent, rationale and diversity in emphasis and wording of any recommendations. If present, recommendations were classified as either 'primary', where the recommendation was specific for WG, or 'secondary', where recommendations were made in order to achieve another (primary) target, most often dietary fibre intake. In total, 127 organisations were screened, including government, non-governmental organisations, charities and professional bodies, the WHO and European Food Safety Authority, of which forty-nine including WHO provide a WG intake recommendation. Recommendations ranged from 'specific' with specified target amounts (e.g. x g WG/d), 'semi-quantitative' where intake was linked to intake of cereal/carbohydrate foods with proportions of WG suggested (e.g. x servings of cereals of which y servings should be WG) to 'non-specific' based on 'eating more' WG or 'choosing WG where possible'. This lack of a harmonised message may result in confusion for the consumer, lessen the impact of public health messages and pose barriers to trade in the food industry. A science-based consensus or expert opinion on WG recommendations is needed, with a global reach to guide public health decision making and increase WG consumption globally.


Impact of ventriculo-cisternal irrigation on prevention of delayed cerebral infarction in aneurysmal subarachnoid hemorrhage: a single-center retrospective study and literature review.
The aim of this study was to evaluate the effectiveness of ventriculo-cisternal irrigation (VCI) in preventing vasospasms and delayed cerebral infarction (DCI) by washing out subarachnoid clots earlier after aneurysm surgery. We retrospectively identified 340 subarachnoid hemorrhage (SAH) patients with ruptured intracranial aneurysms treated with postoperative VCI at our institution between December 2010 and January 2020. As VCI therapy, a ventricular drain/cisternal drain was placed during aneurysm surgery, and lactated Ringer's solution was used for irrigation until day 4 of SAH, followed by intracranial pressure control at 5-10 cmH2O until day 14. The median age was 65 years (interquartile range 52-75), with 236 female patients (69%). The World Federation of Neurosurgical Societies grade distribution was as follows: grade I or II, 175 patients (51%); grade III or IV, 84 (25%); and grade V, 81 (24%). With VCI management in all patients, total vasospasm occurred in 162 patients (48%), although the DCI incidence was low (23 patients [6.8%]). Major drainage-related complications were observed in five patients (1.5%). Early surgery, performed on SAH day 0 or 1, was identified as a preventive factor against DCI occurrence (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.07-0.67; P = 0.008), while additional surgery (4.76, 1.62-13.98; P = 0.005) and dyslipidemia (3.27, 1.24-8.63; P = 0.017) were associated with DCI occurrence. Managing vasospasms with VCI after SAH is considered a safe and effective method to prevent DCI. Early surgery after SAH may be associated with a decreased risk of DCI with VCI therapy.


FMRP phosphorylation modulates neuronal translation through YTHDF1.
RNA-binding proteins (RBPs) control messenger RNA fate in neurons. Here, we report a mechanism that the stimuli-induced neuronal translation is mediated by phosphorylation of a YTHDF1-binding protein FMRP. Mechanistically, YTHDF1 can condense with ribosomal proteins to promote the translation of its mRNA targets. FMRP regulates this process by sequestering YTHDF1 away from the ribosome; upon neuronal stimulation, FMRP becomes phosphorylated and releases YTHDF1 for translation upregulation. We show that a new small molecule inhibitor of YTHDF1 can reverse fragile X syndrome (FXS) developmental defects associated with FMRP deficiency in an organoid model. Our study thus reveals that FMRP and its phosphorylation are important regulators of activity-dependent translation during neuronal development and stimulation and identifies YTHDF1 as a potential therapeutic target for FXS in which developmental defects caused by FMRP depletion could be reversed through YTHDF1 inhibition.


Middle school injuries: a 20-year (1988-2008) multisport evaluation.
Data on the incidence of injury in middle school sports are limited. To describe overall, practice, and game injury rate patterns in 29 middle school sports. Descriptive epidemiology study. Injury data collected over a 20-year period (1988-2008) at a single school. Boy (n = 8078) and girl (n = 5960) athletes participating in 14 and 15 middle school sports, respectively. Injury status and athlete-exposures (AEs) were collected by certified athletic trainers. Incidence rates per 1000 AEs (injuries/AEs) were calculated for overall incidence, practices and games, injury location, injury type, and injury severity (time lost from participation). Rate ratios (RRs) and 95% confidence intervals (CIs) were used to compare injury rates for sex-matched sports. Football had the highest injury rate for all injuries (16.03/1000 AEs) and for time-loss injuries (8.486/1000 AEs). In matched middle school sports, girls exhibited a higher injury rate for all injuries (7.686/1000 AEs, RR = 1.15, 95% CI = 1.1, 1.2) and time-loss injuries (2.944/1000 AEs, RR = 1.09, 95% CI = 1.0, 1.2) than boys (all injuries: 6.684/1000 AEs, time-loss injuries: 2.702/1000 AEs). Girls had a higher injury rate during practices (3.30/1000 AEs) than games (1.67/1000 AEs, RR = 1.97, 95% CI = 1.7, 2.4) for all sports. Only gymnastics (RR = 0.96, 95% CI = 0.3, 3.8) had a higher game injury rate for girls. Practice and game injury rates were nearly identical for boys in all sports (RR = 0.99, 95% CI = 0.9, 1.1). Only football (RR = 0.49, 95% CI = 0.4, 0.6) and boys' wrestling (RR = 0.50, 95% CI = 0.3, 0.8) reported higher game injury rates. Tendinitis injuries accounted for 19.1% of all middle school injuries. The risk for sport-related injury at the middle school level was greater during practices than games and greater for girls than boys in sex-matched sports. Conditioning programs may be needed to address the high rate of tendinitis injuries.