Protocol for assessing if behavioural functioning of infants born <29 weeks' gestation is improved by omega-3 long-chain polyunsaturated fatty acids: follow-up of a randomised controlled trial.
During the last trimester of pregnancy, the fetal brain undergoes a rapid growth spurt and accumulates essential nutrients including docosahexaenoic acid (DHA). This takes place ex-utero for infants born <29 weeks' gestation, without the in-utero provisions of DHA. Infants born <29 weeks' are more likely to experience behavioural and emotional difficulties than their term-born counterparts. It has been hypothesised that supplementing preterm infants with dietary DHA may alleviate insufficiency and subsequently prevent or minimise behavioural problems. This protocol describes a follow-up of infants born <29 weeks gestation who were enrolled in a randomised controlled trial (RCT) of DHA supplementation. We aim to determine whether DHA supplementation improves the behaviour, and general health of these infants. Infants born <29 weeks' gestation were enrolled in a multicentre blinded RCT of enteral DHA supplementation. Infants were randomised to receive an enteral emulsion that provided 60 mg/kg/day of DHA or a control emulsion commenced within the first 3 days of enteral feeding, until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Families of surviving children (excluding those who withdrew from the study) from the Australian sites (up to 955) will be invited to complete a survey. The survey will include questions regarding child behavioural and emotional functioning, executive functioning, respiratory health and general health. We hypothesise that the DHA intervention will have a benefit on the primary outcome, parent-rated behaviour and emotional status as measured using the Total Difficulties score of the Strengths and Difficulties Questionnaire. Detecting a 2-point difference between groups (small effect size of 0.25 SD) with 90% power will require follow-up of 676 participants. The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/16/WCHN/184). Results will be disseminated in peer-reviewed publications and conference presentations. ACTRN12612000503820.


On the validation of models of forest CO2 exchange using eddy covariance data: some perils and pitfalls.
With the widespread application of eddy covariance technology, long-term records of hourly ecosystem mass and energy exchange are becoming available for forests around the world. These data sets hold great promise for testing and validation of models of forest function. However, model validation is not a straightforward task. The goals of this paper were to: (1) review some of the problems inherent in model validation; and (2) survey the tools available to modelers to improve validation procedures, with particular reference to eddy covariance data. A simple set of models applied to a data set of ecosystem CO2 exchange is used to illustrate our points. The major problems discussed are equifinality, insensitivity and uncertainty. Equifinality is the problem that different models, or different parameterizations of the same model, may yield similar results, making it difficult to distinguish which is correct. Insensitivity arises because the major sources of variation in eddy covariance data are the annual and diurnal cycles, which are represented by even the most basic models, and the size of the response to these cycles can mask effects of other driving variables. Uncertainty arises from three main sources: parameters, model structure and data, each of which is discussed in turn. Uncertainty is a particular issue with eddy covariance data because of the lack of replicated measurements and the potential for unquantified systematic errors such as flux loss due to advection. We surveyed several tools that improve model validation, including sensitivity analysis, uncertainty analysis, residual analysis and model comparison. Illustrative examples are used to demonstrate the use of each tool. We show that simplistic comparisons of model outputs with eddy covariance data are problematic, but use of these tools can greatly improve our confidence in model predictions.


Patient-Specific Quality Assurance in Pencil Beam Scanning by 2-Dimensional Array.
This study aimed to determine the characteristics of 2D ionization chamber array and the confidence limits of the gamma passing rate in pencil beam scanning proton therapy. The Varian ProBeam Compact spot-scanning system and the PTW OCTAVIUS 1500XDR array were used as a proton therapy system and detector, respectively. Our methods consisted of 2 parts: (1) the characteristics of the detector were tested and (2) patient-specific quality assurance was performed and evaluated by gamma analysis using dose-difference and distance-to-agreement criteria of 3% and 2 mm, respectively, with 123 treatment plans in head and neck, breast, chest, abdomen, and pelvic regions. The PTW OCTAVIUS 1500XDR array had good reproducibility, uniformity, linearity, repetition rate, and monitor unit per spot within 0.1%, with accuracy, energy dependence, and measurement depth within 0.5%. The overall uncertainty of the PTW OCTAVIUS 1500XDR array was 2.49%. For field size and range shifter, using gamma analysis, the passing rate was 100%. The overall results of patient-specific quality assurance with the gamma evaluation were 98.9% ± 1.6% in 123 plans and confidence limit was 95.7%. The PTW OTAVIUS 1500XDR offered effective performance in pencil beam scanning proton therapy.


Taxing Working Memory during Retrieval of Emotional Memories Does Not Reduce Memory Accessibility When Cued with Reminders.
Earlier studies have shown that when individuals recall an emotional memory while simultaneously doing a demanding dual-task [e.g., playing Tetris, mental arithmetic, making eye movements (EM)], this reduces self-reported vividness and emotionality of the memory. These effects have been found up to 1 week later, but have largely been confined to self-report ratings. This study examined whether this dual-tasking intervention reduces memory performance (i.e., accessibility of emotional memories). Undergraduates (N = 60) studied word-image pairs and rated the retrieved image on vividness and emotionality when cued with the word. Then they viewed the cues and recalled the images with or without making EM. Finally, they re-rated the images on vividness and emotionality. Additionally, fragments from images from all conditions were presented and participants identified which fragment was paired earlier with which cue. Findings showed no effect of the dual-task manipulation on self-reported ratings and latency responses. Several possible explanations for the lack of effects are discussed, but the cued recall procedure in our experiment seems to explain the absence of effects best. The study demonstrates boundaries to the effects of the "dual-tasking" procedure.


Application of a nurse-managed inpatient smoking cessation program.
This study reports on the effectiveness of a nurse case-managed smoking cessation program for general hospitalized patients that was continued for 3 years after clinical trials were completed. Patients admitted to the hospital who smoked were offered a smoking cessation program during their hospitalization. The program included physician advice, bedside education and counseling with a nurse specially trained in smoking cessation techniques, take-home materials (videotape, workbook, and relaxation audiotape), nicotine replacement therapy if requested or indicated, and four nurse-initiated post-discharge telephone counseling calls. Of the 2091 patients identified as smokers, 52% enrolled in the program, 18% wanted to quit on their own, 20% did not want to quit, and 10% were ineligible. The 12-month self-reported cessation rate (7-day point prevalence) was 35% if patients lost to follow-up were considered smokers, 49% if not. Patients hospitalized for cancer, cardiovascular, or pulmonary reasons were most likely to participate and had the highest self-reported cessation rates (63%, 57%, and 46%, respectively). This nurse-managed smoking cessation intervention was effective when it was put into standard hospital practice outside of its originating randomized clinical trial structure. The program, relatively inexpensive to deliver, appears to be acceptable to the majority of smokers who are hospitalized, resulted in high 1-year cessation rates, and can be extended to hospital employees and their families, work-sites, and communities on a cost-recovery basis.


Anthocyanin determination in blueberry extracts from various cultivars and their antiproliferative and apoptotic properties in B16-F10 metastatic murine melanoma cells.
Blueberry consumption is associated with health benefits contributing to a reduced risk for cardiovascular disease, diabetes and cancer. The aim of this study was to determine the anthocyanin profile of blueberry extracts and to evaluate their effects on B16-F10 metastatic melanoma murine cells. Seven blueberry cultivars cultivated in Romania were used. The blueberry extracts were purified over an Amberlite XAD-7 resin and a Sephadex LH-20 column, in order to obtain the anthocyanin rich fractions (ARF). The antioxidant activity of the ARF of all cultivars was evaluated by ABTS, CUPRAC and ORAC assays. High performance liquid chromatography followed by electrospray ionization mass spectrometry (HPLC-ESI-MS) was used to identify and quantify individual anthocyanins. The anthocyanin content of tested cultivars ranged from 101.88 to 195.01 mg malvidin-3-glucoside/100g fresh weight. The anthocyanin rich-fraction obtained from cultivar Torro (ARF-T) was shown to have the highest anthocyanin content and antioxidant activity, and inhibited B16-F10 melanoma murine cells proliferation at concentrations higher than 500 μg/ml. In addition, ARF-T stimulated apoptosis and increased total LDH activity in metastatic B16-F10 melanoma murine cells. These results indicate that the anthocyanins from blueberry cultivar could be used as a chemopreventive or adjuvant treatment for metastasis control.


Transcatheter Closure of Perimembranous Ventricular Septal Defects Using Different Generations of Amplatzer Devices: Multicenter Experience.
To demonstrate safety and efficacy of using different generations of softer Amplatzer™ devices for ventricular septal defect (VSD) closure to avoid serious complications at follow-up. Transcatheter closure of perimembranous ventricular septal defects (PmVSD) is a well-established procedure; however, it is associated with unacceptable incidence of complete heart block. Great advantages have been achieved by using softer devices for VSD transcatheter closure. The first and second generation of Amplatzer™ occluders (AVP II, ADO, and ADO II) seem to offer a safe and attractive alternative for this procedure. These devices can be delivered using either an arterial (retrograde) or venous (prograde) approach. Patients with congenital PmVSD who underwent transcatheter closure using ADO, ADO II, and AVP II devices were included. Primary end point was to determine efficacy and safety of these generations of devices and to determine the incidence of complications at follow-up (complete AV block and aortic/tricuspid/mitral regurgitation). One hundred and nineteen patients underwent VSD closure at a median age of 5 years (8 months-54 years). During the catheterization, there were only minor complications and at follow-up of 36 ± 25.7 months (up to 99 months), the closure rate was high of 98.3% and freedom from AV block was 100%. The use of softer Amplatzer™ devices is a good alternative to achieve PmVSD closure safely with no risk of AVB during the procedure or at midterm follow-up.


A sequential folding model predicts length-independent secondary structure properties of long ssRNA.
We introduce a simple model for folding random-sequence RNA molecules, arguing that it provides a direct route to predicting and rationalizing several average properties of RNA secondary structures. The first folding step involves identifying the longest possible duplex, thereby dividing the molecule into a pair of daughter loops. Successive steps involve identifying similarly the longest duplex in each new pair of daughter loops, with this process proceeding sequentially until the loops are too small for a viable duplex to form. Approximate analytical solutions are found for the average fraction of paired bases, the average duplex length, and the average loop size, all of which are shown to be independent of sequence length for long enough molecules. Numerical solutions to the model provide estimates for these average secondary structure properties that agree well with those obtained from more sophisticated folding algorithms. We also use the model to derive the asymptotic power law for the dependence of the maximum ladder distance on chain length.


Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death.
Ongoing honey bee (Apis mellifera) colony losses are of significant international concern because of the essential role these insects play in pollinating crops. Both chemical and non-chemical stressors have been implicated as possible contributors to colony failure; however, the potential role(s) of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptors (nAChRs) in the central nervous system to eliminate pest insects. However, mounting evidence indicates that neonicotinoids also may adversely affect beneficial pollinators, such as the honey bee, via impairments on learning and memory, and ultimately foraging success. The specific mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. The objective of this review was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between activation of the physiological target site, the nAChR, and colony level consequences. Potential for exposure was not a consideration in AOP development and therefore this effort should not be considered a risk assessment. Nonetheless, development of the AOPs described herein has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect normal colony functions, causing colony instability and subsequent bee population failure. A putative AOP network was developed, laying the foundation for further insights as to the role of combined chemical and non-chemical stressors in impacting bee populations. Insights gained from the AOP network assembly, which more realistically represents multi-stressor impacts on honey bee colonies, are promising toward understanding common sensitive nodes in key biological pathways and identifying where mitigation strategies may be focused to reduce colony losses.


A retrospective analysis of congenital anomalies in congenital hypothyroidism.
Objectives We evaluated the spectrum of diseases accompanying congenital hypothyroidism (CH) in the United Arab Emirates and compared them with internationally studied patterns. Methods The presented retrospective cross-sectional study took place in two government tertiary care centres. In total, 204 patients with a confirmed diagnosis of CH and a minimum period of follow-up of 1 year were included. Patients with Down syndrome, infants born at <35 weeks of gestation, and babies with TORCH (Toxoplasma gondii, Other viruses [HIV, measles, etc.], Rubella, Cytomegalovirus, and Herpes simplex) infections were subsequently excluded from the study. Results Of the subjects with CH, 39% had associated extrathyroidal anomalies (ETAs); among these, 25% had a single anomaly. A significant proportion of Arab males were affected by CH as compared to other ethnic groups. Dyshormonogenesis was the commonest aetiological cause (55%) of CH. Males with an ectopic lingual thyroid gland had significant ETAs as compared to females of the same cohort. The most common ETAs were congenital heart disease (16%), followed by urogenital tract anomalies (14%). Conclusions Detection of a high rate and variability of ETAs associated with CH necessitates the formulation of a structured screening programme including appropriate clinical, laboratory, and imaging tools to detect ETAs at an earlier stage.


Congenital malformations in the newborn population: a population study and analysis of the effect of sex and prematurity.
Congenital malformation (CM) is a leading cause of infant mortality. We hypothesized that the current estimates of the prevalence of CM are obsolete because of the increased rate of terminating fetuses with severe CMs and the widespread use of prenatal vitamins. This population-based cross-sectional study analyzed the effect of sex and prematurity on CM prevalence. All data were derived from birth entries in the 2008 Nationwide Inpatient Sample (NIS) database. Our objectives were to determine the prevalence of CM diagnoses among all birth hospitalizations in 2008 and to analyze the effect of sex and gestational maturity on CM prevalence. We identified 29,312 patients with CMs from among 1,014,261 live births, which yielded a CM prevalence of 28.9 per 1000 live births. Associated genetic syndromes were present in 1172 (4%) patients. Among newborns with nonsyndromic CM, 91% of newborns had an isolated CM and 9% of newborns had multiple CMs. The cardiovascular system was the most commonly involved organ system. The risk of CM was significantly higher in preterm newborns for an isolated CM [odds ratio (OR), 1.5; confidence interval (CI), 1.4-1.5]; multiple CMs (OR, 2.1; CI, 2.0-2.3); and overall CMs (OR, 1.4; CI, 1.3-1.5). Males had higher risk of isolated CMs (OR, 1.3; CI, 1.2-1.5). However, there was no sex difference in the risk of overall CM. We reported up-to-date national estimates of the prevalence of CM, which is important for monitoring trends, determining service planning, and assessing disease burden because of congenital malformations in the United States of America. We also showed a strong association between CM and prematurity. Further study of this association is needed to provide insight into the etiology of these relatively common public health problems.


The ratio of posterior-anterior medial temporal lobe volumes predicts source memory performance in healthy young adults.
A functional gradient has been proposed across the medial temporal lobes (MTL) such that the anterior MTL is thought to support processing of individual items (e.g., item memory and complex object perception), whereas the posterior MTL is thought to support item-context retrieval (e.g., source memory). Whereas functional imaging studies have provided evidence supporting this anatomical organization, results from structural analyses remain inconclusive. The current study examined the relationship between volume of MTL regions of interest (ROIs), and performance on a source memory task and a fine-grain complex object perception task, in healthy young adults (mean age = 21.5, range = 18-29). Using a semiautomated procedure, we segmented the parahippocampal and perirhinal cortices (PHC, PRC), posteromedial and anterolateral entorhinal cortices (pmERC, alERC), and posterior and anterior hippocampus (postHC, antHC) on high-resolution T2-weighted MRIs. Regional volumes were computed as proportions of intracranial volume, and as posterior-anterior volumetric ratios (PHC:PRC, pmERC:alERC, postHC:antHC). Partial-least squares regressions were applied to predict source and item memory, and perceptual discrimination accuracy, based on ROI and ratio volumes. In our ROI regressions, we found that postHC volume was positively correlated with a latent factor predicting source memory, and PRC and antHC volumes were negatively correlated to this latent factor. In our ratio regressions, we observed an effect relating the posterior-anterior distribution of gray matter across the MTL with source memory. Our results demonstrate differential associations between anterior and posterior MTL and source memory performance. Findings from this study highlight the importance of considering patterns of structure-behavior associations in the neurobiology of episodic memory.


Turkish version of the Drug Hypersensitivity Quality of Life Questionnaire: assessment of reliability and validity.
The first disease-specific quality-of-life questionnaire in patients with drug hypersensitivity, Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q), was developed and validated recently. The aim of this study was to assess validity, reliability and responsiveness to interventions of the Turkish version of the DrHy-Q. The Turkish version of the DrHy-Q was administered to prospectively enrolled 736 patients with drug hypersensitivity from ten allergy units. To assess validity, all patients completed the validated Turkish version of Psychological General Well-Being Index (PGWBI). For test-retest reliability, 182 patients completed the DrHy-Q 1 week after the first questionnaire administration without any intervention. Responsiveness was assessed on 97 patients who had a DrHy-Q recorded at a follow-up visit after the intervention. The internal consistency and test-retest reliability of the scale were adequate (Cronbach's alpha = 0.934, intra-class correlation coefficient = 0.783). The DrHy-Q scores showed weak negative correlations with the PGWBI total and domain scores (r = - 0.378 to -0.254, p < 0.001). DrHy-Q was able to discriminate the patients with one drug hypersensitivity reaction from the patients with two and above two reactions (p = 0.012 and p < 0.001, respectively), and the patients who experienced a respiratory reaction from the patients who did not (p = 0.018). However, it did not discriminate the patients with comorbid disease including psychiatric comorbidity (p > 0.05). The baseline DrHy-Q scores were significantly higher than the post-intervention scores (p = 0.008). The Turkish version of DrHy-Q is reliable and valid for evaluating quality of life in patients with drug hypersensitivity, and it appeared responsive to interventions.


Oral health workforce planning part 2: figures, determinants and trends in a sample of World Dental Federation member countries.
A range of factors needs to be taken into account for an ideal oral health workforce plan. The figures related to dentists, specialists, auxiliaries, practice patterns, undergraduate and continuing dental education, laws/regulations, the attitudes of oral health-care providers and the general trends affecting the practice patterns, work conditions and preferences of oral health-care providers are among such determinants. Thus, the aim of the present study was to gather such information from a sample of World Dental Federation (FDI) member countries with different characteristics. A cross-sectional survey study was carried out among a sample of FDI member countries between March 2, 2012 and March 27, 2012. A questionnaire was developed addressing some main determinants of oral health workforce, such as its structure, involvement of the public/private sector to provide oral health-care services, specialty services, dental schools, trends in workforce and compliance with oral health needs, and a descriptive analysis was performed. The countries were classified as developed and developing countries and Mann-Whitney U-tests and chi-square tests were used to identify potential significant differences (P > 0.05) between developed and developing countries. All data were processed in SPSS v.19. In the18 questionnaires processed, the median number of dentists (P = 0.005), dental practices (P = 0.002), hygienists (P = 0.005), technicians (P = 0.013) and graduates per year (P = 0.037) was higher in developed countries. Only 12.5% of developed and 22.2% of developing countries reported having optimal number of graduates per year. It was noted that 66.7% of developing countries had more regions lacking enough dentists to meet the demand (P = 0.050) and 77.8% lacked the necessary specialist care (P = 0.015). Although developing countries reported mostly an oversupply of dentists, regardless of the level of development most countries did not report an oversupply of specialists. Most developed countries did not feel that their regulations (87.5%) complied with the needs and demands of the population and most developing countries did not feel that their undergraduate dental education (62.5%) complied. Migrating to other countries was a trend seen in developing countries, while, despite increased numbers of dentists, underserved areas and communities were reported. The cross-sectional survey study suggests that figures related to optimum or ideal oral health workforce and fair distribution of the available workforce does not seem to be achieved in many parts of the world. Further attention also needs to be dedicated to general trends that have the capacity to affect future oral health workforce.


Idiopathic root resorption of the entire permanent dentition: systematic review and report of a case.
A rare case of idiopathic root resorption affecting the entire dentition was described. Root resorptions of all of the maxillary and mandibular teeth were coincidentally diagnosed on patient's radiographic examination. The patient's medical and dental findings were non-contributory, other than the increased mobility of upper incisors. No significant familial findings could be identified. Detailed radiographic examination revealed resorption affecting the apical part of the roots, resulting in vertical shortening of the teeth. The character of the resorption was as if a tapering occurred throughout the lateral root surfaces. Involved teeth were endodontically treated and the patient was subsequently followed-up for 18 months. Following endodontic therapy, all periapical lesions demonstrated clinical and radiographic evidence of healing. Endodontic therapy resulted in a high degree of success to stop resorption process and maintain the dentition.


Who among patients with acquired brain injury returned to work after occupational rehabilitation? The rapid-return-to-work-cohort-study.
Acquired brain injury (ABI) is known to be severely disabling. On average, 40% of employees return to work (RTW) within two years after injury. There is, however, limited research on what might contribute to successful RTW. To examine factors that might impact the time-to first RTW for patients with ABI, participating in a RTW-program. The study was designed as a cohort study of patients on sick leave due to mild or moderate ABI (n = 137). The mean age of the patients was 51 years, and 58% were men. The most common diagnoses were stroke (75%) and traumatic brain injury (12%). Data were collected through questionnaires, and combined with register data on sickness absence. Survival analyses were used to analyse the effect of different variables on time to first RTW (full or partial), at one- and two-year follow-up. Generally, women (HR = 0.447; CI: 0.239-0.283) had higher RTW-rates than men, and patients with non-comorbid impairments returned to work earlier than patients with multiple impairments. Although not statistically significant, receiving individual consultations and participating in group-sessions were generally associated with a delayed RTW at both follow-up-times. The only service-related factor significantly associated with delayed RTW was meetings with the social insurance office (HR = 0.522; CI: 0.282-0.965), and only at one-year follow-up. Women and patients with non-comorbid impairments returned to work earlier than men and patients with multiple impairments. There seems to be an association between intense and long-lasting participation in the RTW program and prolonged time-to first-RTW, even after controlling for level of cognitive impairments and comorbidity. Implications for Rehabilitation Acquired brain injury (ABI) is known to be severely disabling, and persons with ABI often experience difficulties in regard to returning to work. This study provides information on prognostic factors that might contribute to return to work (RTW) for patients with acquired brain injury, both at the individual level, but also in regard to service and timing characteristics. Knowledge about such factors provide rehabilitation professionals with information about effective service components that might help patients with ABI to RTW, and thus makes it possible to adapt and adjust the services to the patient's situation. Furthermore, having more knowledge on factors that contribute to RTW gives clinics the opportunity to select patients that might benefit the most from these services, thereby making them more effective.


Identification and functional analysis of a splice variant of mouse sodium-dependent phosphate transporter Npt2c.
Mutations in the SLC34A3 gene, a sodium-dependent inorganic phosphate (Pi) cotransporter, also referred to as NaPi IIc, causes hereditary hypophosphatemic rickets with hypercalciuria (HHRH), an autosomal recessive disorder. In human and rodent, NaPi IIc is mainly localized in the apical membrane of renal proximal tubular cells. In this study, we identified mouse NaPi IIc variant (Npt2c-v1) that lacks the part of the exon 3 sequence that includes the assumed translation initiation site of Npt2c. Microinjection of mouse Npt2c-v1 cRNA into Xenopus oocytes demonstrated that Npt2c-v1 showed sodium-dependent Pi cotransport activity. The characterization of pH dependency showed activation at extracellular alkaline-pH. Furthermore, Npt2c-v1 mediated Pi transport activity was significantly higher at any pH value than those of Npt2c. In an in vitro study, the localization of the Npt2c-v1 protein was detected in the apical membrane in opossum kidney cells. The expression of Npt2c-v1 mRNA was detected in the heart, spleen, testis, uterus, placenta, femur, cerebellum, hippocampus, diencephalon and brain stem of mouse. Using mouse bone primary cultured cells, we showed the expression of Npt2c-v1 mRNA. In addition, the Npt2c protein was detected in the spermatozoa head. Thus, Npt2c-v1 was expressed in extra-renal tissues such as epididymal spermatozoa and may function as a sodium-dependent phosphate transporter.


Incapacitation of fibrosarcoma cell by polyclonally activated murine T cell.
A piece of lymph node containing polyclonally-activated lymphocytes when transplanted in the anterior eye chamber of mouse along with solid piece of fibrosarcoma from syngeneic Swiss mice, dramatically inhibited the tumour-induced-vasodilatation and neo-vascularization. If the tumour explants were incubated in vitro with activated lymphocytes prior to transplantation, such angiogenic reactions was significantly reduced. These explants were incapable of incorporating radioactive thymidine in vitro. Furthermore, the cytotoxic ability of activated lymphocytes towards 51Cr labelled tumour target cells was of significant level indicating the possible mechanism of immunological reactiveness of Con A-stimulated lymphocytes to 3'-methylcholanthrene-induced tumour cells of syngeneic origin.


Early Postnatal Heart Rate Variability in Healthy Newborn Infants.
Despite the increasing interest in fetal and neonatal heart rate variability (HRV) analysis and its potential use as a tool for early disease stratification, no studies have previously described the normal trends of HRV in healthy babies during the first hours of postnatal life. We prospectively recruited 150 healthy babies from the postnatal ward and continuously recorded their electrocardiogram during the first 24 h after birth. Babies were included if born in good condition and stayed with their mother. Babies requiring any medication or treatment were excluded. Five-minute segments of the electrocardiogram (non-overlapping time-windows) with more than 90% consecutive good quality beats were included in the calculation of hourly medians and interquartile ranges to describe HRV trends over the first 24 h. We used multilevel mixed effects regression with auto-regressive covariance structure for all repeated measures analysis and t-tests to compare group differences. Non-normally distributed variables were log-transformed. Nine out of 16 HRV metrics (including heart rate) changed significantly over the 24 h [Heart rate p < 0.01; Standard deviation of the NN intervals p = 0.01; Standard deviation of the Poincaré plot lengthwise p < 0.01; Cardiac sympathetic index (CSI) p < 0.01; Normalized high frequency power p = 0.03; Normalized low frequency power p < 0.01; Total power p < 0.01; HRV index p = 0.01; Parseval index p = 0.03], adjusted for relevant clinical variables. We observed an increase in several HRV metrics during the first 6 h followed by a gradual normalization by approximately 12 h of age. Between 6 and 12 h of age, only heart rate and the normalized low frequency power changed significantly, while between 12 and 18 h no metric, other than heart rate, changed significantly. Analysis with multilevel mixed effects regression analysis (multivariable) revealed that gestational age, reduced fetal movements, cardiotocography and maternal chronic or pregnancy induced illness were significant predictors of several HRV metrics. Heart rate variability changes significantly during the first day of life, particularly during the first 6 h. The significant correlations between HRV and clinical risk variables support the hypothesis that HRV is a good indicator of overall wellbeing of a baby and is sensitive to detect birth-related stress and monitor its resolution over time.


Prospects for the clinical application of neural transplantation with the use of conditionally immortalized neuroepithelial stem cells.
Although neural transplantation has made a relatively successful transition from the animal laboratory to human neurosurgery for the treatment of Parkinson's disease, the use of human embryonic brain tissue as the source of transplants raises difficult ethical and practical problems. These are likely to impede the widespread use of this otherwise promising therapy across the range of types of brain damage to which the results of animal experiments suggest its potential applicability. Various alternative approaches are reviewed briefly, aimed at developing sources of tissue for transplantation that can be maintained in vitro until needed, so obviating the requirement for fresh embryonic tissue at each occasion of surgery. Particularly promising are conditionally immortalized neuroepithelial stem cell lines in which the immortalizing gene is downregulated upon transplantation into a host brain. We describe experiments from our laboratory with the use of cells of this kind, the multipotent MHP clonal cell lines, derived from the developing hippocampus of a transgenic mouse harbouring a temperature-sensitive oncogene. Implanted into the hippocampus of rats and marmosets with damage to the CA1 cell field, the MHP36 line gave rise to healthy surviving grafts and to essentially complete recovery of cognitive function. Postmortem study of the implanted rat brains indicated that MHP36 cells migrate to the region of damage, adopt both neuronal (pyramidal) and glial phenotypes in vivo, and reconstitute the normal laminated appearance of the CA1 cell field. We have previously shown that, when primary differentiated foetal tissue is used as the source of grafts in rats with CA1 damage, there is a stringent requirement for replacement with homotypic CA1 cells. We interpret our results as showing that the MHP36 cell line responds to putative signals associated with damage to the hippocampus and takes up a phenotype appropriate for the repair of this damage; they therefore open the way to the development of a novel strategy with widespread applicability to the treatment of the diseased or damaged human brain.


Evidence that the stalk of Drosophila kinesin heavy chain is an alpha-helical coiled coil.
Kinesin is a mechanochemical enzyme composed of three distinct domains: a globular head domain, a rodlike stalk domain, and a small globular tail domain. The stalk domain has sequence features characteristic of alpha-helical coiled coils. To gain insight into the structure of the kinesin stalk, we expressed it from a segment of the Drosophila melanogaster kinesin heavy chain gene and purified it from Escherichia coli. When observed by EM, this protein formed a rodlike structure 40-55 nm long that was occasionally bent at a hingelike region near the middle of the molecule. An additional EM study and a chemical cross-linking study showed that this protein forms a parallel dimer and that the two chains are in register. Finally, using circular dichroism spectroscopy, we showed that this protein is approximately 55-60% alpha-helical in physiological aqueous solution at 25 degrees C, and approximately 85-90% alpha-helical at 4 degrees C. From these results, we conclude that the stalk of kinesin heavy chain forms an alpha-helical coiled coil structure. The temperature dependence of the circular dichroism signal has two major transitions, at 25-30 degrees C and at 45-50 degrees C, which suggests that a portion of the alpha-helical structure in the stalk is less stable than the rest. By producing the amino-terminal (coil 1) and carboxy-terminal (coil 2) halves of the stalk separately in E. coli, we showed that the region that melts below 30 degrees C lies within coil 1, while the majority of coil 2 melts above 45 degrees C. We suggest that this difference in stability may play a role in the force-generating mechanism or regulation of kinesin.


Determination of some phenolic compounds in Crocus sativus L. corms and its antioxidant activities study.
It is well known that phenolic compounds are constituents of many plants. In this study, the total phenolics content in Crocus sativus L. corms in dormancy and waking stages were determined by the Folin-Ciocalteu method. Analysis was carried out by gas chromatography-mass spectrometry (GC-MS) after silylation by N-methyl-N-trimethylsilyl trifluroacetamide (MSTFA) + %1 trimethyl iodosilane (TMIS). Numerous compounds were detected and 11 compounds were identified. The highest phenolics content in waking corms was observed for gentisic acid (5.693 ± 0.057 μg/g) and the lowest for gallic acid (0.416 ± 0.006 μg/g); also these two phenolic compounds are the highest (0.929 ± 0.015 μg/g) and lowest (0.017 ± 0.001 μg/g) phenolics in dormant corms, respectively. The results from quantization and GC-MS analysis showed a high concentration of phenolic compounds in waking corms than the dormant stage. Furthermore, the radical scavenging activities of saffron corms were studied by 1,1-diphenyl-2-pycrylhydrazyl (DPPH) test and EC (50)values were determined about 2055 ppm and 8274 ppm for waking and dormant corms, respectively.


Remote sensing based change analysis of rice environments in Odisha, India.
The rainfed rice-growing environment is perhaps one of the most vulnerable to water stress such as drought and floods. It is important to determine the spatial extent of the stress-prone areas to effectively and efficiently promote proper technologies (e.g., stress-tolerant varieties) to tackle the problem of sustainable food production. This study was conducted in Odisha state located in eastern India. Odisha is predominantly a rainfed rice ecosystem (71% rainfed and 29% canal irrigated during kharif-monsoon season), where rice is the major crop and staple food of the people. However, rice productivity in Odisha is one of the lowest in India and a significant decline (9%) in rice cultivated area was observed in 2002 (a drought year). The present study analyzed the temporal rice cropping pattern in various ecosystems and identified the stress-prone areas due to submergence (flooding) and water shortage. The spatial distribution of rice areas was mapped using MODIS (MOD09Q1) 250-m 8-day time-series data (2000-2010) and spectral matching techniques. The mapped rice areas were strongly correlated (R(2) = 90%) with district-level statistics. Also the class accuracy based on field-plot data was 84.8%. The area under the rainfed rice ecosystem continues to dominate, recording the largest share among rice classes across all the years. The use of remote-sensing techniques is rapid, cost-effective, and reliable to monitor changes in rice cultivated area over long periods of time and estimate the reduction in area cultivated due to abiotic stress such as water stress and submergence. Agricultural research institutes and line departments in the government can use these techniques for better planning, regular monitoring of land-use changes, and dissemination of appropriate technologies.


Acetone Efficient Degradation under Simulated Humid Conditions by Mn-O-Pt Interaction Taming-Triggered Water Dissociation Intensification.
As a generally existing component in industrial streams, H2O usually inhibits the catalytic degradation efficiency of volatile organic compounds (VOCs) greatly. Here, we propose a novel strategy that accelerates the H2O dissociation and facilitates positive feedbacks during VOC oxidation by fabricating citric acid (CA)-assisted Pt(K)-Mn2O3/SiO2 (Pt-Mn/KS-xCA). Results reveal that the complexation of carboxyl groups of citric acid with Mn cations leads to the formation of small Mn2O3 (4.1 ± 0.2 nm) and further enhances the Mn-O-Pt interaction (strengthened by the Si-O-Mn interaction), which can transfer more electrons from Pt-Mn/KS-6CA to H2O, thus facilitating its breaking of covalent bonds. It subsequently produces abundant surface hydroxyl groups, improving the adsorption and activation abilities of acetone reactant and ethanol intermediate. Attributing to these, the acetone turnover frequency value of Pt-Mn/KS-6CA is 1.8 times higher than that of Pt-Mn/KS at 160 °C, and this multiple changes to 6.3 times in the presence of H2O. Remarkably, acetone conversion over Pt-Mn/KS-6CA increases by up to 14% in the presence of H2O; but it decreases by up to 26% for Pt-Mn/KS due to its weak dissociation ability and high adsorption capacity toward H2O. This work sheds new insights into the design of highly efficient catalytic materials for VOC degradation under humid conditions.


Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products.
Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS)


2015 ISSVD, ISSWSH, and IPPS Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia.
In 2014, the executive council of the International Society for the Study of Vulvovaginal Disease, the boards of directors of the International Society for the Study of Women's Sexual Health, and the International Pelvic Pain Society acknowledged the need to revise the current terminology of vulvar pain, on the basis of the significant increase in high-quality etiologic studies published in the last decade. The new terminology was achieved in the following 4 steps. The first involved a terminology consensus conference with representatives of the 3 societies, held in April 2015. Then, an analysis of the relevant published studies was used to establish a level of evidence for each factor associated with vulvodynia. The terminology was amended on the basis of feedback from members of the societies. Finally, each society's board accepted the new terminology. In 2015, the International Society for the Study of Vulvovaginal Disease, International Society for the Study of Women's Sexual Health, and International Pelvic Pain Society adopted a new vulvar pain and vulvodynia terminology that acknowledges the complexity of the clinical presentation and pathophysiology involved in vulvar pain and vulvodynia, and incorporates new information derived from evidence-based studies conducted since the last terminology published in 2003.


Minimum-distance requirements could harm high-performing critical-access hospitals and rural communities.
Since the inception of the Medicare Rural Hospital Flexibility Program in 1997, over 1,300 rural hospitals have converted to critical-access hospitals, which entitles them to Medicare cost-based reimbursement instead of reimbursement based on the hospital prospective payment system (PPS). Several changes to eligibility for critical-access status have recently been proposed. Most of the changes focus on mandating that hospitals be located a certain minimum distance from the nearest hospital. Our study found that critical-access hospitals located within fifteen miles of another hospital generally are larger, provide better quality, and are financially stronger compared to critical-access hospitals located farther from another hospital. Returning to the PPS would have considerable negative impacts on critical-access hospitals that are located near another hospital. We conclude that establishing a minimum-distance requirement would generate modest cost savings for Medicare but would likely be disruptive to the communities that depend on these hospitals for their health care.


Human 18 kDa phosphotyrosine protein phosphatase (ACP1) polymorphism: studies of rare variants provide evidence that substitutions within or near alternatively spliced exons affect splicing result.
The mammalian low molecular weight phosphotyrosine protein phosphatase is expressed as two distinct isoforms. The human 'fast' and 'slow' isoforms differ only in the sequence of an internal segment of 34 residues, and the ACP1 gene contains two adjacent exons (E3F and E3S) which encode these segments. We have previously suggested that the fast and slow isoforms are generated by mutually exclusive pre-mRNA splicing of E3F and E3S. The common alleles ACP1*A, *B and *C express the fast and slow isoforms in different ratios. The *A and *C alleles differ from *B by C --> T transitions in E3S and E3F respectively. To test the idea that the fast : slow ratio is determined by nucleotide substitutions in the E3F-I3F-E3S region, four groups of rare ACP1 variants with unusual fast : slow ratios and the rare *E and *R alleles, expressing fast∶slow ratios similar to *C and *B, respectively, were analysed. Gene segments of the I2-I3S region were amplified by PCR and analysed by SSCP and variant bands were excised and sequenced. For each of the rare isozymic variants one of six different nucleotide substitutions in E3F (nts+42, +85, +109, +110), I3F (nt+1) and I3S (nt+8) was observed. The *E and *R alleles showed C and B sequence, respectively, in accordance with the fast : slow ratio. The results support the hypothesis that the fast : slow ratio is constitutive.


PERMANENT GENETIC RESOURCES: PCR primers for 100 microsatellites in red drum (Sciaenops ocellatus).
One hundred nuclear-encoded microsatellites from a genomic library of red drum (Sciaenops ocellatus) were isolated and characterized. Eight microsatellites had tetranucleotide motifs; 92 had dinucleotide motifs. The average number of alleles per microsatellite (sample of 22-24 fish) was 17.7 (range = 2-30); gene diversity averaged 0.796 (range = 0.227-1.000). Following Bonferroni correction, genotype frequencies at 90 microsatellites did not deviate significantly from Hardy-Weinberg equilibrium expectations. Occurrence of null alleles was inferred at 15 microsatellites; alleles differing by only a single base were observed at 11 microsatellites. The microsatellites developed should prove useful for population-genetic studies of 'wild' red drum and in construction of a genetic map.


An empirical evaluation of recovery transformation at a large community psychiatric rehabilitation organization.
In recent decades, the concept of "recovery" from Severe Mental Illness (SMI) has gained increased prominence among organizations providing behavioral health services. Many states and organizations are currently developing plans to transform their mental health systems in accordance with recovery-oriented care. Even though efforts to bring the principles of recovery to mental health agencies have been well documented in the United States and abroad, there is little empirical evidence to suggest that recovery-oriented services are advantageous. The purpose of this longitudinal study was to evaluate the effectiveness of a recovery-oriented transformation carried out by a large, private, not-for-profit psychiatric rehabilitation organization serving individuals with SMI. This transformation targeted the philosophy and specific procedures involved in the provision of care to residents within the organization. The outcome variables selected to evaluate the impact of the transformation were grouped into the following categories: (a) objective indicators of recovery, (b) self-report indicators of recovery, (c) indicators of staff competency, and (d) processes that promote recovery. Six-hundred and 27 residents and 490 staff participated in the evaluation. The findings suggest that recovery-oriented services had a positive impact on rates of overnight hospitalization, residents' ability to function in the community, some professional skills of employees, and working alliance between direct care providers and residents. This indicates that comprehensive and well-structured recovery-oriented care may offer a cost-efficient and effective alternative to the deficit approach to mental health care.


Repeat γ knife surgery for incompletely obliterated cerebral arteriovenous malformations.
The causes of failure after an initial Gamma procedure were studied, along with imaging and clinical outcomes, in a series of 140 patients with cerebral arteriovenous malformations (AVMs) treated with repeat Gamma Knife surgery (GKS). Causes of initial treatment failure included inaccurate nidus definition in 14 patients, failure to fill part of the nidus as a result of hemodynamic factors in 16, recanalization of embolized AVM compartments in 6, and suboptimal dose (<20 Gy) in 23. Nineteen patients had repeat GKS for subtotal obliteration of AVMs. In 62 patients, the AVM failed to obliterate despite correct target definition and adequate dose. At the time of retreatment, the nidus volume ranged from 0.1 to 6.9 cm3 (mean, 1.4 cm3), and the mean prescription dose was 20.3 Gy. Repeat GKS yielded a total angiographic obliteration in 77 patients (55%) and subtotal obliteration in 9 (6.4%). In 38 patients (27.1%), the AVMs remained patent, and in 16 patients (11.4%), no flow voids were observed on magnetic resonance imaging. Clinically, 126 patients improved or remained stable, and 14 experienced deterioration (8 resulting from a rebleed, 2 caused by persistent arteriovenous shunting, and 4 related to radiation-induced changes). By using repeat GKS, we achieved a 55% angiographic cure rate. Although radiation-induced changes as visualized on magnetic resonance imaging occurred in 48 patients (39%), only 4 patients (3.6%) developed permanent neurological deficits. These findings may be useful in deciding the management of AVMs in whom total obliteration after initial GKS was not achieved.


Single-Subject Studies in Translational Nutrition Research.
There is a great deal of interest in personalized, individualized, or precision interventions for disease and health-risk mitigation. This is as true of nutrition-based intervention and prevention strategies as it is for pharmacotherapies and pharmaceutical-oriented prevention strategies. Essentially, technological breakthroughs have enabled researchers to probe an individual's unique genetic, biochemical, physiological, behavioral, and exposure profile, allowing them to identify very specific and often nuanced factors that an individual might possess, which may make it more or less likely that he or she responds favorably to a particular intervention (e.g., nutrient supplementation) or disease prevention strategy (e.g., specific diet). However, as compelling and intuitive as personalized nutrition might be in the current era in which data-intensive biomedical characterization of individuals is possible, appropriately and objectively vetting personalized nutrition strategies is not trivial and requires novel study designs and data analytical methods. These designs and methods must consider a very integrated use of the multiple contemporary biomedical assays and technologies that motivate them, which adds to their complexity. Single-subject or N-of-1 trials can be used to assess the utility of personalized interventions and, in addition, can be crafted in such a way as to accommodate the necessarily integrated use of many emerging biomedical technologies and assays. In this review, we consider the motivation, design, and implementation of N-of-1 trials in translational nutrition research that are meant to assess the utility of personalized nutritional strategies. We provide a number of example studies, discuss appropriate analytical methods given the complex data they generate and require, and consider how such studies could leverage integration of various biomarker assays and clinical end points. Importantly, we also consider the development of strategies and algorithms for matching nutritional needs to individual biomedical profiles and the issues surrounding them. Finally, we discuss the limitations of personalized nutrition studies, possible extensions of N-of-1 nutritional intervention studies, and areas of future research.


Designing a Framework for Remote Cancer Care Through Community Co-design: Participatory Development Study.
Recent shifts to telemedicine and remote patient monitoring demonstrate the potential for new technology to transform health systems; yet, methods to design for inclusion and resilience are lacking. The aim of this study is to design and implement a participatory framework to produce effective health care solutions through co-design with diverse stakeholders. We developed a design framework to cocreate solutions to locally prioritized health and communication problems focused on cancer care. The framework is premised on the framing and discovery of problems through community engagement and lead-user innovation with the hypothesis that diversity and inclusion in the co-design process generate more innovative and resilient solutions. Discovery, design, and development were implemented through structured phases with design studios at various locations in urban and rural Kentucky, including Appalachia, each building from prior work. In the final design studio, working prototypes were developed and tested. Outputs were assessed using the System Usability Scale as well as semistructured user feedback. We co-designed, developed, and tested a mobile app (myPath) and service model for distress surveillance and cancer care coordination following the LAUNCH (Linking and Amplifying User-Centered Networks through Connected Health) framework. The problem of awareness, navigation, and communication through cancer care was selected by the community after framing areas for opportunity based on significant geographic disparities in cancer and health burden resource and broadband access. The codeveloped digital myPath app showed the highest perceived combined usability (mean 81.9, SD 15.2) compared with the current gold standard of distress management for patients with cancer, the paper-based National Comprehensive Cancer Network Distress Thermometer (mean 74.2, SD 15.8). Testing of the System Usability Scale subscales showed that the myPath app had significantly better usability than the paper Distress Thermometer (t63=2.611; P=.01), whereas learnability did not differ between the instruments (t63=-0.311; P=.76). Notable differences by patient and provider scoring and feedback were found. Participatory problem definition and community-based co-design, design-with methods, may produce more acceptable and effective solutions than traditional design-for approaches.


Optimization of Protocols Using Neuromuscular Electrical Stimulation for Paralyzed Lower-Limb Muscles to Increase Energy Expenditure in People With Spinal Cord Injury.
The aim of this study was to evaluate whether using surface neuromuscular electrical stimulation (NMES) for paralyzed lower-limb muscles results in an increase in energy expenditure and whether the number of activated muscles and duty cycle affect the potential increase. This was a cross-sectional study. Energy expenditure during all NMES protocols was significantly higher than the condition without NMES (1.2 ± 0.2 kcal/min), with the highest increase (+51%; +0.7 kcal/min, 95% confidence interval, 0.3-1.2) for the protocol with more muscles activated and the duty cycle with a shorter rest period. A significant decrease in muscle contraction size during NMES was found with a longer stimulation time, more muscles activated, or the duty cycle with a shorter rest period. Using NMES for paralyzed lower-limb muscles can significantly increase energy expenditure compared with sitting without NMES, with the highest increase for the protocol with more muscles activated and the duty cycle with a shorter rest period. Muscle fatigue occurred significantly with the more intense NMES protocols, which might cause a lower energy expenditure in a longer protocol. Future studies should further optimize the NMES parameters and investigate the long-term effects of NMES on weight management in people with SCI.


Rift Valley fever.
Rift Valley fever (RVF) is an arthropod-borne viral disease of ruminants, camels and humans. It is also a significant zoonosis which may be encountered as an uncomplicated influenza-like illness, but may also present as a haemorrhagic disease with liver involvement; there may also be ocular or neurological lesions. In animals, RVF may be inapparent in non-pregnant adults, but outbreaks are characterised by the onset of abortions and high neonatal mortality. Jaundice hepatitis and death are seen in older animals. Outbreaks of RVF are associated with persistent heavy rainfall with sustained flooding and the appearance of large numbers of mosquitoes, the main vector. Localised heavy rainfall is seldom sufficient to create conditions for an outbreak; the simultaneous emergence of large numbers of first generation transovarially infected mosquitoes is also required. After virus amplification in vertebrates, mosquitoes act as secondary vectors to sustain the epidemic.


A randomized, multicenter, double blind, double dummy trial of single dose azithromycin versus high dose amoxicillin for treatment of uncomplicated acute otitis media.
High dose amoxicillin is recommended for the initial treatment of children with acute otitis media (AOM), particularly patients at risk for having drug-resistant Streptococcus pneumoniae. Single dose azithromycin (30 mg/kg) is considered an alternative agent for the treatment of AOM. To compare the clinical efficacy and safety of single dose azithromycin with that of high dose amoxicillin among children with uncomplicated AOM. This was a double blind, double dummy, multinational, clinical trial in which children (6-30 months of age) with AOM were randomized to treatment with single dose azithromycin (30 mg/kg) or high dose amoxicillin (90 mg/kg/d, in 2 divided doses) for 10 days. Tympanocentesis was performed at baseline and clinical responses were assessed at days 12-14 (end of therapy) and at days 25-28 (end of study). The study enrolled 313 patients, and 83% of the patients were < or =2 years of age. A total of 158 patients in the azithromycin group and 154 in the amoxicillin group were considered clinical modified intent-to-treat patients. A middle ear pathogen was detected for 212 patients (68%). Haemophilus influenzae was the most common pathogen (isolated for 96 patients), followed by S. pneumoniae (92 patients), Moraxella catarrhalis (23 patients) and Streptococcus pyogenes (23 patients). beta-Lactamase production was observed for 17% of H. influenzae isolates and 100% of M. catarrhalis isolates. Thirty-five (38%) S. pneumoniae isolates were penicillin-nonsusceptible and 24 (26%) isolates were macrolide-resistant. At the end of therapy, clinical success rates for azithromycin and amoxicillin were comparable for all patients (84 and 84%, respectively) and for children < or =2 years of age (82 and 82%, respectively). At the end of therapy and end of study, clinical efficacies among all microbiologic modified intent-to-treat evaluable subjects were comparable for patients treated with azithromycin (80%) and patients treated with amoxicillin (83%). The rates of treatment-related adverse events for azithromycin and amoxicillin were 20% and 29%, respectively (P = 0.064). Diarrhea was more common in the amoxicillin group than in the azithromycin group (17.5 and 8.2%, respectively) (P = 0.017). Compliance, defined as completion of > or =80% of the study medication, was higher in the azithromycin group (100%) than in the amoxicillin group (90%) (P = 0.001). In this study, single dose azithromycin was as effective as high dose amoxicillin for the treatment of children with AOM, whereas rates of adverse events were lower and compliance improved with the simplified single dose regimen.


Expression Of Intracellular Components of the NF-κB Alternative Pathway (NF-κB2, RelB, NIK and Bcl3) is Associated With Clinical Outcome of NSCLC Patients.
A growing number of studies has shed light on the role of the NF-κΒ in non-small-cell lung cancer (NSCLC). To address the significance of major effectors of the NF-κΒ alternative pathway, we investigated the relationship between NF-κΒ2, RelB, NIK and Bcl3 expression (mRNA and protein) and the clinical outcome of NSCLC patients. NF-κΒ2, RelB, NIK and Bcl3 protein expression levels were assessed by immunohistochemistry in tissue samples from 151 NSCLC patients who had curative resection. mRNA levels were also evaluated in 69 patients using quantitative real-time PCR. Although all studied proteins were overexpressed in NSCLC (P < 0.001 for all), only RelB mRNA levels were strongly increased in cancerous specimens compared to tumor-adjacent non-neoplastic tissues (P = 0.009). Moreover, NF-κB2, RelB and Bcl3 expression was associated with overall survival (OS). In particular, cytoplasmic and mRNA expression of RelB was related to 5-year OS (P = 0.014 and P = 0.006, respectively). Multivariate analysis also showed that Bcl3 expression (nuclear and cytoplasmic) was associated with increased 5-year OS (P = 0.002 and P = 0.036, respectively). In addition, higher Bcl3 mRNA levels were associated with inferior OS in stages I & II and improved OS in stages III and IV after 5-year follow-up (P = 0.004 and P = 0.001, respectively). Furthermore, stage I patients with lower NF-κB2 mRNA levels had better 5-year survival in univariate and multivariate analysis (P = 0.031 and P = 0.028, respectively). Interestingly, RelB expression (cytoplasmic and mRNA) was inversely associated with relapse rates (P = 0.027 and P = 0.015, respectively), while low NIK cytoplasmic expression was associated with lower relapse rates (P = 0.019). Cytoplasmic NIK expression as well as NF-κB2/ Bcl3 detection was associated with lymph node infiltration (P = 0.039 and P = 0.014, respectively). The present study confirms the deregulation of the NF-κB alternative pathway in NSCLC and also demonstrates the importance of this pathway in prognosis, recurrence and infiltration of regional lymph nodes.


wrk-1 and rig-5 control pioneer and follower axon navigation in the ventral nerve cord of Caenorhabditis elegans in a nid-1 mutant background.
During nervous system development, neurons send out axons, which must navigate large distances to reach synaptic targets. Axons grow out sequentially. The early outgrowing axons, pioneers, must integrate information from various guidance cues in their environment to determine the correct direction of outgrowth. Later outgrowing follower axons can at least in part navigate by adhering to pioneer axons. In Caenorhabditis elegans, the right side of the largest longitudinal axon tract, the ventral nerve cord, is pioneered by the AVG axon. How the AVG axon navigates is only partially understood. In this study, we describe the role of two members of the IgCAM family, wrk-1 and rig-5, in AVG axon navigation. While wrk-1 and rig-5 single mutants do not show AVG navigation defects, both mutants have highly penetrant pioneer and follower navigation defects in a nid-1 mutant background. Both mutations increase the fraction of follower axons following the misguided pioneer axon. We found that wrk-1 and rig-5 act in different genetic pathways, suggesting that we identified two pioneer-independent guidance pathways used by follower axons. We assessed general locomotion, mechanosensory responsiveness, and habituation to determine whether axonal navigation defects impact nervous system function. In rig-5 nid-1 double mutants, we found no significant defects in free movement behavior; however, a subpopulation of animals shows minor changes in response duration habituation after mechanosensory stimulation. These results suggest that guidance defects of axons in the motor circuit do not necessarily lead to major movement or behavioral defects but impact more complex behavioral modulation.


Magnesium in human semen: possible role in premature ejaculation.
Although magnesium is involved in many biological process and it is found higher levels in semen than serum, its role in human semen has not been elucidated. This investigation was conducted to evaluate the relationship between premature ejaculation and the levels of seminal magnesium. The levels of magnesium, zinc, copper, and selenium were evaluated with an atomic absorption spectrophotometer in serum and seminal plasma in 3 groups of men: (a) normal sperm parameters (15) (b) oligoasthenozoospermia (15), and genuine premature ejaculation (9). There were normal serum and semen levels of all the elements in the three groups, but significantly lower seminal plasma magnesium levels in men with premature ejaculation. The hormonal profile, body mass index (BMI) had no association with premature ejaculation. Decreased levels of magnesium gives rise to vasoconstriction from increased thromboxane level, increased endothelial intracellular Ca2+, and decreased nitric oxide. This may lead to premature emission and ejaculation processes. Magnesium is probably involved in semen transport. More research into the role of magnesium in the male physiology of reproductive tract, especially its association with premature ejaculation, is advocated.


The Percentage of Dietary Phosphorus Excreted in the Urine Varies by Dietary Pattern in a Randomized Feeding Study in Adults.
Urinary phosphorus excretion has been proposed as a recovery biomarker of dietary phosphorus intake. However, it is unclear whether phosphorus excretion is constant across a range of dietary and nondietary factors. We assessed whether percentage urinary phosphorus excretion is constant across 3 dietary patterns in the Dietary Approaches to Stop Hypertension (DASH) trial. DASH is a completed feeding study of 459 prehypertensive and stage 1 hypertensive adults (52% male, 56% black). After a 3-wk run-in on a typical American (control) diet, participants were randomly assigned to the control diet, a diet rich in fruits and vegetables (FV diet), or a diet rich in fruits, vegetables, and low-fat dairy with reduced saturated fat and cholesterol (DASH diet) for 8 wk. We estimated the percentage phosphorus excretion as urinary phosphorus excretion (from 24 h urine) divided by phosphorus intake (from analyzed food composites). Differences between group means for all 3 diets were compared by ANOVA followed by pairwise comparisons with Tukey's honest significant difference test. At the end of the intervention, the mean phosphorus intake was 1176 mg/d (95% CI: 1119, 1233 mg/d), 1408 mg/d (1352, 1464 mg/d), and 2051 mg/d (1994, 2107 mg/d) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). The mean phosphorus excretion was 734 mg/d (682, 787 mg/d), 705 mg/d (654, 756 mg/d), and 872 mg/d (820, 923 mg/d) in the control, FV, and DASH diet, respectively (P = 0.74 control vs. FV, P < 0.001 all other comparisons). The mean percentage phosphorus excretion was 63% (60%, 67%), 51% (48%, 54%), and 43% (39%, 46%) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). These findings in prehypertensive and stage 1 hypertensive adults strongly suggest that urinary phosphorus excretion should not be used as a recovery biomarker for dietary phosphorus intake, given the wide range of urinary phosphorus excretion across dietary patterns. This trial is registered at clinicaltrials.gov as NCT0000054.


Combining autophagy and immune characterizations to predict prognosis and therapeutic response in lung adenocarcinoma.
Autophagy, a key regulator of programmed cell death, is critical for maintaining the stability of the intracellular environment. Increasing evidence has revealed the clinical importance of interactions between autophagy and immune status in lung adenocarcinoma. The present study evaluated the potential of autophagy-immune-derived biomarkers to predict prognosis and therapeutic response in patients with lung adenocarcinoma. Patients from the GSE72094 dataset were randomized 7:3 to a training set and an internal validation set. Three independent cohorts, TCGA, GSE31210, and GSE37745, were used for external verification. Unsupervised hierarchical clustering based on autophagy- and immune-associated genes was used to identify autophagy- and immune-associated molecular patterns, respectively. Significantly prognostic autophagy-immune genes were identified by LASSO analysis and by univariate and multivariate Cox regression analyses. Differences in tumor immune microenvironments, functional pathways, and potential therapeutic responses were investigated to differentiate high-risk and low-risk groups. High autophagy status and high immune status were associated with improved overall survival. Autophagy and immune subtypes were merged into a two-dimensional index to characterize the combined prognostic classifier, with 535 genes defined as autophagy-immune-related differentially expressed genes (DEGs). Four genes (C4BPA, CD300LG, CD96, and S100P) were identified to construct an autophagy-immune-related prognostic risk model. Survival and receiver operating characteristic (ROC) curve analyses showed that this model was significantly prognostic of survival. Patterns of autophagy and immune genes differed in low- and high-risk patients. Enrichment of most immune infiltrating cells was greater, and the expression of crucial immune checkpoint molecules was higher, in the low-risk group. TIDE and immunotherapy clinical cohort analysis predicted that the low-risk group had more potential responders to immunotherapy. GO, KEGG, and GSEA function analysis identified immune- and autophagy-related pathways. Autophagy inducers were observed in patients in the low-risk group, whereas the high-risk group was sensitive to autophagy inhibitors. The expression of the four genes was assessed in clinical specimens and cell lines. The autophagy-immune-based gene signature represents a promising tool for risk stratification in patients with lung adenocarcinoma, guiding individualized targeted therapy or immunotherapy.


The epidemiology of dual diagnosis.
The English language literature on the epidemiology of dual diagnosis is reviewed. The literature shows mental disorders to be significantly related to alcohol and drug use disorders. The strongest associations involve externalizing mental disorders and alcohol-drug dependence. Mental disorders are associated with alcohol-drug use, problems among users, dependence among problem users, and persistence among people with lifetime dependence. These dual diagnoses are associated with severity and persistence of both mental and alcohol-drug disorders. A wider range of mental disorders is associated with nicotine dependence. Most people with dual diagnosis report their first mental disorder occurred at an earlier age than their first substance disorder. Prospective studies confirm this temporal order, although significant predictive associations are reciprocal. Analyses comparing active and remitted mental disorders suggest that some primary mental disorders are markers and others are causal risk factors for secondary substance disorders. The article closes with a discussion of ways epidemiologic research can be used to help target and evaluate interventions aimed at preventing secondary substance use disorders by treating early-onset primary mental disorders.


[Frequency of diabetes mellitus and hyperglycemia in chagasic and non-chagasic women].
Medical records of > or = 40 years old female seen at University Hospital from June/93 to July/95 were submitted to a cross-sectional study. According to Chagas' disease tests, patients were divided into chagasic (n = 362) and controls (n = 285). Diabetes mellitus was defined on the basis of two fasting blood glucose levels > or = 140 mg/dl and hyperglycemia as fasting blood glucose > 110 mg/dl. Chagasic patients were divided into groups with the cardiac form of the disease (n = 179), with megas (n = 58), and asymptomatic (n = 125). Groups were compared by the chi 2 test, analysis of variance, Student's "t" test, and Kruskal-Wallis and Mann-Whitney tests. A significant difference was assumed when p < 0.05. Chagasic and control groups were matched for age, white color and body mass index. Diabetes mellitus was more prevalent in patients with the cardiac form of Chagas' disease than in controls, or patients with the megas or the asymptomatic form (15.1%, 7.4%, 7.4%, and 5.6%, respectively); the same was observed for hyperglycemia (37.4%, 26.7%, 25.9%, 27.2%), in agreement with the hypothesis that the reduced parasympathetic activity caused by Trypanosoma cruzi leads to relative sympathetic hyperactivity.


A theory for the temperature effect on the chain length dependence of the diffusivity of oligomers.
The effect of temperature on the chain length (N) dependence of the diffusivity of oligomers (with N = 10-60 carbon atoms) was theoretically studied using the free volume theory of Wong and Choi [Soft Matter, 2019, 15, 9300-9309] along with the experimental data of von Meerwall et al. [J. Chem. Phys., 1998, 108, 4299-4304]. Experimental data showed that Dcm∼Nv and that becomes less negative as temperature increases but is always stronger than -1 as obtained in the Rouse model. The theory successfully predicts the exponent v as a function of temperature.


Influence of Ca2+ on the structure of reptilase-derived and thrombin-derived fibrin gels.
The effects of Ca2+ ion on the structure of thrombin-derived and reptilase-derived fibrin gels formed at various ionic strengths were studied turbidimetrically. For both enzymes clotting times were shorter, final gel turbidities were higher and fibre mass/length ratios were increased as the ionic strength was lowered. The addition of 5 mM-Ca2+ augmented each of these effects for any given ionic strength. In the thrombin system, Ca2+ increased the final gel turbidity from 0.04 to 0.26 A632.8 at ionic strength 0.15. Under identical conditions in the reptilase system, the final gel turbidity increased from 0.03 A632.8 in the absence of Ca2+ to 0.345 A632.8 in the presence of 5 mM-Ca2+. In the thrombin system, fibre mass/length ratios increased from 0.4 X 10(12) to 6.9 X 10(12) Da/cm in the absence of Ca2+, and from 4.4 X 10(12) to 7.9 X 10(12) Da/cm in the presence of Ca2+, as the ionic strengths were decreased from 0.15 to 0.08 and to 0.11 respectively. In the reptilase system, the mass/length ratios increased from 0.9 X 10(12) to 5.8 X 10(12) Da/cm in the absence of Ca2+, and from 4.8 X 10(12) to 8.7 X 10(12) Da/cm in the presence of Ca2+, as the ionic strengths were decreased from 0.15 to 0.08 and to 0.10 respectively. At ionic strengths below 0.10, the presence of 5 mM-Ca2+ caused precipitation and macroscopic aggregation of fibrinogen upon the addition of either enzyme. In the presence of 5 mM-Ca2+, the fibres composing thrombin-induced and reptilase-induced gels were virtually identical.


Calibration and application of the Chemcatcher® passive sampler for monitoring acidic herbicides in the River Exe, UK catchment.
Acidic herbicides are used to control broad-leaved weeds. They are stable, water-soluble, and with low binding to soil are found frequently in surface waters, often at concentrations above the EU Drinking Water Directive limit of 0.10 μg L-1. This presents a problem when such waters are abstracted for potable supplies. Understanding their sources, transport and fate in river catchments is important. We developed a new Chemcatcher® passive sampler, comprising a 3M Empore™ anion-exchange disk overlaid with a polyethersulphone membrane, for monitoring acidic herbicides (2,4-D, dicamba, dichlorprop, fluroxypyr, MCPA, MCPB, mecoprop, tricolpyr). Sampler uptake rates (Rs = 0.044-0.113 L day-1) were measured in the laboratory. Two field trials using the Chemcatcher® were undertaken in the River Exe catchment, UK. Time-weighted average (TWA) concentrations of the herbicides obtained using the Chemcatcher® were compared with concentrations measured in spot samples of water. The two techniques gave complimentary monitoring data, with the samplers being able to measure stochastic inputs of MCPA and mecoprop occurring in field trial 1. Chemcatcher® detected a large input of MCPA not found by spot sampling during field trial 2. Devices also detected other pesticides and pharmaceuticals with acidic properties. Information obtained using the Chemcatcher® can be used to develop improved risk assessments and catchment management plans and to assess the effectiveness of any mitigation and remediation strategies.


Clostridium difficile trehalose metabolism variants are common and not associated with adverse patient outcomes when variably present in the same lineage.
Clostridium difficile ribotype-027, ribotype-078, and ribotype-017 are virulent and epidemic lineages. Trehalose metabolism variants in these ribotypes, combined with increased human trehalose consumption, have been hypothesised to have contributed to their emergence and virulence. 5232 previously whole-genome sequenced C. difficile isolates were analysed. Clinical isolates were used to investigate the impact of trehalose metabolism variants on mortality. Import data were used to estimate changes in dietary trehalose. Ribotype-027 virulence was investigated in a clinically reflective gut model. Trehalose metabolism variants found in ribotype-027 and ribotype-017 were widely distributed throughout C. difficile clade-2 and clade-4 in 24/29 (83%) and 10/11 (91%) of sequence types (STs), respectively. The four-gene trehalose metabolism cluster described in ribotype-078 was common in genomes from all five clinically-important C. difficile clades (40/167 [24%] STs). The four-gene cluster was variably present in 208 ribotype-015 infections (98 [47%]); 27/208 (13%) of these patients died within 30-days of diagnosis. Adjusting for age, sex, and infecting ST, there was no association between 30-day all-cause mortality and the four-gene cluster (OR 0.36 [95%CI 0.09-1.34, p = 0.13]). Synthetic trehalose imports in the USA, UK, Germany and the EU were < 1 g/capita/year during 2000-2006, and < 9 g/capita/year 2007-2012, compared with dietary trehalose from natural sources of ~100 g/capita/year. Trehalose supplementation did not increase ribotype-027 virulence in a clinically-validated gut model. Trehalose metabolism variants are common in C. difficile. Increases in total dietary trehalose during the early-mid 2000s C. difficile epidemic were likely relatively minimal. Alternative explanations are required to explain why ribotype-027, ribotype-078 and ribotype-017 have been successful. National Institute for Health Research. Gut model experiments only: Hayashibara Co. Ltd.


Cocaine-related attentional bias following trauma cue exposure among cocaine dependent in-patients with and without post-traumatic stress disorder.
Although the co-occurrence of post-traumatic stress disorder (PTSD) and cocaine dependence is associated with a wide range of negative clinical outcomes, little is known about the mechanisms that underlie this association. This study investigated one potential mechanism-attentional bias to cocaine imagery following trauma cue exposure. Male and female cocaine-dependent in-patients with and without PTSD were exposed to both a neutral and personalized trauma script on separate days, followed by a visual dot-probe task. A 2 (PTSD versus non-PTSD) × 2 (neutral versus trauma script) × 2 (male versus female) design was used to examine hypotheses. Participants were recruited from a residential substance use disorder (SUD) treatment center. Participants were 60 trauma-exposed cocaine dependent in-patients, 30 with current PTSD and 30 without a history of PTSD. Attentional bias was assessed using a visual dot-probe task depicting cocaine-related imagery following both a neutral script and personalized trauma script. Following neutral script exposure, PTSD (versus non-PTSD) participants exhibited an attentional bias away from cocaine imagery. This effect was reversed following trauma script exposure, with PTSD participants exhibiting a greater attentional bias towards the location of cocaine imagery than non-PTSD participants. Severity of subjective distress following trauma script exposure predicted level of attentional bias among PTSD participants. Cocaine appears to serve an emotion-regulating function among post-traumatic stress disorder patients and may be a potential target for brief post-traumatic stress disorder-substance use disorder interventions that can facilitate residential substance use disorder treatment retention.


Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction.
Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction.


Analysis of the Diagnostic Effect of EUS-RTE on Giant Cystic Tumours of the Oesophagus Based on Cluster Analysis.
This paper presents an in-depth analysis and study of the diagnostic effectiveness of EUS-RTE in giant cystic tumours of the oesophagus utilizing cluster analysis. A new form of interval data expression was designed based on the cluster analysis algorithm, as well as a new way of updating the cluster radius and cluster centre. Feature triads are defined, eliminating the need to access all historical data at the time of update. It also prevents the case of overfusion of clusters and outputting only one cluster. If there exist a very low number of clusters, the newly merged clusters are reclustered according to the density clustering method for the internal data objects based on the cluster segmentation so that the data objects in the same cluster have a high similarity as possible. All accumulated electronic files of oesophageal cancer cases were collected and comprehensively organized, and all clinical data of 129 eligible cases with a total of 356 consultations were screened in strict accordance with inclusion and exclusion criteria. A database of oesophageal cancer cases was established using Visual FoxPro software, and frequency distribution, cluster analysis, association rule, and chi-square test were used to focus on mining the association between symptoms, disease mechanisms, prescriptions, and medications. The results were analysed and summarized. Overall, the therapeutic efficacy and safety of the three groups of treatment modalities for gastric mesenchymal tumours were positive, and the preoperative endoscopic treatment modalities should be selected based on the EUS-RTE characteristics of the tumour, the site, and the operator's skill level in a comprehensive manner.


The expression of Toll-like receptor 8 and its relationship with VEGF and Bcl-2 in cervical cancer.
Cervical cancer is one of the most common cancers in women worldwide, often associated with the infection of human papillomavirus (HPV). Toll-like receptor 8 (TLR8), a pattern recognition receptor, is involved in viral nucleic acid sensing. Recently TLR8 has been shown to be expressed in cancer cells, and it has been suggested that it may help cancer cell growth and tumor development. The objective of this study is to investigate the expression of TLR8 expression and its relationship with Bcl-2 and VEGF in cervical cancer cells. The mRNA expression levels of Bcl-2, VEGF and TLR-7,-8,-9 in newly diagnosed cervical cancer patients were detected by quantitative real-time PCR (qRT- PCR). Epifluorescence microscope was used to determine the presence of TLR8 protein in Hela cells. The cell cycle and apoptosis were analyzed by flow cytometer, and the cell proliferation was measured by MTT assay. Our data showed the increased mRNA levels of TLR8 in human cervical cancer samples as well as in HeLa cells, a cell line derived from a human cervical cancer. In addition, there was a positive correlation between the expression levels of TLR8 and Bcl-2 and VEGF in cervical cancer patients. When Hela cells were treated with TLR8 agonist CL075, the percentage of cells in G2/M +S was remarkably increased, accompanied by increased COX-2, BCL-2 and VEGF mRNA levels. The mRNA expression level of TLR8 in the patients with cervical cancer and Hela cells were up-regulated, it consistent with the increased expression of VEGF and Bcl-2. The results suggest that TLR8 may be an interesting therapeutic target in cervical cancer.


[Lipoma of the corpus callosum with extracranial extension through frontal bone defect].
Intracranial lipoma are usually localized in the corpus callosum and rarely extends to the subgaleal region. Only eight cases of lipoma of the corpus callosum with extracranial extension were reported in the literature. Seizures and mental retardation were the most common clinical findings in these patients. Data from the literature show that resection of intracranial lipoma has catastrophic results. The resection must be restricted to the extracranial portion. We report a child with lipoma of the corpus callosum with extracranial extension with no neurologic deficit submitted to resection of the extracranial extension.


Evaluation of a PCR-immunoassay technique for detection of Neisseria meningitidis in cerebrospinal fluid and peripheral blood.
A multiplex PCR-immunoassay for the rapid diagnosis of bacterial meningitis from cerebrospinal fluid (CSF) or peripheral blood was compared with conventional microbiological techniques used in the routine diagnostic laboratory. The multiplex PCR was designed to detect simultaneously a universal conserved sequence coding for bacterial 16S rRNA and the Neisseria meningitidis porA gene. The PCR-immunoassay had a detection limit of (3-5) x 10(2) cfu/ml (equivalent to 1-3 cfu/PCR) with spiked CSF or blood samples, compared with (3-5) x 10(3) cfu/ml for PCR followed by conventional agarose gel electrophoresis for detection of PCR products. Of 294 CSF samples from patients suspected on clinical grounds of suffering from meningitis, the PCR-immunoassay detected bacterial DNA in 29 CSF samples, 15 of which were also positive for N. meningitidis DNA. The 29 positive CSF samples comprised 25 samples that were also reported positive and four that were reported negative by conventional methodology; the latter four were all positive for N. meningitidis by the PCR-immunoassay. Of 173 peripheral blood samples examined, the PCR-immunoassay detected bacterial DNA in 18 samples, 14 of which were also positive for N. meningitidis DNA. In comparison, only 10 samples were reported positive for N. meningitidis by conventional methodology. All negative PCR-immunoassay results correlated with those obtained by conventional methodology for both CSF and blood samples. The sensitivity and speed of the PCR-immunoassay system indicated that it could be used as a routine diagnostic test for meningococcal meningitis, enabling a diagnosis to be made within 4 h of receipt of the specimen.


[Pharmacological properties of adicin, Soviet alpha-acetyldigitoxin].
Adicin, Soviet alpha-acetyldigitoxin, obtained from Digitalis lanata Ehrh., c. Scrophulariaceae after isolation from it of celanid is a highly effective cardiotonic of the digitalis type of action. It exerts a favourable ino- and tonotropic and an adverse chronotropic action on the heart. This action is brought up in varied animal species and can be observed for a long time (over 3 hours). Adicin produces no adverse effect on the coronary blood flow and it is conducive to the improvement of venous circulation. The drug does not differ considerably from acedoxin (Hungarian alpha-acetyldigitoxin) from the standpoint of the cardiotonic effect, cumulative properties, elimination rate, biological activity and toxicity. Adicin is recommended for clinical trials with a purpose of replacing imported drugs.


Jones fractures in the elite football player.
The Jones fracture, defined as a proximal junctional metaphyseal/diaphyseal fracture of the fifth metatarsal, presents a challenge to the orthopaedic surgeon, especially in the competitive athlete. The purpose of this study is to characterize the Jones fracture in the elite athletic community and review the variety of treatments for these fractures in the National Football League (NFL). Between 1988 and 2002, 4758 elite collegiate football players participated in the NFL Combine. All athletes were evaluated clinically and radiographically. There were 86 Jones fractures identified in 83 athletes (incidence of 1.8%). Fifty-three percent (46 of 86) of the fractures were treated surgically. Eighty-nine percent (41 of 46) healed without complications and 7% (3 of 46) developed a nonunion. Twenty percent (8 of 40) of the fractures treated nonoperatively developed a nonunion while 80% (32 of 40) healed. The NFL injury surveillance system was also studied and revealed 17 Jones fractures occurred during the seasons 1996--2001. All of these fractures were treated with intramedullary screw fixation. The union rate was 94% (16 of 17 fractures). A questionnaire was also sent to all NFL team physicians regarding their experience with these fractures. The concensus was that this is not a common injury, but when it occurs, surgical treatment is recommended (77%) over nonsurgical treatment (23%). After reviewing the data, it was found that intramedullary screw fixation of Jones fractures is the treatment of choice for most physicians who treat elite collegiate and professional football athletes.


Evaluation of Explant Responses to STING Ligands: Personalized Immunosurgical Therapy for Head and Neck Squamous Cell Carcinoma.
Surgeons have unique in situ access to tumors enabling them to apply immunotherapies to resection margins as a means to prevent local recurrence. Here, we developed a surgical approach to deliver stimulator of interferon genes (STING) ligands to the site of a purposeful partial tumor resection using a gel-based biomaterial. In a range of head and neck squamous cell carcinoma (HNSCC) murine tumor models, we demonstrate that although control-treated tumors recur locally, tumors treated with STING-loaded biomaterials are cured. The mechanism of tumor control required activation of STING and induction of type I IFN in host cells, not cancer cells, and resulted in CD8 T-cell-mediated cure of residual cancer cells. In addition, we used a novel tumor explant assay to screen individual murine and human HNSCC tumor responses to therapies ex vivo We then utilized this information to personalize the biomaterial and immunotherapy applied to previously unresponsive tumors in mice. These data demonstrate that explant assays identify the diversity of tumor-specific responses to STING ligands and establish the utility of the explant assay to personalize immunotherapies according to the local response.Significance: Delivery of immunotherapy directly to resection sites via a gel-based biomaterial prevents locoregional recurrence of head and neck squamous cell carcinoma. Cancer Res; 78(21); 6308-19. ©2018 AACR.


[Structure of the tricyclic triaminotricarboxylic acid (Y) from the antibiotic actinoidin].
The products of triaminotricarboxylic acid (Y) transformation in alkaline and reduction (HI/P) hydrolysis and the PMR spectra of the Y-Phe dipeptide were studied and the nature of the 3 amino acid substitutes and their position in the aromatic nuclei were determined. With regard to the data on the structure of the aromatic skeleton published earlier the structure of the Y amino acid as 3-(2-chlor-4-seryl-phenoxy)-5-(4-seryl-phenoxy)-p-hydroxyphenylglycine was suggested. The presence of 2 alcoholic groups of the phenylserine fragments of the Y amino acid in the actinoidine aglycone was shown with additional acetylation (Ac2O/Py) of N-acetylmethoxyaglycone. It was found with O-acetylation of N-acetylmethoxyactinosaminyl aglycone that the actinosamine amino sugar in the actinoidine molecule was bound with one of the above groups.


A Philanthropic Approach to Supporting Emergent Disaster Response and Recovery.
In August 2017, Hurricane Harvey struck the US Gulf Coast and caused more than US $125 billion in damages in Texas. The loss of lives and the economic damages resulted in an outpouring of support for the recovery efforts in the form of federal assistance and private donations. The latter has supported more creative approaches to recovery. Organizations that normally would not receive funding were able to obtain resources to use in novel manners. Using the framework of Dynes typology to identify groups and their respective structures and tasks, this report from the field analyzes Hurricane Harvey and the financial support mechanisms used to support recovery efforts in Texas, what organizations were funded to do, and where they fit into Dynes typology. The authors close by noting the importance of these emerging organizations and the need to support diversity in funding disaster response and recovery efforts beyond large nonprofit organizations.


Comparison of inflation of third dose diphtheria tetanus pertussis (DTP3) administrative coverage to other vaccine antigens.
Third dose diphtheria tetanus pertussis (DTP3) administrative coverage is a commonly used indicator for immunization program performance, although studies have demonstrated data quality issues with administrative DTP3 coverage. It is possible that administrative coverage for DTP3 may be inflated more than for other antigens. To examine this, theory, we compiled immunization coverage estimates from recent country surveys (n=71) and paired these with corresponding administrative coverage estimates, by country and cohort year, for DTP3 and 4 other antigens. Median administrative coverage was higher than survey estimates of coverage for all antigens (median differences from 26 to 30%), however this difference was similar for DTP3 as for all other antigens. These findings were consistent when countries were stratified by income level and eligibility for Gavi funding. Our findings demonstrate that while country administrative coverage estimates tend to be higher than survey estimates, DTP3 administrative coverage is not inflated more than other antigens.