Utility of digital stereo images for optic disc evaluation.
To assess the suitability of digital stereo images for optic disc evaluations in glaucoma. Stereo color optic disc images in both digital and 35-mm slide film formats were acquired contemporaneously from 29 subjects with various cup-to-disc ratios (range, 0.26-0.76; median, 0.475). Using a grading scale designed to assess image quality, the ease of visualizing optic disc features important for glaucoma diagnosis, and the comparative diameters of the optic disc cup, experienced observers separately compared the primary digital stereo images to each subject's 35-mm slides, to scanned images of the same 35-mm slides, and to grayscale conversions of the digital images. Statistical analysis accounted for multiple gradings and comparisons and also assessed image formats under monoscopic viewing. Overall, the quality of primary digital color images was judged superior to that of 35-mm slides (P < 0.001), including improved stereo (P < 0.001), but the primary digital color images were mostly equivalent to the scanned digitized images of the same slides. Color seemingly added little to grayscale optic disc images, except that peripapillary atrophy was best seen in color (P < 0.0001); both the nerve fiber layer (P < 0.0001) and the paths of blood vessels on the optic disc (P < 0.0001) were best seen in grayscale. The preference for digital over film images was maintained under monoscopic viewing conditions. Digital stereo optic disc images are useful for evaluating the optic disc in glaucoma and allow the application of advanced image processing applications. Grayscale images, by providing luminance distinct from color, may be informative for assessing certain features.


Scenario planning with linked land-sea models inform where forest conservation actions will promote coral reef resilience.
We developed a linked land-sea modeling framework based on remote sensing and empirical data, which couples sediment export and coral reef models at fine spatial resolution. This spatially-explicit (60 × 60 m) framework simultaneously tracks changes in multiple benthic and fish indicators as a function of land-use and climate change scenarios. We applied this framework in Kubulau District, Fiji, to investigate the effects of logging, agriculture expansion, and restoration on coral reef resilience. Under the deforestation scenario, models projected a 4.5-fold sediment increase (>7,000 t. yr-1) coupled with a significant decrease in benthic habitat quality across 1,940 ha and a reef fish biomass loss of 60.6 t. Under the restoration scenario, models projected a small (<30 t. yr-1) decrease in exported sediments, resulting in a significant increase in benthic habitat quality across 577 ha and a fish biomass gain of 5.7 t. The decrease in benthic habitat quality and loss of fish biomass were greater when combining climate change and deforestation scenarios. We evaluated where land-use change and bleaching scenarios would impact sediment runoff and downstream coral reefs to identify priority areas on land, where conservation or restoration could promote coral reef resilience in the face of climate change.


Talker-listener accent interactions in speech-in-noise recognition: effects of prosodic manipulation as a function of language experience.
Previous work has shown that accents affect speech recognition accuracy in noise, with intelligibility being modulated by the similarity between the talkers' and listeners' accents, particularly in the case where they have different L1s. The present study examined the contribution of prosody to recognizing native (L1) and non-native (L2) speech in noise, and how this is affected by the listener's L2 experience. A group of monolingual English listeners and two groups of French listeners with varying L2 English experience were presented with English sentences produced by L1 and L2 (French) speakers. The stimuli were digitally processed to exchange the pitch and segment durations between recordings of the same sentences produced by different speakers (e.g., imposing a French-accented prosody onto recordings made from English speakers). The results revealed that English listeners were more accurate at recognizing L1 English with English prosody, the French inexperienced listeners were more accurate at recognizing French-accented speech with French prosody, and the French experienced listeners varied in the cues that they used depending on the noise level, showing more flexibility of processing. The use of prosodic cues in noise thus appears to be modulated by language experience and varies according to listening context.


Bayesian analysis of the short-term association of NO2 exposure with local burden of asthmatic symptoms in children.
Short-term exposure to air pollution has been associated with exacerbation of respiratory diseases such as asthma. Substantial heterogeneity in effect estimates has been observed between previous studies. This study aims to quantify the local burden of daily asthma symptoms in asthmatic children in a medium-sized city. Air pollution exposure was estimated using the nearest sensor in a fine resolution urban air quality sensor network in the city of Eindhoven, the Netherlands. Bayesian estimates of the exposure response function were obtained by updating a priori information from a meta-analysis with data from a panel study using a daily diary. Five children participated in the panel study, resulting in a total of 400 daily diary records. Positive associations between NO2 and lower respiratory symptoms and medication use were observed. The odds ratio for any lower respiratory symptoms was 1.07 (95% C.I. 0.92, 1.28) expressed per 10 μg m-3 for current day NO2 concentration, using data from the panel study only (uninformative prior). Odds ratios for dry cough and phlegm were close to unity. The pattern of associations agreed well with the updated meta-analysis. The meta-analytic random effects summary estimate was 1.05 (1.02, 1.07) for LRS. Credible intervals substantially narrowed when adding prior information from the meta-analysis. The odds ratio for lower respiratory symptoms with an informative prior was 1.06 (0.99, 1.14). Burden of disease maps showed a strong spatial variability in the number of asthmatic symptoms associated with ambient NO2 derived from a regression kriging model. In total, 70 cases of asthmatic symptoms can daily be associated with NO2 exposure in the city of Eindhoven. We conclude that Bayesian estimates are useful in estimation of specific local air pollution effect estimates and subsequent local burden of disease calculations. With the fine resolution air quality network, neighborhood-specific burden of asthmatic symptoms was assessed.


[Recovery of acetylcholinesterase activity in the axolotl embryo following inhibition with the organophosphorus inhibitor Gd-7].
The restoration of acetylcholinesterase (AChE) activity in axolotl Ambystoma mexicanum embryo after treatment at 38-42 stages with irreversibly AChE-inhibiting Gd-7 phosphororganic inhibitor in concentrations, significantly decreasing AChE activity level, but not interfering with ontogenesis has been studied. The rate of AChE activity restoration in Gd-7 treated axolotl embryo depends on the level of the enzyme restraint and the stage of the embryo development. The value of maximal restoration of AChE activity differs; it is less in embryos, treated with Gd-7 at later stages of development. The ability of the embryos to swim restores parallel to the increase in AChE activity. The data obtained suggest that axolotl embryo possess compensatory mechanism for increasing AChE biosynthesis after decrease in its activity caused by Gd-7. Acetylcholine, accumulating in the organism at partial inactivation of AChE by phosphororganic inhibitor may participate in this mechanism.


Function and Regulation of Chloroplast Peroxiredoxin IIE.
Peroxiredoxins (PRX) are thiol peroxidases that are highly conserved throughout all biological kingdoms. Increasing evidence suggests that their high reactivity toward peroxides has a function not only in antioxidant defense but in particular in redox regulation of the cell. Peroxiredoxin IIE (PRX-IIE) is one of three PRX types found in plastids and has previously been linked to pathogen defense and protection from protein nitration. However, its posttranslational regulation and its function in the chloroplast protein network remained to be explored. Using recombinant protein, it was shown that the peroxidatic Cys121 is subjected to multiple posttranslational modifications, namely disulfide formation, S-nitrosation, S-glutathionylation, and hyperoxidation. Slightly oxidized glutathione fostered S-glutathionylation and inhibited activity in vitro. Immobilized recombinant PRX-IIE allowed trapping and subsequent identification of interaction partners by mass spectrometry. Interaction with the 14-3-3 υ protein was confirmed in vitro and was shown to be stimulated under oxidizing conditions. Interactions did not depend on phosphorylation as revealed by testing phospho-mimicry variants of PRX-IIE. Based on these data it is proposed that 14-3-3υ guides PRX‑IIE to certain target proteins, possibly for redox regulation. These findings together with the other identified potential interaction partners of type II PRXs localized to plastids, mitochondria, and cytosol provide a new perspective on the redox regulatory network of the cell.


Protective effects of topical antioxidants in humans.
Human studies have convincingly demonstrated pronounced photoprotective effects of 'natural' and synthetic antioxidants when applied topically before UVR exposure. Particularly with respect to UVB-induced skin damage such as erythema formation, the photoprotective effects of antioxidants are significant when applied in distinct mixtures in appropriate vehicles. Topical application of such combinations may result in a sustained antioxidant capacity of the skin, possibly due to antioxidant synergisms. And, since UVA-induced skin alterations are believed to be largely determined by oxidative processes [26], topical administration of antioxidants might be particularly promising [27, 28]. In fact, topical application of antioxidants or antioxidant mixtures resulted in a remarkable increase in the minimal dose to induce immediate pigment darkening after UVA exposure [18, 23] and diminished the severity of UVA-induced photodermatoses [22] in humans. In conclusion, regular application of skin care products containing antioxidants may be of the utmost benefit in efficiently preparing our skin against exogenous oxidative stressors occurring during daily life. Furthermore, sunscreening agents may also benefit from combination with antioxidants resulting in increased safety and efficacy of such photoprotective products [11, 29].


How does infant behaviour relate to weight gain and adiposity?
An understanding of how infant eating behaviour relates to later obesity is required if interventions in infancy are to be attempted. The aim of this paper is to review findings from the Gateshead Millennium Study to describe (i) what we have already established about the relationship between infant feeding transitions, infancy weight gain and eating behaviour and (ii) describe new analyses that examine how infant eating behaviour and temperament relate to infancy weight gain and childhood adiposity. The Gateshead Millennium Study recruited 1029 infants at birth and parents completed questionnaires five times in the first year. We have already described how starting solids and ceasing breast-feeding seems to be a response to rapid early weight gain, rather than a cause, and that parents identify and respond to the individual appetite characteristics of their child. A number of questions about eating behaviour at 12 months were used to construct an infancy eating avidity score that was positively associated with height at age 7-8 years, but not with an adiposity index constructed using bioelectrical impedance, waist and skinfolds. Infancy eating avidity score was associated with greater fussiness and lower satiety responsivity on the Child Eating Behaviour Questionnaire at age 6-8 years. Temperament measured at age 6 weeks and 8 months showed no consistent associations with either infancy weight gain or adiposity at 6-8 years. While infancy may seem a logical time to intervene with children at risk of future obesity, the collective findings from this substantial population-based study largely suggest otherwise.


Effects of artesunate, dihydroartemisinin, and an artesunate-dihydroartemisinin combination against Toxoplasma gondii.
The effect of artesunate and its metabolite dihydroartemisinin against the cerebral cysts of Toxoplasma gondii was studied. In vitro experiments were performed with the THP-1 cell line and showed an inhibition of parasite growth of approximately 70% with 0.1-0.5 microg/ml of dihydroartemisinin for 96 hr. However, with artesunate, dihydroartemisinin, or a combination (50:50) of them, the number of tachyzoites decreased approximately 40-50% and they appeared motionless. Fifty-eight to 72 hr after washing of the tachyzoites and THP-1 cells in culture, parasitized cells reappeared. In vivo, the 50:50 artesunate-dihydroartemisinin combination produced a decrease in cerebral cysts of approximately 40% after only 5 days of treatment. However, transplantations into naive mice using brains of treated mice gave positive results.


Genetic background of attenuated Salmonella typhimurium has profound influence on infection and cytokine patterns in human dendritic cells.
Salmonella typhimurium (ST) can cause infection in man, and attenuated strains are under consideration as live vaccine vectors. However, little is known about the interaction of ST with human dendritic cells (DC). Here, we compared the consequences of exposure of human, monocyte-derived DC with different attenuated strains of ST. Infection was observed with all four strains tested (wild type, PhoP-, PhoPc, and AroA), but the PhoPc strain was by far the most efficient. Intracellular persistence of wild type and PhoP- was longer than that of PhoPc and AroA, both of which were largely eliminated within 24 h. Most DC survived infection by the attenuated strains, although apoptosis was observed in a fraction of the exposed cells. All strains induced DC maturation, independent from the extent of infection. Although all strains stimulated secretion of TNF-alpha and IL-12 strongly, PhoPc induced significantly less IL-10 than the other three strains and as much as 10 times less IL-10 than heat-killed PhoPc, suggesting that this mutant suppressed the secretion of IL-10 by the DC. These data indicate that infectivity, bacterial elimination, and cytokine secretion in human DC are controlled by the genetic background of ST.


Evaluation of radiological examination for sensorineural hearing loss.
The accuracy of radiological examinations has improved and their diagnostic ability has markedly increased. However, the cost of such examinations has also recently become an issue. In this study, the clinical significance of radiological examinations for sensorineural hearing loss (SNHL) was evaluated and the value of their utilization was reconsidered. A total of 1,276 ears of 724 patients who demonstrated unilateral or bilateral SNHL was studied retrospectively. Findings of radiological examinations such as plain X-ray (X-p), computed tomography (CT) and magnetic resonance imaging (MRI) of the brain or the temporal bone were investigated. Temporal bone X-p was usually performed to rule out acoustic tumors (AT). CT was further performed in 119 patients (16.4%) and MRI in 84 patients (11.6%) in total. The reasons or symptoms for further examination such as CT or MRI were X-p findings or auditory symptoms suspicious for AT or vertigo/dizziness suspicious for intracranial disease. Of five causes with AT, two with a small tumor exhibited normal findings for the internal auditory canal on temporal bone X-p. These small ATs were finally confirmed by MRI. MRI could also detect lacunar infarctions, cerebral atrophy and high jugular bulb which might be related to SNHL. These findings confirmed that MRI is very useful for detecting small ATs and suggested that MRI also reveals cerebral vascular insufficiency in patients with SNHL.


Suppression of prion protein in livestock by RNA interference.
Given the difficulty of applying gene knockout technology to species other than mice, we decided to explore the utility of RNA interference (RNAi) in silencing the expression of genes in livestock. Short hairpin RNAs (shRNAs) were designed and screened for their ability to suppress the expression of caprine and bovine prion protein (PrP). Lentiviral vectors were used to deliver a transgene expressing GFP and an shRNA targeting PrP into goat fibroblasts. These cells were then used for nuclear transplantation to produce a cloned goat fetus, which was surgically recovered at 81 days of gestation and compared with an age-matched control derived by natural mating. All tissues examined in the cloned fetus expressed GFP, and PCR analysis confirmed the presence of the transgene encoding the PrP shRNA. Most relevant, Western blot analysis performed on brain tissues comparing the transgenic fetus with control demonstrated a significant (>90%) decrease in PrP expression levels. To confirm that similar methodologies could be applied to the bovine, recombinant virus was injected into the perivitelline space of bovine ova. After in vitro fertilization and culture, 76% of the blastocysts exhibited GFP expression, indicative that they expressed shRNAs targeting PrP. Our results provide strong evidence that the approach described here will be useful in producing transgenic livestock conferring potential disease resistance and provide an effective strategy for suppressing gene expression in a variety of large-animal models.


Population genomic monitoring provides insight into conservation status but no correlation with demographic estimates of extinction risk in a threatened trout.
The current extinction crisis requires effective assessment and monitoring tools. Genetic approaches are appealing given the relative ease of field sampling required to estimate genetic diversity characteristics assumed related to population size, evolutionary potential, and extinction risk, and to evaluate hybridization with non-native species simultaneously. However, linkages between population genetic metrics of diversity from survey-style field collections and demographic estimates of population size and extinction risk are still in need of empirical examples, especially for remotely distributed species of conservation concern where the approach might be most beneficial. We capitalized on an exceptional opportunity to evaluate congruence between genetic diversity metrics and demographic-based estimates of abundance and extinction risk from a comprehensive Multiple Population Viability Analysis (MPVA) in a threatened fish, the Lahontan cutthroat trout (LCT). We sequenced non-native trout reference samples and recently collected and archived tissue samples of most remaining populations of LCT (N = 60) and estimated common genetic assessment metrics, predicting minimal hybridization with non-native trout, low diversity, and declining diversity over time. We further hypothesized genetic metrics would correlate positively with MPVA-estimated abundance and negatively with extinction probability. We uncovered several instances of hybridization that pointed to immediate management needs. After removing hybridized individuals, cautious interpretation of low effective population sizes (2-63) suggested reduced evolutionary potential for many LCT populations. Other genetic metrics did not decline over time nor correlate with MPVA-based estimates of harmonic mean abundance or 30-year extinction probability. Our results demonstrate benefits of genetic monitoring for efficiently detecting hybridization and, though genetic results were disconnected from demographic assessment of conservation status, they suggest reduced evolutionary potential and likely a higher conservation risk than currently recognized for this threatened fish. We emphasize that genetic information provides essential complementary insight, in addition to demographic information, for evaluating species status.


Management of Acute Ankle Fractures in Patients With Diabetes.
Ankle fractures in patients with diabetes can be difficult to manage, especially when patients present with hyperglycemia. Treatment often requires a combination of both medical and surgical care, especially in patients with poorly controlled diabetes. The goal of any treatment is to obtain a well-aligned ankle fracture that heals without any further displacement and to avoid the development of a Charcot joint. Nonsurgical treatment is usually reserved for nondisplaced fractures. Displaced fractures often require surgical treatment, and there are different options available, including standard fixation, fixation with multiple syndesmotic screw placement, external (thin wire) fixation alone, hybrid or combined internal and external fixation techniques, and primary arthrodesis. It is important to discuss the approach to the evaluation and treatment of these patients.


The molecular genetics of the long QT syndrome: genes causing fainting and sudden death.
The congenital long QT syndrome is an autosomal-dominant genetic disorder of cardiac electrical repolarization. It is caused by mutations of at least six genes, of which four, all encoding for cardiac ion channels, have been identified: KVLQT1, HERG, and Min K encode for cardiac potassium ion channels, and SCN5A encodes for the cardiac sodium ion channel. In each case the altered ion channel function produces prolongation of the action potential and propensity to torsade de pointes ventricular tachycardia. A fifth gene locus is known to be on chromosome 4, but the gene has not been isolated. At least one other gene must exist, and there may be several more. Long QT syndrome is a frequent but often overlooked cause of unexpected syncope and sudden death in children and young adults. Characteristic findings are prolongation of the QT interval and T wave abnormalities on the electrocardiogram. However, the QT interval at presentation is normal about 10% of the time and just borderline prolonged another 30%, so diagnosis may be difficult. Symptoms are syncope and sudden death, typically occurring during exercise or emotional upset. The manifestations vary, depending on the genotype present. The phenotype also probably varies, depending on the specific mutation involved. Phenotypic heterogeneity is also caused by variable penetrance and expressivity.


Breaking strain of neutron star crust and gravitational waves.
Mountains on rapidly rotating neutron stars efficiently radiate gravitational waves. The maximum possible size of these mountains depends on the breaking strain of the neutron star crust. With multimillion ion molecular dynamics simulations of Coulomb solids representing the crust, we show that the breaking strain of pure single crystals is very large and that impurities, defects, and grain boundaries only modestly reduce the breaking strain to around 0.1. Because of the collective behavior of the ions during failure found in our simulations, the neutron star crust is likely very strong and can support mountains large enough so that their gravitational wave radiation could limit the spin periods of some stars and might be detectable in large-scale interferometers. Furthermore, our microscopic modeling of neutron star crust material can help analyze mechanisms relevant in magnetar giant flares and microflares.


Carotid Artery Stiffening With Aging: Structural Versus Load-Dependent Mechanisms in MESA (the Multi-Ethnic Study of Atherosclerosis).
Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. Differentiating these closely coupled mechanisms is important to understanding vascular aging. MESA (Multi-Ethnic Study of Atherosclerosis) participants with B-mode carotid ultrasound and brachial blood pressure at exam 1 and exam 5 (year 10) were included in this study (n=2604). Peterson and Young elastic moduli were calculated to represent total stiffness. Structural stiffness was calculated by adjusting Peterson and Young elastic moduli to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Changes in carotid artery stiffness mechanisms over 10 years were compared by age groups with ANCOVA models adjusted for baseline cardiovascular disease risk factors. The 75- to 84-year age group had the greatest change in total, structural, and load-dependent stiffening compared with younger groups (P<0.05). Only age and cessation of antihypertensive medication were predictive of structural stiffening, whereas age, race/ethnicity, education, blood pressure, cholesterol, and antihypertensive medication were predictive of increased load-dependent stiffening. On average, structural stiffening accounted for the vast majority of total stiffening, but 37% of participants had more load-dependent than structural stiffening. Rates of structural and load-dependent carotid artery stiffening increased with age. Structural stiffening was consistently observed, and load-dependent stiffening was highly variable. Heterogeneity in arterial stiffening mechanisms with aging may influence cardiovascular disease development.


Privacy by Design Solution for Robust Fall Detection.
The majority of falls leading to death occur among the elderly population. The use of fall detection technology can help to ensure quick help for fall victims by automatically informing caretakers. Our fall detection method is based on depth data and has a high level of reliability in detecting falls while maintaining a low false alarm rate. The technology has been deployed in over 1,200 installations, indicating user acceptance and technological maturity. We follow a privacy by design approach by using range maps for the analysis instead of RGB images and process all the data in the sensor. The literature review shows that real-world fall detection evaluation is scarce, and if available, is conducted with a limited amount of participants. To our knowledge, our depth image based fall detection method has achieved the largest field evaluation up to date, with more than 100,000 events manually annotated and an evaluation on a dataset with 2.2 million events. We additionally present an 8-months study with more than 120,000 alarms analysed, provoked by 214 sensors located in 16 care facilities in Austria. We learned that on average 2.3 times more falls happen than are documented. Consequently, the system helps to detect falls that are otherwise overseen. The presented solution has the potential to make a significant impact in reducing the risk of accidental falls.


Trends in the incidence and outcome of sepsis using data from a Japanese nationwide medical claims database-the Japan Sepsis Alliance (JaSA) study group.
Trends in the incidence and outcomes of sepsis using a Japanese nationwide database were investigated. This was a retrospective cohort study. Adult patients, who had both presumed serious infections and acute organ dysfunction, between 2010 and 2017 were extracted using a combined method of administrative and electronic health record data from the Japanese nationwide medical claim database, which covered 71.5% of all acute care hospitals in 2017. Presumed serious infection was defined using blood culture test records and antibiotic administration. Acute organ dysfunction was defined using records of diagnosis according to the international statistical classification of diseases and related health problems, 10th revision, and records of organ support. The primary outcomes were the annual incidence of sepsis and death in sepsis per 1000 inpatients. The secondary outcomes were in-hospital mortality rate and length of hospital stay in patients with sepsis. The analyzed dataset included 50,490,128 adult inpatients admitted between 2010 and 2017. Of these, 2,043,073 (4.0%) patients had sepsis. During the 8-year period, the annual proportion of patients with sepsis across inpatients significantly increased (slope = + 0.30%/year, P < 0.0001), accounting for 4.9% of the total inpatients in 2017. The annual death rate of sepsis per 1000 inpatients significantly increased (slope = + 1.8/1000 inpatients year, P = 0.0001), accounting for 7.8 deaths per 1000 inpatients in 2017. The in-hospital mortality rate and median (interquartile range) length of hospital stay significantly decreased (P < 0.001) over the study period and were 18.3% and 27 (15-50) days in 2017, respectively. The Japanese nationwide data indicate that the annual incidence of sepsis and death in inpatients with sepsis significantly increased; however, the annual mortality rates and length of hospital stay in patients with sepsis significantly decreased. The increasing incidence of sepsis and death in sepsis appear to be a significant and ongoing issue.


Analysis of Clostridium difficile-associated diarrhea among patients hospitalized in tertiary care academic hospital.
The frequency of Clostridium difficile strains in stool samples of patients with diarrhea hospitalized in the hematology/oncology, surgery, orthopedics, transplantology ward, and emergency room of Davis Medical Center was analyzed. A total of 786 stool samples collected from patients with diarrhea and 180 samples taken from the hospital environment were cultured for C. difficile by routine methods. There were 119 strains of C. difficile isolated: 97 (12.3%) strains from patients' stools (no enteropathogen other than C. difficile was detected in these stool samples) and 22 (12.2%) strains from the hospital environment. It was confirmed that hospital environment plays an important role in transmission of C. difficile by AP-PCR and PCR ribotyping. Among 97 C. difficile strains isolated from patient' stools 25 were nontoxigenic (A-/B-), 67 were toxigenic (A+/B+), and 5 strains were toxin B-positive/toxin A-negative. Analysis of concomitant symptoms among hospitalized patients with diarrhea demonstrated significantly longer duration of diarrhea caused by nontoxigenic strains than in cases of diarrhea caused by toxigenic strains. On the other hand, among patients infected by toxigenic strains, significantly higher leukocytosis and longer duration of fever were observed. The resistance of isolated C. difficile strains to erythromycin and clindamycin indicated the possibility of transmission in the hospital strains with macrolide-lincosamide-streptogramin B resistance type.


Evidence regarding an effect of marine n-3 fatty acids on preterm birth: a systematic review and meta-analysis.
Preterm delivery remains a substantial healthcare problem, complicating 5-10% of pregnancies, and is the major cause of perinatal morbidity and mortality in the developed world. Few effective methods to prevent preterm delivery have been identified to date. To review systematically the evidence from randomized controlled trials with respect to the hypothesis that increased consumption of marine n-3 fatty acids in pregnancy can prevent preterm birth. Electronic searches of the following databases were performed: PubMed (1995-2009), SCOPUS including EMBASE (1995-2009), and Cochrane Library. A combination of key words and text words related to fish oil, marine n-3 fatty acids, fish consumption, preterm birth, preterm delivery, prematurity, pregnancy duration, gestational age, parturition, delivery and pregnancy were used. A systematic review of randomized controlled trials of relevance was conducted. Three trials were included, comprising 921 women for whom data on gestational age and 1 187 women for whom data on birthweight were available. Overall, 46 (8.9%) of 516 women who received n-3 fatty acids gave birth before 37 completed weeks of gestation, compared with 66 (16.3%) of 405 in the control group [relative risk 0.61; 95% confidence interval (CI) 0.40-0.93; p<0.05]. Data on delivery before 34 completed weeks showed the same trend (relative risk 0.32; 95% CI 0.09-0.95). Overall, the mean birthweight was 71g higher in women who received n-3 fatty acids during pregnancy (95% CI 4.73-138.12; p<0.05). The rate of low birthweight was not statistically significantly different between the intervention and the control groups. The mean gestational age at delivery was significantly higher by 4.5 days in the intervention group supplemented with n-3 fatty acids compared with placebo (95% CI 2.3-6.8; p<0.05). Marine n-3 fatty acids administered in pregnancy reduce the rate of preterm birth and increase birthweight.


Review of frequency of dysmenorrhea and some associated factors and evaluation of the relationship between dysmenorrhea and sleep quality in university students.
To determine the frequency of dysmenorrhea in university students, review some associated factors and evaluate the relationship between dysmenorrhea and sleep quality. The study group included 520 students. Survey forms prepared previously in line with the study objective were completed by the students under supervision. The severity of dysmenorrhea was rated with Visual Analogue Scale. Pittsburgh Sleep Quality Index was used to evaluate the sleep quality. The χ(2) test, Mann-Whitney U test and Kruskal-Wallis test were used for the analyses. Statistical significance level was accepted at p < 0.05. Mean age of the students was 20.23 ± 1.59 years (range 17-25). Frequency of dysmenorrhea was determined to be 69.0% (n = 359). Frequency of dysmenorrhea was higher in smokers, those with menstrual irregularity, those who use drugs for menstrual regulation and those having a family history (p < 0.05 for each). The most frequent symptoms in those having dysmenorrhea history were weakness (59.6%), fatigue (58.5%) and breast tenderness (45.4%), respectively. Sleep quality was found to be poorer in the students having a history of dysmenorrhea (p < 0.05). Dysmenorrhea is an important health problem in young women. Dysmenorrhea affects the sleep quality negatively.


Drosophila UTX coordinates with p53 to regulate ku80 expression in response to DNA damage.
UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultured cells and in third instar larvae. We further showed that UTX mediates the expression of ku80 by the demethylation of H3K27me3 at the ku80 promoter upon exposure to ionizing radiation (IR) in a p53-dependent manner. UTX interacts physically with p53, and both UTX and p53 are recruited to the ku80 promoter following IR exposure in an interdependent manner. In contrast, the loss of utx has little impact on the expression of ku70, mre11, hid and reaper, suggesting the specific regulation of ku80 expression by UTX. Thus, our findings further elucidate the molecular function of UTX.


Duration of the horizontal decubitus position for prevention of cerebrospinal fluid leakage following transection of a tight filum terminale.
The untethering of a tethered spinal cord in patients with a tight filum terminale is a relatively simple procedure that can prevent or improve neurological symptoms. Postoperatively, patients are usually kept in the horizontal decubitus position to prevent a CSF leak. However, the optimal period for keeping patients flat has not been determined yet. The authors compared 2 cohorts with different periods of horizontal decubitus; one with 72 hours and the other with 8 days. The authors retrospectively analyzed surgical results in 2 cohorts of pediatric patients who had tethered spinal cord with a tight filum terminale. One cohort was maintained flat for 8 days and the other cohort for 72 hours postoperatively. The patients' charts were reviewed for demographic data, clinical presentation, surgical therapy, and clinical course. Three hundred fifty-four patients underwent sectioning of a tight filum terminale. Of those, 238 were kept lying flat for 8 days postoperatively, and 116 were maintained flat for 72 hours. Magnetic resonance imaging was performed 1 to 2 weeks after the surgery. None of the patients in either cohort developed a CSF leak. Pseudomeningocele, which was confirmed by MRI, developed in 1 patient who had been kept flat for 8 days. The occurrence rates of a CSF leak and pseudomeningocele were not significantly different in either cohort. Keeping patients flat for longer than 72 hours did not change the rate of postoperative CSF leakage or pseudomeningocele. Seventy-two hours or less would be an appropriate period for maintaining patients flat after transection of a tight filum terminale.


Biocompatible chitin-encapsulated CdS quantum dots: Fabrication and antibacterial screening.
Chitin-encapsulated cadmium sulfide quantum dots (CdS@CTN QDs) were successfully synthesized from chitin and Cd(NO3)2 precursor using the colloidal chemistry method, toward the development of biocompatible and biodegradable QDs for biomedical applications. CdS@CTN QDs exhibited the nanocrystalline cubic CdS encapsulated by α-chitin. The average particle size of CdS@CTN QDs was estimated using empirical Henglein model to be 3.9 nm, while their crystallite size was predicted using Scherrer equation to be 4.3 nm, slightly larger compared to 3-mercaptopropionic acid-capped CdS QDs (3.2 and 3.6 nm, respectively). The mechanism of formation was interpreted based on the spectroscopic data and X-ray crystal structures of CdS@CTN QDs fabricated at different pH values and mass ratios of chitin to Cd(NO3)2 precursor. As an important step to explore potential biomolecular and biological applications of CdS@CTN QDs, their antibacterial activities were tested against four different bacterial strains; i.e. Escherichia coli, Bacillus subtillus, Staphylococcus aureus and Pseudomonas aeruginosa.


Socioeconomic Inequities in Diet Quality and Nutrient Intakes among Australian Adults: Findings from a Nationally Representative Cross-Sectional Study.
Poor diet may represent one pathway through which lower socioeconomic position (SEP) leads to adverse health outcomes. This study examined the associations between SEP and diet quality, its components, energy, and nutrients in a nationally representative sample of Australians. Dietary data from two 24-h recalls collected during the cross-sectional Australian Health Survey 2011-13 (n = 4875; aged ≥ 19 years) were analysed. Diet quality was evaluated using the Dietary Guidelines Index (DGI). SEP was assessed by index of area-level socioeconomic disadvantage, education level, and household income. Linear regression analyses investigated the associations between measures of SEP and dietary intakes. Across all of the SEP indicators, compared with the least disadvantaged group, the most disadvantaged group had 2.5-4.5 units lower DGI. A greater area-level disadvantage was associated with higher carbohydrate and total sugars intake. Lower education was associated with higher trans fat, carbohydrate, and total sugars intake and lower poly-unsaturated fat and fibre intake. Lower income was associated with lower total energy and protein intake and higher carbohydrate and trans fat intake. Lower SEP was generally associated with poorer diet quality and nutrient intakes, highlighting dietary inequities among Australian adults, and a need to develop policy that addresses these inequities.


Pharmacology of ACE inhibitors versus AT1 blockers.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor blockers share a number of common properties, including their ability to lower blood pressure. However, they can be differentiated based on their individual effects on the renin-angiotensin system, the fibrinolytic system and the actions of bradykinin. They act at different points in the cascade of events that constitute the renin-angiotensin system. In animal models of atherosclerosis, ACE inhibition was associated with a significant reduction in the percentage surface area of lesions, while no similar effect was evident with AT1 receptor blockade. In the fibrinolytic system, both ACE inhibition and AT1 receptor blockade were associated with reduced aldosterone levels, although the effect was greater with ACE inhibition; only ACE inhibition was associated with a significant reduction in plasminogen activation inhibitor-1. By blocking the degradation of bradykinin, ACE inhibitors potentiate the ability of bradykinin to reduce blood pressure and stimulate the release of tissue-type plasminogen activator from the vasculature, an effect not seen with AT1 receptor blockers.


Dynamic association with donor cell filopodia and lipid-modification are essential features of Wnt8a during patterning of the zebrafish neuroectoderm.
Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning.


Timely Diagnosis of Histoplasmosis in Non-endemic Countries: A Laboratory Challenge.
Human histoplasmosis is a fungal infection caused by the inhalation of microconidia of the thermally dimorphic fungi Histoplasma capsulatum. Autochthonous cases of histoplasmosis have been diagnosed in almost every country, but it is considered an endemic infection in specific areas of the world. Many of them are popular travel destinations or the source of migratory movements. Thus, the vast majority of the registered cases in non-endemic countries are imported. They correspond to people having been exposed to the fungus in endemic locations as immigrants, expatriates, transient workers or tourists, with reported cases also associated to organ donation. Misdiagnosis and delays in initiation of treatment are not uncommon in cases of imported histoplasmosis. They are associated to high fatality-rates specially in patients with compromised cellular immunity in which progressive disseminated forms develop. The diagnosis of this infection in non-endemic countries is hampered by the lack of clinical suspicion and a dearth of available diagnostic tools adequate to offer rapid and accurate results. Non-culture-based assays such as nucleic-acid amplification tests present as a suitable alternative in this situation, offering improved sensitivity and specificity, shortened turnaround time, and increased biosafety by avoiding culture manipulation. In non-endemic regions, molecular techniques are being used mainly in laboratories from countries that have registered an increase in the incidence of imported cases. However, the number of published techniques is limited and lack consensus. Efforts are currently under way to standardize nucleic acid amplification-based techniques for its implementation in areas registering a rising number of imported cases.


Selenium biochemistry.
The toxicity of selenium to animals and plants has been known and extensively documented since the 1930's, but it is only during the past 15 years that selenium has also been shown to be an essential micronutrient for animals and bacteria. Very little is known about the specific role or roles of selenium and, to date, there are only three enzyme-catalyzed reactions that have been shown to require the participation of a selenium-containing protein. These are the reactions catalyzed by (i) formate dehydrogenase of bacteria, (ii) glycine reductase of clostridia, and (iii) glutathione peroxidase of erythrocytes. The common denominator of these selenium-dependent processes is that they are all oxidation-reduction reactions. A fourth selenoprotein has been isolated from skeletal muscle of sheep but its catalytic function has not been identified. The form in which selenium occurs in these selenoproteins is unknown. The selenoprotein of clostridial glycine reductase contains selenium in a covalently bound form. Studies in progress indicate that this may be an organoselenium compound not previously detected in nature. Identification of the chemical nature of selenium in proteins participating in electron transport processes should enable us to determine its specific role and to understand the basic defects in certain cardiac and skeletal muscle degenerative diseases which are selenium-deficiency syndromes. The greater availability and ease of isolation of the selenoprotein of the bacterial glycine reductase system makes this the biological material of choice for studies on the mechanism of action of selenium. An added attractive feature of this system is that it can conserve the energy made available by the reductive deamination of glycine in a biologically useful form by synthesizing ATP.


Application of the Resazurin Cell Viability Assay to Monitor Escherichia coli and Salmonella Typhimurium Inactivation Mediated by Phages.
Bacterial inactivation using bacteriophages (or phages) has emerged as an effective solution for bacterial infections, but the screening methods used to evaluate the effectiveness of the phages to inactivate bacteria are not fast, reliable or precise enough. The efficiency of bacterial inactivation by phages has been evaluated by monitoring bacterial concentration either by counting colony-forming units (CFU), a laborious and time-consuming method, or by monitoring the optical density (OD), a less sensitive method. In this study, the resazurin cell viability assay was used to monitor the viability of bacteria from different genera during the inactivation by different phages, and the results were compared with the standard methods used to assess bacterial inactivation. The results showed that the resazurin colorimetric cell viability assay produces similar results to the standard method of colony-counting and giving, and also more sensitive results than the OD method. The resazurin assay can be used to quickly obtain the results of the cell viability effect profile using two different bacterial strains and several different phages at the same time, which is extremely valuable in screening studies. Moreover, this methodology is established as an effective, accurate and rapid method when compared to the ones widely used to monitor bacterial inactivation mediated by phages.


The use and trends of information and communication technology (ICT) during middle childhood.
Information and communication technologies (ICT) have become an integral part of people's lives. Trends suggest that the age when technology is used for the first time is rapidly decreasing and that children are exposed to ICT daily. However, the focus of the existing research has been on adolescents, and there is a dearth of knowledge about the use of ICT amongst children in middle childhood in South Africa. The objective of this study was to address this issue. The research participants included 12 children aged between 6 and 12 years old from two private schools (a boys' school and a girls' school) in the Gauteng region. A phenomenological approach was used to explore the use and trends of ICT among this age group. A semi-structured interview approach was employed for the data collection and each interview was tape-recorded and transcribed by the researcher. The Interpretative Phenomenological Analysis was used to analyse and interpret the data collected. Various themes were identified. While all the participants had been exposed to and used ICT, a clear developmental trend was observed: not only were younger children less sophisticated users of ICT, but they were also less informed about the dangers of ICT usage. The participants were generally not supervised but some rules were implemented by the parents. Although the children did not experience cyber bullying, they did report exposure to pornography. The results suggest various implications for developmental trends and protection of children.


Sildenafil for pulmonary arterial hypertension associated with connective tissue disease.
Pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) is difficult to manage, and has a poor prognosis. The phosphodiesterase-5 inhibitor sildenafil citrate enhances vasodilatation, has antiproliferative effects, and is effective in the treatment of PAH. We examined the efficacy and safety of oral sildenafil in patients with PAH-CTD. In a 12-week, double-blind study (SUPER-1), 278 patients with PAH were randomized to oral placebo, sildenafil 20 mg, sildenafil 40 mg, or sildenafil 80 mg 3 times daily (tid). In a post-hoc subgroup analysis of 84 patients with PAH-CTD, exercise capacity, hemodynamic measures, World Health Organization functional class, and tolerability were assessed. Forty-five percent of the patients had scleroderma, 23% had systemic lupus erythematosus, and the rest (32%) were categorized as other. Patients were predominantly functional class II (38%) or III (61%) at baseline. Sildenafil-treated patients exhibited mean increases in 6-minute walk distance at Week 12 of 42 m (95% CI 20, 64) for 20 mg, 36 m (95% CI 14, 58) for 40 mg, and 15 m (95% CI -24, 54) for 80 mg, while placebo-treated patients exhibited a mean decrease of 13 m (95% CI -36, 10). Improvement of at least 1 functional class occurred in 29%-42% of sildenafil-treated patients, compared to 5% for placebo. Significant improvements in mean pulmonary arterial pressure and pulmonary vascular resistance were observed with sildenafil 20 mg, and sildenafil was generally well tolerated. In patients with PAH-CTD, sildenafil improves exercise capacity, hemodynamic measures (at the 20 mg dose), and functional class after 12 weeks of treatment.


Emergence of a predominant clone of community-acquired Staphylococcus aureus among children in Houston, Texas.
Community-acquired (CA), methicillin-resistant Staphylococcus aureus (MRSA) infections among children are increasing in the United States. At Texas Children's Hospital (TCH), surveillance has been in place since August 2001. The objectives of this study were to describe the distribution of CA S. aureus among patients at TCH and to study genomic relationships of isolates collected between August 2001 and July 2003. Genomic relationships were determined with repetitive element-polymerase chain reaction (PCR). Multilocus sequence typing was performed for selected strains representing major clones. Molecular characterization of CA-MRSA was performed with PCR, including staphylococcal cassette chromosome (SCCmec), pvl (lukS-PV plus lukF-PV), hla, hlb and selected microbial surface components recognizing adhesive matrix molecule genes, ie, cna, clfA, fnbA and fnbB. A 62% increase was observed in CA S. aureus infections from year 1 (2001-2002) to year 2 (2002-2003), whereas the annual number of hospital admissions was unchanged. CA methicillin-sensitive S. aureus isolates were more likely to be associated with invasive infections than were CA-MRSA isolates (P < 0.01). TCH clone A, sequence type (ST) 8, was responsible for approximately 94% of all CA-MRSA isolated from children in the greater Houston area. Clone A differed from clones B (ST30) and C (ST1) by lacking the cna gene while carrying the fnbB gene. One CA-MRSA clone, TCH clone A, has become the predominant cause of CA S. aureus infections among children in the Houston area. It causes a wide spectrum of diseases, including complicated pneumonia.


Reformation of the marginal band of avian erythrocytes in vitro using calf-brain tubulin: peripheral determinants of microtubule form.
The microtubules of nucleated erythrocytes form an extraordinary structure: they are organized into a marginal band at the periphery of the cell. This unusual organelle, recurring in detail in each cell, provides an excellent opportunity to study the determinants of microtubule form. We have been able to reform the marginal band, using detergent-extracted erythrocytes that have been depleted of microtubules in vivo and phosphocellulose-purified tubulin from calf brain. We find that detergent-extracted cytoskeletons incubated under these conditions again have microtubules, and that the pattern of these microtubules recapitulates several features of the intact marginal band. In particular, most of the microtubules after regrowth are located in a band at the periphery of the cell, and curve to form an ellipse. These results support the hypothesis that the specification of microtubule location and shape in these cells is governed by determinants that reside at the periphery of the cell.


Neuregulin-1 immunoglobulin-like domain mutant mice: clozapine sensitivity and impaired latent inhibition.
Genetic and behavioral studies in humans and mouse mutants have implicated the gene encoding neuregulin-1 (Nrg-1) as a candidate susceptibility gene for schizophrenia. We examined the behavior of mice heterozygous for a mutation in neuregulin-1's immunoglobulin (Ig)-like domain (Ig-nrg-1 mice). We found that these animals displayed behaviors related to a schizophrenia-like phenotype, such as clozapine suppression of open-field and running wheel activity and impaired latent inhibition. Contrary to findings with other nrg-1 mutants, Ig-nrg-1 mice did not exhibit significantly elevated locomotion relative to littermate controls. These results suggest that Ig-Nrg-1's contribute to some - but not all - aspects of the schizophrenia-like phenotype of nrg-1 mutants, and further support nrg-1 as a candidate gene for schizophrenia.


Double Lumen Polyamide Tube-stent for the Treatment of Recurrent Postcorrosive Esophageal Stenosis.
This article presents the results of endoscopic treatment for recurrent postcorrosive esophageal stenosis with a tube-stent developed at our institution. The tube-stent was implanted in 5 children with corrosive esophageal injury at the age of 2 to 8.5 years after 7 to 64 dilatation sessions during 5 to 118 months. In total, 13 tube-stents were implanted. One patient had undergone 9 procedures during 2.5 years and the tube-stent remained in place for 14 to 250 days. This patient was tube-stent-dependent due to the lack of any possibility of surgical reconstruction. Two patients had the tube-stent removed after 150 to 205 days and they remain free from esophageal restenosis. One patient did not tolerate the tube-stent, evacuated it after 1 day and was referred for surgical esophagus replacement. One patient is currently still being treated with the tube-stent. Tube-stent was well tolerated and it may be effective in children with recurrent critical postcorrosive esophageal stenosis.


Effects of epidermal growth factor on proliferation and migration of cardiosphere-derived cells expanded from adult human heart.
Recent studies have provided evidence that the human heart has an endogenous reserve of cardiac stem cells (CSCs) that can be activated to reconstitute the dead myocardium. Current efforts are now directed towards the identification of factors favoring the growth and expansion of the CSC pool in the heart. Accordingly, in the present study, effects of different growth factors on cardiosphere-derived cells (CDCs), expanded from atrial biopsies from patients undergoing elective coronary artery bypass surgery, were analyzed. CSCs appear to respond to epidermal growth factor (EGF) more efficiently than other widely used growth factors such as vascular endothelial growth factor, insulin-like growth factor, basic fibroblast growth factor, hepatocyte growth factor, transforming growth factor, and platelet-derived growth factor. EGF significantly promoted cardiosphere formation (p < 0.05) and proliferation (p < 0.005), migration (p < 0.0005), and wound healing (p < 0.005) activities of CDCs in comparison to the other growth factors studied. Pretreatment with EGF enhanced the expression of cardiac markers cTN1(+) and MHC(+) in CDCs in comparison to untreated controls.


The YebC family protein PA0964 negatively regulates the Pseudomonas aeruginosa quinolone signal system and pyocyanin production.
Bacterial pathogenicity is often manifested by the expression of various cell-associated and secreted virulence factors, such as exoenzymes, protease, and toxins. In Pseudomonas aeruginosa, the expression of virulence genes is coordinately controlled by the global regulatory quorum-sensing systems, which includes the las and rhl systems as well as the Pseudomonas quinolone signal (PQS) system. Phenazine compounds are among the virulence factors under the control of both the rhl and PQS systems. In this study, regulation of the phzA1B1C1D1E1 (phzA1) operon, which is involved in phenazine synthesis, was investigated. In an initial study of inducing conditions, we observed that phzA1 was induced by subinhibitory concentrations of tetracycline. Screening of 13,000 mutants revealed 32 genes that altered phzA1 expression in the presence of subinhibitory tetracycline concentrations. Among them, the gene PA0964, designated pmpR (pqsR-mediated PQS regulator), has been identified as a novel regulator of the PQS system. It belongs to a large group of widespread conserved hypothetical proteins with unknown function, the YebC protein family (Pfam family DUF28). It negatively regulates the quorum-sensing response regulator pqsR of the PQS system by binding at its promoter region. Alongside phzA1 expression and phenazine and pyocyanin production, a set of virulence factors genes controlled by both rhl and the PQS were shown to be modulated by PmpR. Swarming motility and biofilm formation were also significantly affected. The results added another layer of regulation in the rather complex quorum-sensing systems in P. aeruginosa and demonstrated a clear functional clue for the YebC family proteins.


Red and green algal origin of diatom membrane transporters: insights into environmental adaptation and cell evolution.
Membrane transporters (MTs) facilitate the movement of molecules between cellular compartments. The evolutionary history of these key components of eukaryote genomes remains unclear. Many photosynthetic microbial eukaryotes (e.g., diatoms, haptophytes, and dinoflagellates) appear to have undergone serial endosymbiosis and thereby recruited foreign genes through endosymbiotic/horizontal gene transfer (E/HGT). Here we used the diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum as models to examine the evolutionary origin of MTs in this important group of marine primary producers. Using phylogenomics, we used 1,014 diatom MTs as query against a broadly sampled protein sequence database that includes novel genome data from the mesophilic red algae Porphyridium cruentum and Calliarthron tuberculosum, and the stramenopile Ectocarpus siliculosus. Our conservative approach resulted in 879 maximum likelihood trees of which 399 genes show a non-lineal history between diatoms and other eukaryotes and prokaryotes (at the bootstrap value ≥70%). Of the eukaryote-derived MTs, 172 (ca. 25% of 697 examined phylogenies) have members of both red/green algae as sister groups, with 103 putatively arising from green algae, 19 from red algae, and 50 have an unresolved affiliation to red and/or green algae. We used topology tests to analyze the most convincing cases of non-lineal gene history in which red and/or green algae were nested within stramenopiles. This analysis showed that ca. 6% of all trees (our most conservative estimate) support an algal origin of MTs in stramenopiles with the majority derived from green algae. Our findings demonstrate the complex evolutionary history of photosynthetic eukaryotes and indicate a reticulate origin of MT genes in diatoms. We postulate that the algal-derived MTs acquired via E/HGT provided diatoms and other related microbial eukaryotes the ability to persist under conditions of fluctuating ocean chemistry, likely contributing to their great success in marine environments.


Increased Ocular Pulse Amplitude Associated with Unilateral Dysgenesis of the Orbital Roof.
Two patients (one with neurofibromatosis type 1) presented with unilateral ocular pulsation. A CT scan of the orbits revealed extensive dysgenesis of the orbital roof with herniation of the frontal lobe into the orbit in both cases. PASCAL dynamic contour tonometry was performed. The ipsilateral ocular pulse amplitude (OPA) was greater than the contralateral side, and the ocular pulse waveform morphology more closely approximated the known intracranial waveform in these patients. We hypothesize that the greater OPA was due to stronger transmission of the intracranial pressure waveform amplitude and morphology in the absence of the orbital roof.


Teratomas of the head and neck region.
Teratomas are exceptionally rare malformations in the head and neck region. They are mostly benign but as a direct result of their rarity, most clinician's experience of these tumours is very limited, and consequently most of the associated literature consists of single case reports. In this paper, however, all the cases managed by a major Craniofacial Unit (the Australian Craniofacial Unit) were reviewed to attempt to identify common problems encountered in their management. All cases managed by the Australian Craniofacial Unit over the last 25 years were reviewed. In total a series of nine cases was identified, but two were seen and operated on in overseas centres and the data in these cases were incomplete, and have been excluded from the study. Case note, radiology and pathology review was undertaken to collect data. In total a series of seven cases was identified as suitable for inclusion in this study. Six of these have had a minimum of 9 years follow-up, three having completed growth. The initial and subsequent management demonstrates that these tumours when benign can be successfully removed, but depending on the affected site may require continued multidisciplinary management until growth has finished.


Semiconstrained total elbow replacement for the treatment of post-traumatic osteoarthrosis.
Forty-one consecutive patients were managed for post-traumatic osteoarthrosis or dysfunction of the elbow with use of a non-customized semiconstrained Coonrad-Morrey total elbow prosthesis. The average age at the time of the operation was fifty-seven years (range, thirty-two to eighty-two years). The patients were followed for an average of five years and eight months (range, two to twelve years). Radiographs were made at least two years postoperatively (average, five years and one month; range, two to twelve years) for thirty-nine of the forty-one patients. According to the Mayo elbow performance score, sixteen patients (39 per cent) had an excellent result, eighteen (44 per cent) had a good result, five (12 per cent) had a fair result, and two (5 per cent) had a poor result. Thirty-six (95 per cent) of the thirty-eight patients who had a functioning implant at the time of follow-up considered the outcome to be satisfactory. Preoperatively, thirty-seven patients (90 per cent) had moderate or severe pain; postoperatively, thirty (73 per cent) had no or only mild discomfort. Motion improved from an average arc of flexion of 40 to 118 degrees preoperatively to an average arc of flexion of 27 to 131 degrees postoperatively. All thirty-eight functioning implants rendered the elbow stable. Eleven patients (27 per cent) had a major complication. Nine of them (22 per cent of the series) needed an additional operation. There was no aseptic loosening, and most of the complications were primarily due to so-called mechanical failure. The ulnar component fractured in five patients (12 per cent), and the polyethylene bushings wore out in two (5 per cent). These complications were attributed principally to the performance of strenuous physical labor, such as lifting more than ten kilograms on a regular basis, against the advice of the surgeon; excessive preoperative deformity of the joint; or an unstable traumatic injury. Two patients (5 per cent) had an infection. Semiconstrained joint replacement of the elbow can be a reliable form of treatment, and frequently is the only viable option, for the difficult problems encountered with post-traumatic destruction of a joint. Restoration of function, relief of pain, and patient satisfaction can be achieved even when a patient is less than sixty years old if that patient has low demands and a low level of activity. However, the mechanical failures underscore the fact that this procedure is relatively contraindicated in patients who anticipate strenuous physical activity or who are not expected to comply with the postoperative protocol. This observation reflects the tendency for increased and excessive use of a previously functionless joint, after it has been rendered stable and pain-free, to lead to mechanical failure.


Multiobjective optimization for model selection in kernel methods in regression.
Regression plays a major role in many scientific and engineering problems. The goal of regression is to learn the unknown underlying function from a set of sample vectors with known outcomes. In recent years, kernel methods in regression have facilitated the estimation of nonlinear functions. However, two major (interconnected) problems remain open. The first problem is given by the bias-versus-variance tradeoff. If the model used to estimate the underlying function is too flexible (i.e., high model complexity), the variance will be very large. If the model is fixed (i.e., low complexity), the bias will be large. The second problem is to define an approach for selecting the appropriate parameters of the kernel function. To address these two problems, this paper derives a new smoothing kernel criterion, which measures the roughness of the estimated function as a measure of model complexity. Then, we use multiobjective optimization to derive a criterion for selecting the parameters of that kernel. The goal of this criterion is to find a tradeoff between the bias and the variance of the learned function. That is, the goal is to increase the model fit while keeping the model complexity in check. We provide extensive experimental evaluations using a variety of problems in machine learning, pattern recognition, and computer vision. The results demonstrate that the proposed approach yields smaller estimation errors as compared with methods in the state of the art.


A Prospective Study on Prevalence and Causes of Anaemia in Patients with Acute Coronary Syndrome.
Anaemia is a contributor for adverse prognosis in Acute Coronary Syndrome (ACS), but the epidemiology and causes of anaemia in such patients is not defined. To study the prevalence and aetiology of anaemia in hospitalized patients with ACS. All consecutive patients admitted with ACS from January to March, 2010 were included. Their clinical information was recorded. Of 130 (87 males) consecutive admissions for ACS, 47.7% had unstable angina, 10% had Non ST-Elevation Myocardial Infarction (NSTEMI) and 42.3% had ST-Elevation Myocardial Infarction (STEMI). Overall prevalence of anaemia (haemoglobin <130 g/l in men and <120 g/l in women) was 51.5% (n=67) and was more prevalent in women (n=30, 69.8%) than men (n=37, 42.5%). Moderate to severe anaemia was more in women (34.9%) compared to men (20.8%). Anaemia was more common in unstable angina patients (58.2%) than in NSTEMI (11.9%) or STEMI (29.9%) patients (p=0.013). Aspirin (p<0.01) and/or clopidogrel intake (p<0.01) and raised serum creatinine (p<0.01) were more often in anaemic patients. Heart failure (p<0.01) and triple vessel disease (p<0.05) were associated with anaemia. Multivariate predictors of duration of hospital stay were haemoglobin (p<0.05) at admission and revascularisation procedure (p=0.01) during hospital stay. The most common cause of anaemia was iron deficiency (29.9%). Anaemia was common in our patients admitted with ACS. Female gender, antiplatelet drug intake and raised creatinine were associated with anaemia, which in turn was associated with adverse in-hospital outcomes. The impact of correcting anaemia on outcomes in ACS needs long term prospective study.


Computational studies of the unusual water adduct [Cp2TiMe(OH2)](+): the roles of the solvent and the counterion.
The recently reported cationic titanocene complex [Cp2TiMe(OH2)](+) was subjected to detailed computational studies using density functional theory (DFT). The calculated NMR spectra revealed the importance of including the anion and the solvent (CD2Cl2) in order to calculate spectra which were in good agreement with the experimental data. Specifically, two organic solvent molecules were required to coordinate to the two hydrogens of the bound OH2 in order to achieve such agreement. Further elaboration of the role of the solvent led to Bader's QTAIM and natural bond order calculations. The zirconocene complex [Cp2ZrMe(OH2)](+) was simulated for comparison.


One-pot synthesis of sialo-containing glycosyl amino acids by use of an N-trichloroethoxycarbonyl-beta-thiophenyl sialoside.
We describe an efficient synthesis of 2,6- and 2,3-sialyl T antigens linked to serine in a one-pot glycosylation. We first investigated the glycosidation of thiosialosides by varying the N-protecting group. Modification of the C-5 amino group of beta-thiosialosides into the N-9-fluorenylmethoxycarbonyl, N-2,2,2-trichloroethoxycarbonyl (N-Troc), and N-trichloroacetyl derivatives enhanced the reactivity of these compounds towards glycosidation. Addition of a minimum amount of 3 A molecular sieves was also effective in improving the yield of alpha-linked sialosides. Next, we conducted one-pot syntheses of the glycosyl amino acids by using the N-Troc sialyl donor. The N-Troc derivative can be converted into the N-acetyl derivative without racemization of the amino acids. Branched-type one-pot glycosylation, initiated by regioselective glycosylation of the 3,6-dihydroxy galactoside with the N-Troc-beta-thiophenyl sialoside, provided the protected 2,6-sialyl T antigen in good yield. Linear-type one-pot glycosylation, initiated by chemoselective glycosylation of galactosyl fluoride with the N-Troc-beta-thiophenyl sialoside, afforded the protected 2,3-sialyl T antigen in excellent yield. Both protected glycosyl amino acids were converted into the fully deprotected 2,6- and 2,3-sialyl T antigens linked to serine in good yields.


[Evolutionary ecology and epidemiology of interactions between Anopheles mosquitoes and malaria].
The transmission of malaria is largely determined by two parameters: the biting rate of the mosquito vector and its mortality. In this paper, data on the interactions among these parameters are reviewed to describe possible evolutionary mechanisms underlying the parasite's life cycle. In particular, in contrast to conventional wisdom about medical entomology, the author suggests that malaria parasites are not always expected to minimise the damage they inflict on their mosquito host. Rather, when they have developed into the infectious stage, they can increase their transmission by manipulating the mosquito to bite more frequently; this, however, is associated with a higher risk of being killed by the human host. This example illustrates that parameters determining malaria transmission can only be understood by integrating ecological and evolutionary ideas into more traditional epidemiology. Such an evolutionary view of malaria and mosquitoes will eventually lead to a better understanding of the epidemiology of malaria and may help to predict the effect of malaria control.


The Prospect of Hydrolytic Enzymes from Bacillus Species in the Biological Control of Pests and Diseases in Forest and Fruit Tree Production.
Plant diseases and insect pest damage cause tremendous losses in forestry and fruit tree production. Even though chemical pesticides have been effective in the control of plant diseases and insect pests for several decades, they are increasingly becoming undesirable due to their toxic residues that affect human life, animals, and the environment, as well as the growing challenge of pesticide resistance. In this study, we review the potential of hydrolytic enzymes from Bacillus species such as chitinases, β-1,3-glucanases, proteases, lipases, amylases, and cellulases in the biological control of phytopathogens and insect pests, which could be a more sustainable alternative to chemical pesticides. This study highlights the application potential of the hydrolytic enzymes from different Bacillus sp. as effective biocontrol alternatives against phytopathogens/insect pests through the degradation of cell wall/insect cuticles, which are mainly composed of structural polysaccharides like chitins, β-glucans, glycoproteins, and lipids. This study demonstrates the prospects for applying hydrolytic enzymes from Bacillus sp. as effective biopesticides in forest and fruit tree production, their mode of biocidal activity and dual antimicrobial/insecticidal potential, which indicates a great prospect for the simultaneous biocontrol of pests/diseases. Further research should focus on optimizing the production of hydrolytic enzymes, and the antimicrobial/insecticidal synergism of different Bacillus sp. which could facilitate the simultaneous biocontrol of pests and diseases in forest and fruit tree production.


Biodegradability of terephthalic acid in terylene artificial silk printing and dyeing wastewater.
As the characteristic pollutant, terephthalic acid (TA) was in charge of 40%-78% of the total COD of terylene artificial silk printing and dyeing wastewater (TPW-water). The studies on biodegradability of TA were conducted in a serial of activated sludge reactors with TPW-water. TA appeared to be readily biodegradable with removal efficiency over 96.5% under aerobic conditions, hardly biodegradable with removal efficiency below 10% under anoxic conditions and slowly biodegradable with a turnover between 31.4% and 56.0% under anaerobic conditions. TA also accounted for the majority of BOD in TPW-water. The process combined by anoxic, anaerobic and aerobic activated sludge reactor was suitable for TA degradation and TPW-water treatment, Further, the aerobic process was essentially much more effective than the anaerobic or anoxic one to degrade TA in TPW-water.


[Isolation of Helicobacter pylori in gastric mucosa, dental plaque and saliva in a population from the Venezuelan Andes].
Helicobacter pylori infection is common in people. However, the existence of extra gastric reservoirs and transmission routes remain controversial in the field. Because the oral cavity has been proposed as a reservoir for H. pylori, a study was carried out to determine the presence of H. pylori in dental plaque and saliva. The results were asociated with those obtained in the gastric biopsy. Ninety-seven dyspeptic and fifty asymptomatic patients were studied and samples taken for biopsy, dental plaque and saliva. The gastric biopsies were evaluated using microbiology and histology methods. Cultures and urease tests were carried out on the oral cavity samples and included pretreatment methods using urea and HCl. The frequency of H. pylori for all the patients evaluated was 75.5%. H. pylori was not isolated in saliva or dental plaque in any of the two groups studied with or without sample pretreatment. The urease test in dental plaque was positive in 99.3% of the patients and 89.8% in saliva. There was no statistically significant difference between the infection prevalence by H. pylori in dyspeptic or not dyspeptic patients. The obtained results suggest that the methodology used for the detection of H. pylori is not sufficiently sensitive for the determination of the microorganism in the oral cavity.


Reasoned discourse or a holy war: postscript to a report on ECT.
The author points out that both favorable and unfavorable opinions regarding the value of electroconvulsive therapy have become entrenched in the absence of adequate data. These opinions are discussed in relation to the training, experience, and personal orientation of the psychiatrist. The inability of some psychiatrists to tolerate uncertainty is held responsible for their denial of the validity of alternative methods of treatment. The author recommends that psychiatrists tolerate a certain amount of ambiguity and uncertainty: postponing closure may lead to the conclusion that treatment styles (including use of psychotherapy and ECT) are not mutually exclusive.


Status of drowning in Nepal: A study of central police data.
Background: Drowning is a serious and mostly preventable injury-related cause of death. Low-and-middle income countries represent over 90% of total drowning deaths worldwide. There is lack of epidemiological studies of drowning in Nepal. The aim of this paper is to describe the status of drowning in Nepal. Methods: Cases of drowning, occurring between 1 January 2013 and 31 December 2015 were extracted from the Daily Incident Recording System of Nepal Police. Drowning cases were extracted and analysed regardless of their intent. Variables on age, sex of the deceased, types of water bodies, geographical locations, season when drowning occurred and activities of deceased were extracted and descriptive analysis was conducted. Results: A total of 1,507 drowning cases were recorded over a 3 year period. The rate of drowning was 1.9 per 100,000 (2.95 for males and 0.92 for females). Majority of drowning occurred among males (76%) and more than half were (53%) under 20 years of age. Mostly drowning occurred in rivers (natural water bodies). The findings provide strong indication that drowning occurs throughout the year in Nepal. Children were highly vulnerable to drowning. The magnitude of drowning was found to be lower than estimated by global burden of disease (GBD) study. Conclusion: The burden of drowning in Nepal is considerable, but mostly unknown to the public. Despite only having access to a limited data source, this study provides useful evidence that comprehensive research in Nepal is needed urgently.


A breast prosthesis infection update: Two-year incidence, risk factors and management at single institution.
Infection following augmentation and prosthetic-based breast reconstruction can cause significant physical and psychological distress for patients. It may delay adjuvant therapies and compromise aesthetic outcomes. The aim of this study is to identify modifiable risk factors for infection and identify common bacterial isolates to achieve optimal outcomes for patients. A retrospective cohort study was performed for patients undergoing implant-based breast reconstruction over a 2-year period. In each case, we documented demographics, co-morbidities, complications and antibiotic use. We reviewed treatments, infectious species cultured where applicable and all outcomes. A total of 292 patients met the inclusion criteria. Fifty-five patients (19%) developed an infection. Univariate analysis showed a significantly increased infection rate with longer operative times (P = 0.001) and use of tissue expanders (P = 0.001). Multiple logistic regression analysis confirmed drain use and elevated body mass index (BMI) as risk factors (odds ratio [OR] 2.427 and 1.061, respectively). After controlling for BMI, smoking status and radiation, we found an increased odd of infection with allograft use (OR 1.838) and a decreased odd with skin preparation using 2% chlorhexidine gluconate in 70% isopropyl (OR 0.554), though not statistically significant. Forty of 55 patients with infections had cultures, with 62.5% of isolates being Gram-positive species and 30% Gram-negative species. The median time to clinical infection was 25 days. Implant salvage with surgical interventions was achieved in 61.5% of patients. This study identified judicious use of drains and efficiency in the operating room as modifiable risk factors for infections following implant-based breast reconstruction. Prospective trials to analyse techniques for infection prevention are warranted. Implant salvage following infection is a possible end-point in the appropriate patient.


Salvage of isolated vaginal recurrences in women with surgical stage I endometrial cancer: a multiinstitutional experience.
The objective of this study was to evaluate the treatment outcomes and risk factors of women with surgical stage I endometrial adenocarcinoma who were initially treated with surgery alone and subsequently developed isolated vaginal recurrences. Patients with surgical stage I endometrial adenocarcinoma diagnosed from 1975 to 2002 were identified from tumor registry databases at seven institutions. All patients were treated with surgery alone including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic (+/- para-aortic) lymph node dissection, and peritoneal cytology and did not receive postoperative radiation therapy. Vaginal recurrences were documented histologically. Metastatic disease in the chest and abdomen was excluded by radiologic studies. Overall survival was calculated by the Kaplan-Meier method. Sixty-nine women with surgical stage I endometrial cancer with isolated vaginal recurrences were identified. Of the 69 patients, 10 (15%) were diagnosed with stage IA disease, 43 (62%) were diagnosed with stage IB disease, and 16 (23%) were diagnosed with stage IC disease. Patients diagnosed with grade 1 disease were 22 (32%), grade 2 disease were 26 (38%), and grade 3 disease were 21 (30%). Among women, 81% with isolated vaginal recurrences were salvaged with radiation therapy. The mean time to recurrence was 24 months, and the mean follow-up was 63 months. Among women, 18% died from subsequent recurrent disease. The 5-year overall survival was 75%. The majority of isolated vaginal recurrences in women with surgical stage I endometrial cancer can be successfully salvaged with radiation therapy, further questioning the role of adjuvant therapy for patients with uterine-confined endometrial cancer at the time of initial diagnosis.


Coverage-Based Designs Improve Sample Mining and Hyperparameter Optimization.
Sampling one or more effective solutions from large search spaces is a recurring idea in machine learning (ML), and sequential optimization has become a popular solution. Typical examples include data summarization, sample mining for predictive modeling, and hyperparameter optimization. Existing solutions attempt to adaptively trade off between global exploration and local exploitation, in which the initial exploratory sample is critical to their success. While discrepancy-based samples have become the de facto approach for exploration, results from computer graphics suggest that coverage-based designs, e.g., Poisson disk sampling, can be a superior alternative. In order to successfully adopt coverage-based sample designs to ML applications, which were originally developed for 2-D image analysis, we propose fundamental advances by constructing a parameterized family of designs with provably improved coverage characteristics and developing algorithms for effective sample synthesis. Using experiments in sample mining and hyperparameter optimization for supervised learning, we show that our approach consistently outperforms the existing exploratory sampling methods in both blind exploration and sequential search with Bayesian optimization.


The type I and type II bovine scavenger receptors expressed in Chinese hamster ovary cells are trimeric proteins with collagenous triple helical domains comprising noncovalently associated monomers and Cys83-disulfide-linked dimers.
Scavenger receptors have been implicated in the development of atherosclerosis and other macrophage-associated functions. The structures and processing of type I and type II bovine macrophage scavenger receptors were examined using polyclonal anti-receptor antibodies. Pulse/chase metabolic labeling experiments showed that both types of scavenger receptors expressed in Chinese hamster ovary (CHO) cells behaved as typical cell surface membrane glycoproteins. They were synthesized as endoglycosidase H-sensitive precursors which were converted to endoglycosidase H-resistant mature forms expressed on the cell surface. The reduced precursor and mature forms were doublets on sodium dodecyl sulfate-gel electrophoresis, primarily because of heterogeneous N-glycosylation. The approximate molecular sizes were: type I precursor, 65/63 kDa; type I mature, 82/76 kDa; type II precursor, 57/53 kDa; and type II mature, 72/65 kDa. During post-translational processing, the cysteine-rich C terminus (SRCR domain) of some of the type I receptors was proteolytically removed to form a relatively stable, approximately 69-kDa degradation product. Type II receptors differ from type I receptors in that they do not have SRCR domains and an analogous proteolytic cleavage was not observed. Several experiments provided strong evidence that the Gly-X-Y-repeat domains in the scavenger receptors oligomerize into collagenous triple helices. For example, alpha,alpha'-dipyridyl, an inhibitor of the collagen-modifying enzymes prolyl and lysyl hydroxylases, interfered with both the kinetics and nature of post-translational receptor processing, and both precursor and mature forms of the receptors in intact cells could be cross-linked with difluorodinitrobenzene into reduction-resistant trimers. In intact cells, precursor receptor trimers (type I, 198 kDa; type II, 176 kDa) were assembled in the endoplasmic reticulum by the noncovalent association of monomers and Cys83-disulfide-linked dimers (type I, 129 kDa; type II, 119 kDa). When cells were lysed in the absence of the sulfhydryl trapping agent iodoacetamide, oxidation of the side chain of Cys17 in the cytoplasmic domain leads to the artifactual formation of reduction-sensitive covalently linked trimers. The approximate masses of the mature dimer and trimer forms were 162 and 237 kDa for type I receptors and 147 and 219 kDa for type II receptors. Cys83-disulfide-linked dimer formation was not required for function because mutant receptors (Cys83----Gly83) assembled into trimers of noncovalently associated monomers and exhibited normal receptor activity. Treatment of cells with difluorodinitrobenzene cross-linked some of the receptors into complexes larger than trimers, raising the possibility that the trimers may assemble into higher order oligomers.


In silico gene expression profiling in Cannabis sativa.
The cannabis plant and its active ingredients (i.e., cannabinoids and terpenoids) have been socially stigmatized for half a century. Luckily, with more than 430,000 published scientific papers and about 600 ongoing and completed clinical trials, nowadays cannabis is employed for the treatment of many different medical conditions. Nevertheless, even if a large amount of high-throughput functional genomic data exists, most researchers feature a strong background in molecular biology but lack advanced bioinformatics skills. In this work, publicly available gene expression datasets have been analyzed giving rise to a total of 40,224 gene expression profiles taken from cannabis plant tissue at different developmental stages. The resource presented here will provide researchers with a starting point for future investigations with Cannabis sativa.


Effect of synchronous remote-based interventions on suicidal behaviours: protocol for a systematic review and meta-analysis.
Suicide is among the leading causes of preventable death worldwide. The impact of suicide affects the personal, social and economic levels. Therefore, its prevention is a priority for public health systems. Previous studies seem to support the efficacy of providing active contact to people who have made a suicide attempt. The current systematic review and meta-analysis aims to investigate the efficacy of distance suicide prevention strategies implemented through synchronous technology-based interventions. This protocol is designed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. The bibliographical searches were conducted in the databases PubMed, PsycINFO, Scopus and Web of Science in April 2022, with no restrictions on the time of publication and limited to publications in English or Spanish. The search strategy was performed using free-text terms and Medical Subject Headings terms: suicide, follow-up, synchronous, remote, telehealth, telephone, hotline, video-conference and text message. Two reviewers will independently conduct study screening, selection process, data extraction and risk of bias assessment. The analysis and synthesis of the results will be both qualitative and quantitative. A narrative synthesis, presented in a comprehensive table, will be performed and meta-analysis will be conducted, as appropriate, if sufficient data are provided. The present review and meta-analysis will not require ethical approval, as it will use data collected from previously published primary studies. The findings of this review will be published in peer-reviewed journals and widely disseminated. CRD42021275044.


Fighting for life: a qualitative analysis of the process of psychotherapy-assisted self-help in patients with metastatic cancer.
This exploratory study is an attempt to define psychological attributes related to longer survival in patients with metastatic cancers. Previous published analyses have been limited in two ways. First, they have almost always been carried out on patients not receiving therapy; we have followed people receiving a year of group therapy, on the assumption that if mental qualities are to affect cancer progression, substantial mental change would be needed to alter the established balance between the cancer cells and host regulatory mechanisms. Second, the methods typically used to characterize patients' psychology have been self-report inventories, and many decades of research with such methods have largely failed to produce a consensus on what mental qualities, if any, promote survival. By contrast, we have used qualitative methods, allowing a much more in-depth analysis of the patients, without preliminary assumptions as to what would be important. The present report describes the results of a detailed qualitative analysis of data collected from 22 participants over a year of weekly group therapy. Using grounded methods, categories were derived from the extensive verbal data (comprising patients' written homework and therapists' notes), and linked in a model of change. By applying ratings to some of these categories, and combining these ratings, we derived a quantitative estimate of patients' "involvement in self-help." Rankings on degree of involvement corresponded quite closely with the quality of patients' experience and with their survival duration. There was a great range in degree of involvement, and various subgroupings could be discerned. Nine of the participants were classed as "highly involved," meaning that they devoted regular daily time, often several hours, to such self-help strategies as relaxation, mental imaging, meditation, cognitive monitoring and journalling. All but 1 of these patients enjoyed a good quality of life and lived at least 2 years. Two of them have remained in complete remission for 7 years. At the other end of the scale, 8 patients showed little application to the work, being either unconvinced that it would help them or hampered by psychological problems such as low self-esteem. None of these was rated as having a good quality of life, and only 1 lived more than 2 years, although, as a group, their medical prognoses were no more unfavorable at the onset of therapy than for the "high involvement" group. The different subgroups and aspects of the model are illustrated by representative quotations.


A case report of an unusual complication from bee sting: acute brachial plexopathy.
Brachial plexopathy is usually related to trauma like direct injury to the nerve and stretching injuries. Neurological complications following bee sting are uncommon. Here, we describe a rare case of acute brachial plexopathy as a neurological complication following bee sting. A23-year-old maleinitially presented with angioedema and anaphylactic shock one hour after a bee stung at his neck. Twenty four hours after the incidence, he presented with sudden onset of left upper limb weakness. Nerve conduction study and electromyography had shown evidence of left brachial plexopathy.


The transport of 25-hydroxycholecalciferol in a New World monkey.
Albumin is responsible for the transport of 25-hydroxycholecalciferol in the Capuchin monkey. This was confirmed by gel filtration, analytical polyacrylamide-disc-gel electrophoresis, polyacrylamide-gel isoelectric focusing and a competitive protein-binding assay. Association constants of the serum transport proteins of a New and an Old World monkey towards 25-hydroxycholecalciferol were calculated; the transport protein in the New World monkey has a lower affinity for the vitamin D metabolite than the transport protein in the Old World primate.


Why do men with urethritis in Cameroon prefer to seek care in the informal health sector?
To study the impact of cost of treatment for sexually transmitted diseases (STDs) on the preference of men with urethritis to seek care in the informal sector. A random sample of young men from the general population of Yaoundé and Douala, Cameroon, and of employees of a Yaoundé factory underwent a structured interview on the occurrence of STD-related complaints and health seeking behaviour. Men who consulted in the formal sector were compared with men consulting in the informal sector, with regards to cost of medication and level of education. Sixteen percent of men in the general population and 20% of factory employees reported a history of urethritis in the 12 months preceding the interview. Of the men in the general population 53% had sought care in the formal sector; among the factory employees this proportion was 56%. Men who did not consult in the formal sector spent significantly less on drugs than men who did consult in the formal sector: median cost $14.4 versus $24.0 (p = 0.02) for drugs purchased in pharmacies; median cost $8 versus $32 for drugs purchased in small stores or from acquaintances. Preference for formal health services was associated with higher educational attainment. In large towns in Cameroon the utilisation of formal health services for STD related complaints is low and the high cost of treatment in the formal sector may play an important role in the choice of care option.


Feasibility of field-based light scattering spectroscopy.
Light scattering spectroscopy (LSS) is a new technique capable of accurately measuring the features of nuclei and other cellular organelles in situ. We present the considerations required to implement and interpret field-based detection in LSS, where the scattered electric field is detected interferometrically, and demonstrate that the technique is experimentally feasible. A theoretical formalism for modeling field-based LSS signals based on Mie scattering is presented. Phase-front uniformity is shown to play an important and novel role. Results of heterodyne experiments with polystyrene microspheres that localize LSS signals to a region about 30 microns in axial extent are reported. In addition, differences between field-based LSS and the earlier intensity-based LSS are discussed.


Soluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung cancer.
Small cell lung cancer (SCLC) has a 5-year survival rate of <7%. Rapid emergence of acquired resistance to standard platinum-etoposide chemotherapy is common and improved therapies are required for this recalcitrant tumour. We exploit six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. Soluble guanylate cyclase (sGC) is recurrently upregulated in post-chemotherapy progression CDX models, which correlates with acquired chemoresistance. Expression and activation of sGC is regulated by Notch and nitric oxide (NO) signalling with downstream activation of protein kinase G. Genetic targeting of sGC or pharmacological inhibition of NO synthase re-sensitizes a chemoresistant CDX progression model in vivo, revealing this pathway as a mediator of chemoresistance and potential vulnerability of relapsed SCLC.