Mechanisms of inactivation of E-cadherin in breast cancer cell lines.
Loss of E-cadherin (CDH1) function is thought to contribute to progression in breast cancer and other solid tumors by increasing proliferation, invasion, and/or metastasis. In some cases, the restoration of CDH1 function may be an important therapeutic option. This possibility will depend on the mechanism by which CDH1 is inactivated. Here we present analyses of CDH1 expression, genetic mutation, and promoter methylation in CDH1 in 10 commonly used breast cancer cell lines. Five cell lines (BT-474, MCF-7, MDA-MB-361, MDA-MB-468, and T-47D) expressed CDH1 and were genetically normal. Five others (SK-BR-3, 600 MPE, MDA-MB-134 IV, CAMA1, and MDA-MB-435) did not express CDH1. Fluorescence in situ hybridization analyses of each of these cell lines showed evidence for the physical deletion of one allele of CDH1, and three cell lines were found to carry homozygous deletions. SK-BR-3 was deleted from exon 12 through the promoter; exon 6 was deleted in MDA-MB-134 IV cells, and 600 MPE cells carried a 21-bp deletion in the splicing acceptor site for exon 9. CAMA1 seemed to have been inactivated through promoter methylation. No explanation was found for the inactivation of CDH1 in MDA-MB-435.


Slow medical education.
Slow medical education borrows from other "slow" movements by offering a complementary orientation to medical education that emphasizes the value of slow and thoughtful reflection and interaction in medical education and clinical care. Such slow experiences, when systematically structured throughout the curriculum, offer ways for learners to engage in thoughtful reflection, dialogue, appreciation, and human understanding, with the hope that they will incorporate these practices throughout their lives as physicians. This Perspective offers several spaces in the medical curriculum where slowing down is possible: while reading and writing at various times in the curriculum and while providing clinical care, focusing particularly on conducting the physical exam and other dimensions of patient care. Time taken to slow down in these ways offers emerging physicians opportunities to more fully incorporate their experiences into a professional identity that embodies reflection, critical awareness, cultural humility, and empathy. The authors argue that these curricular spaces must be created in a very deliberate manner, even on busy ward services, throughout the education of physicians.


Ginger (Zingiber officinale) and chemotherapy-induced nausea and vomiting: a systematic literature review.
Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of cytotoxic treatment. It continues to affect a significant proportion of patients despite the widespread use of antiemetic medication. In traditional medicine, ginger (Zingiber officinale) has been used to prevent and treat nausea in many cultures for thousands of years. However, its use has not been confirmed in the chemotherapy context. To determine the potential use of ginger as a prophylactic or treatment for CINV, a systematic literature review was conducted. Reviewed studies comprised randomized controlled trials or crossover trials that investigated the anti-CINV effect of ginger as the sole independent variable in chemotherapy patients. Seven studies met the inclusion criteria. All studies were assessed on methodological quality and their limitations were identified. Studies were mixed in their support of ginger as an anti-CINV treatment in patients receiving chemotherapy, with three demonstrating a positive effect, two in favor but with caveats, and two showing no effect on measures of CINV. Future studies are required to address the limitations identified before clinical use can be recommended.


The island model of population differentiation: a general solution.
The island model deals with a species which is subdivided into a number of discrete finite populations, races or subspecies, between which some migration occurs. If the number of populations is small, an assumption of equal rates of migration between each pair of populations may be reasonable approximation. Mutation at a constant rate to novel alleles may also be assumed.-A general solution is given for the process of population divergence under this model following subdivision of a single parental population, expressed in terms of the observed average frequency of heterozygotes within and between subpopulations at a randomly chosen set of independently segregating loci. No restriction is imposed on the magnitude of the migration or mutation rates involved, nor on the number of populations exchanging migrants.-The properties of two fundamental measures of genetic divergence are deduced from the theory. One is a parameter related to varphi, the coefficient of kinship, and the other, gamma, measures the rate of mutational divergence between the sub-populations.


Telomerase activity in human ovarian carcinoma.
Telomeres fulfill the dual function of protecting eukaryotic chromosomes from illegitimate recombination and degradation and may aid in chromosome attachment to the nuclear membrane. We have previously shown that telomerase, the enzyme which synthesizes telomeric DNA, is not detected in normal somatic cells and that telomeres shorten with replicative age. In cells immortalized in vitro, activation of telomerase apparently stabilizes telomere length, preventing a critical destabilization of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomeres of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the development and progression of tumors, we have measured enzyme activity and telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintained in these cells and that tumor cells, but not isogenic nonmalignant cells, express telomerase. Our findings suggest that progression of malignancy is ultimately dependent upon activation of telomerase and that telomerase inhibitors may be effective antitumor drugs.


The angiopathy of subarachnoid hemorrhage I. Role of vessel wall catecholamines.
Subarachnoid hemorrhage (SAH) due to rupture of the right middle cerebral artery (RMCA) produced specific anatomical and biophysiological responses in the involved feline vessels. The RMCA showed morphological alterations that became progressively more severe with time and were widespread within the cerebral vascular tree. SAH also resulted in an acute depletion of vessel catecholamine levels which remained depressed over a 30 day period. When the cerebral vessels of cats were severely depleted of catecholamines (using reserpine) prior to induced SAH, morphological alterations were significantly reduced both in severity and in degree of spread within the cerebral vascular network. The results of this study suggest that the concentration of norepinephrine within the vessel at the time of hemorrhage plays a significant role in the production of the angiopathy that follows SAH.


Evolution of the NANOG pseudogene family in the human and chimpanzee genomes.
The NANOG gene is expressed in mammalian embryonic stem cells where it maintains cellular pluripotency. An unusually large family of pseudogenes arose from it with one unprocessed and ten processed pseudogenes in the human genome. This article compares the NANOG gene and its pseudogenes in the human and chimpanzee genomes and derives an evolutionary history of this pseudogene family. The NANOG gene and all pseudogenes except NANOGP8 are present at their expected orthologous chromosomal positions in the chimpanzee genome when compared to the human genome, indicating that their origins predate the human-chimpanzee divergence. Analysis of flanking DNA sequences demonstrates that NANOGP8 is absent from the chimpanzee genome. Based on the most parsimonious ordering of inferred source-gene mutations, the deduced evolutionary origins for the NANOG pseudogene family in the human and chimpanzee genomes, in order of most ancient to most recent, are NANOGP6, NANOGP5, NANOGP3, NANOGP10, NANOGP2, NANOGP9, NANOGP7, NANOGP1, and NANOGP4. All of these pseudogenes were fixed in the genome of the human-chimpanzee common ancestor. NANOGP8 is the most recent pseudogene and it originated exclusively in the human lineage after the human-chimpanzee divergence. NANOGP1 is apparently an unprocessed pseudogene. Comparison of its sequence to the functional NANOG gene's reading frame suggests that this apparent pseudogene remained functional after duplication and, therefore, was subject to selection-driven conservation of its reading frame, and that it may retain some functionality or that its loss of function may be evolutionarily recent.


Relationship between height and outcomes among critically ill adults: a cohort study.
Many diagnostic and therapeutic interventions for critically ill adult patients are not performed according to patient size, but are standardized for an idealized 174-cm man (ideal body weight 70 kg). This study aims to determine whether critically ill patients with heights significantly different from a standardized patient have higher hospital mortality or greater resource utilization. Retrospective cohort study of consecutive patients admitted to 210 intensive care units (ICUs) in the United Kingdom participating in the Intensive Care National Audit and Research Centre's Case Mix Programme Database from April 1, 2009, to March 31, 2015. Primary outcome was hospital mortality, adjusted for age, comorbid disease, severity of illness, socioeconomic status and body mass index, using hierarchical modeling to account for clustering by ICU. Data were stratified by sex, and the effect of height was modeled continuously using restricted cubic splines. The cohort included 233,308 men and 184,070 women, with overall hospital mortality of 22.5% and 20.6%, respectively. After adjustment for potential confounders, hospital mortality decreased with increasing height; predicted mortality (holding all other covariates at their mean value) decreased from 24.1 to 17.1% for women and from 29.2 to 21.0% for men across the range of heights. Similar patterns were observed for ICU mortality and several additional secondary outcomes. Short stature may be a risk factor for mortality in critically ill patients. Further work is needed to determine which unmeasured patient characteristics and processes of care may contribute to the increased risk observed.


Effects of developmental methylphenidate (MPH) treatment on monoamine neurochemistry of male and female rats.
Attention Deficit Hyperactivity Disorder (ADHD) is estimated to affect 4-5% of the adult human population (Kessler et al., 2006; Willcutt, 2012). Often prescribed to attenuate ADHD symptoms (Nair and Moss, 2009), methylphenidate hydrochloride (MPH) can have substantial positive effects. However, there is a paucity of literature regarding its use during pregnancy. Thus, adult women with ADHD face a difficult decision when contemplating pregnancy. In this study, pregnant Sprague-Dawley rats were orally treated a total of 0 (water), 6 (low), 18 (medium), or 42 (high) mg MPH/kg body weight/day (divided into three doses) on gestational days 6-21 (i.e., the low dose received 2 mg MPH/kg body weight 3×/day). Offspring were orally treated with the same daily dose as their dam (divided into two doses) on postnatal days (PNDs) 1-21. One offspring/sex/litter was sacrificed at PND 22 or PND 104 (n=6-7/age/sex/treatment group) and the striatum was quickly dissected and frozen. High Performance Liquid Chromatography (HPLC) coupled to a Photo Diode Array detector (PDA) was used to analyze monoamine content in the striatum of one side while a sandwich ELISA was used to analyze tyrosine hydroxylase (TH) from the other side. Age significantly affected monoamine and metabolite content as well as turnover ratios (i.e., DA, DOPAC, HVA, DOPAC/DA, HVA/DA, 5-HT and 5-HIAA); however, there were no significant effects of sex. Adult rats of the low MPH group had higher DA levels than control adults (p<0.05). At both ages, subjects of the low MPH group had higher TH levels than controls (p<0.05), although neither effect (i.e., higher DA or TH levels) exhibited an apparent dose-response. PND 22 subjects of the high MPH treatment group had higher ratios of HVA/DA and DOPAC/DA than same-age control subjects (p<0.05). The increased TH levels of the low MPH group may be related to the increased DA levels of adult rats. While developmental MPH treatment appears to have some effects on monoamine system development, further studies are required to determine if these alterations manifest as functional changes in behavior.


Pathogen selection drives nonoverlapping associations between HLA loci.
Pathogen-mediated selection is commonly invoked as an explanation for the exceptional polymorphism of the HLA gene cluster, but its role in generating and maintaining linkage disequilibrium between HLA loci is unclear. Here we show that pathogen-mediated selection can promote nonrandom associations between HLA loci. These associations may be distinguished from linkage disequilibrium generated by other population genetic processes by virtue of being nonoverlapping as well as nonrandom. Within our framework, immune selection forces the pathogen population to exist as a set of antigenically discrete strains; this then drives nonoverlapping associations between the HLA loci through which recognition of these antigens is mediated. We demonstrate that this signature of pathogen-driven selection can be observed in existing data, and propose that analyses of HLA population structure can be combined with laboratory studies to help us uncover the functional relationships between HLA alleles. In a wider coevolutionary context, our framework also shows that the inclusion of memory immunity can lead to robust cyclical dynamics across a range of host-pathogen systems.


Is the Armadale epidemic over? Air pollution and mortality from lung cancer and other diseases, 1961-82.
In Armadale, a town in central Scotland, the standardised mortality ratios (SMRs) for lung cancer were exceptionally high during 1968-74. A large cluster of cases was found in a residential zone downwind from a foundry. In the present study death certificates in the mortality registers of three town parishes were analysed for 1961-82 and the time trends of mortality from major categories of disease were examined. The distribution of mortality from lung cancer within Armadale's six residential zones was compared with that of the other diseases for the periods 1968-75 and 1976-82; the zone of particular interest was that containing the original cluster of lung cancer. The distribution of lung cancer was also compared with the pattern of air pollution by metals, collected by Sphagnum moss bags. The annual numbers of deaths from respiratory cancer in Armadale rose to a plateau in 1968-77; after a fall during 1978-80, the numbers returned in 1981 and 1982 to their previous high values. Between 1968-75 and 1976-82 the mean SMRs for all the disease categories except respiratory cancer rose. The SMR for total mortality in 1976-82 was the same as in preceding years when the standardised death rate for Armadale was the highest for Scotland in the annual reports of the Registrar General. In the zone with the highest mortality from lung cancer in 1968-75 the SMR for that disease continued to be higher than expected. That zone also showed the highest SMRs for cancer of the upper alimentary tract, cerebrovascular disease, hypertension, and coronary heart disease; its SMR for bronchitis was the second highest in the town. Pollution studies indicated that zones with high SMRs for respiratory and non-respiratory cancer were exposed to air pollution by metals. The temporal and spatial patterns are consistent with the view that the problem of mortality from cancer and non-malignant diseases in Armadale remains.


How to assess and prepare health systems in low- and middle-income countries for integration of services-a systematic review.
Despite growing support for integration of frontline services, a lack of information about the pre-conditions necessary to integrate such services hampers the ability of policy makers and implementers to assess how feasible or worthwhile integration may be, especially in low- and middle-income countries (LMICs). We adopted a modified systematic review with aspects of realist review, including quantitative and qualitative studies that incorporated assessment of health system preparedness for and capacity to implement integrated services. We searched Medline via Ovid, Web of Science and the Cochrane library using terms adapted from Dudley and Garner's systematic review on integration in LMICs. From an initial list of 10 550 articles, 206 were selected for full-text review by two reviewers who independently reviewed articles and inductively extracted and synthesized themes related to health system preparedness. We identified five 'context' related categories and four health system 'capability' themes. The contextual enabling and constraining factors for frontline service integration were: (1) the organizational framework of frontline services, (2) health care worker preparedness, (3) community and client preparedness, (4) upstream logistics and (5) policy and governance issues. The intersecting health system capabilities identified were the need for: (1) sufficiently functional frontline health services, (2) sufficiently trained and motivated health care workers, (3) availability of technical tools and equipment suitable to facilitate integrated frontline services and (4) appropriately devolved authority and decision-making processes to enable frontline managers and staff to adapt integration to local circumstances. Moving beyond claims that integration is defined differently by different programs and thus unsuitable for comparison, this review demonstrates that synthesis is possible. It presents a common set of contextual factors and health system capabilities necessary for successful service integration which may be considered indicators of preparedness and could form the basis for an 'integration preparedness tool'.


Optimum input states of polarization for Mueller matrix measurement in a system having finite polarization-dependent loss or gain.
We present the theoretical and simulation results of the relationship between three input states of polarization (SOP) and the Mueller matrix measurement error in an optical system having birefringence and finite polarization-dependent loss or gain (PDL/G). By using the condition number as the criterion, it can be theoretically demonstrated that the three input SOPs should be equally-spaced on the Poincaré sphere and centered on the reversed PDL/G vector to achieve better measurement accuracy in a single test. Further, an upper bound of the mean of the Mueller matrix measurement error is derived when the measurement errors of output Stokes parameters independently and identically follow the ideal Gaussian distribution. This upper bound also shows that the statistically best Mueller matrix measurement accuracy can be obtained when the three input SOPs have the same relationship mentioned above. Simulation results confirm the validity of the theoretical findings.


Evaluation of the Antibacterial Activity of 75 Mushrooms Collected in the Vicinity of Oxford, Ohio (USA).
Antibiotic-resistant bacteria are an increasing and serious health concern worldwide, and multidrug-resistant pathogens are increasingly emerging among patients across the United States. Researchers are exploring sources of traditional medicines, including mushrooms, to find new antibiotic compounds. In this study, the antibiotic activities of 75 mushrooms collected in the area surrounding Oxford, Ohio (USA), were assayed for antibiotic activity against 6 bacterial strains (Pseudomonas aeruginosa reference strains PAO1 and PA14, P. fluorescens, Bacillus subtilis, Staphylococcus epidermidis, and Micrococcus luteus). Mushroom samples were identified by using DNA ribotyping. We used methanol and water extracts of mushrooms in agar diffusion assays to screen for antibiotic activity toward each bacterial strain. A total of 25 mushroom species had antibacterial activity against at least 1 bacterium. Water extracts of Polyporus squamosus, Ganoderma applanatum, Lentinellus subaustralis, Laetiporus sulphureus, G. lucidum, and Trametes versicolor exhibited strong antibiotic activity against all bacterial strains tested. Water and methanol extracts from 25 mushroom species had significant activity against most of the bacteria tested. A minimum inhibitory concentration (MIC) against S. epidermidis was determined for all samples that exhibited antibiotic activity in the disk assay. The G. lucidum and L. sulphureus extracts displayed the strongest inhibition, with an MIC of 0.1 mg/mL.


An argument for the use of multiple segment stents in curved arteries.
Stenting of curved arteries is generally perceived to be more challenging than straight vessels. Conceptually implanting multiple shorter stents rather than a single longer stent into such a curved artery represents a promising concept, but little is known about the impact of such an approach. The objective of this study is to evaluate the effectiveness of using a multiple segment stent rather than a single long stent to dilate a curved artery using the finite element method. A double segment stent (DSS) and a single segment stent (SSS) were modeled. The stents were compared when expanded into a model of a curved artery. The model predicts that the DSS provides higher flexibility, more conformity, and lower recoil in comparison to the SSS. The volume of arterial tissue experiencing high levels of stress due to stent implantation is also reduced for the DSS. It is suggested that a multiple segment stenting system is a potential solution to the problem of higher rates of in-stent restenosis in curved arteries and mechanically challenging environments.


Characterization of a myosin heavy chain in the conductive system of the adult and developing chicken heart.
A monoclonal antibody (anterior latissimus dorsi 58 [ALD58]; antimyosin heavy chain, MHC) directed against myosin from slow tonic muscle was found to react specifically with the striated muscle cells of the conductive system in the adult chicken heart. This monoclonal antibody was used to study the expression of myosin in the conductive system of the adult and developing heart. Using immunofluorescence microscopy with ALD58, muscle cells of the conductive system were demonstrated in both the atria and ventricles of the adult heart as previously shown by Sartore et al. (Sartore, S., S. Pierobon-Bormioli, and S. Schiafinno, 1978, Nature (Lond.), 274: 82-83). Radioactive myosin from adult atria and ventricles was precipitated with ALD58 and subjected to limited proteolysis and subsequent peptide mapping. Peptide maps of ALD58 reactive myosin from atria and ventricles were very similar, if not identical, but differed from peptide maps of ordinary atrial and ventricular myosin. The same antibody was used to study cardiac myogenesis in the chick embryo. When ALD58 was reacted with myosin isolated from atria and ventricles at selected stages of development in radioimmunoassays, reactivity was not observed until the last week of embryonic life (greater than 15 d of egg incubation). Thereafter concomitant and progressively increased reactivity was observed in atrial and ventricular preparations. Also, no ALD58 positive cells were observed in immunofluorescence studies of embryonic hearts until 17 d of egg incubation. Primary cell cultures of embryonic hearts also proved to be negative for this antibody. This study demonstrates that an epitope recognized by ALD58 associated with an antimyosin heavy chain of striated muscle cells of the adult heart conductive system is absent or present in only small amounts in the early embryonic heart.


The blood supply of the osteocutaneous free fibular graft.
The use of an osteocutaneous free fibular graft as a single-stage reconstructive procedure for composite tissue loss is increasingly common. Detailed anatomical study in cadavers of the blood supply to the graft demonstrates cutaneous arteries arising from the peroneal artery and then passing along the posterior surface of the lateral intermuscular septum. These vessels pierce the crural fascia and then ramify to supply the skin. Knowledge of the vascular anatomy of the skin overlying the fibula is essential to the success of the graft.


Investigation of the impact of commonly used medications on the oral microbiome of individuals living without major chronic conditions.
Commonly used medications produce changes in the gut microbiota, however, the impact of these medications on the composition of the oral microbiota is understudied. Saliva samples were obtained from 846 females and 368 males aged 35-69 years from a Canadian population cohort, the Atlantic Partnership for Tomorrow's Health (PATH). Samples were analyzed by 16S rRNA gene sequencing and differences in microbial community compositions between nonusers, single-, and multi-drug users as well as the 3 most commonly used medications (thyroid hormones, statins, and proton pump inhibitors (PPI)) were examined. Twenty-six percent of participants were taking 1 medication and 21% were reported taking 2 or more medications. Alpha diversity indices of Shannon diversity, Evenness, Richness, and Faith's phylogenetic diversity were similar among groups, likewise beta diversity as measured by Bray-Curtis dissimilarity (R2 = 0.0029, P = 0.053) and weighted UniFrac distances (R2 = 0.0028, P = 0.161) were non-significant although close to our alpha value threshold (P = 0.05). After controlling for covariates (sex, age, BMI), six genera (Saprospiraceae uncultured, Bacillus, Johnsonella, Actinobacillus, Stenotrophomonas, and Mycoplasma) were significantly different from non-medication users. Thyroid hormones, HMG-CoA reductase inhibitors (statins) and PPI were the most reported medications. Shannon diversity differed significantly among those taking no medication and those taking only thyroid hormones, however, there were no significant difference in other measures of alpha- or beta diversity with single thyroid hormone, statin, or PPI use. Compared to participants taking no medications, the relative abundance of eight genera differed significantly in participants taking thyroid hormones, six genera differed in participants taking statins, and no significant differences were observed with participants taking PPI. The results from this study show negligible effect of commonly used medications on microbial diversity and small differences in the relative abundance of specific taxa, suggesting a minimal influence of commonly used medication on the salivary microbiome of individuals living without major chronic conditions.


Impact of smoking on speed and coordination of upper limb movement.
The purpose of this study was to determine the effect of smoking on speed and coordination of upper-limb movement. A total of 62 healthy, young individuals were randomly selected for participation in this study. Out of total subjects, 31 were smokers with a mean age 20.84 years and 31 were non-smokers with a mean age 19.97 years and placed in group A and group B, respectively. Plate taping test was administered to all the subjects to determine their speed and coordination of upper limb. Student's t-test was applied between both groups to see the difference in their plate taping test's time; its t-value was 5.03. Statistical significant difference was seen between both the groups in the result of plate taping test, which suggests that smoking can affect the speed and coordination of upper limb in a negative way and cause its deterioration. Therefore, immediate quitting from smoking is of high value and requirements to have a good speed and coordination of upper-limb movements.


Unraveling the Breast: Advances in Mammary Biology and Cancer Methods.
The field of mammary gland biology and breast cancer research encompasses a wide range of topics and scientific questions, which span domains of molecular, cell and developmental biology, cancer research, and veterinary and human medicine, with interdisciplinary overlaps to non-biological domains. Accordingly, mammary gland and breast cancer researchers employ a wide range of molecular biology methods, in vitro techniques, in vivo approaches as well as in silico analyses. The list of techniques is ever-expanding; together with the refinement of established, staple techniques in the field, new technologies keep emerging thanks to technological advances and scientific creativity. This issue of the Journal of Mammary Gland Biology and Neoplasia represents a compilation of original articles and reviews focused on methods used in mammary gland biology and breast cancer research.


Long-term comparison of endovascular and open repair of abdominal aortic aneurysm.
Whether elective endovascular repair of abdominal aortic aneurysm reduces long-term morbidity and mortality, as compared with traditional open repair, remains uncertain. We randomly assigned 881 patients with asymptomatic abdominal aortic aneurysms who were candidates for both procedures to either endovascular repair (444) or open repair (437) and followed them for up to 9 years (mean, 5.2). Patients were selected from 42 Veterans Affairs medical centers and were 49 years of age or older at the time of registration. More than 95% of the patients underwent the assigned repair. For the primary outcome of all-cause mortality, 146 deaths occurred in each group (hazard ratio with endovascular repair versus open repair, 0.97; 95% confidence interval [CI], 0.77 to 1.22; P=0.81). The previously reported reduction in perioperative mortality with endovascular repair was sustained at 2 years (hazard ratio, 0.63; 95% CI, 0.40 to 0.98; P=0.04) and at 3 years (hazard ratio, 0.72; 95% CI, 0.51 to 1.00; P=0.05) but not thereafter. There were 10 aneurysm-related deaths in the endovascular-repair group (2.3%) versus 16 in the open-repair group (3.7%) (P=0.22). Six aneurysm ruptures were confirmed in the endovascular-repair group versus none in the open-repair group (P=0.03). A significant interaction was observed between age and type of treatment (P=0.006); survival was increased among patients under 70 years of age in the endovascular-repair group but tended to be better among those 70 years of age or older in the open-repair group. Endovascular repair and open repair resulted in similar long-term survival. The perioperative survival advantage with endovascular repair was sustained for several years, but rupture after repair remained a concern. Endovascular repair led to increased long-term survival among younger patients but not among older patients, for whom a greater benefit from the endovascular approach had been expected. (Funded by the Department of Veterans Affairs Office of Research and Development; OVER ClinicalTrials.gov number, NCT00094575.).


A systematic review of the content and quality of wrist outcome instruments.
To assess the content and quality of published wrist outcome instruments using standardized criteria. An analytical study that examined 32 wrist outcome instruments sourced from textbooks, Medline (1951 to present) and Current Contents. The content of each instrument was classified into four categories: traditional measures (such as range of movement and strength), measures of the ability to perform daily activities, compensatory mechanisms used, and 'other'. Analysis included the frequency of assessment per category and the method of assessment. In addition, each instrument was graded using 13 quality criteria. Three criteria (scientific justification of the content and scoring system used, demographic utility) were considered to be essential. Eighty-two per cent of instruments reviewed for this paper contained traditional measures, of which most were assessed objectively. The ability to perform specific daily activities was assessed in 31% of the instruments whereas compensatory mechanisms were evaluated in only one instrument. These variables were not assessed in a consistent manner. Using the quality scoring system derived for this study, the quality of the instruments was generally poor. Only one instrument fulfilled all of the essential criteria. Only four instruments completely satisfied more than 50% of the criteria. Most wrist outcome instruments neglected to assess the impact of the disorder on the individual. Outcome was generally not expressed in functional terms or in terms that were relevant to each individual. The majority of the reviewed articles had poor quality. Thus use of these instruments may preclude sensitive evaluation of the efficacy of any intervention.


Size-dependent stability of ultra-small α-/β-phase tin nanocrystals synthesized by microplasma.
Nanocrystals sometimes adopt unusual crystal structure configurations in order to maintain structural stability with increasingly large surface-to-volume ratios. The understanding of these transformations is of great scientific interest and represents an opportunity to achieve beneficial materials properties resulting from different crystal arrangements. Here, the phase transformation from α to β phases of tin (Sn) nanocrystals is investigated in nanocrystals with diameters ranging from 6.1 to 1.6 nm. Ultra-small Sn nanocrystals are achieved through our highly non-equilibrium plasma process operated at atmospheric pressures. Larger nanocrystals adopt the β-Sn tetragonal structure, while smaller nanocrystals show stability with the α-Sn diamond cubic structure. Synthesis at other conditions produce nanocrystals with mean diameters within the range 2-3 nm, which exhibit mixed phases. This work represents an important contribution to understand structural stability at the nanoscale and the possibility of achieving phases of relevance for many applications.


Dietary patterns and non-communicable disease risk in Indian adults: secondary analysis of Indian Migration Study data.
Undernutrition and non-communicable disease (NCD) are important public health issues in India, yet their relationship with dietary patterns is poorly understood. The current study identified distinct dietary patterns and their association with micronutrient undernutrition (Ca, Fe, Zn) and NCD risk factors (underweight, obesity, waist:hip ratio, hypertension, total:HDL cholesterol, diabetes). Data were from the cross-sectional Indian Migration Study, including semi-quantitative FFQ. Distinct dietary patterns were identified using finite mixture modelling; associations with NCD risk factors were assessed using mixed-effects logistic regression models. India. Migrant factory workers, their rural-dwelling siblings and urban non-migrants. Participants (7067 adults) resided mainly in Karnataka, Andhra Pradesh, Maharashtra and Uttar Pradesh. Five distinct, regionally distributed, dietary patterns were identified, with rice-based patterns in the south and wheat-based patterns in the north-west. A rice-based pattern characterised by low energy consumption and dietary diversity ('Rice & low diversity') was consumed predominantly by adults with little formal education in rural settings, while a rice-based pattern with high fruit consumption ('Rice & fruit') was consumed by more educated adults in urban settings. Dietary patterns met WHO macronutrient recommendations, but some had low micronutrient contents. Dietary pattern membership was associated with several NCD risk factors. Five distinct dietary patterns were identified, supporting sub-national assessments of the implications of dietary patterns for various health, food system or environment outcomes.


A genetically clamped renin transgene for the induction of hypertension.
Experimental analysis of the effects of individual components of complex mammalian systems is frequently impeded by compensatory adjustments that animals make to achieve homeostasis. We here introduce a genetic procedure for eliminating this type of impediment, by using as an example the development and testing of a transgene for "genetically clamping" the expression of renin, the major homeostatically responding component of the renin-angiotensin system, one of the most important regulators of blood pressure. To obtain a renin transgene whose expression is genetically clamped at a constant level, we have used single-copy chosen-site gene targeting to insert into a liver-specific locus a single copy of a modified mouse renin transgene driven by a liver-specific promoter/enhancer. The resulting transgene expresses renin ectopically at a constant high level in the liver and leads to elevated plasma levels of prorenin and active renin. The transgenic mice display high blood pressure, enhanced thirst, high urine output, proteinuria, and kidney damage. Treatment with the angiotensin II type I receptor antagonist, losartan, reduces the hypertension, albuminuria, and kidney damage, but does not affect expression of the transgene. This genetically clamped renin transgene can be used in models in which hypertension and its complications need to be investigated in a high prorenin/renin environment that is not subject to homeostatic compensations by the animal when other factors are changed.


Long term risk for hypertension, renal impairment, and cardiovascular disease after gastroenteritis from drinking water contaminated with Escherichia coli O157:H7: a prospective cohort study.
To evaluate the risk for hypertension, renal impairment, and cardiovascular disease within eight years of gastroenteritis from drinking water contaminated with Escherichia coli O157:H7 and Campylobacter. A prospective cohort study. Setting Walkerton, Ontario, Canada. 1977 adult participants in the Walkerton Health Study recruited between 2002 and 2005 after an outbreak of gastroenteritis in May 2000, when a municipal water system was contaminated, with no pre-outbreak history of outcome measures. Information was collected annually via survey, physical examination, and laboratory assessment. Primary measures were acute gastroenteritis (diarrhoeal illness lasting >3 days, bloody diarrhoea, or >3 loose stools/day), hypertension (blood pressure ≥140/90 mm Hg), and renal impairment (microalbuminuria or estimated glomerular filtration rate <60 ml/min/1.73 m(2)). Self reported physician diagnosis of cardiovascular disease (myocardial infarction, stroke, or congestive heart failure) was a secondary outcome. Acute gastroenteritis at the time of the outbreak was reported by 1067 (54%) of participants. Incident hypertension was detected in 697 (35%) (294 (32%) of group not exposed to acute gastroenteritis v 403 (38%) of exposed group). While 572 (29%) had at least one indicator of renal impairment (266 (29%) of unexposed v 306 (29%) of exposed), only 30 (1.5%) had both (8 (0.9%) of unexposed v 22 (2.1%) of exposed). Cardiovascular disease was reported by 33/1749 (1.9%). The adjusted hazard ratios for hypertension and cardiovascular disease after acute gastroenteritis were 1.33 (95% confidence interval 1.14 to 1.54) and 2.13 (1.03 to 4.43) respectively. The adjusted hazard ratio for the presence of either indicator of renal impairment was 1.15 (0.97 to 1.35) and was 3.41 (1.51 to 7.71) for the presence of both. Gastroenteritis from drinking water contaminated with E coli O157:H7 and Campylobacter was associated with an increased risk for hypertension, renal impairment, and self reported cardiovascular disease. Annual monitoring of blood pressure and periodic monitoring of renal function may be warranted for individuals who experience E coli O157:H7 gastroenteritis.


[Posterior reversible encephalopathy syndrome].
Reversible Posterior Leukoencephalopathy Syndrome was introduced into clinical practice in 1996 in order to describe unique syndrome, clinically expressed during hypertensive and uremic encephalopathy, eclampsia and during immunosuppressive therapy [1]. First clinical investigations showed that leucoencephalopathy is major characteristic of the syndrome, but further investigations showed no significant destruction in white cerebral tissue [2, 3, 4]. In majority of cases changes are localise in posterior irrigation area of the brain and in the most severe cases anterior region is also involved. Taking into consideration all above mentioned facts, the suggested term was Posterior Reversible Encephalopathy Syndrome (PRES) for the syndrome clinically expressed by neurological manifestations derived from cortical and subcortical changes localised in posterior regions of cerebral hemispheres, cerebral trunk and cerebellum [5]. Patient, aged 53 years, was re-hospitalized in Cardiovascular Institute "Dediwe" two months after successful aorto-coronary bypass performed in June 2001 due to the chest bone infection. During the treatment of the infection (according to the antibiogram) in September 2001, patient in evening hours developed headache and blurred vision. The recorded blood pressure was 210/120 mmHg so antihypertensive treatment was applied (Nifedipin and Furosemid). After this therapy there was no improvement and intensive headache with fatigue and loss of vision developed. Neurological examination revealed cortical blindness and left hemiparesis. Manitol (20%, 60 ccm every 3 hours) and i.v. Nytroglicerin (high blood pressure). Brain CT revealed oedema of parieto-occipital regions of both hemispheres, more emphasized on the right. (Figure 1a, b, c). There was no sign of focal ischemia even in deeper sections (Figure 1d, e, f). Following three days enormous high blood pressure values were registered. On the fourth day the significant clinical improvement occurred with lowering of blood pressure, better mental state and better vision. There was no sign of left hemiparesis on the 7th day. On the 9th day there were no symptoms or sign of disease. Control brain CT (15th day) was normal. ETHIOPATHOGENESIS: Most common causes of PRES are hypertensive encephalopathy [6-8], pre-eclampsia/eclampsia [9-12] cyclosporin A administration [13-22] and uremic encephalopathy [23]. There are several theories about the mechanism for PRES in hypertensive encephalopathy (reversible vasospasm and hyperperfusion) and administration of cyclosporin A (neurotoxic effect). Most common symptoms are headache, nausea, vomiting, confusion, behavioural changes, changes of conciousness (from somnolencia to stupor), vision disturbances (blurred vision, haemianopsia, cortical blindness) and epileptic manifestations (mostly focal attacks with secondary generalisation). Mental functions are characterised with decreased activity and reactivity, confusion, loss of concentration and mild type of amnesia. Lethargy is often initial sign, sometimes accompanied with phases of agitation. Stupor and coma rarely occurred. In patients with hypertensive encephalopathy and eclampsia high blod pressure is registered. Neurological examination revealed vision changes and damages of mental function as well as increased reflex activity. Today, brain MRI and CT are considered the most important diagnostic method for the diagnosis and follow-up of patients with PRES [6]. Brain MRI better detects smaller focal parenhim abnormalities than brain CT. The most often neuroradiological finding is relatively symmetrical oedema of white cerebral tissue in parieto-occipital regions of both cerebral hemispheres. Gray cerebral tissue is sometimes involved, usually in mild form of disease. Diagnosis of this "cortical" form of PRES is possible by MR FLAIR (Fluid-Attenuated Inversion Recovery) technique [5]. Therapeutic strategy depends on the cause of PRES and clinical picture. Most important are blood pressure regulation (labetalol, nitroprusid, diuretici), control of epileptic attacks (phenytoin), anti-oedema therapy. (Manitol), Induction of vaginal delivery in eclampsia and discontinuation of cyclosporin therapy. In most cases there are no neurological manifestations after the 7th day, but some studies showed normalisation of clinical finding after one year and more.


Relapsing antibody-negative patients with features of neuromyelitis optica spectrum disorders: Differences in N-acetylaspartate level in the cervical spinal cord indicate distinct underlying processes.
Due to lack of biomarkers, antibody-negative patients with features of neuromyelitis optica spectrum disorders (NMOSD) are among the most challenging to diagnose and treat. Using unsupervised clustering, we recently identified 'MS-like', 'spinal MS-like', 'classic NMOSD-like' and 'NMOSD-like with brain involvement' subgroups in this cohort. We used magnetic resonance spectroscopy (MRS) to examine differences in the level of key metabolites in the spinal cord between the four identified subgroups. Twenty-five relapsing antibody-negative patients with NMOSD features classified by the unsupervised algorithm to one of the subgroups underwent a prospective cervical spinal cord MRS. Spectra from 16 patients fulfilled quality criteria and were included in the analysis. Total N-acetylaspartate (tNAA), but not total choline (tCho) or myo-inositol (Ins), was significantly different between the four subgroups (p = 0.03). In particular, tNAA was 47.8% lower in the 'MS-like' subgroup as compared with the 'classic NMOSD-like' subgroup (p = 0.02). While we found a negative overall correlation between tNAA and disability score (r = -0.514, p = 0.04) in the whole cohort, the disability score did not differ significantly between the subgroups to explain subgroup differences in tNAA level. Significant differences in the cervical spinal cord tNAA measurements confirm that the previously identified clinico-radiologic subgroups contain patients with distinct underlying disease processes.


Sensitive fluorescence detection of mercury(ii) in aqueous solution by the fluorescence quenching effect of MoS2 with DNA functionalized carbon dots.
A rapid and sensitive fluorescent sensor based on the MoS2 nanosheet/DNA/carbon dot nanoassembly has been developed towards the detection of mercury(ii) present in environmental samples. Bio-carbon dots (CDs) having strong fluorescence maxima at 451 nm were synthesized via one-step treatment with honey under low temperature carbonization. These CDs were nearly spherical with good size distribution and excellent monodispersity, and the average sizes of CD were around 2-4 nm as evidenced from transmission electron microscopy. The conjugation of DNA strands on the surface of the carbon dots provided an efficient fluorescent probe. The fluorescence of the MoS2 nanosheet/DNA/carbon dot nanoassembly enhanced gradually with the increase in the concentration of Hg2+ ions and the detection limit was found to be 1.02 nM. Furthermore, the fluorescence intensity was found to be linear with the concentration of Hg2+ ions in the range from 0 to 10 nM and their respective coefficient of determination was found to be 0.93676 and 0.98178. The present MoS2 nanosheet/DNA/carbon dot nanoassembly is highly selective toward Hg2+ ions over a wide range of metal ions tested.


Which substance is most dangerous? Perceived harm ratings among students in urban and rural Norway.
Recent studies have challenged the idea that illegal substances are necessarily associated with more harm than those that are legal. This study investigates perceived drug harm among students at the University of Oslo (UO) and at a smaller university located on Norway's coast in a more conservative and religious region, called 'Coastal University' (CU). This study consisted of surveys (n=458) about perceived physical harm, mental health conditions, dependence, injuries and social consequences that may be associated with the use of tobacco, alcohol and cannabis. Information about substance use was also collected. Analyses of variance and multiple regression analyses were used to examine whether harm ratings differed for different drugs, whether drug type, gender and university site interacted in predicting harm ratings, and what role the participants' own substance use played in their harm ratings. UO students rated cannabis as overall less harmful than alcohol, while the opposite was true for CU students. Tobacco received the highest physical harm score. Alcohol was rated as most harmful with regard to injuries; cannabis was rated as most harmful with regard to mental health consequences. Use of the substance in question was associated with a reduced harm rating. This was particularly true for cannabis. Norwegian students rate the harm of substances differently from previous reports from the Norwegian general population. Most importantly, their relative ratings of cannabis harm were lower. However, the pattern was most evident among students from the urban Oslo area.


8:45-9:00. Using PET 18F-FDG, 11CO, and 15O-water for Monitoring Prostate Cancer During a Phase II Anti-angiogenic Drug Trial with Thalidomide.
Assessing prostate metastases is difficult with conventional radiographic modalities as few patients have soft tissue involvement and most have only bone lesions. Even with FDG PET, problems due to decreased avidity compared to other tumor types can occur. We assessed PET's ability to monitor changes in such tumors during an anti-angiogenic therapy. We measured changes in tumor blood flow (15O), blood volume (11CO), 18F-FDG uptake and "metabolic volume" before and during thalidomide treatment, to see if these changes correlated with changes in PSA values.Six patients with androgen-independent prostate cancer were imaged with 18F-FDG, 11CO, and 15O water before and during (mean interval 63 days, range 55-76 days) thalidomide therapy (200-1200mg/day). Lesions were visually identified on FDG images (9 bone, 5 soft tissue lesions). VOI's were generated by 3D region growing, with a 50% maximum pixel threshold. These VOI's were registered with, and applied to, the 11CO and water studies. Correlations with PSA values were done using the Spearman rank test.The change in maximum (r = 0.77, p = 0.06) and mean FDG value (r = 0.83, p = 0.03), functional FDG volume (r = 0.66, p = 0.14), and 11-CO blood volume (r = 0.77, p = 0.06) all correlated with the change in PSA. Changes in blood flow values were smaller than the variance of the method for repeated measures, likely due to low flow values in bone.Changes in blood volume measured by 11CO, and the mean and peak activity and functional volume measured by 18F-FDG, correlate with changes in PSA and may be useful in monitoring anti-angiogenic therapy in prostate cancer.


Between-subject variability in the influence of mental imagery on conscious perception.
Mental imagery and visual perception rely on similar neural mechanisms, but the function of this overlap remains unclear. One idea is that imagery can influence perception. Previous research has shown that imagining a stimulus prior to binocular presentation of rivalling stimuli increases the chance of perceiving the imagined stimulus. In this study we investigated how this effect interacts with bottom-up sensory input by comparing psychometric response curves for congruent and incongruent imagery in humans. A Bayesian hierarchical model was used, allowing us to simultaneously study group-level effects as well as effects for individual participants. We found strong effects of both imagery as well as its interaction with sensory evidence within individual participants. However, the direction of these effects were highly variable between individuals, leading to weak effects at the group level. This highlights the heterogeneity of conscious perception and emphasizes the need for individualized investigation of such complex cognitive processes.


Suicidal Ideation and Related Factors Among Korean High School Students: A Focus on Cyber Addiction and School Bullying.
The purpose of the study was to explore the association among suicidal ideation, cyber addiction, and school bullying of Korean high school students. This descriptive cross-sectional study included 416 students. The data were collected using structured questionnaires on suicidal ideation, Internet and smartphone addiction, experiences of school bullying, impulsiveness, and depression. Students who were bullied (odds ratio [ OR] = 3.0, 95% CI [1.1, 8.4]) and more depressed ( OR = 10.8, 95% CI [2.4, 48.2]) were more likely to have higher scores for suicidal ideation; however, when a lower stringency was used, female gender ( OR = 2.3, 95% CI [1.3, 4.0]) and addiction to smartphones ( OR = 2.4, 95% CI [1.1, 5.4]) were also statistically significant contributors to the presence of suicidal ideation. Students with suicidal ideation that is higher than average, but lower than the classical thresholds for risk group designation, should also be carefully assessed for early detection and intervention. Cyber addiction may be a particularly significant contributor to suicidal ideation, in addition to bullying and depressive mood, among Korean adolescents.


Automatic Segmentation of Mechanically Inhomogeneous Tissues Based on Deformation Gradient Jump.
Variations in properties, active behavior, injury, scarring, and/or disease can all cause a tissue's mechanical behavior to be heterogeneous. Advances in imaging technology allow for accurate full-field displacement tracking of both in vitro and in vivo deformation from an applied load. While detailed strain fields provide some insight into tissue behavior, material properties are usually determined by fitting stress-strain behavior with a constitutive equation. However, the determination of the mechanical behavior of heterogeneous soft tissue requires a spatially varying constitutive equation (i.e., one in which the material parameters vary with position). We present an approach that computationally dissects the sample domain into many homogeneous subdomains, wherein subdomain boundaries are formed by applying a betweenness based graphical analysis to the deformation gradient field to identify locations with large discontinuities. This novel partitioning technique successfully determined the shape, size and location of regions with locally similar material properties for: (1) a series of simulated soft tissue samples prescribed with both abrupt and gradual changes in anisotropy strength, prescribed fiber alignment, stiffness, and nonlinearity, (2) tissue analogs (PDMS and collagen gels) which were tested biaxially and speckle tracked (3) and soft tissues which exhibited a natural variation in properties (cadaveric supraspinatus tendon), a pathologic variation in properties (thoracic aorta containing transmural plaque), and active behavior (contracting cardiac sheet). The routine enables the dissection of samples computationally rather than physically, allowing for the study of small tissues specimens with unknown and irregular inhomogeneity.


Expression of the Opc protein correlates with invasion of epithelial and endothelial cells by Neisseria meningitidis.
Whereas capsulate strains of Neisseria meningitidis are dependent on pili for adhesion to human endothelial and epithelial cells, strains which lacked assembled pili and were partially capsule-deficient adhered to and invaded human endothelial and epithelial cells if they expressed the Opc protein. Bacteria expressing low or undetectable levels of Opc protein failed to adhere to or invade eukaryotic cells. In addition, the presence of OpaAC751 protein on the surface of bacteria did not increase bacterial interactions with host cells. Association of Opc-expressing bacteria was inhibited by antibodies against Opc. Invasion was dependent on the host-cell cytoskeletal activity and was inhibited by cytochalasin D. In some cells, infected at the apical surface, bacteria emerging from basal surface were detected by electron microscopy. Opc is found in diverse meningococci and may represent a common virulence factor which facilitates adherence and invasion by these bacteria.


Apoptotic retinal cell death induced by antirecoverin autoantibodies of cancer-associated retinopathy.
Recoverin has been identified as a target autoantigen for antirecoverin antibodies found in the sera of some patients with cancer-associated retinopathy. The aim of this study was to investigate the role of antirecoverin antibodies in cancer-associated retinopathy. Human, rat, and rabbit antirecoverin antibodies were purified using a recoverin-affinity column. Purified biotinylated antibodies were cultured with recoverin-positive rat retinal cells E1A.NR3. Antibody uptake by retinal cells in vitro was analyzed by immunocytochemistry. Cytotoxic effect of antibodies on retinal cells was measured by the MTT colorimetric method. Apoptosis was shown by the ladder DNA fragmentation method and by fluorescent dye chromatin fragmentation analysis. Antirecoverin antibodies obtained either from sera from five cancer-associated retinopathy patients or from sera of immunized animals were internalized by E1A.NR3 cells. Only specific, antirecoverin antibodies produced destruction of the cells in a dose- and time-dependent manner. Normal immunoglobulin G did not have such effects on retinal cells. No additional cell destruction was observed in the presence of complement as compared with cultures incubated with antirecoverin antibodies alone. Internucleosomal DNA fragmentation and presence of apoptotic cells was observed throughout the culture treated with recoverin specific antibodies but not with normal antibodies. Cells not expressing recoverin (Y79, PC12, and GH3) were not susceptible to cell destruction because of antirecoverin antibody action. These studies showed that antibodies specific to recoverin are able to enter and cause death of cells expressing recoverin. In humans, autoantibodies originally elicited against recoverin expressed in tumor cells may damage retinal photoreceptors and play a role in the pathogenesis of cancer-associated retinopathy. Results suggest that autoantibody to recoverin, when given access to recoverin in the retina through the blood-retina barrier, could initiate photoreceptor degeneration leading to blindness. Such mechanism may be common for other paraneoplastic disorders or autoimmune diseases where antibodies interfere with the normal cell physiology.


Comparison of two immortalized human cell lines to study nuclear receptor-mediated CYP3A4 induction.
Since CYP3A4 is responsible for the biotransformation of over 50% of all clinically used drugs, induction results in an increased clearance of many concomitantly administered drugs, thereby decreasing treatment efficacy or, in the case of prodrugs, lead to severe intoxications. CYP3A4 induction is regulated by the pregnane X receptor, constitutive androstane receptor, and vitamin D receptor. Since these nuclear receptors show large interspecies differences, accurate prediction of nuclear receptor-mediated CYP3A4 induction in humans requires the use of human systems. Because primary cultures of human hepatocytes or enterocytes have major drawbacks like poor availability and poor reproducibility, human cell lines are a good alternative. In this study, the widely used HepG2 cell line was compared with the LS180 cell line to serve as a model to study CYP3A4 induction. There was a clear difference between the cell lines with respect to CYP3A enzyme expression and induction. In LS180, CYP3A4 was expressed and was found to be induced by prototypical nuclear receptor agonists, whereas in HepG2, CYP3A4 was nonresponsive to treatment with rifampicin, CITCO [6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-3,4-dichlorobenzyl) oxime], or calcitriol. We subsequently evaluated whether these host-cell differences also have an effect on CYP3A4 reporter gene activity. We clearly show that there are differences in CYP3A4 reporter activity between the cell lines, and based on these results and those found on mRNA and protein level, we conclude that LS180 is a more suitable cell line to study CYP3A4 induction than the widely used HepG2.


[Burden of rotavirus-related disease among children under five, Colombia, 2004].
To establish an in-hospital surveillance system for diarrhea in children under five, to estimate the burden of rotavirus-related disease, and to identify the most common rotavirus genotypes. Included in the study were children who were hospitalized for serious complications of diarrhea in three medical care facilities in Bogotá, Barranquilla, and Cali, Colombia. A solid-phase enzyme-linked immunosorbent assay (ELISA) was used to detect rotavirus, and reverse-transcriptase polymerase chain reaction (RT-PCR) was the genotyping method employed. The frequencies, central tendency, and dispersion of the variables were determined. Stratified analysis and bivariate analysis were performed by applying a chi squared test or Fisher's exact test, or a chi squared test for trends, depending on the type of data analyzed. Relative risks were established. For analyzing trends we performed linear regression and calculated correlation coefficients and P values. Between December 2003 and November 2004, 893 children were hospitalized in the three participating centers included in the study. Of these children, 68% were between 6 and 23 months of age; 2.7% of hospitalized patients showed clinical signs of hypovolemic shock, and 1.2% died. Only 57% of the mothers had given their children an oral rehydration solution before hospitalization. Rotavirus infection was the cause of 50% of hospitalizations (correlation coefficient [r] > 0.8) and was linked to an inability to hold down orally-ingested fluids (relative risk [RR] = 1.45; 95% confidence interval [95% CI]: 1.24 to 1.69; P < 0.0000) and to intractable vomiting (RR = 1.47; 95% CI: 1.16 to 1.86; P < 0.01). Rotavirus infection led to one death per 2 000 children; 16 hospitalizations per 1 000 children, and 631 medical visits per 1 000 children. A seasonal trend was noted for G1P[8], G2P[4], and G3P[8] rotavirus genotypes, and this did not vary as a result of geographic distance or differences in temperature, humidity, and rainfall among cities. Rotavirus infection is an important cause of morbidity and mortality from diarrhea, particularly during the first years of life, when children are more susceptible to serious complications. It is important for prevention strategies to have a high impact before 6 months of age, and vaccination against rotavirus can be a good complementary intervention strategy. No description was found in the international scientific literature of the seasonal variations in rotavirus genotypes. It is important to carry out cost-effectiveness studies in order to promote the investment of resources in accordance with population needs, and to continue surveillance activities so as to better understand how the virus behaves.


Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans.
Prokaryote-eukaryote interactions are ubiquitous and have important medical and environmental significance. Despite this, a paucity of data exists on the mechanisms and pathogenic consequences of bacterial-fungal encounters within a living host. We used the nematode Caenorhabditis elegans as a substitute host to study the interactions between two ecologically related and clinically troublesome pathogens, the prokaryote, Acinetobacter baumannii, and the eukaryote, Candida albicans. After co-infecting C. elegans with these organisms, we observed that A. baumannii inhibits filamentation, a key virulence determinant of C. albicans. This antagonistic, cross-kingdom interaction led to attenuated virulence of C. albicans, as determined by improved nematode survival when infected with both pathogens. In vitro coinfection assays in planktonic and biofilm environments supported the inhibitory effects of A. baumannii toward C. albicans, further showing a predilection of A. baumannii for C. albicans filaments. Interestingly, we demonstrate a likely evolutionary defense by C. albicans against A. baumannii, whereby C. albicans inhibits A. baumannii growth once a quorum develops. This counteroffensive is at least partly mediated by the C. albicans quorum-sensing molecule farnesol. We used the C. elegans-A. baumannii-C. albicans coinfection model to screen an A. baumannii mutant library, leading to the identification of several mutants attenuated in their inhibitory activity toward C. albicans. These findings present an extension to the current paradigm of studying monomicrobial pathogenesis in C. elegans and by use of genetic manipulation, provides a whole-animal model system to investigate the complex dynamics of a polymicrobial infection.


Sciatica: what the rheumatologist needs to know.
Sciatica is a set of symptoms rather than a specific diagnosis, and is caused by a herniated lumbar disc in the vast majority of cases. The most important symptom is lower limb pain radiating below the knee and into the foot and toes. The clinical course of acute sciatica is generally favorable, with most pain and related disability improving within 2-4 weeks with or without treatment. Diagnosis mainly involves history taking and physical examination. Imaging is warranted if there is evidence of an underlying pathology other than disc herniation, such as infection or malignancy, and in patients with severe symptoms that do not improve after 6-8 weeks of conservative treatment. MRI is the preferred imaging modality, as it can visualize soft tissues better than CT and does not expose the patient to ionizing radiation. Conservative treatment is generally the first-line option in patients with sciatica; however, the currently available evidence does not show any intervention--including a broad range of conservative and surgical approaches--to have clearly superior outcomes. Thus, patient preference seems to be an important factor in the clinical management of sciatica.


Comparison of the in vivo and in vitro antileukemic activity of monosubstituted derivatives of 4'-(9-acridinylamino)methanesulfon-m-anisidide.
The growth-inhibitory activity of 4'-(9-acridinylamino)methanesulfon-m-anisidide and 47 acridine-monosubstituted derivatives has been measured using cultures of L1210 murine leukemia cells grown for 3 days in the presence of each drug. The results have been compared with previously published in vivo antitumor activity and physicochemical properties related to DNA binding, acridine base strength, stability to chemical attack by thiols, and lipophilicity. Multiple-parameter regression equations show that both dose potency and host toxicity in mice are related to a combination of in vitro activity and a nonlinear (quadratic) term in lipophilicity. The in vitro activity can in turn be modeled as a combination of terms representing DNA binding, ability to quench the fluorescence of DNA-bound ethidium stability to thiolysis, and lipophilicity. It is hypothesized that the terms for thiolytic stability and lipophilic-hydrophilic balance describe the availability of the drug to the cell, and that the DNA binding constant determines what proportion of the available drug is bound to DNA, the proposed target site. The remaining terms could reflect changes in the geometry of drug-DNA binding, which in turn affect the intrinsic activity of these drugs when bound at their site of action.


Male circumcision, HIV and sexually transmitted infections: a review.
Three randomized controlled trials in sub-Saharan Africa have shown that circumcision reduces the risk of acquiring HIV infection in men by approximately 60%. In this paper, we review the evidence that male circumcision protects against infection with HIV and other sexually transmitted infections (STIs) in men and their female partners. Data from the clinical trials indicate that circumcision may be protective against genital ulcer disease, Herpes simplex type 2, Trichomonas vaginalis and human papillomavirus infection in men. No evidence exists of a protective effect against Chlamydia trachomatis or Neisseria gonorrhea. There is weak evidence that circumcision has a direct protective effect on HIV infection in women, although there is likely to be an indirect benefit, since HIV prevalence is likely to be lower in circumcised male partners. Although there is little evidence from the trials of serious adverse events from the procedure and of behavioural risk compensation among circumcised men, essential operational research is being conducted to evaluate these key issues outside the trial setting as circumcision services are expanded. Following the publication of the clinical trial results in early 2007, the World Health Organization/UNAIDS has advised that promotion of male circumcision should be included as an additional HIV strategy for the prevention of heterosexually acquired HIV infection in men in areas of high HIV prevalence. As circumcision services are expanded in settings where resources are limited, non-physician providers including nurses will play an important role in the provision of services.


Coxiella burnetii exposure in northern sea otters Enhydra lutris kenyoni.
Valvular endocarditis has been well described in northern sea otters Enhydra lutris kenyoni of Alaska and in many cases no cause has been identified. It is also one of the most common conditions observed in people with chronic Coxiella burnetii infection. Given the high levels of C. burnetii exposure in marine mammals distributed throughout the same geographic range as the northern sea otter, and the presence of valvular lesions seen in otters, the objective of this study was to determine the level of C. burnetii exposure in otters and investigate any association between exposure, infection and valvular disease in this species. Archived serum from 75 live captured, apparently healthy otters (25 from each of 3 stocks) and 30 dead otters were tested for C. burnetii antibodies by indirect florescent antibody assay (IFA). Archived bone marrow and heart valves were tested for C. burnetii DNA by real-time PCR (qPCR). Overall, the seroprevalence in live otters was 17%, with significantly more exposed animals in the south central (40%) stock relative to the southwest (8%) and southeast (4%). The seroprevalence of animals sampled post mortem was 27%, although none of the bone marrow or heart valve samples were positive by qPCR. Results of this study failed to demonstrate a significant association between C. burnetii infection and valvular endocarditis in sea otters; however, the differing seroprevalence suggests that exposure opportunities vary geographically.


Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer's disease.
During the past few years, an increasing set of evidence has supported the major role of deregulation of the interaction patterns between glial cells and neurons in the pathway toward neuronal degeneration. Neurons and glial cells, together with brain vessels, constitute an integrated system for brain function. Inflammation is a process related with the onset of several neurodegenerative disorders, including Alzheimer's disease (AD). Several hypotheses have been postulated to explain the pathogenesis of AD, but none provides insight into the early events that trigger metabolic and cellular alterations in neuronal degeneration. The amyloid hypothesis was sustained on the basis that Abeta-peptide deposition into senile plaques is responsible for neurodegeneration. However, recent findings point to Abeta oligomers as responsible for synaptic impairment in neuronal degeneration. Amyloid is only one among many other major factors affecting the quality of neuronal cells. Another explanation derives from the tau hypothesis, supported by the observations that tau hyperphosphorylations constitute a common feature of most of the altered signaling pathways in degenerating neurons. Altered tau patterns have been detected in the cerebrospinal fluids of AD patients, and a close correlation was observed between the levels of hyperphosphorylated tau isoforms and the degree of cognitive impairment. On the other hand, the anomalous effects of cytokines and trophic factors share in common the activation of tau hyperphosphorylation patterns. In this context, a neuroimmunological approach to AD becomes relevant. When glial cells that normally provide neurotrophic factors essential for neurogenesis are activated by a set of stressing events, they overproduce cytokines and NGF, thus triggering altered signaling patterns in the etiopathogenesis of AD. A solid set of discoveries has strengthened the idea that altered patterns in the glia-neuron interactions constitute early molecular events within the cascade of cellular signals that lead to neurodegeneration in AD. A direct correlation has been established between the Abeta-induced neurodegeneration and cytokine production and its subsequent release. In effect, neuroinflammation is responsible for an abnormal secretion of proinflammatory cytokines that trigger signaling pathways that activate brain tau hyperphosphorylation in residues that are not modified under normal physiological conditions. Other cytokines such as IL-3 and TNF-alpha seem to display neuroprotective activities. Elucidation of the events that control the transitions from neuroprotection to neurodegeneration should be a critical point toward elucidation of AD pathogenesis.


Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury.
Severe lung damage resulting from COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways, and genes present across the spectrum of histopathological damage in COVID-19-affected lung tissue. We applied correlation network-based approaches to deconvolve gene expression data from 46 areas of interest covering more than 62,000 cells within well-preserved lung samples from 3 patients. Despite substantial interpatient heterogeneity, we discovered evidence for a common immune-cell signaling circuit in areas of severe tissue that involves crosstalk between cytotoxic lymphocytes and pro-inflammatory macrophages. Expression of IFNG by cytotoxic lymphocytes was associated with induction of chemokines, including CXCL9, CXCL10, and CXCL11, which are known to promote the recruitment of CXCR3+ immune cells. The TNF superfamily members BAFF (TNFSF13B) and TRAIL (TNFSF10) were consistently upregulated in the areas with severe tissue damage. We used published spatial and single-cell SARS-CoV-2 data sets to validate our findings in the lung tissue from additional cohorts of patients with COVID-19. The resulting model of severe COVID-19 immune-mediated tissue pathology may inform future therapeutic strategies.


Hyperpolarized (3)He pulmonary functional magnetic resonance imaging prior to radiation therapy.
Radiation-induced lung injury (RILI) is the primary dose-limiting toxicity for radiation therapy of the lung, and although the effects of radiation dose on RILI development have been well characterized, the influence of chronic obstructive pulmonary disease (COPD) on the development of RILI and other outcomes is not well understood. The purpose of this small pilot study was to evaluate the relationship between hyperpolarized (3)He magnetic resonance imaging (MRI) measurements of COPD with RILI and 12-month survival in lung cancer patients undergoing radical radiotherapy and to evaluate the feasibility of pulmonary functional MRI as an image guidance∕planning tool for radiation therapy. Fifteen non-small cell and small cell lung cancer patients underwent pulmonary function tests, x-ray computed tomography (CT), and hyperpolarized (3)He MRI prior to radical radiation therapy (≥60 Gy). Conventional thoracic (1)H and hyperpolarized (3)He MRI were acquired to generate ventilation defect percent and the apparent diffusion coefficient for the ipsilateral and contralateral lungs independently. CT was acquired postradiation therapy and qualitatively evaluated for radiological evidence of RILI and 12-month survival was reported. Hyperpolarized (3)He MRI measurements of COPD classified 10∕15 subjects with contralateral lung COPD (CLC), and five subjects without COPD [contralateral lung normal (CLN)]. Of the 10 subjects with CLC, only four had a previous clinical diagnosis of COPD. CT images were acquired postradiation therapy for 13 subjects, and for eight (62%) of these there was qualitative evidence of RILI, including 5∕9 CLC and 3∕4 CLN subjects. The one-year survival was 2∕10 for CLC and 3∕5 for CLN subjects. In this small pilot study, we report the use of (3)He MRI to stratify lung cancer patients based on MRI evidence of COPD and showed that comorbid COPD was present in the majority of lung cancer subjects stratified for radiation therapy. Lung cancer patients with imaging evidence of COPD did not have an increased incidence of RILI compared to patients without COPD. However, preliminary data presented here indicated that one-year survival in COPD subjects was lower than expected based on previously published survival rates, which may have implications for radiation therapy in lung cancer patients with comorbid COPD.


Sleep enhances memory consolidation in children.
Sleep is an active state that plays an important role in the consolidation of memory. It has been found to enhance explicit memories in both adults and children. However, in contrast to adults, children do not always show a sleep-related improvement in implicit learning. The majority of research on sleep-dependent memory consolidation focuses on adults; hence, the current study examined sleep-related effects on two tasks in children. Thirty-three typically developing children aged 6-12 years took part in the study. Actigraphy was used to monitor sleep. Sleep-dependent memory consolidation was assessed using a novel non-word learning task and the Tower of Hanoi cognitive puzzle, which involves discovering an underlying rule to aid completion. Children were trained on the two tasks and retested following approximately equal retention intervals of both wake and sleep. After sleep, children showed significant improvements in performance of 14% on the non-word learning task and 25% on the Tower of Hanoi task, but no significant change in score following the wake retention interval. Improved performance on the Tower of Hanoi may have been due to children consolidating explicit aspects of the task, for example rule-learning or memory of previous sequences; thus, we propose that sleep is necessary for consolidation of explicit memory in children. Sleep quality and duration were not related to children's task performance. If such experimental sleep-related learning enhancement is generalizable to everyday life, then it is clear that sleep plays a vital role in children's educational attainment.


Increased structural connectivity in grapheme-color synesthesia.
Diffusion tensor imaging allowed us to validate for the first time the hypothesis that hyperconnectivity causes the added sensations in synesthesia. Grapheme-color synesthetes (n = 18), who experience specific colors with particular letters or numbers (for example, 'R is sky blue'), showed greater anisotropic diffusion compared with matched controls. Greater anisotropic diffusion indicates more coherent white matter. Anisotropy furthermore differentiated subtypes of grapheme-color synesthesia. Greater connectivity in the inferior temporal cortex was particularly strong for synesthetes who see synesthetic color in the outside world ('projectors') as compared with synesthetes who see the color in their 'mind's eye' only ('associators'). In contrast, greater connectivity (as compared with non-synesthetes) in the superior parietal or frontal cortex did not differentiate between subtypes of synesthesia. In conclusion, we found evidence that increased structural connectivity is associated with the presence of grapheme-color synesthesia, and has a role in the subjective nature of synesthetic color experience.


Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii.
The caudal nucleus of the solitary tract (NTS) serves as the site of the first synapse for visceral sensory inputs to the central nervous system. The NTS sends functional projections to multiple brain nuclei, with gastric-related projections primarily targeting the dorsal motor nucleus of the vagus (DMV). Previous studies have demonstrated that the majority of caudal NTS neurons that project to the DMV respond robustly to nicotine and express nicotinic acetylcholine receptors (nAChRs). However, the cytochemical identity and relationship with specific viscera of DMV-projecting, nicotine-responsive caudal NTS neurons have not been determined. The present study used transgenic mice that express enhanced green fluorescent protein (EGFP) under a GAD67 promoter in a subset of GABAergic neurons, in vivo retrograde pseudorabies viral labeling to identify gastric-related vagal complex neurons, and patch-clamp electrophysiology in acute brain stem slices to test the hypothesis that gastric-related and GABAergic inhibitory synaptic input to the DMV from the caudal NTS is under a robust modulatory control by nAChRs. Our results suggest that activation of nAChRs in the caudal NTS, but not DMV, potentiates GABAergic, but not glutamatergic, input to the DMV. Gastric-related caudal NTS and DMV neurons are directly involved in this nicotine-sensitive circuitry. Understanding the central patterns of nicotinic modulation of visceral sensory-motor circuitry may help develop therapeutic interventions to restore autonomic homeostasis in patients with autonomic impairments.


Bioengineered three-dimensional physiological model of colonic longitudinal smooth muscle in vitro.
The objective of this study was to develop a physiological model of longitudinal smooth muscle tissue from isolated longitudinal smooth muscle cells arranged in the longitudinal axis. Longitudinal smooth muscle cells from rabbit sigmoid colon were isolated and expanded in culture. Cells were seeded at high densities onto laminin-coated Sylgard surfaces with defined wavy microtopographies. A highly aligned cell sheet was formed, to which addition of fibrin resulted in delamination. (1) Acetylcholine (ACh) induced a dose-dependent, rapid, and sustained force generation. (2) Absence of extracellular calcium attenuated the magnitude and sustainability of ACh-induced force by 50% and 60%, respectively. (3) Vasoactive intestinal peptide also attenuated the magnitude and sustainability of ACh-induced force by 40% and 60%, respectively. These data were similar to force generated by longitudinal tissue. (4) Bioengineered constructs also maintained smooth muscle phenotype and calcium-dependence characteristics. This is a novel physiologically relevant in vitro three-dimensional model of colonic longitudinal smooth muscle tissue. Bioengineered three-dimensional longitudinal smooth muscle presents the ability to generate force, and respond to contractile agonists and relaxant peptides similar to native longitudinal tissue. This model has potential applications to investigate the underlying pathophysiology of dysfunctional colonic motility. It also presents as a readily implantable band-aid colonic longitudinal muscle tissue.


Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs.
Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti, ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.


Escitalopram modulates neuron-remodelling proteins in a rat gene-environment interaction model of depression as revealed by proteomics. Part I: genetic background.
The wide-scale analysis of protein expression provides a powerful strategy for the molecular exploration of complex pathophysiological mechanisms, such as the response to antidepressants. Using a 2D proteomic approach we investigated the Flinders Sensitive Line (FSL), a genetically selected rat model of depression, and the control Flinders Resistant Line (FRL). To evaluate gene-environment interactions, FSL and FRL pups were separated from their mothers for 3 h (maternal separation, MS), as early-life trauma is considered an important antecedent of depression. All groups were treated with either escitalopram (Esc) admixed to food (25 mg/kg.d) or vehicle for 1 month. At the week 3, forced swim tests were performed. Protein extracts from prefrontal/frontal cortex and hippocampus were separated by 2D electrophoresis. Proteins displaying statistically significant differences in expression levels were identified by mass spectrometry. Immobility time values in the forced swim test were higher in FSL rats and reduced by antidepressant treatment. Moreover, the Esc-induced reduction in immobility time was not detected in MS rats. The impact of genetic background in response to Esc was specifically investigated here. Bioinformatics analyses highlighted gene ontology terms showing tighter associations with the modulated proteins. Esc modulated protein belonging to cytoskeleton organization in FSL; carbohydrate metabolism and intracellular transport in FRL. Proteins differently modulated in the two strains after MS and Esc play a role in cytoskeleton organization, vesicle-mediated transport, apoptosis regulation and macromolecule catabolism. These findings suggest pathways involved in neuronal remodelling as molecular correlates of response to antidepressants in a model of vulnerability.


Aerosol delivery of muramyl dipeptide to rodent lungs.
Tuberculosis is the single most serious infectious disease worldwide. The respiratory tract is the primary site of infection by Mycobacterium tuberculosis(MTB). A number of immunogenic components of the cell wall of MTB, if delivered to the lungs as aerosols, can be used to study the local immune response. The site of deposition of these aerosols can be employed to control their residence time in the lungs. Muramyl dipeptide (MDP) aerosols were delivered to alveolar macrophages in the lungs of rodents. Guinea pig macrophages harvested by bronchoalveolar lavage were examined by differential interference contrast microscopy for morphological changes indicative of activation. Bronchoalveolar lavage fluid was analyzed for the presence of alkaline phosphatase, lactate dehydrogenase, N-acetyl-glucosaminidase (NAG), and total protein content. Rat alveolar macrophages were studied for the production of nitric oxide, by induction of nitric oxide synthase. Twenty-four hours following exposure to an aerosol of MDP, alveolar macrophages exhibited morphological characteristics (spreading and pseudopodia), enzyme activity (NAG 50% above control), and production of the reactive intermediate nitric oxide. Rat macrophages subjected to aerosol exposure to MDP when challenged with a second dose of MDP or lipopolysaccharide exhibited a linear dose response as measured by nitric oxide production. These studies indicate that the topical delivery of an MTB bacterial cell wall component, muramyl dipeptide, results in activation of alveolar macrophages. This approach may be useful in elucidating elements of the immune response to MTB.


Anatomical features of the canine C2-C3 spinal cord vascular environment.
Interarcuate branch (IAB) is a vascular structure, particularly developed in C2-3 intervertebral space, forming a dorsal bridge that connects ventral venous plexi in the vertebral canal. While precisely described in the human, the precise anatomical features of IABs have not been reported in the veterinary literature. The purpose of this study is to describe the features and relations of IABs in the C2-3 vertebral canal. 10 dogs were enrolled; 5 dogs for necropsy and 5 dogs for histology. The ventral venous plexi in the cervical spine of 5 dogs were injected with latex and underwent vertebral canal dissection for visual assessment of the IAB. Two out of 5 dogs were injected with the addition of barium sulfate and underwent a CT scan. The C2-3 regions of 5 small-breed dogs were harvested for histological examinations. IABs arose from the ventral venous plexus at the level of the intervertebral vein; they originated from 2 separate branches located caudally and cranially to the intervertebral foramen, forming a ventrodorsal triangle surrounding the spinal nerve root. No dorsal anastomosis was observed on the CT scan nor at dissection but were observed histologically. A cervical fibrous sheath was observed all around the vertebral canal. IABs are voluminous venous structures at the C2-3 intervertebral space in dogs and found within a split of the cervical fibrous sheath, which is adherent to the interarcuate ligament and the ligamentum flavum. This anatomical description is paramount when planning an approach to the C2-3 intervertebral space.


Mass cytometry analysis reveals a distinct immune environment in peritoneal fluid in endometriosis: a characterisation study.
Endometriosis is a gynaecological condition characterised by immune cell infiltration and distinct inflammatory signatures found in the peritoneal cavity. In this study, we aim to characterise the immune microenvironment in samples isolated from the peritoneal cavity in patients with endometriosis. We applied mass cytometry (CyTOF), a recently developed multiparameter single-cell technique, in order to characterise and quantify the immune cells found in peritoneal fluid and peripheral blood from endometriosis and control patients. Our results demonstrate the presence of more than 40 different distinct immune cell types within the peritoneal cavity. This suggests that there is a complex and highly heterogeneous inflammatory microenvironment underpinning the pathology of endometriosis. Stratification by clinical disease stages reveals a dynamic spectrum of cell signatures suggesting that adaptations in the inflammatory system occur due to the severity of the disease. Notably, among the inflammatory microenvironment in peritoneal fluid (PF), the presence of CD69+ T cell subsets is increased in endometriosis when compared to control patient samples. On these CD69+ cells, the expression of markers associated with T cell function are reduced in PF samples compared to blood. Comparisons between CD69+ and CD69- populations reveal distinct phenotypes across peritoneal T cell lineages. Taken together, our results suggest that both the innate and the adaptive immune system play roles in endometriosis. This study provides a systematic characterisation of the specific immune environment in the peritoneal cavity and identifies cell immune signatures associated with endometriosis. Overall, our results provide novel insights into the specific cell phenotypes governing inflammation in patients with endometriosis. This prospective study offers a useful resource for understanding disease pathology and opportunities for identifying therapeutic targets.


Motion-map constrained image reconstruction (MCIR): application to four-dimensional cone-beam computed tomography.
Utilization of respiratory correlated four-dimensional cone-beam computed tomography (4DCBCT) has enabled verification of internal target motion and volume immediately prior to treatment. However, with current standard CBCT scan, 4DCBCT poses challenge for reconstruction due to the fact that multiple phase binning leads to insufficient number of projection data to reconstruct and thus cause streaking artifacts. The purpose of this study is to develop a novel 4DCBCT reconstruction algorithm framework called motion-map constrained image reconstruction (MCIR), that allows reconstruction of high quality and high phase resolution 4DCBCT images with no more than the imaging dose as well as projections used in a standard free breathing 3DCBCT (FB-3DCBCT) scan. The unknown 4DCBCT volume at each phase was mathematically modeled as a combination of FB-3DCBCT and phase-specific update vector which has an associated motion-map matrix. The motion-map matrix, which is the key innovation of the MCIR algorithm, was defined as the matrix that distinguishes voxels that are moving from stationary ones. This 4DCBCT model was then reconstructed with compressed sensing (CS) reconstruction framework such that the voxels with high motion would be aggressively updated by the phase-wise sorted projections and the voxels with less motion would be minimally updated to preserve the FB-3DCBCT. To evaluate the performance of our proposed MCIR algorithm, we evaluated both numerical phantoms and a lung cancer patient. The results were then compared with the (1) clinical FB-3DCBCT reconstructed using the FDK, (2) 4DCBCT reconstructed using the FDK, and (3) 4DCBCT reconstructed using the well-known prior image constrained compressed sensing (PICCS). Examination of the MCIR algorithm showed that high phase-resolved 4DCBCT with sets of up to 20 phases using a typical FB-3DCBCT scan could be reconstructed without compromising the image quality. Moreover, in comparison with other published algorithms, the image quality of the MCIR algorithm is shown to be excellent. This work demonstrates the potential for providing high-quality 4DCBCT during on-line image-guided radiation therapy (IGRT), without increasing the imaging dose. The results showed that (at least) 20 phase images could be reconstructed using the same projections data, used to reconstruct a single FB-3DCBCT, without streak artifacts that are caused by insufficient projections.


Peripheral anterior synechiae and ultrasound biomicroscopic parameters in angle-closure glaucoma suspects.
To investigate the correlation between peripheral anterior synechia (PAS) and the quantitative anterior chamber angle parameters measured by ultrasound microscopy (UBM) in angle-closure glaucoma suspect (ACGS) eyes. Eyes were defined ACGS as having occludable angles and intraocular pressure less than 21 mm Hg without glaucomatous optic nerve head. The gonioscopic criteria for ACGS were the trabecular meshwork invisible in 3 or more quadrants of the entire angle and the angular width less than 20 degrees by Shaffer classification. Twenty-seven eyes of 20 patients underwent anterior chamber angle and ciliary body imaging with UBM. Angle opening distance (AOD(500)), angle recess area (ARA), trabecular-ciliary process distance (TCPD) and trabecular-iris angle (TIA) were measured from the UBM images at each quadrant. The AOD(500), ARA, and TIA were not significantly different between the eyes with PAS (9 eyes) and without PAS (18 eyes) at each quadrant. However, the TCPD was significantly shorter in the superior quadrant when compared with the eyes without PAS (mean: 405.3+/-70.9 microm vs 536.4+/-140.5 microm) (p<0.05). The results suggest that the shorter distance from trabecular meshwork to ciliary body or the anterior placement of ciliary process may play a role in the development of PAS in ACGS eyes.


Impact of level five lockdown on the incidence of COVID-19: lessons learned from South Africa.
the level five (L5) lockdown was a very stringent social distancing measure taken to reduce the spread of COVID-19 infections. This study assessed the impact of the L5 lockdown and its association with the incidence of COVID-19 cases in South Africa (SA). data was obtained from the National Department of Health (NDoH) from the 5th March to the 30th April 2020. A basic reproductive number (R0) and a serial interval were used to calculate estimated cases (EC). A double exponential smoothing model was used to forecast the number of cases during the L5 lockdown period. A Poisson regression model was fitted to describe the association between L5 lockdown status and incident cases. a total of 5,737 laboratory-confirmed cases (LCC) were reported by 30th April 2020, 4,785 (83%) occurred during L5 lockdown. Our model forecasted 30,629 cases of COVID-19 assuming L5 lockdown was not imposed. High incidence rates of COVID-19 were recorded in KwaZulu-Natal and Mpumalanga Provinces during the L5 lockdown compared to the other provinces. Nationally, the incident rate of COVID-19 was 68.00% higher in L5 lockdown than pre-lockdown for LCC. the L5 lockdown was very effective in reducing the incidence of COVID-19 cases. However, the incident rates of LCC and EC were higher nationally, and in some provinces during the L5 lockdown.