How do spanning external fixators on knee dislocation patients affect the use of MRI and knee stability?
This study sought to determine the following: (1) Does the external fixator compromise quality of imaging obtained? (2) How do findings from the evaluation under anesthesia at the time of external fixator removal compare with the initial magnetic resonance imaging (MRI) findings? This was a retrospective study of a consecutive patient series at an academic level 1 trauma center. There were 19 consecutive patients with traumatic knee dislocations and spanning external fixator applied. Each patient had a knee MRI with the external fixator in place and examination at the time of external fixator removal. A review of knee stability at the time of external fixator removal with physical examination and stress fluoroscopy were performed. Our study revealed only minor incidence of poorly visualized structures. Clinical stability was present after fixator removal in only 11 of 14 medial collateral ligament tears, 4 of 16 lateral collateral ligament tears, 1 of 19 anterior cruciate ligament tears and 3 of 19 posterior cruciate ligament tears. MRI is a useful imaging modality in the setting of knee dislocations placed in spanning external fixators. Patients' knees largely remain unstable after external fixator removal.


Use of probiotics in aquaculture.
The growth of aquaculture as an industry has accelerated over the past decades; this has resulted in environmental damages and low productivity of various crops. The need for increased disease resistance, growth of aquatic organisms, and feed efficiency has brought about the use of probiotics in aquaculture practices. The first application of probiotics occurred in 1986, to test their ability to increase growth of hydrobionts (organisms that live in water). Later, probiotics were used to improve water quality and control of bacterial infections. Nowadays, there is documented evidence that probiotics can improve the digestibility of nutrients, increase tolerance to stress, and encourage reproduction. Currently, there are commercial probiotic products prepared from various bacterial species such as Bacillus sp., Lactobacillus sp., Enterococcus sp., Carnobacterium sp., and the yeast Saccharomyces cerevisiae among others, and their use is regulated by careful management recommendations. The present paper shows the current knowledge of the use of probiotics in aquaculture, its antecedents, and safety measures to be carried out and discusses the prospects for study in this field.


Response speed, contingent negative variation and P300 in Alzheimer's disease and MCI.
Decreased speed of information processing is a hallmark of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Recent studies suggest that response speed (RS) measures are very sensitive indicators of changes in longitudinal follow-up studies. Insight into the psycho-physiological underpinnings of slowed RS can be provided by measuring the associated event-related potentials (ERP). The current study aims to investigate the relation between RS and its psycho-physiological correlates in AD and MCI. Fifteen psychoactive drug-naïve AD patients, 20 MCI patients and twenty age-matched, healthy control subjects participated. Response speed was measured during a simple (SRT) and choice reaction time task (CRT). An oddball and contingent negative variation (CNV) paradigm were used to elicit ERP. To evaluate test-retest reliability (TRR), subjects underwent a similar assessment one week after the first. The SRT and CRT distinguished the patient groups significantly. The P300 amplitude and latency also distinguished the groups and showed a significant correlation with response speed. The CNV amplitude did not reveal a significant difference between groups and also showed a low TRR. The TRR of the SRT, CRT and P300 amplitude and latency in general was moderate to high. The current study suggests that response speed measures on a behavioural and psycho-physiological level deserve attention as a possible marker in the diagnosis and follow-up of AD.


Do we need sex-oriented clinical practice guidelines for the treatment of schizophrenia?
Clinical practice guidelines (CPGs) do not usually offer a sex-specific approach for the management of schizophrenia. With this narrative review, we aim to give an integrated and synthesized overview of the current state of knowledge regarding sex-specific aspects in schizophrenia and how this topic may be adapted in the development of CPGs. Recent studies further suggest sex-specific differences in epidemiologic features, the course of illness, underlying pathomechanisms, response likelihood to antipsychotic medication and differences in tolerability. Beyond this, selective estrogen receptor modulators like raloxifene have shown beneficial effects on symptom severity and cognition in women with schizophrenia. Sex-specific aspects can already be integrated in clinical guideline recommendations, especially with regard to efficacy and tolerability of antipsychotic treatment. Moreover, these aspects may be used for an individual risk-stratification. Recent studies provide evidence supporting the hypothesis of sex-specific modulation in schizophrenia and build the groundwork for sex-specific novel treatment options. However, there remains a clear need for additional studies focusing on women with schizophrenia to substantiate current findings.


Understanding the association between county-level unemployment and health stratified by education and income in the southwestern United States.
Past research on the relationship between unemployment rates and population health has produced mixed findings. The relationship can be influenced by the kinds of health outcomes observed, time frame, level of geographic aggregation, and other factors. Given these mixed findings, there is a need to add to our knowledge about how unemployment rates and population health are related. There is limited research that examines the association of unemployment rates with both physical and mental health, while simultaneously stratifying populations by income and education levels. Using survey-based self-reported data, this first population-based study examined the association between unemployment rates and physically and mentally unhealthy days in the southwestern United States, by county-level stratification of income (high and low) as well as education (high and low), from 2015 to 2019. After controlling for covariates, associations were modelled using negative binomial regression, with autocorrelative residuals, and were reported as rate ratios (RR). Overall, we found that a 1% rise in unemployment rates was significantly associated with an increase in physically unhealthy days [adjusted RR 1.007; 95% CI, 1.004-1.011, P < 0.001] and mentally unhealthy days [RR 1.006; 95% CI, 1.003-1.009, P < 0.001]. Upon stratification, a significant risk was found among the high education and high income category [RR 1.035; 95% CI, 1.021-1.049, P < 0.001], as well as for the high education and low income category [RR 1.026; 95% CI, 1.013-1.040, P < 0.001]. A better understanding of how unemployment is associated with the health of communities with different education and income levels could help reduce the burden on society through tailored interventions and social policies not only in the United States, but also in other developed nations.


High rates of intestinal colonization with extended-spectrum lactamase-producing Enterobacteriaceae among healthy individuals.
Infections caused by extended-spectrum β-lactamase (ESBL)-producing bacteria become an emerging problem in the community setting in many parts of the world. The objective of the study was to determine fecal carriage of ESBL-producing organisms in a community setting. A total of 632 fecal specimens from healthy individuals were screened for ESBL using the agar screening test with MacConkey agar plates supplemented with 1 μg/mL of cefotaxime for selection of ESBL-producing strains and confirmed by the Clinical Laboratory Standards Institute combined disk method. Four hundred isolates (63.3%) were ESBL producers. Two hundred eighty-five isolates (71.25%) of them were Escherichia coli and 96 (24.0%) Klebsiella pneumoniae. We concluded that the community could be a reservoir of these ESBL-producing bacteria and enzymes.


Using high density EEG to assess TMS treatment in patients with schizophrenia.
We present preliminary results from the ongoing study entitled "Icelandic AVH-TMS" which aim is to study the effectiveness of repetitive transcranial magnetic stimulation (rTMS) treatment for patients with schizophrenia and with persistent auditory verbal hallucinations (AVH) using symptoms and psychometric scales and high-density EEG system (256 channels). The aim of the present work was to describe cortical topography of the auditory evoked responses like P50 and N100-P300 complex in healthy participants and patients with schizophrenia and to define a robust methodology of signal quantification using dense-array EEG. Preliminary data is shown for three healthy participants and three patients in baseline conditions and for two patients we show the results recorded before and after 10 days rTMS treatment. Our results show differences in sensory gating (P50 suppresion) and a stronger N100-P300 response to rare audio stimulus after the treatment. Moreover we show the value of assessing brain electrical activity from high-density EEG (256 channels) analyzing the results in different regions of interest. However, it is premature and hazardous to assume that rTMS treatment effectiveness in patients with AVH can be assessed using P50 suppression ratio.


Perceived barriers to mental health care and goal setting among depressed, community-dwelling older adults.
Older adults are particularly vulnerable to the deleterious effects of depression and tend to underutilize mental health services. The current study aims to characterize the perceived barriers to care and goal setting in a sample of depressed, community-dwelling older adults. We report on the association among perceived barriers to care, goal setting and accepting a mental health referral using a subset of data from a larger study. The Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms. Forty-seven participants completed the study (Mean age = 82, SD = 7.8, 85% female). Accessing and paying for mental health treatment were the barriers most frequently cited by participants. Clinical improvement and improved socialization were most cited goals. In bivariate associations, participants who set goals (chi(2) = 5.41, p = 0.02) and reported a logistic barrier (chi(2) = 5.30, p = 0.02) were more likely to accept a mental health referral. Perceived barriers to care and goal setting appear to be central to accepting a mental health referral among community dwelling older, depressed adults. Developing interventions that can be used to increase mental health service utilization of older adults is necessary.


Effects of intracellular adenosine-5'-diphosphate and orthophosphate on the sensitivity of sodium efflux from squid axon to external sodium and potassium.
A study was made of sodium efflux from squid giant axon, and its sensitivity to external K and Na. When sodium efflux from untreated axons was strongly stimulated by K(o), Na(o) was inhibitory; when dependence on K(o) was low, Na(o) had a stimulatory effect. Incipient CN poisoning or apyrase injection, which produces high intracellular levels of ADP(1) and P(i), rendered sodium efflux less dependent on external K and more dependent on external Na. Injection of ADP, AMP, arginine, or creatine + creatine phosphokinase, all of which raise ADP levels without raising P(i) levels, had the same effect as incipient CN poisoning. P(i) injection had no effect on the K sensitivity of sodium efflux. Axons depleted of arginine and phosphoarginine by injection of arginase still lost their K sensitivity when the ATP:ADP ratio was lowered and regained it partially when the ratio was raised. Rough calculations show that sodium efflux is maximally K(o)-dependent when the ATP:ADP ratio is about 10:1, becomes insensitive to K(o) when the ratio is about 1:2, and is inhibited by K(o) when the ratio is about 1:10. Deoxy-ATP mimicked ADP when injected into intact axons. Excess Mg, as well as P(i), inhibited both strophanthidin-sensitive and strophanthidin-insensitive sodium efflux. An outline is presented for a model which might explain the effects of ADP, P(i) and deoxy-ATP.


Comparison of Survival Outcomes With/Without Adjuvant Radiation Therapy in Desmoplastic Melanoma.
Desmoplastic melanoma (DM) is a rare variant of cutaneous melanoma with a high rate of local recurrence. Recent studies have indicated a potential benefit in local control with the addition of adjuvant radiotherapy (RT). This study sought to evaluate the outcomes of adjuvant RT for patients with DM. The National Cancer Database was queried (2004-2015) for patients with newly diagnosed, nonmetastatic DM. Patients were divided into 2 groups based on the adjuvant therapy they received: RT or observation. Statistics included multivariable logistic regression to determine factors predictive of receiving adjuvant RT, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. There was no difference in median OS between patients treated with RT when compared with patients observed (111.4 months vs 133.9 months, p = .1312). On multivariable analysis, older age, T stage ≥2, N stage ≥1, and no receipt of immunotherapy were associated with worse OS. In this large study evaluating efficacy of adjuvant RT in DM, no overall survival benefit was observed among patients receiving adjuvant RT.


Cohort versus patient level simulation for the economic evaluation of single versus combination immuno-oncology therapies in metastatic melanoma.
Background: Model structure, despite being a key source of uncertainty in economic evaluations, is often not treated as a priority for model development. In oncology, partitioned survival models (PSMs) and Markov models, both types of cohort model, are commonly used, but patient responses to newer immuno-oncology (I-O) agents suggest that more innovative model frameworks should be explored. Objective: A discussion of the theoretical pros and cons of cohort level vs patient level simulation (PLS) models provides the background for an illustrative comparison of I-O therapies, namely nivolumab/ipilimumab combination and ipilimumab alone using patient level data from the CheckMate 067 trial in metastatic melanoma. PSM, Markov, and PLS models were compared on the basis of coherence with short-term clinical trial endpoints and long-term cost per QALY outcomes reported. Methods: The PSM was based on Kaplan-Meier curves from CheckMate 067 with 3-year data on progression free survival (PFS) and overall survival (OS). The Markov model used time independent transition probabilities based on the average trajectory of PFS and OS over the trial period. The PLS model was developed based on baseline characteristics hypothesized to be associated with disease as well as significant mortality and disease progression risk factors identified through a proportional hazards model. Results: The short-term Markov model outputs matched the 1-3 year clinical trial results approximately as well as the PSMs for OS but not PFS. The fixed (average) cohort PLS results corresponded as well as the PSMs for OS in the combination therapy arm and PFS in the monotherapy arm. Over the lifetime horizon, the PLS produced an additional 5.95 quality adjusted life years (QALYs) associated with combination therapy relative to ipilimumab alone, resulting in an incremental cost-effectiveness ratio (ICER) of £6,474 per QALY, compared with £14,194 for the PSMs which gave an incremental benefit of between 2.2 and 2.4 QALYs. The Markov model was an outlier (∼ £49,000 per QALY in the base case). Conclusions: The 4- and 5-state versions of the PSM cohort model estimated in this study deviate from the standard 3-state approach to better capture I-O response patterns. Markov and PLS approaches, by modeling state transitions explicitly, could be more informative in understanding I-O immune response, the PLS particularly so by reflecting heterogeneity in treatment response. However, both require a number of assumptions to capture the immune response effectively. Better I-O representation with surrogate endpoints in future clinical trials could yield greater model validity across all models.


Abscission Couples Cell Division to Embryonic Stem Cell Fate.
Cell fate transitions are key to development and homeostasis. It is thus essential to understand the cellular mechanisms controlling fate transitions. Cell division has been implicated in fate decisions in many stem cell types, including neuronal and epithelial progenitors. In other stem cells, such as embryonic stem (ES) cells, the role of division remains unclear. Here, we show that exit from naive pluripotency in mouse ES cells generally occurs after a division. We further show that exit timing is strongly correlated between sister cells, which remain connected by cytoplasmic bridges long after division, and that bridge abscission progressively accelerates as cells exit naive pluripotency. Finally, interfering with abscission impairs naive pluripotency exit, and artificially inducing abscission accelerates it. Altogether, our data indicate that a switch in the division machinery leading to faster abscission regulates pluripotency exit. Our study identifies abscission as a key cellular process coupling cell division to fate transitions.


The relationship between skill and ground reaction force variability in amateur golfers.
It is accepted that highly skilled golfers are more consistent in their clubhead presentation and shot outcomes than their lesser skilled counterparts. However, the relationships between movement variability, outcome variability and skill in golf are not particularly well understood. This study examined the ground reaction force variability of one-hundred and four amateur golfers for shots with drivers and 5-irons. Principal component analysis was used as a data reduction technique and allowed all three components of ground reaction force to be considered together. There were statistically significant trends for the higher skilled golfers to display lower variability in two of the five principal components (driver) and four of the five principal components (5-iron). A similar trend was also observed in the other principal components, but these trends were not statistically significant. Intra-individual variability was much lower than inter-individual variability across all golfers; the golfers were each relatively consistent in maintaining their own ground reaction force patterns. Lower variability in ground reaction forces may partly explain how highly skilled golfers maintain lower variability in shot outcomes.


Expression analysis of maspin in invasive ductal carcinoma of breast and modulation of its expression by curcumin in breast cancer cell lines.
In breast cancer, maspin, a serine protease inhibitor, can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. The clinical significance of maspin expression in breast cancer, especially in the sequence of ductal carcinoma in situ (DCIS)-invasive cancer-lymph node metastasis is well known in the Western countries, but its status in the rapidly increasing breast cancers in India remains unknown. The present study was designed to determine the clinical significance of maspin expression in invasive ductal carcinomas of breast (IDCs) in North Indian population and modulation of its expression by curcumin. Immunohistochemical analysis of maspin showed loss or reduced cytoplasmic expression in 36 of 59 (61%) tumors. Furthermore, breast cancer cells (MCF-7 (wild type p53) and MDA-MB-231 (mutant p53)) were treated with curcumin and the effect on expression of maspin gene at transcription and translation levels was analyzed by RT-PCR, immunofluorescence and Western blotting. Maspin expression was also correlated with p53 and Bcl-2 levels. Curcumin inhibited cell growth, induced apoptosis and upregulated maspin gene expression in MCF-7 cells and these findings were further correlated with the upregulation of p53 protein and downregulation of Bcl-2, suggesting maspin mediated apoptosis in MCF-7 cells. To our knowledge this is the first report showing the upregulation of maspin expression by curcumin in breast cancer cells and taken together with the clinical data suggests a potential therapeutic role for curcumin in inducing maspin mediated inhibition of invasion of breast carcinoma cells.


Characterization of the H4IIE rat hepatoma cell bioassay for evaluation of environmental samples containing polynuclear aromatic hydrocarbons (PAHs).
The H4IIE rat hepatoma cell bioassay has been extensively used to assess the toxic equivalents (TEQs) of complex mixtures of halogenated aromatic hydrocarbons in environmental samples. However, there is often a discrepancy between bioassay induction results and toxic equivalents calculated from chemical analysis of samples; the former generally yield higher bioassay-TEQs. Polynuclear aromatic hydrocarbons (PAHs) are a class of chemicals which can significantly contribute to induction-TEQs. Benzo(a)pyrene (BAP), dibenz(a, h)anthracene (DBA), benz(a)anthracene (BA), benzo(k)fluoranthene (BkF), benzo(b)fluoranthene (BbF), chrysene (Chr), and indeno(1,2,3-c,d) pyrene (IdP) are carcinogenic PAHs found in environmental samples, including oysters collected from Galveston Bay. The induction potency of these PAHs relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was determined individually in rat hepatoma H4IIE cells seeded in 6-well plates, and the induction-derived equivalency factors (EFs) relative to TCDD were 0. 000354, 0.00203, 0.000025, 0.00478, 0.00253, 0.00020, 0.0011 for BAP, DBA, BA, BkF, BbF, Chr, and IdP, respectively. Dilutions of a reconstituted PAH mixture containing 23 PAHs (744 to 4466 ng/g total PAHs) with constant percentages of BAP (4.5%), DBA (3.5%), BA (2.4%), BkF (3.7%), BbF (3.5%), Chr (4.7%), and IdP (4.2%) yielded bioassay-derived induction-EQs that ranged from 0.52 to 1.44 ng/g. Oysters exposed in the laboratory to the same PAH mixture for 30 days differentially accumulated the PAHs with time. Bioassay-EQs for these oyster extracts ranged from 0.94 to 5.79 ng/g. These results were similar to the chemically calculated EQs which varied from 0.81 to 3.13 ng/g.


The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador.
Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by ∼ 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP.


Effect of subthalamic coordinated reset deep brain stimulation on Parkinsonian gait.
Coordinated Reset Deep Brain Stimulation (CR DBS) is a novel DBS approach for treating Parkinson's disease (PD) that uses lower levels of burst stimulation through multiple contacts of the DBS lead. Though CR DBS has been demonstrated to have sustained therapeutic effects on rigidity, tremor, bradykinesia, and akinesia following cessation of stimulation, i.e., carryover effect, its effect on Parkinsonian gait has not been well studied. Impaired gait is a disabling symptom of PD, often associated with a higher risk of falling and a reduced quality of life. The goal of this study was to explore the carryover effect of subthalamic CR DBS on Parkinsonian gait. Three non-human primates (NHPs) were rendered Parkinsonian and implanted with a DBS lead in the subthalamic nucleus (STN). For each animal, STN CR DBS was delivered for several hours per day across five consecutive days. A clinical rating scale modified for NHP use (mUPDRS) was administered every morning to monitor the carryover effect of CR DBS on rigidity, tremor, akinesia, and bradykinesia. Gait was assessed quantitatively before and after STN CR DBS. The stride length and swing speed were calculated and compared to the baseline, pre-stimulation condition. In all three animals, carryover improvements in rigidity, bradykinesia, and akinesia were observed after CR DBS. Increased swing speed was observed in all the animals; however, improvement in stride length was only observed in NHP B2. In addition, STN CR DBS using two different burst frequencies was evaluated in NHP B2, and differential effects on the mUPDRS score and gait were observed. Although preliminary, our results indicate that STN CR DBS can improve Parkinsonian gait together with other motor signs when stimulation parameters are properly selected. This study further supports the continued development of CR DBS as a novel therapy for PD and highlights the importance of parameter selection in its clinical application.


Ruminal degradability of dry matter, crude protein, and amino acids in soybean meal, canola meal, corn, and wheat dried distillers grains.
Different protein sources, such as canola meal (CM) or dried distillers grains (DDG), are currently used in dairy rations to replace soybean meal (SBM). However, little data exists comparing their rumen degradation in a single study. Therefore, the objective of this study was to compare the ruminal degradation of dry matter (DM), crude protein (CP), and AA of SBM, CM, high-protein corn DDG (HPDDG), and wheat DDG plus solubles (WDDGS). In situ studies were conducted with 4 rumen-fistulated lactating Holstein cows fed a diet containing 38% grass hay and 62% corn-based concentrate. Each protein source was incubated in the rumen of each cow in nylon bags for 0, 2, 4, 8, 16, 24, and 48 h to determine DM and CP rumen degradation kinetics, whereas additional bags were also incubated for 16 h to evaluate AA ruminal disappearance. Rumen DM and CP degradability was calculated from rumen-undegraded residues corrected or not for small particle loss. Data were fitted to an exponential model to estimate degradation parameters and effective degradability (ED) was calculated with a passage rate of 0.074 h(-1). The WDDGS and SBM had higher uncorrected ED (DM=75.0 and 72.6%; CP=84.8 and 66.0%, respectively) than CM and HPDDG (DM=57.2 and 55.5%; CP=59.3 and 48.2%, respectively), due to higher soluble fraction in WDDGS and a combination of higher potentially degradable fraction and rate of degradation in SBM. Correction for small particle loss from bags, higher for WDDGS than for the other protein sources, decreased estimated ED but did not alter feed ranking. The ruminal disappearance of AA after 16 h of incubation reflected the overall pattern of CP degradation between protein supplements, but the ruminal disappearance of individual AA differed between protein supplements. Overall, these results indicate that, in the current study, (1) SBM and WDDGS were more degradable in the rumen than CM and HPDDG, and (2) that small particle loss correction is relevant but does not alter this ranking.


Association of age, sex, and pyrethroid resistance status on survival and cytochrome P450 gene expression in Aedes aegypti (L.).
Aedes aegypti is a vector of viruses that negatively impact human health. Insecticide resistance complicates mosquito control efforts, but understanding the mechanisms of resistance can help to improve management practices. This study examined different factors that could influence the interpretation of toxicity bioassays and gene expression studies in A. aegypti, including sex and age, in the context of resistance to pyrethroids. Bioassays using a pyrethroid-resistant strain, Puerto Rico (PR), and a pyrethroid-susceptible strain, Rockefeller (Rock), of A. aegypti were conducted with females and males of three age groups to determine differences in mortality induced by deltamethrin. Overall, strain was the only factor with a significant effect on the LD50. Enzyme assays showed that cytochrome P450 monooxygenase activity in PR was constitutively higher than in Rock, and that pretreatment with the cytochrome P450 inhibitor piperonyl butoxide (PBO) followed by a topical application of deltamethrin (LD25) significantly increased mortality in both strains. Evaluation of the expression levels of seven CYP9J genes previously reported to be involved in pyrethroid resistance revealed that CYP9J10, CYP9J19, and CYP9J28 were more highly expressed in PR than in Rock at all ages of females and males, indicating that they may be essential for resistance. The expression of CYP9J24, CYP9J26, CYP9J27, and CYP9J32 was higher in PR males compared to other groups, including PR females. Significant differences in expression between sexes and strains were also observed as a result of age.


The 5-HT3 Receptor Affects Rotavirus-Induced Motility.
Rotavirus infection is highly prevalent in children, and the most severe effects are diarrhea and vomiting. It is well accepted that the enteric nervous system (ENS) is activated and plays an important role, but knowledge of how rotavirus activates nerves within ENS and to the vomiting center is lacking. Serotonin is released during rotavirus infection, and antagonists to the serotonin receptor subtype 3 (5-HT3 receptor) can attenuate rotavirus-induced diarrhea. In this study, we used a 5-HT3 receptor knockout (KO) mouse model to investigate the role of this receptor in rotavirus-induced diarrhea, motility, electrolyte secretion, inflammatory response, and vomiting reflex. The number of diarrhea days (P = 0.03) and the number of mice with diarrhea were lower in infected 5-HT3 receptor KO than wild-type pups. In vivo investigation of fluorescein isothiocyanate (FITC)-dextran transit time showed that intestinal motility was lower in the infected 5-HT3 receptor KO compared to wild-type mice (P = 0.0023). Ex vivo Ussing chamber measurements of potential difference across the intestinal epithelia showed no significant difference in electrolyte secretion between the two groups. Immediate early gene cFos expression level showed no difference in activation of the vomiting center in the brain. Cytokine analysis of the intestine indicated a low effect of inflammatory response in rotavirus-infected mice lacking the 5-HT3 receptor. Our findings indicate that the 5-HT3 receptor is involved in rotavirus-induced diarrhea via its effect on intestinal motility and that the vagus nerve signaling to the vomiting center occurs also in the absence of the 5-HT3 receptor. IMPORTANCE The mechanisms underlying rotavirus-induced diarrhea and vomiting are not yet fully understood. To better understand rotavirus pathophysiology, characterization of nerve signaling within the ENS and through vagal efferent nerves to the brain, which have been shown to be of great importance to the disease, is necessary. Serotonin (5-HT), a mediator of both diarrhea and vomiting, has been shown to be released from enterochromaffin cells in response to rotavirus infection and the rotavirus enterotoxin NSP4. Here, we investigated the role of the serotonin receptor 5-HT3, which is known to be involved in the nerve signals that regulate gut motility, intestinal secretion, and signal transduction through the vagus nerve to the brain. We show that the 5-HT3 receptor is involved in rotavirus-induced diarrhea by promoting intestinal motility. The findings shed light on new treatment possibilities for rotavirus diarrhea.


Investigating the role of the IGF axis as a predictor of biochemical recurrence in prostate cancer patients post-surgery.
Between 20% and 35% of prostate cancer (PCa) patients who undergo treatment with curative intent (ie, surgery or radiation therapy) for localized disease will experience biochemical recurrence (BCR). Alterations in the insulin-like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa. We examined the expression of the insulin receptor (INSR), IGF-1 receptor (IGF-1R), PTEN, and AKT in radical prostatectomy tissue of patients who developed BCR post-surgery. Tissue microarrays (TMA) of 130 patients post-radical prostatectomy (65 = BCR, 65 = non-BCR) were stained by immunohistochemistry for INSR, IGF-1R, PTEN, and AKT using optimized antibody protocols. INSR, IGF1-R, PTEN, and AKT expression between benign and cancerous tissue, and different Gleason grades was assessed. Kaplan-Meier survival curves were used to examine the relationship between proteins expression and BCR. INSR (P < 0.001), IGF-1R (P < 0.001), and AKT (P < 0.05) expression was significantly increased and PTEN (P < 0.001) was significantly decreased in cancerous versus benign tissue. There was no significant difference in INSR, IGF-1R, or AKT expression in the cancerous tissue of non-BCR versus BCR patients (P = 0.149, P = 0.990, P = 0.399, respectively). There was a significant decrease in PTEN expression in the malignant tissue of BCR versus non-BCR patients (P = 0.011). Combinational analysis of the tissue proteins identified a combination of decreased PTEN and increased AKT or increased INSR was associated with worst outcome. We found that in each case, our hypothesized worst group was most likely to experience BCR and this was significant for combinations of PTEN+INSR and PTEN+AKT but not PTEN+IGF-1R (P = 0.023, P = 0.028, P = 0.078, respectively). Low PTEN is associated with BCR and this association is strongly modified by high INSR and high AKT expression. Measurement of these proteins could help inform appropriate patient selection for postoperative adjuvant therapy and prevent BCR.


A large pericardial cyst presenting with compression of the right-side cardiac chambers.
Pericardial cysts are rare, usually congenital. Cysts frequently occur in the right cardiophrenic angle and their diagnosis is usually suspected after an abnormal chest X ray. The present case report shows a case of pericardial cyst with atypical radiographic aspect in an athletic patient who presented clinical with symptoms of right ventricular failure. The diagnosis was suggested by echocardiogram and subsequently was confirmed by pathologic examination.


Transcriptional regulation of the stem cell leukemia gene (SCL)--comparative analysis of five vertebrate SCL loci.
The stem cell leukemia (SCL) gene encodes a bHLH transcription factor with a pivotal role in hematopoiesis and vasculogenesis and a pattern of expression that is highly conserved between mammals and zebrafish. Here we report the isolation and characterization of the zebrafish SCL locus together with the identification of three neighboring genes, IER5, MAP17, and MUPP1. This region spans 68 kb and comprises the longest zebrafish genomic sequence currently available for comparison with mammalian, chicken, and pufferfish sequences. Our data show conserved synteny between zebrafish and mammalian SCL and MAP17 loci, thus suggesting the likely genomic domain necessary for the conserved pattern of SCL expression. Long-range comparative sequence analysis/phylogenetic footprinting was used to identify noncoding conserved sequences representing candidate transcriptional regulatory elements. The SCL promoter/enhancer, exon 1, and the poly(A) region were highly conserved, but no homology to other known mouse SCL enhancers was detected in the zebrafish sequence. A combined homology/structure analysis of the poly(A) region predicted consistent structural features, suggesting a conserved functional role in mRNA regulation. Analysis of the SCL promoter/enhancer revealed five motifs, which were conserved from zebrafish to mammals, and each of which is essential for the appropriate pattern or level of SCL transcription.


Time trends of hypertension and diabetes mellitus prevalence among adults registered in the Brazilian National Health System, in Florianópolis, Santa Catarina State, Brazil, 2004-2011.
to investigate the time trend of prevalence of hypertension, diabetes mellitus, and both diseases combined, from 2004 to 2011; and to analyze their association with sociodemographic factors in adults registered in the Brazilian National Health System (SUS) in Florianópolis-SC, Brazil, in 2011. time-series study using secondary data from the Primary Health Care Information System of adults (≥20 years) at SUS; Prais-Winsten regression was used. from 2004 to 2011, prevalences of hypertension (7 to 13.5%), diabetes (2.2 to 4.2%) and both diseases combined (1.2 to 2.9%) increased; after adjustment, the occurrence of the diseases was higher among women (except for the association of hypertension with diabetes), the elderly, less educated and residents in the Mainland and South sanitary districts. the occurrence of the investigated diseases doubled from 2004 to 2011. However, the prevalences found are below the ones described in the Brazilian scientific literature.


Magnetic resonance morphologic features predict progression of incidental pancreatic cystic lesions during follow-up.
We aimed to evaluate which morphologic features on magnetic resonance imaging (MRI) could predict the progression of pancreatic cystic lesions (PCLs) that are suitable for follow-up. A total of 2176 MRI findings of PCLs were retrospectively reviewed between January 2009 and December 2016. The study population was composed of 223 patients. Clinical data and morphologic features of PCLs were recorded. We divided the individuals into two sub-groups according to the final features on MRI. Univariable and multivariable regression analyses were performed to identify independent risk factors for progression of PCLs. A total of 84 PCLs (37.7%) progressed during follow-up, while 139 PCLs (62.3%) were stable. Age (odds ratio [OR], 1.042; P = 0.017), number of lesions (OR, 0.491; P = 0.048), communication to pancreatic duct (PD) (OR, 2.425; P = 0.007) and presence of septa (OR, 6.105; P < 0.001) were significant independent factors for progression of PCLs. Among 84 lesions that progressed, 23 lesions (27.4%) increased to ≥ 30 mm in diameter or showed worrisome imaging features at the end of follow-up that needed clinical intervention. The initial size and communication to PD were independent factors for progression of PCLs necessitating clinical intervention (P < 0.001 and P = 0.011, respectively). Age, number of the lesions, communication to PD and presence of septa were independent risk factors for the progression of PCLs, and the initial size and communication to PD could potentially predict PCLs needing clinical interventions.


The accuracy of implant placement with computer-guided surgery in partially edentulous patients and possible influencing factors: A systematic review and meta-analysis.
To review the current clinical studies regarding the accuracy of implant computer-guided surgery in partially edentulous patients and investigate potential influencing factors. Electronic searches on the PubMed and Cochrane Central Register of Controlled Trials databases, and subsequent manual searches were performed. Two reviewers selected the studies following our inclusion and exclusion criteria. Qualitative review and meta-analysis of the implant placement accuracy were performed to analyze potential influencing factors. Angular deviation, coronal deviation, apical deviation, and depth deviation were evaluated as the accuracy outcomes. Eighteen studies were included in this systematic review, including six randomized controlled trials, nine prospective studies, and three retrospective clinical studies. A total of 1317 implants placed in 642 partially edentulous patients were reviewed. Eight studies were evaluated using meta-analysis. Fully guided surgery showed statistically higher accuracy in angular (P <0.001), coronal (P <0.001), and apical deviation (P <0.05) compared with pilot-drill guided surgery. A statistically significant difference (P <0.001) was also observed in coronal deviation between the bounded edentulous (BES) and distal extension spaces (DES). A significantly lower angular deviation (P <0.001) was found in implants placed using computer-aided design/computer-aided manufacturing (CAD/CAM) compared to the conventional surgical guides. The edentulous space type, surgical guide manufacturing procedure, and guided surgery protocol can influence the accuracy of computer-guided surgery in partially edentulous patients. Higher accuracy was found when the implants were placed in BES, with CAD/CAM manufactured surgical guides, using a fully guided surgery protocol.


An Optimized Ustilago maydis for Itaconic Acid Production at Maximal Theoretical Yield.
Ustilago maydis, a member of the Ustilaginaceae family, is a promising host for the production of several metabolites including itaconic acid. This dicarboxylate has great potential as a bio-based building block in the polymer industry, and is of special interest for pharmaceutical applications. Several itaconate overproducing Ustilago strains have been generated by metabolic and morphology engineering. This yielded stabilized unicellular morphology through fuz7 deletion, reduction of by-product formation through deletion of genes responsible for itaconate oxidation and (glyco)lipid production, and the overexpression of the regulator of the itaconate cluster ria1 and the mitochondrial tricarboxylate transporter encoded by mttA from Aspergillus terreus. In this study, itaconate production was further optimized by consolidating these different optimizations into one strain. The combined modifications resulted in itaconic acid production at theoretical maximal yield, which was achieved under biotechnologically relevant fed-batch fermentations with continuous feed.


Zero Endemic Cases of Wildlife Rabies (Classical Rabies Virus, RABV) in the European Union by 2020: An Achievable Goal.
The elimination of rabies transmitted by Classical Rabies Virus (RABV) in the European Union (EU) is now in sight. Scientific advances have made it possible to develop oral vaccination for wildlife by incorporating rabies vaccines in baits for foxes. At the start of the 1980s, aerial distribution of vaccine baits was tested and found to be a promising tool. The EU identified rabies elimination as a priority, and provided considerable financial and technical resources to the infected EU Member States, allowing regular and large-scale rabies eradication programs based on aerial vaccination. The EU also provides support to non-EU countries in its eastern and south eastern borders. The key elements of the rabies eradication programs are oral rabies vaccination (ORV), quality control of vaccines and control of their distribution, rabies surveillance and monitoring of the vaccination effectiveness. EU Member States and non-EU countries with EU funded eradication programs counted on the technical support of the rabies subgroup of the Task Force for monitoring disease eradication and of the EU Reference Laboratory (EURL) for rabies. In 2018, eight rabies cases induced by classical rabies virus RABV (six in wild animals and two in domestic animals) were detected in three EU Member States, representing a sharp decrease compared to the situation in 2010, where there were more than 1500 cases in nine EU Member States. The goal is to reach zero cases in wildlife and domestic animals in the EU by 2020, a target that now seems achievable.


Predictors of nonfunctional arteriovenous access at hemodialysis initiation and timing of access creation: A registry-based study.
Determinants of nonfunctional arteriovenous (AV) access, including timing of AV access creation, have not been sufficiently described. We studied 29 945 patients who had predialysis AV access placement and were included in the French REIN registry from 2005 through 2013. AV access was considered nonfunctional when dialysis began with a catheter. We estimated crude and adjusted odds ratio (OR) with 95% confidence intervals (CI) of nonfunctional versus functional AV access associated with case-mix, facility characteristics, and timing of AV access creation. Analyses were stratified by dialysis start condition (planned or as an emergency) and comorbidity profile. Overall, 18% patients had nonfunctional AV access at hemodialysis initiation. In the group with planned dialysis start, female gender (OR 1.43, 95% CI 1.32-1.56), diabetes (OR 1.28, 95% CI 1.15-1.44), and a higher number of cardiovascular comorbidities (OR 1.27, 95% CI 1.09-1.49, and 1.31, 1.05-1.64, for 3 and >3 cardiovascular comorbidities versus none, respectively) were independent predictors of nonfunctional AV access. A higher percentage of AV access creation at the region level was associated with a lower rate of nonfunctional AV access (OR 0.98, 95% CI 0.98-0.99 per 1% increase). The odds of nonfunctional AV access decreased as time from creation to hemodialysis initiation increased up to 3 months in nondiabetic patients with fewer than 2 cardiovascular comorbidities and 6 months in patients with diabetes or 2 or more such comorbidities. In conclusion, both patient characteristics and clinical practices may play a role in successful AV access use at hemodialysis initiation. Adjusting the timing of AV access creation to patients' comorbidity profiles may improve functional AV access rates.


Comparative effectiveness of tetracycline, minocycline and doxycycline in treatment of acute-on-chronic bronchitis. A study based on sputum levels.
After the administration of minocycline, doxycyline and tetracycline in recommended therapeutic doses to 11, 10 and 12 patients respectively, sputum levels of these antibiotics were determined. Only 20% of patients given doxcycline had a satisfactory sputum level and in the remainder levels were either low or absent. For patients receiving tetracycline and minocycline, 67% and 64% respectively had satisfactory sputum levels. Patients selected for this study had a history of chronic bronchitis and were producing copious amounts of purulent sputum. Minimum inhibitory concentrations of these three antibiotics were similar for 25 freshly isolated strains of Haemophilus influenzae, with minocycline being the most inhibitory and doxcycline the least inhibitory.


EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation.
Uveal melanoma (UM) is a rare eye tumor. There are two classes of UM, which can be discriminated by the chromosome 3 status or global mRNA expression profile. Metastatic progression is predominantly originated from class II tumors or from tumors showing loss of an entire chromosome 3 (monosomy 3). We performed detailed EFS (embryonal Fyn-associated substrate) methylation analyses in UM, cultured uveal melanocytes and normal tissues, to explore the role of the differentially methylated EFS promoter region CpG island in tumor classification and metastatic progression. EFS methylation was determined by direct sequencing of PCR products from bisulfite-treated DNA or by sequence analysis of individual cloned PCR products. The results were associated with clinical features of tumors and tumor-related death of patients. Analysis of 16 UM showed full methylation of the EFS CpG island in 8 (50%), no methylation in 5 (31%) and partial methylation in 3 (19%) tumors. Kaplan-Meier analysis revealed a higher risk of metastatic progression for tumors with EFS methylation (p = 0.02). This correlation was confirmed in an independent set of 24 randomly chosen tumors. Notably, only UM with EFS methylation gave rise to metastases. Real-time quantitative RT-PCR expression analysis revealed a significant inverse correlation of EFS mRNA expression with EFS methylation in UM. We further found that EFS methylation is tissue-specific with full methylation in peripheral blood cells, and no methylation in sperm, cultured primary fibroblasts and fetal muscle, kidney and brain. Adult brain samples, cultured melanocytes from the uveal tract, fetal liver and 3 of 4 buccal swab samples showed partial methylation. EFS methylation always affects both alleles in normal and tumor samples. Biallelic EFS methylation is likely to be the result of a site-directed methylation mechanism. Based on partial methylation as observed in cultured melanocytes we hypothesize that there might be methylated and unmethylated precursor cells located in the uveal tract. The EFS methylation of a UM may depend on which type of precursor cell the tumor originated from.


Beats produced between a rhythmic applied force and the resting tremor of Parkinsonism.
Rhythmic forces have been applied to the wrist of patients with Parkinsonism tremor by means of a printed motor. The tremor rate was not altered to that of the applied force. On the contrary, beats were established, the rate of which depended on the difference in rate between the tremor and the applied rhythm. Most of the observations have been for horizontal motion of the hand but similar phenomena have been seen for vertical movements, and for other parts of the body--for example, foot, elbow, finger joint, and head. The observations are regarded as supporting the view that the tremorgenic mechanism is central. There was no electromyographic evidence of servo driving or servo assistance in the genesis of the tremor.


Results of endovesical hyaluronic acid/chondroitin sulfate in the treatment of Interstitial Cystitis/Painful Bladder Syndrome.
The aim of our study was to test the effect of a more viscous compound than existent hyaluronic acid formulation in helping to restore a defective glycosaminoglycan layer, and therefore in improving Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) symptoms when administered intravesically in IC/PBS patients. A total of 23 female patients completed the study. Patients received endovesical administration of hyaluronic acid and chondroitin sulfate in normal saline, 40 ml, weekly for 12 weeks and then bi-weekly for 6 months, if there was initial response. After 12 weeks treatment both Interstitial Cystitis Symptom and Problem Index (ICSI/ICPI), pelvic pain and Urgency/Frequency Symptom Scale (PUF) showed a mean significant improvement, which was maintained thereafter. The average number of voidings and mean voiding volumes revealed significant improvement after the 12 weeks' treatment period, with a significant reduction and increase, respectively. Mean voiding volume increased from 143 ml to 191, which apparently was not reflected in a corresponding reduction of number of daily voids (from 15,5 to 14). VAS values decreased from 5,4 to 3,6 (pain) and from 6,0 to 3,5 (urgency) after the treatment cycle, showing a significant improvement. In our preliminary experience, the administration of intravesical hyaluronic acid plus chondroitine sulphate appears to be a safe and efficacious method of treatment in IC/PBS.


Long-term risk for depressive symptoms after a medical diagnosis.
This study examines the risk of development of significant depressive symptoms after a new diagnosis of cancer, diabetes, hypertension, heart disease, arthritis, chronic lung disease, or stroke. The study used 5 biennial waves (1992-2000) of the Health and Retirement Study to follow a sample of 8387 adults (aged 51 to 61 years and without significant depressive symptoms in 1992) from 1994 to 2000. Time-dependent Cox regression models estimated adjusted hazard ratios (HRs) for an episode of significant depressive symptoms after a new diagnosis for each of the 7 medical conditions. Within 2 years of initial diagnosis, subjects with cancer had the highest hazard of depressive symptoms (HR, 3.55; 95% confidence interval [CI], 2.79-4.52), followed by subjects with chronic lung disease (HR, 2.21; 95% CI, 1.64-2.79) and heart disease (HR, 1.45; 95% CI, 1.09-1.93). The hazard for depressive symptoms for most of these diseases decreased over time; however, subjects with heart disease continued to have a higher risk for depressive symptoms even 2 to 4 years and 4 to 8 years after diagnosis, and a significantly higher hazard for depressive symptoms developed for persons with arthritis 2 to 4 years after diagnosis (HR, 1.46; 95% CI, 1.11-1.92). The findings identify several high-risk patient groups who might benefit from depression screening and monitoring to improve health outcomes in this vulnerable population facing new medical illnesses.


Differential helper and effector responses of Lyt-2+ T cells to H-2Kb mutant (Kbm) determinants and the appearance of thymic influence on anti-Kbm CTL responsiveness.
The goal of this study was to assess and compare the allorecognition requirements for eliciting Lyt-2+ helper and effector functions from primary T cell populations. By using interleukin 2 (IL 2) secretion as a measure of T helper (Th) function, and cytolytic T lymphocyte (CTL) generation as a measure of effector function, this study compared the responses of Lyt-2+ T cells from wild-type B6 mice against a series of H-2Kb mutant determinants. Although all Kbm determinants stimulated B6 Lyt-2+ T cells to become cytolytic effector cells, the various Kbm determinants differed dramatically in their ability to stimulate Lyt-2+ T cells to function as IL 2-secreting helper cells. For example, in contrast to Kbm1 determinants that stimulated both helper and effector functions, Kbm6 determinants only stimulated B6 Lyt-2+ T cells to become cytolytic and failed to stimulate them to secrete IL 2. The distinct functional responses of Lyt-2+ T cells to Kbm6 determinants was documented by precursor frequency determinations, and was not due to an inability of the Kbm6 molecule to stimulate Lyt-2+ Th cells to secrete IL 2. Rather, it was the specific recognition and response of Lyt-2+ T cells to novel mutant epitopes on the Kbm6 molecule that was defective, such that anti-Kbm6 Lyt-2+ T cells only functioned as CTL effectors and did not function as IL 2-secreting Th cells. The failure of Lyt-2+ anti-Kbm6 T cells to function as IL 2-secreting Th cells was a characteristic of all Lyt-2+ T cell populations examined in which the response to novel mutant epitopes could be distinguished from the response to other epitopes expressed on the Kbm6 molecule. The absence of significant numbers of anti-Kbm6 Th cells in Lyt-2+ T cell populations was examined for its functional consequences on anti-Kbm6 CTL responsiveness. It was found that primary anti-Kbm6 CTL responses could be readily generated in vitro, but unlike responses to most class I alloantigens that can be mediated by Lyt-2+ Th cells, anti-Kbm6 CTL responses were strictly dependent upon self-Ia-restricted L3T4+ Th cells. Because the restriction specificity of L3T4+ Th cells is determined by the thymus, in which their precursors had differentiated, anti-Kbm6 CTL responsiveness, unlike responsiveness to most class I alloantigens, was significantly influenced by the Ia phenotype of the thymus in which the responder cells had differentiated.(ABSTRACT TRUNCATED AT 400 WORDS)


Rapid visualization molecular fluorescence detection of methicillin-resistant Staphylococcus aureus using the multiplex MIRA-qPCR method.
Multidrug-resistant (MDR) bacterial infections constitute a major public health problem worldwide. A rapid method for the detection of methicillin-resistant Staphylococcus aureus (MRSA) is critical for the timely prevention of bacterial infections and the accurate clinical use of drugs. The nuc and mecA genes are potentially indicative of MRSA infection and in this study, a multiplex molecular fluorescence multi-enzyme isothermal rapid amplification visual assay was proposed and established. The method is capable of detecting MRSA at 17 min, 40°C amplification, and is well differentiated from common clinical bacteria in specific assays, with 500 colony-forming units (CFU) mL-1 of MRSA detected under optimal conditions. This method has excellent diagnostic capabilities versus classical methods to detect clinical samples and shows potential in the identification of pathogenic microorganisms in a clinical setting.


Retained cardiac implantable electronic device fragments are not associated with magnetic resonance imaging safety issues, morbidity, or mortality after orthotopic heart transplant.
Cardiac implantable electronic device therapy (CIED) has revolutionized treatment for advanced heart failure. Most patients considered for orthotopic heart transplantation (OHT) are treated with implantable cardioverter defibrillators, cardiac resynchronization therapy, or both. These CIEDs are surgically extracted at the time of transplant. Occasionally, CIEDs are incompletely removed. Little is known about the outcomes of post-OHT patients with retained CIED fragments. We identified 200 consecutive patients that underwent OHT at our institution between April 2006 and December 2014 and performed a retrospective analysis of available radiographic images and clinical records. Chest radiographs prior to and following OHT were reviewed for the presence of CIED or retained CIED fragments. The outcomes of patients with retained CIED fragments that had subsequent magnetic resonance imaging (MRI) studies performed were further investigated. One hundred eighty of 200 patients were identified as having CIED prior to OHT, of which 29 had retained CIED fragments after OHT. Most retained CIED fragments originated from superior vena cava defibrillator coils. There were no adverse events in the retained CIED fragment cohort, and survival was unaffected. Ten patients with retained CIED fragments safely underwent a total of 28 MRIs after OHT, all of diagnostic quality. Retained CIED fragments are not associated with adverse events or increased mortality after OHT. Diagnostic MRI has been safely performed in patients with retained CIED fragments after incomplete device extraction. Retrieval of these fragments prior to MRI does not appear warranted given the demonstrated safety and preserved image quality in this population.


The experience of therapeutic touch from a nursing perspective.
This article describes the phenomenon of therapeutic touch (TT). Similarities and differences in the experience of the phenomenon from the perspective of a novice practitioner and healthy volunteers are highlighted. A qualitative analysis of findings indicates that the experiences of giving and receiving TT can be classified within two categories: the cognitive (knowing in the widest sense); and conative (instinct and feeling). The key constructs which emerged in this study are associated with feelings such as tingling, warmth, coolness, comfort, peace, calm and security. Formulation of the two main categories, cognitive and conative, emphasize the relationship associated with what is known by the mind and instinctively felt by the body. The holistic aspects associated with the phenomenon of TT are confirmed in the therapeutic relationship which can be formed between the practitioner and recipient during the administration of TT. It is suggested that TT, when provided by the nurse in the clinical setting, can promote feelings of comfort, peace, calm and security among patients.


S100B protein maternal and fetal bloodstreams gradient in healthy and small for gestational age pregnancies.
Brain S100B assessment in maternal blood has been proposed as a useful tool for early perinatal brain damage detection. Among potential confounding factors the possibility of a protein gradient between maternal and fetal bloodstreams under pathophysiological conditions is consistent. The present study investigates in healthy and small gestational age fetuses (SGA) whether S100B concentrations differ among fetal and maternal bloodstreams. We conducted a case-control study in 160 pregnancies (SGA: n=80; healthy: n=80), in which standard monitoring parameters were recorded. S100B was assessed in arterial cord and in maternal blood samples at birth. Eighty non pregnant women (NP), matched for age at sampling, served as controls (1 SGA vs. 1 healthy vs. 1 NP). Fetal S100B in SGA and healthy groups was significantly higher (P<0.01) than that detected in the maternal district and in NP women groups, respectively. No differences in protein's gradient between fetal and maternal bloodstreams (P>0.05) were observed between groups. No differences (P>0.05) in fetal S100B have been found between the studied groups. Maternal S100B of SGA and healthy groups was significantly higher (P<0.01) than that detected in NP women. No differences in maternal S100B concentrations (P>0.05) were observed between SGA and control groups. The present study shows that S100B is pregnancy-dependent with the presence of a protein's gradient between fetal and maternal bloodstreams. The present data suggests that non-invasive fetal brain monitoring is becoming possible in opening a new cue on further investigations on S100B fetal/maternal gradient changes under pathological conditions.


New Thiodiketopiperazine and 3,4-Dihydroisocoumarin Derivatives from the Marine-Derived Fungus Aspergillus terreus.
Aspergillus terreus has been reported to produce many secondary metabolites that exhibit potential bioactivities, such as antibiotic, hypoglycemic, and lipid-lowering activities. In the present study, two new thiodiketopiperazines, emestrins L (1) and M (2), together with five known analogues (3-7), and five known dihydroisocoumarins (8-12), were obtained from the marine-derived fungus Aspergillus terreus RA2905. The structures of the new compounds were elucidated by analysis of the comprehensive spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HRESIMS), one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) data. This is the first time that the spectroscopic data of compounds 3, 8, and 9 have been reported. Compound 3 displayed antibacterial activity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 32 μg/mL) and antifungal activity against Candida albicans (MIC = 32 μg/mL). In addition, compound 3 exhibited an inhibitory effect on protein tyrosine phosphatase 1 B (PTP1B), an important hypoglycemic target, with an inhibitory concentration (IC)50 value of 12.25 μM.


Limited evidence for blood eQTLs in human sexual dimorphism.
The genetic underpinning of sexual dimorphism is very poorly understood. The prevalence of many diseases differs between men and women, which could be in part caused by sex-specific genetic effects. Nevertheless, only a few published genome-wide association studies (GWAS) were performed separately in each sex. The reported enrichment of expression quantitative trait loci (eQTLs) among GWAS-associated SNPs suggests a potential role of sex-specific eQTLs in the sex-specific genetic mechanism underlying complex traits. To explore this scenario, we combined sex-specific whole blood RNA-seq eQTL data from 3447 European individuals included in BIOS Consortium and GWAS data from UK Biobank. Next, to test the presence of sex-biased causal effect of gene expression on complex traits, we performed sex-specific transcriptome-wide Mendelian randomization (TWMR) analyses on the two most sexually dimorphic traits, waist-to-hip ratio (WHR) and testosterone levels. Finally, we performed power analysis to calculate the GWAS sample size needed to observe sex-specific trait associations driven by sex-biased eQTLs. Among 9 million SNP-gene pairs showing sex-combined associations, we found 18 genes with significant sex-biased cis-eQTLs (FDR 5%). Our phenome-wide association study of the 18 top sex-biased eQTLs on >700 traits unraveled that these eQTLs do not systematically translate into detectable sex-biased trait-associations. In addition, we observed that sex-specific causal effects of gene expression on complex traits are not driven by sex-specific eQTLs. Power analyses using real eQTL- and causal-effect sizes showed that millions of samples would be necessary to observe sex-biased trait associations that are fully driven by sex-biased cis-eQTLs. Compensatory effects may further hamper their detection. Our results suggest that sex-specific eQTLs in whole blood do not translate to detectable sex-specific trait associations of complex diseases, and vice versa that the observed sex-specific trait associations cannot be explained by sex-specific eQTLs.


Hepatitis G virus and human immunodeficiency virus coinfection: response to interferon-alpha therapy.
The prevalence and consequences of hepatitis G virus (HGV) infection were determined in 180 patients with human immunodeficiency virus (HIV) infection (predominantly male homosexuals) who participated in a trial that compared treatment with zidovudine versus interferon (IFN)-alpha versus the combination. HGV RNA levels were measured by branched DNA signal amplification assay. Initially, 66 (37%) had HGV RNA. Sexual transmission was the sole risk factor for infection in all but 4 subjects. Pretreatment clinical features were similar between HGV RNA-positive and -negative patients. After 6 months, only 5% treated with zidovudine became HGV RNA negative, compared with 95% who received IFN-alpha alone and 66% on combination therapy with low-dose IFN-alpha. After therapy, HGV RNA levels returned to baseline in most subjects. Thus, HGV infection is common among HIV-infected homosexual males but does not appear to influence clinical features in early HIV infection. HGV RNA levels are suppressed by IFN but not by zidovudine.


Giant viruses infecting algae.
Paramecium bursaria chlorella virus (PBCV-1) is the prototype of a family of large, icosahedral, plaque-forming, double-stranded-DNA-containing viruses that replicate in certain unicellular, eukaryotic chlorella-like green algae. DNA sequence analysis of its 330, 742-bp genome leads to the prediction that this phycodnavirus has 376 protein-encoding genes and 10 transfer RNA genes. The predicted gene products of approximately 40% of these genes resemble proteins of known function. The chlorella viruses have other features that distinguish them from most viruses, in addition to their large genome size. These features include the following: (a) The viruses encode multiple DNA methyltransferases and DNA site-specific endonucleases; (b) PBCV-1 encodes at least part, if not the entire machinery to glycosylate its proteins; (c) PBCV-1 has at least two types of introns--a self-splicing intron in a transcription factor-like gene and a splicesomal processed type of intron in its DNA polymerase gene. Unlike the chlorella viruses, large double-stranded-DNA-containing viruses that infect marine, filamentous brown algae have a circular genome and a lysogenic phase in their life cycle.


Helicobacter pylori strain types and risk of gastric cancer: a case-control study.
The aim of this novel endoscopy clinic-based case-control study was to explore the influence of different Helicobacter pylori strain types on the risk of gastric adenocarcinoma using isolated bacterial strains, tissue samples, and sera. We included 72 cases with gastric adenocarcinoma and 324 age- and sex-matched controls. Histological characterization, culture, molecular typing of H. pylori genes by PCR (cagA/vacA), conventional IgG ELISA, and immunoblotting (Western blot) for the CagA and VacA proteins were performed. With four tests combined, H. pylori infection was detected in 57 (79%) cases and 213 (66%) controls. A positive association between H. pylori infection and gastric cancer risk was found [odds ratio (OR), 2.1; 95% confidence interval, 1.1-3.9]. Type I (OR, 1.8), intermediate (OR, 2.0), and type H (OR, 0.2) strains of H. pylori presented different serum antibody levels and different levels of association with gastric cancer. Our case-control study, based on molecular characterization and serology, provides further evidence that infection by more virulent strains of H. pylori and the presence of antibodies toward the CagA protein can be used as markers for an increased risk of gastric adenocarcinoma and that the strain types of H. pylori could be used in the future to determine disease outcome.


Cerebral circulation after head injury. Part 2: The effects of traumatic brain edema.
The authors have assessed the effects of subacute traumatic brain edema (BE) on cerebral circulation and metabolism, and on clinical outcome. Fifty-five severely injured, comatose, young patients who survived for more than 24 hours were studied on 78 occasions within 30 days of injury. After hematomas had been surgically evacuated, BE was diagnosed by radiological evidence of brain swelling, demonstrated by cerebral angiograms and ventriculograms. At identical levels of carbon dioxide pressure, intracranial pressure was significantly elevated in the Edema Group to twice the value in the No Edema Group (27.1 vs 14.1 torr). There were, however, no significant differences in cerebral perfusion pressure cerebral blood flow, resistance to blood flow, cerebral metabolic oxygen rate, ventricular cerebrospinal fluid acid-base, lactate, K+ or Na+ concentrations, or in clinical outcome. It is concluded that this type of subacute traumatic BE, which is significantly associated with surgical lesions, is not of major hemodynamic or clinical significance in intensively treated patients, and does not cause cerebral ischemia. Patient outcome is determined more by the severity of the initial diffuse cortical and subcortical injury than by the presence or absence of subacute BE.


Critical requirement for the membrane-proximal cytosolic tyrosine residue for CD28-mediated costimulation in vivo.
The YMNM motif that exists in the CD28 cytoplasmic domain is known as a binding site for phosphatidylinositol 3-kinase and Grb-2 and is considered to be important for CD28-mediated costimulation. To address the role of the YMNM motif in CD28 cosignaling in primary T cells, we generated transgenic mice on a CD28 null background that express a CD28 mutant lacking binding ability to phosphatidylinositol 3-kinase and Grb-2. After anti-CD3 and anti-CD28 Ab stimulation in vitro, the initial proliferative response and IL-2 secretion in CD28 Y189F transgenic T cells were severely compromised, while later responses were intact. In contrast to anti-CD3 and anti-CD28 Ab stimulation, PMA and anti-CD28 Ab stimulation failed to induce IL-2 production from CD28 Y189F transgenic T cells at any time point. Using the graft-vs-host reaction system, we assessed the role of the YMNM motif for CD28-mediated costimulation in vivo and found that CD28 Y189F transgenic spleen cells failed to engraft and could not induce acute graft-vs-host reaction. Together, these results suggest that the membrane-proximal tyrosine of CD28 is required for costimulation in vivo. Furthermore, these results indicate that the results from in vitro assays of CD28-mediated costimulation may not always correlate with T cell activation in vivo.


Unfounded worries about cancer in patients attending a routine otolaryngology clinic.
To investigate a suspicion that many ear, nose and throat patients have unfounded concerns about cancer, we questioned 50 patients who had attended a routine clinic after screening-out of those with possibly cancer-related features. None of the 50 proved to have cancer. 15 (30%) had been worried about cancer and 7 of these were still worried despite the consultation. Unwarranted fears about cancer are best dealt with by the referring clinician, especially when the wait for an appointment will be long. Such fears also need to be recognized and addressed by the specialist.


Transferring the Purchasing Role from International to National Organizations During the Scale-Up Phase of Performance-Based Financing in Cameroon.
Abstract-The World Bank and the government of Cameroon launched a performance-based financing (PBF) program in Cameroon in 2011. To ensure its rapid implementation, the performance purchasing role was sub-contracted to a consultancy firm and a nongovernmental organization, both international. However, since the early stage, it was agreed upon that this role would later be transferred to a national entity. This explanatory case study aims at analyzing the process of this transfer using Dolowitz and Marsh's framework. We performed a document review and interviews with various stakeholders (n = 33) and then conducted thematic analysis of interview recordings. Sustainability, ownership, and integration of the PBF intervention into the health system emerged as the main reasons for the transfer. The different aspects of transfer from international entities to a national body consisted of (1) the decision-making power, (2) the "soft" elements (e.g., ideas, expertise), and (3) the "hard" elements (e.g., computers, vehicles). Factors facilitating the transfer included the fact that it was planned from the start and the modification of the legal status of the national organization that became responsible for strategic purchasing. Other factors hindered the transfer, such as the lack of a legal act clarifying the conditions of the transfer and the lack of posttransition support agreements. The Cameroonian experience suggests that key components of a successful transfer of PBF functions from international to national organizations may include clear guidelines, co-ownership and planning of the transition by all parties, and posttransition support to new actors.


Influvac Tetra: clinical experience on safety, efficacy, and immunogenicity.
This paper summarizes the safety and immunogenicity data of Influvac Tetra across all age groups starting from 6 months of age, obtained during its clinical development program. The article covers the clinical development program of Influvac Tetra based on five registration studies that included different age groups, different comparators, and participants from Europe and Asia. Safety and immunogenicity were assessed in all studies and in one study, the efficacy of Influvac Tetra was assessed. Seasonal influenza is a vaccine-preventable disease that can cause serious complications. Several types of influenza vaccines are available, including egg-based (standard dose, high dose, and adjuvanted), cell-based, and recombinant. The COVID-19 pandemic has stimulated innovation in the development such as mRNA vaccines. However, these vaccines are still in development and the true value still has to be proven. Regardless of the type of vaccine, it is also important to increase overall vaccination coverage. ECDC recommends that EU Member States implement action plans and policies aimed at reaching 75% coverage in at-risk groups and healthcare workers. Even so, vaccine coverage is still far from recommended.


Maturation of the QT Variability Index is Impaired in Preterm Infants.
Reduced heart rate (HR) variability in preterm infants compared with full-term infants suggests that autonomic cardiac control is developmentally delayed. However, the association between developmental changes in myocardial repolarization and gestational age remains unknown. This study investigated the association between the myocardial repolarization lability index, namely the QT variability index (QTVI) = log10 [(QTv/QTm2)/(HRv/HRm2)], and the perinatal profile of healthy 1-month-old infants. We included 209 infants (143 boys and 87 girls; mean gestational weeks at birth, 38.6 ± 1.7) who were born in university hospitals between 2014 and 2015 without apparent cardiac disease. We compared the ECG variability indices in 28 infants born before 37 gestational weeks (mean gestational weeks at birth, 35.6 ± 1.1 as preterm) and 181 infants born at the average number of gestational weeks (mean gestational weeks at birth, 38.8 ± 1.1 as controls). There was a negative correlation between the QTVI and gestational weeks (r = - 0.460, p = 0.035). QTVI values in preterm infants were larger than those in the controls (0.01 ± 0.50 vs. -0.26 ± 0.48, p = 0.023). In conclusion, the QTVI is negatively correlated with gestational age. The QTVI can serve as an index of the maturity of the cardiac autonomic nervous system and myocardial depolarization.


Interplay between Theory and Experiment for Ammonia Synthesis Catalyzed by Transition Metal Complexes.
Nitrogen fixation is an essential chemical process both biologically and industrially. Since the discovery of the first transition-metal-dinitrogen complex in 1965, a great deal of effort has been devoted to the development of artificial nitrogen fixation systems that work under mild reaction conditions. However, the transformation of chemically inert dinitrogen using homogeneous catalysts is still challenging because of the difficulty in breaking the strong triple bond of dinitrogen, and a very limited number of transition metal complexes have exhibited the catalytic activity for the direct transformation of dinitrogen into ammonia with low turnover numbers. To develop more effective nitrogen fixation systems, it is necessary to retrieve as much information as possible from the limited successful examples. Computational chemistry will provide valuable insights in the understanding of the reaction mechanisms involving unstable intermediates that are hard to isolate or characterize. We have been applying it for clarifying detailed mechanisms of dinitrogen activation and functionalization by transition metal complexes as well as for designing new catalysts for more effective nitrogen fixation. This Account summarizes recent progress in the elucidation of catalytic mechanisms of nitrogen fixation by using mono- and dinuclear molybdenum complexes, as well as cubane-type metal-sulfido clusters from a theoretical point of view. First, we briefly introduce experimental and theoretical contributions to the elucidation of the reaction mechanism of nitrogen fixation catalyzed by a mononuclear Mo-triamidoamine complex. Special attention is paid to our recent studies on Mo-catalyzed nitrogen fixation using dinitrogen-bridged dimolybdenum complexes. A possible catalytic mechanism is proposed based on theoretical and experimental investigations. The catalytic mechanism involves the formation of a monuclear molybdenum-nitride (Mo≡N) intermediate, as well as the regeneration of a dimolybdenum intermediate with the Mo-N≡N-Mo moiety. Comparison of the reactivity of di- and monomolybdenum complexes suggests that the dimolybdenum structure is essential for the catalytic activity. Synergy between the two Mo cores connected with a bridging N2 ligand is observed in the protonation of coordinated N2. Intermetallic electron transfer through the bridging N2 ligand reductively activates the coordinated N2 to be protonated. On the basis of the proposed catalytic mechanism, we used DFT calculations for rational design of dimolybdenum complexes serving as more effective catalysts for nitrogen fixation. Newly prepared dimolybdenum complexes with modified PNP-type pincer ligands exhibit greater catalytic activity than the original one.


Antifungal prophylaxis in adult stem cell transplantation and haematological malignancy.
Antifungal prophylaxis can be recommended in patients undergoing induction chemotherapy for acute myeloid leukemia and treatment for grade 2 or greater or chronic extensive graft versus host disease. The evidence for prophylaxis is less clear in other clinical settings although certain groups such as patients with prolonged neutropenia after stem cell transplants using bone marrow or cord blood sources and with impaired cell mediated immunity secondary to treatments such as Alemtuzumab are at high risk. The decision to use prophylaxis and which agent to use will be influenced by effectiveness, number needed to treat and the likelihood of toxicity and drug interactions. The availability of rapid diagnostic tests for fungal infection and institutional epidemiology will also influence the need for and choice of prophylaxis. Whilst prophylaxis can be beneficial, it may impede the ability to make a rapid diagnosis of fungal infection by reducing the yield of diagnostic tests and change the epidemiology of fungal infection. As non-culture based diagnostic tests are refined and become more available there may be a shift from prophylaxis to early diagnosis and treatment.


Expectant management of small, recurrent, noninvasive papillary bladder tumors.
The majority of patients with stage Ta or T1 bladder cancer will have a subsequent tumor. Many of these patients invariably undergo multiple transurethral resections to manage small subsequent tumors or recurrences. We report our experience monitoring patients whose subsequent tumors appear to be small, low grade and papillary. A total of 32 patients with small, papillary, low grade appearing tumors and a history of Ta or T1 transitional cell carcinoma were monitored. The decision to delay resection or fulguration and observe these tumors was based on bladder cancer history, endoscopic appearance of the tumor and presence or lack of symptoms. All patients had a previous Ta tumor, and the tumor being observed was always papillary and appeared to be low grade. The decision to resect the tumor(s) was based on change in appearance (size or configuration) at followup endoscopy or hematuria. Patient records were reviewed, and bladder cancer history and tumor observation periods were recorded. Several patients underwent a number of observation periods. Tumor grade and stage before the observation interval were compared to the pathology of the observed tumor(s) after eventual resection. Tumor growth rate was calculated based on estimated tumor size documented at each interval. Mean patient age was 72 years (range 39 to 88). Mean time since diagnosis of bladder cancer (initial urothelial tumor event) was 71 months (range 12 to 139). Mean number of subsequent tumor episodes or recurrences per patient was 3.8 (range 1 to 10). Mean number of transurethral resections was 3.8. Mean tumor-free interval before development of a subsequent tumor or mean time to recurrence was 13.4 months based on 104 tumor episodes. Not all tumor recurrences were observed. Mean number of tumor observation periods per patient was 1.8 (range 1 to 5) with a mean duration of 10.09 months per period based on 56 observation intervals. Mean time since the beginning of the initial observation period was 38 months (range 6 to 126). Mean tumor growth rate for 37 tumors was 1.77 mm per month (range 0 to 5.8). Only 3 of 45 (6.7%) patients had tumor progression from a pre-observation, low grade, noninvasive (TaG1 to 2) to a high grade Ta or T1 tumor. In the 3 observation periods in which the patient's most recent tumor was T1, 2 (67%) patients had TaG1 on resection after observation. Every patient with a T1 tumor before observation of a small new tumor had a history of a Ta tumor. No disease progressed to muscle invasion. Small, recurrent, low grade appearing bladder tumors are slow growing and pose minimal risk. Therefore, as an alternative to in office fulguration to minimize morbidity and cost associated with repeat transurethral resection it may not be necessary to remove these tumors promptly at new tumor occurrence or recurrence.


Change my body, change my mind: the effects of illusory ownership of an outgroup hand on implicit attitudes toward that outgroup.
The effect of multisensory-induced changes on body-ownership and self-awareness using bodily illusions has been well established. More recently, experimental manipulation of bodily illusions have been combined with social cognition tasks to investigate whether changes in body-ownership can in turn change the way we perceive others. For example, experiencing ownership over a dark-skin rubber hand reduces implicit bias against dark-skin groups. Several studies have also shown that processing of skin color and facial features play an important role in judgements of racial typicality and racial categorization independently and in an additive manner. The present study aimed at examining whether using multisensory stimulation to induce feelings of body-ownership over a dark-skin rubber hand would lead to an increase in positive attitudes toward black faces. We here show, that the induced ownership of a body-part of a different skin color affected the participants' implicit attitudes when processing facial features, in addition to the processing of skin color shown previously. Furthermore, when the levels of pre-existing attitudes toward black people were taken into account, the effect of the rubber hand illusion on the post-stimulation implicit attitudes was only significant for those participants who had a negative initial attitude toward black people, with no significant effects found for those who had positive initial attitudes toward black people. Taken together, our findings corroborate the hypothesis that the representation of the self and its relation to others, as given to us by body-related multisensory processing, is critical in maintaining but also in changing social attitudes.


Physical activity and cancer prevention: a systematic review of clinical trials.
Physically active individuals have lower rates of many cancers and improved cancer outcomes. Controlled exercise trials measuring putative biomarkers of cancer risk are being conducted to further understand the role of exercise in cancer etiology and progression. We aimed to systematically review the effect of exercise on various biomarkers. A comprehensive search strategy identified 353 publications from January 1980 to August 2010. We included those clinical trials of exercise measuring biomarkers following minimum 4-week intervention among cancer survivors or people with one or more cancer risk factors. Two reviewers abstracted data and assessed quality independently. Effect sizes and 95% confidence intervals were estimated. Four primary prevention and five tertiary prevention trials were included. Exercise had a small to moderate effect on improving concentrations of several blood biomarkers implicated in breast and colon cancer pathways including insulin, leptin, estrogens, and apoptosis regulation. In breast cancer survivors, exercise had a small to moderate effect on improving some biomarkers associated with prognosis including various insulin-like growth factor axis proteins, insulin, and inflammation; and a large effect on enhancing immune function. Data are few, but there is some evidence to support the role of exercise in modulating various cancer pathways.


Structural and enzymatic properties of the AAA protein Drg1p from Saccharomyces cerevisiae. Decoupling of intracellular function from ATPase activity and hexamerization.
The AAA protein Drg1 from yeast was affinity-purified, and its ATPase activity and hexamerization properties were analyzed. The same parameters were also determined for several mutant proteins and compared in light of the growth characteristics of the corresponding cells. The protein from a thermosensitive mutant exhibited reduced ATPase activity and hexamerization. These defects were not reversed by an intragenic suppressor mutation, although this allele supported growth at the nonpermissive temperature. A different set of mutants was generated by site-specific mutagenesis intended to adjust the Walker A box of the D2 domain of Drg1p to that of the D1 domain. A S562G exchange in D2 produced a nonfunctional protein that did not hexamerize but showed above-normal ATPase activity. The C561T mutant protein, on the other hand, was functional but hexamerized less readily and had reduced ATPase activity. In contrast, the C561T/S562G protein hexamerized less than wild type but had much higher ATPase activity. We distinguished strong and weak ATP-binding sites in the wild type protein but two weak sites in the C561T/S562G protein, indicating that the stronger site resides in D2. These observations are discussed in terms of the inter-relationship of ATPase activity per se, oligomeric status, and intracellular function for AAA proteins.


Associations of maternal obesity and psychosocial factors with breastfeeding intention, initiation, and duration.
Psychosocial factors influence breastfeeding outcomes, but little is known about these characteristics and how they influence breastfeeding behavior of obese women, who are a group that experiences poor breastfeeding outcomes. Our objectives were to determine whether 1) maternal prepregnancy body mass index (BMI) is associated with social knowledge of, social influence toward, maternal confidence in, and behavioral beliefs about breastfeeding; 2) BMI and these psychosocial factors predict outcomes of intention to breastfeed, ever breastfed, and the duration of breastfeeding; and 3) BMI and psychosocial factors are associated with these breastfeeding outcomes independent of each other. Participants (n = 2824) in the Infant Feeding Practices Study II provided data on psychosocial characteristics and breastfeeding outcomes. In this prospective cohort study, data were analyzed by using logistic and proportional hazards regression models. Prepregnancy BMI was associated with confidence in (P < 0.0001), social influence toward (P = 0.02), and social knowledge of (P < 0.0001) breastfeeding but not with behavioral beliefs about breastfeeding (P = 0.45). Obese women did not differ from under- and normal-weight women in the intention to breastfeed (P = 0.07) but had lower odds of ever breastfeeding (P = 0.04) and were at greater risk of an earlier cessation of exclusive (P = 0.0009) and any (P = 0.03) breastfeeding. Only the association with exclusive breastfeeding remained significant after controlling for psychosocial factors (P = 0.01). All psychosocial factors were positively associated with each breastfeeding outcome. Despite their intentions to breastfeed, women with high prepregnancy BMI had psychosocial characteristics associated with poor breastfeeding outcomes. However, these characteristics did not fully explain the association between maternal obesity and breastfeeding outcomes.


Advanced tissue characterization in non-ischemic cardiomyopathies using contrast-enhanced cardiac magnetic resonance imaging.
Cardio-vascular magnetic resonance imaging (CMR) can be used to obtain integrated information on both cardiac function and on advanced tissue characteristics. Using contrast-enhanced techniques, highly diagnostic information on tissue viability, inflammatory changes, and on storage diseases can be obtained within a 45-minute examination. The combination of functional information (using steady-state free precession sequences cine techniques), assessment of myocardial edema (using T2-based techniques), of reversible injury (for example in inflammatory diseases; using T1-based techniques), and irreversible injury (for example in infarction and regional fibrosis, using late gadolinium enhancement techniques) allows disease-specific and prognostic information to be obtained in patients with non-ischemic cardiomyopathy. Contrast-enhanced CMR allows the accurate diagnosis of non-ischemic cardiomyopathies, identification of primary and secondary cardiomyopathies, and can be used to guide therapy, thus avoiding the need for invasive measures such as endomyocardial biopsy in many cases.


Hyperkalemia with cardiac arrhythmia. Induction by salt substitutes, spironolactone, and azotemia.
In two patients, severe hyperkalemia and serious cardiac arrhythmia developed after excessive use of potassium-containing salt substitutes. Both had impaired ability to handle and excrete additional potassium load due to chronic congestive heart failure, azotemia, and administration of spironolactone. Prompt recognition of the arrhythmia and immediate restoration of the cardiac rate and rhythm by pacemaker support followed by intensive regimen to lower the serum potassium prevented a potentially fatal outcome. These cases emphasize the potential danger of salt substitutes when used by patients who are predisposed to retain potassium.


Case 301.
History A 38-year-old man who had been in a motor vehicle collision was referred to our institute. He was suspected of having left-sided pneumothorax. This necessitated intercostal drainage with a chest tube, which had been placed elsewhere prior to his arrival. Paraparesis was noted on the initial clinical examination, with adequately maintained vital signs, while the blood work-up revealed a mildly reduced hemoglobin level of 10.1 mg/dL (normal range, 13.8-17.2 mg/dL); however, the rest of the laboratory values were within normal limits (Figs 1-5). The patient was then immediately referred for further evaluation with CT of the brain, cervical spine, and thorax. Thereafter, serial chest radiography was performed for follow-up.


Tensile strength of laser welded cobalt-chromium alloy with and without an argon atmosphere.
The tensile strength and depth of weld of two cobalt chromium alloys before and after laser welding with and without an argon gas atmosphere were investigated. Using two cobalt chromium alloys, rod shaped specimens (5 cm x 1.5 mm) were cast. Specimens were sand blasted, sectioned and welded with a pulsed Nd: YAG laser welding machine and tested in tension using an Instron universal testing machine. A statistically significant difference in tensile strength was observed between the two alloys. The tensile strength of specimens following laser welding was significantly less than the unwelded controls. Scanning electron microscopy showed that the micro-structure of the cast alloy was altered in the region of the weld. No statistically significant difference was found between specimens welded with or without an argon atmosphere.


The relationship of patent foramen ovale location with severity of stroke: A new risk factor for paradoxical embolism.
Patent foramen ovale (PFO) is a common developmental anomaly and is well associated with paradoxical embolism and cryptogenic stroke. The aim of this study was to investigate the relationship of PFO location with severity of cryptogenic stroke. Fifty patients with cryptogenic stroke and echocardiographically proven PFO were classified according to the severity of stroke. In order to define the location of PFOs, an imaginary line dividing the length of interatrial septum vertically into two equal parts was drawn manually at axial plane on cardiac multidetector computed tomography. PFOs located at superior part of this imaginary line was defined as superiorly located PFO, while PFOs located at inferior part of this imaginary line was defined as inferiorly located PFO. Fourteen patients (28%) revealed mild, 20 patients (40%) revealed moderate and 16 patients (32%) had severe stroke. Based on PFO location, there were 34 patients (68%) with superiorly (group 1), and 16 patients (32%) with inferiorly (group 2) located PFO. It was found that patients of group 1 had significantly higher frequency of moderate or severe stroke compared to those of group 2 (p < 0.005) CONCLUSION: In conclusion, the patients with superiorly located PFO had higher frequency of severe stroke compared to the patients with inferiorly located PFO. Since this is a preliminary study, clinical application and importance of this finding necessitates further large-scale interventional studies.


Variability of the start of the growing season in Fennoscandia, 1982-2002.
Fennoscandia is characterized by a large degree of climatic diversity. Vegetation phenology may respond differently to climate change according to the climatic gradients within the region. To map the annual and spatial variability of the start of the growing season (SOS) in Fennoscandia, the twice-monthly GIMMS-NDVI satellite dataset was used. The data set has an 8 x 8 km(2) spatial resolution and covers the period from 1982 to 2002. The mapping was done by applying pixel-specific threshold values to the NDVI data. These threshold values were determined form surface phenology data on birch (Betula sp.). Then, we produced NDVI based maps of SOS for each of the 21 years. Finally, the time differences between the SOS and the last day of snow cover, as well as dates of passing different temperatures, were analyzed for 21 meteorological stations. The analyses showed that 1985 was the most extreme year in terms of late SOS. In terms of early SOS, the year 1990 was by far the most extreme. Locally, the SOS has an average range of 1 month between the earliest and latest recorded SOS, with a trend towards a bigger range in the oceanic parts. The results indicate that a 1 degrees C increase in spring temperatures in general corresponds to an advancement of 5-6 days in SOS. However, there is a clear trend according to the degree of oceanity, with a 1 degrees C increase in the most oceanic parts corresponding roughly to 7-9 days earlier SOS, compared to less than 5 days earlier in the continental parts.


Chromatographic interactions between proteins and sulfoalkylbetaine-based zwitterionic copolymers in fully aqueous low-salt buffers.
Macroporous monoliths containing N,N-dimethyl-N-methacryloyloxyethyl-N-(3-sulfopropyl)ammonium betaine (SPE) have been synthesized via in situ photopolymerization, yielding a stoichiometric balance between sulfur and nitrogen in the final polymer, which is indicative of a genuine strong/strong zwitterionic character. The chromatographic properties of these zwitterionic resins were evaluated with respect to the retention behavior of inorganic ions and proteins. The weak electrostatic nature of the interaction between the sulfobetaine monoliths and proteins provided a high selectivity between basic proteins and peptides. Elution was accomplished with low-ionic-strength fully aqueous mobile phases, whereby high recovery was obtained, even for hydrophobic proteins. Chaotropic ions such as perchlorate or thiocyanate were used as mobile phase modifiers to modulate the apparent ion exchange group density, thus introducing a route for the modulation of the ionic strength that is required to competitively elute the protein. The promising features of polymeric sulfoalkylbetaine interaction layers for separation and analysis of biological extracts was also manifested in an application involving purification of biologically active peptide-pheromone obtained from Enterococcus faecium.