Pediatric home health care in King County, Washington.
Pediatric home health care is one of the fastest growing segments of our health care system. However, our knowledge of the extent and quality of the services provided in this field is generally limited. Despite this shortcoming, pediatric health care providers are increasingly expected to participate in the home health care of their patients. To describe the agencies and services that constitute pediatric home health care in a large metropolitan setting. During the summer of 1995, home health care agencies in King County, WA, were surveyed if they had provided any pediatric services within the preceding 6 months. The agencies were queried about their characteristics and services provided, as well as referral and reimbursement sources. Survey data were supplemented by interviews with agency and state health personnel. Fourteen (88%) of the 16 agencies providing pediatric home health care services completed the survey. Agencies were predominantly for-profit, free-standing, and in business fewer than 10 years. Although there were uniform licensing requirements for agencies, no pediatric-specific regulations existed. In addition, many agencies lacked internal methods to ensure the provision of quality pediatric care. Eighty percent of all pediatric home health care services were provided by only 5 agencies. For intermittent (acute) services, agencies served approximately 450 children per month. The average number of visits per child was two, with 40% receiving only one visit. Services included skilled nursing (60%), infusion (27%), and respiratory therapy (9%). Maintenance (chronic) home health care services, for 156 chronically ill children, were provided almost exclusively by skilled nursing for an average of 9 hours per patient per day. The majority of referrals to agencies (75%) originated from health care providers, although a small number came from insurance companies or individual families. Reimbursement for intermittent care services was divided among commercial insurance (35%), captitated contracts (35%), and Medicaid (20%). In contrast, 90% of reimbursement for the chronically ill was from Medicaid. In King County, WA, pediatric home health care is predominantly an unregulated, for-profit industry, with most agencies having little actual experience in pediatric home health care. In addition, the unique features of pediatric home health care necessitate both a greater understanding of this field and the consideration of more specific guidelines.


Effects of vitamin B6 on beta-aminoproprionitrile-induced palatal cleft formation in the rat.
This study was conducted to evaluate the effects of beta-aminoproprionitrile and vitamin B6 on palatal clefting. In four groups of pregnant Sprague-Dawley rats, beta-aminoproprionitrile (BAPN; 600 mg/kg b.w.) was given by gavage on embryonal day 15, 7 hours to induce palatal clefts. Vitamin B6 (10 mg/kg b.w., IM) was given twice on embryonal day 14, 7 hours and on day 15, 7 hours. The possibility that the food's content of vitamin B6 affected the results was also tested. Palatal cleft formation was divided into four different grades, ranging from no cleft formation to total cleft formation. It was found that BAPN induces cleft palate in rat fetuses and that this defect can be prevented both in number and severity by administration of vitamin B6 before and simultaneously with BAPN.


Exposure to insulating materials and risk of coronary artery diseases: a cross-sectional study.
Although previous reports link exposure to insulating materials with an increased risk of mesothelioma and chronic respiratory diseases, studies evaluating their associations with the risk of coronary artery diseases (CAD) are lacking. We aimed at evaluating the associations between exposure to insulating materials and the 10-year risk of CAD among insulators. In this cross-sectional study, we recruited 643 adults (≥18 years), full-time insulators from the Local 110 Heat and Frost Insulators and Allied Workers Union in Edmonton, Alberta. We obtained demographic information, personal and family history, and job-exposure history, including experience (years) and types of exposure to insulating materials. Clinical profiling including Framingham risk scores (FRS) was assessed. Of all insulators, 89% were men (mean ± SD age: 47 ± 12 years), 27% had a parental history of cardiac diseases, and 22% had a comorbid chronic respiratory disease. In total, 53% reported exposure to asbestos, while 61, 82, and 94% reported exposure to ceramic fibers, fiberglass, and mineral fibers, respectively. In single-exposure multivariable regression models adjusted for experience, marital status, and body mass index (BMI), asbestos was found to be associated with higher FRS (β: 1.004; 95%CI: 0.003-2.00). The association remained consistent in multi-exposure models and a higher association was found between asbestos exposure and FRS among insulators with comorbid chronic respiratory disease. Our study demonstrates that apart from cancer and chronic respiratory diseases, asbestos exposure may also have a cardiac effect, thus warranting the need for systematic surveillance to protect workers from the adverse effects of these materials.


The anticipation and outcome phases of reward and loss processing: A neuroimaging meta-analysis of the monetary incentive delay task.
The processing of rewards and losses are crucial to everyday functioning. Considerable interest has been attached to investigating the anticipation and outcome phases of reward and loss processing, but results to date have been inconsistent. It is unclear if anticipation and outcome of a reward or loss recruit similar or distinct brain regions. In particular, while the striatum has widely been found to be active when anticipating a reward, whether it activates in response to the anticipation of losses as well remains ambiguous. Furthermore, concerning the orbitofrontal/ventromedial prefrontal regions, activation is often observed during reward receipt. However, it is unclear if this area is active during reward anticipation as well. We ran an Activation Likelihood Estimation meta-analysis of 50 fMRI studies, which used the Monetary Incentive Delay Task (MIDT), to identify which brain regions are implicated in the anticipation of rewards, anticipation of losses, and the receipt of reward. Anticipating rewards and losses recruits overlapping areas including the striatum, insula, amygdala and thalamus, suggesting that a generalised neural system initiates motivational processes independent of valence. The orbitofrontal/ventromedial prefrontal regions were recruited only during the reward outcome, likely representing the value of the reward received. Our findings help to clarify the neural substrates of the different phases of reward and loss processing, and advance neurobiological models of these processes.


Heterogeneity of the L2 gene of field isolates of bluetongue virus serotype 17 from the San Joaquin Valley of California.
Genome segment 2 (L2) from six field isolates of bluetongue virus (BTV) serotype 17 was sequenced by cycling sequencing after the amplification of the viral cDNA by the polymerase chain reaction. The viruses were isolated from sheep, cattle and a goat in the San Joaquin Valley of California during the years 1981 and 1990. These viruses exhibit divergent patterns of neutralization with BTV 17-specific monoclonal antibodies. The six L2 genes of the BTV 17 field isolates all encode a protein of 955 amino acids. Similarity of the nucleotide sequences of the L2 genes with respect to the prototype strain ranges between 93.8% and 95.1%, whereas the similarity between the field isolates ranges from 96.8% to 99.1%. Although very closely related, the L2 gene of each virus is distinct. Furthermore, mutations in the L2 gene of field isolates of BTV do not consistently follow a linear pattern of accumulation over time. Some amino acid changes in the VP2 protein of field strains were conserved over time, whereas others were not correlated with the year of isolation and some substitutions were unique to individual viruses. The predicted VP2s constitute a group of non-identical, but closely related proteins. Phylogenetic analyses suggest that the viral variants which co-circulate in the San Joaquin Valley could evolve by different evolutionary pathways.


Definition of arterial hypertension according to age and sex.
Although the historical debate between Pickering and Platt has never been settled, most scientists have felt that hypertension should not be defined as a disease state, qualitatively different from normotension with a sharp dividing line in between them. Still, in clinical practice, there is a need for well defined limits which one should initiate therapeutic actions that should not be taken below such a limit. In fact, in trying to escape to setting up a sharp limit, clinicians have tried to find a level above which benefits of decreasing blood pressure could outweigh the potential harm caused by the therapeutic interventions. However even in that way, finding such a limit is a most difficult enterprise; it has necessitated many large trials which certainly have not resolved yet all our questions. First, one should realize that blood pressure by itself is not a constant value; following blood pressure over a certain period shows its large variations from "normotensive" ranges to clearly "hypertensive" levels in the same individual. As soon as one is spoiled by this type of information, it becomes hardly conceivable to define someone's blood pressure without ambulatory recordings of some kind. This is also valid for finding the above mentioned limit of therapeutic benefit; an European International multicenter studied is being set up in this respect (HOME BP). Moreover, whatever the definition of blood pressure, its relationship to mortality, morbidity and organ damage, also, is not a constant one.(ABSTRACT TRUNCATED AT 250 WORDS)


Evolving endoscopic approaches for treatment of emphysema.
Novel endobronchial methods for reducing lung volume in patients with advanced emphysema are currently being evaluated in clinical trials as potential alternatives to lung volume reduction surgery (LVRS). Three bronchoscopic lung volume reduction (BLVR) approaches have shown promise in initial testing: (1) placement of endobronchial one-way valves to promote atelectasis by blocking inspiratory flow; (2) airway bypass tract formation using a radiofrequency catheter to facilitate emptying of damaged lung regions with long expiratory times; and (3) instillation of biological adhesives designed to collapse and remodel hyperinflated lung. The limited clinical data currently available suggests all three techniques are reasonably safe. However, efficacy signals have been smaller and less durable than those observed after LVRS. Studies to optimize patient selection, refine treatment strategies, characterize procedural safety, elucidate mechanisms of action, and characterize short- and longer-term effectiveness of each approach are ongoing.


Role of the PI3K-Akt Signaling Pathway in the Pathogenesis of Polycystic Ovary Syndrome.
This review aimed to focus on the recent progress of the understanding of the role of phosphatidylinositol 3-kinase (PI3K) in polycystic ovary syndrome (PCOS). In recent years, it has been increasingly recognized that PI3K plays an important role in PCOS whose pathogenesis is unclear. However, research continues into revealing the details of how PI3Ks are involved in developing PCOS. Previous studies have shown that activation of the PI3K-protein kinase B (Akt) signaling pathway has important effects on insulin resistance and endometrial cancer. Knowledge of the action of PI3K in PCOS might provide valuable information to further validate the pathogenesis of PCOS and suggest new methods of treatment.


From concept to content: assessing the implementation fidelity of a chronic care model for frail, older people who live at home.
Implementation fidelity, the degree to which a care program is implemented as intended, can influence program impact. Since results of trials that aim to implement comprehensive care programs for frail, older people have been conflicting, assessing implementation fidelity alongside these trials is essential to differentiate between flaws inherent to the program and implementation issues. This study demonstrates how a theory-based assessment of fidelity can increase insight in the implementation process of a complex intervention in primary elderly care. The Geriatric Care Model was implemented among 35 primary care practices in the Netherlands. During home visits, practice nurses conducted a comprehensive geriatric assessment and wrote a tailored care plan. Multidisciplinary team consultations were organized with the aim to enhance the coordination between professionals caring for a single patient with complex needs. To assess fidelity, we identified 5 key intervention components and formulated corresponding research questions using Carroll's framework for fidelity. Adherence (coverage, frequency, duration, content) was assessed per intervention component during and at the end of the intervention period. Two moderating factors (participant responsiveness and facilitation strategies) were assessed at the end of the intervention. Adherence to the geriatric assessments and care plans was high, but decreased over time. Adherence to multidisciplinary consultations was initially poor, but increased over time. We found that individual differences in adherence between practice nurses and primary care physicians were moderate, while differences in participant responsiveness (satisfaction, involvement) were more distinct. Nurses deviated from protocol due to contextual factors and personal work routines. Adherence to the Geriatric Care Model was high for most of the essential intervention components. Study limitations include the limited number of assessed moderating factors. We argue that a longitudinal investigation of adherence per intervention component is essential for a complete understanding of the implementation process, but that such investigations may be complicated by practical and methodological challenges. The Netherlands National Trial Register (NTR). 2160 .


Polysaccharide hydrogels for modified release formulations.
Hydrogels are three-dimensional, hydrophilic, polymeric networks, with chemical or physical cross-links, capable of imbibing large amounts of water or biological fluids. Among the numerous macromolecules that can be used for hydrogel formation, polysaccharides are extremely advantageous compared to synthetic polymers being widely present in living organisms and often being produced by recombinant DNA techniques. Coming from renewable sources, polysaccharides also have frequently economical advantages over synthetic polymers. Polysaccharides are usually non-toxic, biocompatible and show a number of peculiar physico-chemical properties that make them suitable for different applications in drug delivery systems. We review here a selection of the most important polysaccharides that have been studied and exploited in several fields related to pharmaceutics. Particular attention has been focused on the techniques used for the hydrogel network preparation, on the drug delivery results, on clinical applications as well as on the possible use of such systems as scaffolds for tissue engineering.


Use of physical chemistry and in vivo exposure to investigate the toxicity of formaldehyde bound to carbonaceous particles in the murine lung.
Knowledge about the health effects of exposure to formaldehyde associated with automotive emissions is of pivotal importance in the risk assessment of this agent. Mobile sources emit many combustion-derived pollutants, including formaldehyde, in association with respirable carbon particles. Because it is hydrophilic, most of the inhaled formaldehyde is absorbed in the upper respiratory tract. However, if the organic vapor is adsorbed on respirable particles, formaldehyde may be deposited in the deep lung with the inhaled particles and may be available to interact adversely with cells along the lung parenchyma. On the respiratory surface, the alveolar macrophage phagocytic system plays the pivotal role in defending the lung against infectious agents. Susceptibility to respiratory infections is a relevant and sensitive indicator of the adverse effects of air pollution because acute and chronic exposures to a variety of air pollutants have been shown to decrease pulmonary antibacterial defenses. The goal of this research was to investigate whether exposure to formaldehyde decreases resistance to respiratory infections through dysfunctions of the alveolar macrophage phagocytic system. The study also explored whether interactions between formaldehyde and respirable carbon black particles alter susceptibility to respiratory infections and impairment of alveolar macrophage phagocytosis by delivering adsorbed formaldehyde to the deep lung with the inhaled particles. A carbon black, Regal GR, was used in these studies as a surrogate for the carbonaceous core of Diesel particulate matter. This material was selected to represent the worst-case scenario because the carbon black was expected to adsorb formaldehyde strongly. To accomplish this goal, mice were exposed to formaldehyde and to carbon black and formaldehyde combinations; increased susceptibility to respiratory infections was quantified by alveolar macrophage-dependent intrapulmonary killing of Staphylococcus aureus after an inhalation challenge with the bacterium. The salient findings of the bactericidal studies are as follows: Fifteen parts per million (ppm)* formaldehyde impaired the intrapulmonary killing of S. aureus when exposure followed the bacterial challenge. One ppm formaldehyde impaired the intrapulmonary killing of S. aureus when exposure preceded and was continued after the bacterial challenge. Coexposures to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde, or 10 mg/m3 carbon black and 5 ppm formaldehyde after the bacterial challenge had no effect on the intrapulmonary killing of S. aureus. Preexposure for four hours per day for four days to target concentrations of 3.5 mg/m3 carbon black and 2.5 ppm formaldehyde had no effect on the intrapulmonary killing of S. aureus when the assay was performed one day after the cessation of exposure.(ABSTRACT TRUNCATED AT 400 WORDS)


Retinoic acid and estrogen modulation of insulin-like growth factor binding protein-4 gene expression and the estrogen receptor status of human breast carcinoma cells.
Retinoic acid (RA) and estrogen modulation of insulin like-growth factor binding protein-4 (IGFBP-4) gene expression was investigated in a number of human breast carcinoma (HBC) cell lines. Our results indicate that RA and/or estrogen modulation of IGFBP-4 mRNA levels appear to correlate with the ER-status of HBC cell lines. RA and estrogen enhanced IGFBP-4 mRNA levels in ER-positive MCF-7, RRO-I and ZR-75 cell lines and the effect of both of these agents in combination was additive. Although both individually also enhanced IGFBP-4 mRNA levels in ER-positive T47D cells, their effect in combination was antagonistic in this cell line. Transfection of human ER into ER-negative MDA-MB-231 cells conferred RA and estrogen the ability to enhance IGFBP-4 mRNA but both agents failed to concomitantly modulate IGFBP-4 levels in the CM suggesting a dual regulation by these agents at transcription/post-transcription and translation/secretion levels.


The effects of social isolation stress and discrimination on mental health.
Social isolation and discrimination are growing public health concerns associated with poor physical and mental health. They are risk factors for increased morbidity and mortality and reduced quality of life. Despite their detrimental effects on health, there is a lack of knowledge regarding translation across the domains of experimental research, clinical studies, and real-life applications. Here, we review and synthesize evidence from basic research in animals and humans to clinical translation and interventions. Animal models indicate that social separation stress, particularly in early life, activates the hypothalamic-pituitary-adrenal axis and interacts with monoaminergic, glutamatergic, and GABAergic neurotransmitter systems, inducing long-lasting reductions in serotonin turnover and alterations in dopamine receptor sensitivity. These findings are of particular importance for human social isolation stress, as effects of social isolation stress on the same neurotransmitter systems have been implicated in addictive, psychotic, and affective disorders. Children may be particularly vulnerable due to lasting effects of social isolation and discrimination stress on the developing brain. The effects of social isolation and loneliness are pronounced in the context of social exclusion due to discrimination and racism, during widespread infectious disease related containment strategies such as quarantine, and in older persons due to sociodemographic changes. This highlights the importance of new strategies for social inclusion and outreach, including gender, culture, and socially sensitive telemedicine and digital interventions for mental health care.


Technical Aspects of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: CHEST Guideline and Expert Panel Report.
Endobronchial ultrasound (EBUS) was introduced in the last decade, enabling real-time guidance of transbronchial needle aspiration (TBNA) of mediastinal and hilar structures and parabronchial lung masses. The many publications produced about EBUS-TBNA have led to a better understanding of the performance characteristics of this procedure. The goal of this document was to examine the current literature on the technical aspects of EBUS-TBNA as they relate to patient, technology, and proceduralist factors to provide evidence-based and expert guidance to clinicians. Rigorous methodology has been applied to provide a trustworthy evidence-based guideline and expert panel report. A group of approved panelists developed key clinical questions by using the PICO (population, intervention, comparator, and outcome) format that addressed specific topics on the technical aspects of EBUS-TBNA. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and well-recognized document evaluation tools were used to assess the quality of included studies, to extract meaningful data, and to grade the level of evidence to support each recommendation or suggestion. Our systematic review and critical analysis of the literature on 15 PICO questions related to the technical aspects of EBUS-TBNA resulted in 12 statements: 7 evidence-based graded recommendations and 5 ungraded consensus-based statements. Three questions did not have sufficient evidence to generate a statement. Evidence on the technical aspects of EBUS-TBNA varies in strength but is satisfactory in certain areas to guide clinicians on the best conditions to perform EBUS-guided tissue sampling. Additional research is needed to enhance our knowledge regarding the optimal performance of this effective procedure.


Nematicidal substances from fungi.
This review summarizes the 179 compounds from fungi that have shown to possess nematicidal activities. These compounds belong to diverse chemical groups and they are mainly isolated from a variety of deuteromycete, ascomycete and basidiomycete fungi. Some of them have been patented as nematicidal agents. We review and classify these compounds based on their structural types. Their nematicidal activities are described and their potential roles in natural environments and in the biocontrol of nematodes are discussed.


[Eukaryotic DNA topoisomerase and in vitro recombination between circular supercoiled plasmid DNA's in an in vitro system].
Eukaryotic DNA topoisomerase II was shown to catalyze recombination between circular supercoiled plasmid DNAs in vitro. The results obtained are discussed with regard to the organization of eukaryotic chromosomes in the form of topologically independent domains (loops).


Effect of Soil Geomechanical Properties and Geo-Environmental Factors on Landslide Predisposition at Mount Oku, Cameroon.
In this work, we explored a novel approach to integrate both geo-environmental and soil geomechanical parameters in a landslide susceptibility model. A total of 179 shallow to deep landslides were identified using Google Earth images and field observations. Moreover, soil geomechanical properties of 11 representative soil samples were analyzed. The relationship between soil properties was evaluated using the Pearson correlation coefficient and geotechnical diagrams. Membership values were assigned to each soil property class, using the fuzzy membership method. The information value method allowed computing the weight value of geo-environmental factor classes. From the soil geomechanical membership values and the geo-environmental factor weights, three landslide predisposition models were produced, two separate models and one combined model. The results of the soil testing allowed classifying the soils in the study area as highly plastic clays, with high water content, swelling, and shrinkage potential. Some geo-environmental factor classes revealed their landslide prediction ability by displaying high weight values. While the model with only soil properties tended to underrate unstable and stable areas, the model combining soil properties and geo-environmental factors allowed a more precise identification of stability conditions. The geo-environmental factors model and the model combining geo-environmental factors and soil properties displayed predictive powers of 80 and 93%, respectively. It can be concluded that the spatial analysis of soil geomechanical properties can play a major role in the detection of landslide prone areas, which is of great interest for site selection and planning with respect to sustainable development at Mount Oku.


The 2017 Lush Prize Awards.
This year saw eighteen prizewinning projects from eleven countries, and a new award in recognition of the work of Andrew Tyler.


Fourth ventricular thyrotropin induces satiety and increases body temperature in rats.
Besides its well-known action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 µg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 µg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection ( P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function.


A Dual-VENC Four-Dimensional Flow MRI Framework for Analysis of Subject-Specific Heterogeneous Nonlinear Vessel Deformation.
Advancement of subject-specific in silico medicine requires new imaging protocols tailored to specific anatomical features, paired with new constitutive model development based on structure/function relationships. In this study, we develop a new dual-velocity encoding coefficient (VENC) 4D flow MRI protocol that provides unprecedented spatial and temporal resolution of in vivo aortic deformation. All previous dual-VENC 4D flow MRI studies in the literature focus on an isolated segment of the aorta, which fail to capture the full spectrum of aortic heterogeneity that exists along the vessel length. The imaging protocol developed provides high sensitivity to all blood flow velocities throughout the entire cardiac cycle, overcoming the challenge of accurately measuring the highly unsteady nonuniform flow field in the aorta. Cross-sectional area change, volumetric flow rate, and compliance are observed to decrease with distance from the heart, while pulse wave velocity (PWV) is observed to increase. A nonlinear aortic lumen pressure-area relationship is observed throughout the aorta such that a high vessel compliance occurs during diastole, and a low vessel compliance occurs during systole. This suggests that a single value of compliance may not accurately represent vessel behavior during a cardiac cycle in vivo. This high-resolution MRI data provide key information on the spatial variation in nonlinear aortic compliance, which can significantly advance the state-of-the-art of in-silico diagnostic techniques for the human aorta.


Teratogen update: Lyme disease.
We reviewed the world literature concerning the reproductive effects of Lyme disease (LD). Borrelia burgdorferi, which is the etiology of LD, is a spirochete and, as such, may share the potential for causing fetal infection, which may occur in the setting of maternal spirochetemia. Information concerning the effects of gestational LD derives from case reports and series, epidemiologic studies, and experimental animal models. Although provocative, these studies fail to define a characteristic teratogenic effect. However, skin and cardiac involvement have predominated in some reports. Pregnancy wastage has been suggested primarily by animal studies. Gestational LD appears to be associated with a low risk of adverse pregnancy outcome, particularly with appropriated antibiotic therapy. Suggestions for management of clinical situations are presented.


Host-Specific Adaptive Diversification of Crohn's Disease-Associated Adherent-Invasive Escherichia coli.
Crohn's disease (CD) is an inflammatory bowel disease influenced by bacteria. Adherent-invasive E. coli (AIEC) is associated with CD, yet the adaptations facilitating AIEC gut colonization are unknown. AIEC isolates exhibit high genetic diversity, suggesting strains evolve independently across different gut environments. We tracked the adaptive evolution of AIEC in a murine model of chronic colonization across multiple hosts and transmission events. We detected evolved lineages that outcompeted the ancestral strain in the host through independent mechanisms. One lineage was hypermotile because of a mobile insertion sequence upstream of the master flagellar regulator, flhDC, which enhanced AIEC invasion and establishment of a mucosal niche. Another lineage outcompeted the ancestral strain through improved use of acetate, a short-chain fatty acid in the gut. The presence of hypermotile and acetate-consuming lineages discriminated E. coli isolated from CD patients from healthy controls, suggesting an evolutionary trajectory that distinguishes AIEC from commensal E. coli.


Ejaculation and its disorders.
Ejaculation is the final link of the male sexual function chain "Libido--Erection--Penetration--Achievement of Climax--Ejaculation". Each link is highly androgen-dependent. Although the initiation of a subsequent link is normally dependent on achievement of the previous link, each link has its own mechanisms, and can be made to occur in isolation. The basic requirements for ejaculation are the production of seminal fluid (mostly from the seminal vesicles) and its propulsion. The production of a normal volume of seminal fluid requires the presence of seminal vesicles and the maintenance of their secretion by androgens. The propulsion of seminal fluid is in 3 phases: I. Contraction of seminal vesicles; II. Closure of bladder neck (both due to T9-L2 sympathetic stimulation); III. Expulsion of semen from the bulb of the urethra (due to S2-S3 somatic stimulation). The coordination of these phases is probably at hypothalamic level. Failure of ejaculation may be classified into I. Deficiency of production of seminal fluid from (1) Absence of seminal vesicles or (2) Androgen deficiency from (a) Pituitary dysfunction or (b) Testicular interstitial-cell failure from a number of causes. Correction of androgen deficiency usually restores ejaculation.


Infectious diseases and death among nursing home residents: results of surveillance in 13 nursing homes.
An increasing proportion of the U.S. population resides in nursing homes (NHs). No surveillance system exists for infections in these facilities. To determine the incidence and types of infections in NH residents, and to identify predictors of death among residents with infections, we initiated a surveillance system at 13 NHs in California during a 6-month period from October 1989 through March 1990. The study included 1754 residents, among whom 835 infections were identified during the study period. The most common infections were urinary tract infections (UTIs; 286, 34.2%), respiratory tract infections (RTIs; 259, 31%), and skin infections (150, 17.9%). Of the 259 residents with respiratory tract infections, 69 (27%) had pneumonia. Antimicrobials were prescribed for 646 (77%) of the infectious episodes. Residents with pneumonia were more likely to die than residents with other infections (4 of 69 versus 12 of 766; P = 0.04). Symptoms of altered body temperature (fever, hypothermia, chills) and change in mental status also were associated with an increased risk of a fatal outcome (10 of 260 versus 6 of 575; P = 0.01) and (7 of 127 versus 9 of 708; P = 0.004). This study suggests that the most common infections among NH residents are UTIs, RTIs, and skin infections. Pneumonia, symptoms of fever, and mental status changes all were associated with increased mortality. The frequency of infections among NH residents and their impact on resident outcome highlights the need for infectious disease surveillance in this population.


Molecular detection of HIV-1 subtype B, CRF01_AE, CRF33_01B, and newly emerging recombinant lineages in Malaysia.
A molecular genotyping assay for human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia is difficult to design because of the high level of genetic diversity. We developed a multiplex real-time polymerase chain reaction (PCR) assay to detect subtype B, CRF01_AE, CRF33_01B, and three newly described circulating recombinant forms, (CRFs) (CRF53_01B, CRF54_01B, and CRF58_01B). A total of 785 reference genomes were used for subtype-specific primers and TaqMan probes design targeting the gag, pol, and env genes. The performance of this assay was compared and evaluated with direct sequencing and phylogenetic analysis. A total of 180 HIV-infected subjects from Kuala Lumpur, Malaysia were screened and 171 samples were successfully genotyped, in agreement with the phylogenetic data. The HIV-1 genotype distribution was as follows: subtype B (16.7%); CRF01_AE (52.8%); CRF33_01B (24.4%); CRF53_01B (1.1%); CRF54_01B (0.6%); and CRF01_AE/B unique recombinant forms (4.4%). The overall accuracy of the genotyping assay was over 95.0%, in which the sensitivities for subtype B, CRF01_AE, and CRF33_01B detection were 100%, 100%, and 97.7%, respectively. The specificity of genotyping was 100%, inter-subtype specificities were > 95% and the limit of detection of 10(3) copies/mL for plasma. The newly developed real-time PCR assay offers a rapid and cost-effective alternative for large-scale molecular epidemiological surveillance for HIV-1.


Spatial overlap between environmental policy instruments and areas of high conservation value in forest.
In order to safeguard biodiversity in forest we need to know how forest policy instruments work. Here we use a nationwide network of 9400 plots in productive forest to analyze to what extent large-scale policy instruments, individually and together, target forest of high conservation value in Norway. We studied both instruments working through direct regulation; Strict Protection and Landscape Protection, and instruments working through management planning and voluntary schemes of forest certification; Wilderness Area and Mountain Forest. As forest of high conservation value (HCV-forest) we considered the extent of 12 Biodiversity Habitats and the extent of Old-Age Forest. We found that 22% of productive forest area contained Biodiversity Habitats. More than 70% of this area was not covered by any large-scale instruments. Mountain Forest covered 23%, while Strict Protection and Wilderness both covered 5% of the Biodiversity Habitat area. A total of 9% of productive forest area contained Old-Age Forest, and the relative coverage of the four instruments was similar as for Biodiversity Habitats. For all instruments, except Landscape Protection, the targeted areas contained significantly higher proportions of HCV-forest than areas not targeted by these instruments. Areas targeted by Strict Protection had higher proportions of HCV-forest than areas targeted by other instruments, except for areas targeted by Wilderness Area which showed similar proportions of Biodiversity Habitats. There was a substantial amount of spatial overlap between the policy tools, but no incremental conservation effect of overlapping instruments in terms of contributing to higher percentages of targeted HCV-forest. Our results reveal that although the current policy mix has an above average representation of forest of high conservation value, the targeting efficiency in terms of area overlap is limited. There is a need to improve forest conservation and a potential to cover this need by better targeting high conservation value areas.


Advanced illness index: Predictive modeling to stratify elders using self-report data.
Develop a prediction model to identify persons who have an increased risk of dying within the next 36 months, in order to focus additional resources and assessment in areas related to advanced care planning. Retrospective study with a 3-year observation period. Integrated, not-for-profit managed care organization. Beneficiaries aged 65-105 responding to an annual survey (n = 4888). Survey instrument includes physical function, geriatric syndromes, health care utilization, special equipment use, self-care deficits, caregiving responsibilities, and general health problems. An 11-variable model changed the baseline chi2 from 315.71 (df = 1) to 742.511 (df = 11). The percent of subjects correctly classified was 74.3% and the negative predictive value was 92.2%. Advanced Illness Index (AII) model is stable. Characteristic variables used are not easily reversed: the 1997 cohort classified as at-risk consistently remained at risk or died in the subsequent years (1998, 92%; and 1999, 96%) and 92% of those not at-risk survived the next 36 months. Persons at high risk should at a minimum be made aware of the types of integrated home and community-based services available to them should it be needed. They also should be targeted for elicitation of treatment preferences, values, designation of health care proxy, planning, and advanced care directives.


Fifth Daniel C. Baker Jr. Memorial Lecture. Resident education: past, present and to where.
The specialties in medicine and surgery developed slowly during the later 19th century and the early decades of this century. The American boards were the focal points for sponsoring specialty societies through which these developments occurred. The resident review committees have also played an important role. Otolaryngology resident education has developed into a progressively structured educational experience so that presently otolaryngology resident education is a broad experience in head and neck oncology, plastic and reconstructive surgery, otology, laryngology, rhinology, allergy and immunology, bronchoesophagology, teaching and research. Resident education is not static. The year of 1978 can be noted as the year of change, for the Resident Review Committee in Otolaryngology recommended that resident education be of five years in duration, one year being in surgery, three years in otolaryngology and one year being elective as to content. Such programming can be highly structured to meet a candidate's present and future needs in manpower, superspecialization and general otolaryngology. In this system superspecialization can and will be recognized and awarded through channels already established in otolaryngology. Manpower and general otolaryngology will also profit.


Analgesic Medicine Utilization in Older People in New Zealand from 2005 to 2013.
Older people (aged 65 years and above) consume more analgesics compared with other age groups. Because of the aging of the New Zealand population, it is important to ascertain the trends of analgesic use at a population-level. The aim of this population-based study was to describe and characterize the utilization of analgesic medicines in older people in New Zealand from 2005 to 2013. Repeated cross-sectional analysis of population-level dispensing data was conducted from 2005 to 2013. Dispensing data were obtained from Pharmaceutical Claims Data Mart (Pharms), Ministry of Health, extracted using encrypted national health index numbers as unique identifiers and categorized by the World Health Organization Collaborating Centre for Drug Statistics Methodology (WHOCC) Anatomical Therapeutic Chemical (ATC) classification system. Utilization of analgesics was measured in defined daily dose (DDD) per 1000 older people per day (TOPD). Overall, analgesic medicine utilization increased by 5.44 % from 2005 to 2013. Analgesic utilization increased from 233.66 to 246.36 DDD/TOPD. The increased utilization was mainly driven by analgesics and antipyretics. An increased utilization of analgesics was seen in the 85+ age group. Females consumed more analgesics compared with males. Differences in analgesic utilization across the District Health Boards (DHBs) persisted over the 9-year period. Utilization of anti-migraines was stable over the 9-year period. This population-level utilization study showed a 5.44 % increase in utilization of analgesic medicines in older people in New Zealand from 2005 to 2013. Important findings were that (1) females utilized more analgesics compared with males; (2) non-steroidal anti-inflammatory drug (NSAID) utilization decreased over the years; and (3) the highest utilization was reported in the 85+ group. Further research is warranted to examine the drivers influencing analgesic use in New Zealand.


Label- and slide-free tissue histology using 3D epi-mode quantitative phase imaging and virtual H&E staining.
Histological staining of tissue biopsies, especially hematoxylin and eosin (H&E) staining, serves as the benchmark for disease diagnosis and comprehensive clinical assessment of tissue. However, the process is laborious and time-consuming, often limiting its usage in crucial applications such as surgical margin assessment. To address these challenges, we combine an emerging 3D quantitative phase imaging technology, termed quantitative oblique back illumination microscopy (qOBM), with an unsupervised generative adversarial network pipeline to map qOBM phase images of unaltered thick tissues (i.e., label- and slide-free) to virtually stained H&E-like (vH&E) images. We demonstrate that the approach achieves high-fidelity conversions to H&E with subcellular detail using fresh tissue specimens from mouse liver, rat gliosarcoma, and human gliomas. We also show that the framework directly enables additional capabilities such as H&E-like contrast for volumetric imaging. The quality and fidelity of the vH&E images are validated using both a neural network classifier trained on real H&E images and tested on virtual H&E images, and a user study with neuropathologists. Given its simple and low-cost embodiment and ability to provide real-time feedback in vivo, this deep learning-enabled qOBM approach could enable new workflows for histopathology with the potential to significantly save time, labor, and costs in cancer screening, detection, treatment guidance, and more.


Smart phone technologies and ecological momentary data: is this the way forward on depression management and research?
Depression is a complex and burdensome condition; it often leads to personal, societal and economic costs. Despite advances in treatments, its management over time remains a challenge; many treated for depression do not achieve full recovery or remain well for long. Novel ways to monitor patients are warranted, as well as better understanding of contributors to relapse or sustained wellness. Mobile health technologies (m-Health) are emerging as useful tools for real-time assessments of moods, behaviours and activities in a more convenient and less burdensome manner. Yet, there are numerous questions around privacy, reliability and accuracy of data collected via mobile apps. This review provides a critical overview of advances in m-Health and evaluate the future potential of smartphone technology in the assessment and treatment of depression. There is an abundance of apps in the market that claim to exert beneficial effects on the management of depression; to date, only a small fraction has been validated in clinical trials or has had the support of academic centers. Although promising, the use of mobile health applications in depression warrants further investigation and incorporation into mainstream research to facilitate greater adoption and validation of its clinical utility.


Multimorbidity patterns of and use of health services by Swedish 85-year-olds: an exploratory study.
As life expectancy continues to rise, more elderly are reaching advanced ages (≥80 years). The increasing prevalence of multimorbidity places additional demands on health-care resources for the elderly. Previous studies noted the impact of multimorbidity on the use of health services, but the effects of multimorbidity patterns on health-service use have not been well studied, especially for very old people. This study determines patterns of multimorbidity associated with emergency-room visits and hospitalization in an 85-year-old population. Health and living conditions were reported via postal questionnaire by 496 Linköping residents aged 85 years (189 men and 307 women). Diagnoses of morbidity were reviewed in patients' case reports, and the local health-care register provided information on the use of health services. Hierarchical cluster analysis was applied to evaluate patterns of multimorbidity with gender stratification. Factors associated with emergency-room visits and hospitalization were analyzed using logistic regression models. Cluster analyses revealed five clusters: vascular, cardiopulmonary, cardiac (only for men), somatic-mental (only for men), mental disease (only for women), and three other clusters related to aging (one for men and two for women). Heart failure in men (OR = 2.4, 95% CI = 1-5.7) and women (OR = 3, 95% CI = 1.3-6.9) as a single morbidity explained more variance than morbidity clusters in models of emergency-room visits. Men's cardiac cluster (OR = 1.6; 95% CI = 1-2.7) and women's cardiopulmonary cluster (OR = 1.7, 95% CI = 1.2-2.4) were significantly associated with hospitalization. The combination of the cardiopulmonary cluster with the men's cardiac cluster (OR = 1.6, 95% CI = 1-2.4) and one of the women's aging clusters (OR = 0.5, 95% CI = 0.3-0.8) showed interaction effects on hospitalization. In this 85-year-old population, patterns of cardiac and pulmonary conditions were better than a single morbidity in explaining hospitalization. Heart failure was superior to multimorbidity patterns in explaining emergency-room visits. A holistic approach to examining the patterns of multimorbidity and their relationships with the use of health services will contribute to both local health care policy and geriatric practice.


Prostacyclin agonist with thromboxane synthase inhibitory activity (ONO-1301) attenuates bleomycin-induced pulmonary fibrosis in mice.
The balance between prostacyclin and thromboxane A2 (TXA2) plays an important role in pulmonary homeostasis. However, little information is available regarding the therapeutic potency of these prostanoids for pulmonary fibrosis. We have recently developed ONO-1301, a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. Thus we investigated whether repeated administration of ONO-1301 attenuates bleomycin-induced pulmonary fibrosis in mice. After intratracheal injection of bleomycin or saline, mice were randomized to receive repeated subcutaneous administration of ONO-1301 or vehicle. Bronchoalveolar lavage (BAL) and histological analyses were performed at 3, 7, and 14 days after bleomycin injection. In vitro studies using mouse lung fibroblasts were also performed. ONO-1301 significantly attenuated the development of bleomycin-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content. ONO-1301 significantly reduced total cell count, neutrophil count, and total protein level in BAL fluid in association with a marked reduction of TXB2. A single administration of ONO-1301 significantly increased plasma cAMP level for >2 h. In vitro, ONO-1301 and a cAMP analog dose-dependently reduced cell proliferation in mouse lung fibroblasts. The reduction in cell proliferation by ONO-1301 was attenuated by a protein kinase A (PKA) inhibitor. Furthermore, bleomycin mice treated with ONO-1301 had a significantly higher survival rate than those given vehicle. These results suggest that repeated administration of ONO-1301 attenuates the development of bleomycin-induced pulmonary fibrosis and improves survival in bleomycin mice, at least in part by inhibition of TXA2 synthesis and activation of the cAMP/PKA pathway.


Promoting pellet growth of Trichoderma reesei Rut C30 by surfactants for easy separation and enhanced cellulase production.
It is desirable to modify the normally filamentous Trichoderma reesei Rut C-30 to a pellet form, for easy biomass separation from the fermentation medium containing soluble products (e.g., cellulase). It was found in this study that this morphological modification could be successfully achieved by addition of the biosurfactant rhamnolipid (at ≥ 0.3g/L) and the synthetic Triton X-100 (at ≥ 0.1g/L) to the fermentation broth before the cells started to grow actively. Thirteen other surfactants tested were not as effective. Furthermore, the added rhamnolipid and Triton X-100 increased the maximum cellulase activity (Filter Paper Units) produced in the fungal fermentation; the increase was 68 ± 7.8% for rhamnolipid and 73 ± 12% for Triton X-100. At the concentrations required for pellet formation, rhamnolipid had negative effect on the cell growth: with increasing rhamnolipid concentrations, the growth rate decreased and the lag-phase duration increased linearly. Triton X-100 caused no significant differences in growth rate or lag phase.


Delisting HCV-infected liver transplant candidates who improved after viral eradication: Outcome 2 years after delisting.
Treating patients with decompensated cirrhosis with direct-acting antiviral (DAA) therapy while on the waiting list for liver transplantation results in substantial improvement of liver function allowing 1 in 4 patients to be removed from the waiting list or delisted, as reported in a previous study promoted by the European Liver and Intestine Transplant Association (ELITA). The aim of this study was to report on clinical outcomes of delisted patients, including mortality risk, hepatocellular carcinoma development and clinical decompensation requiring relisting. One hundred and forty-two HCV-positive patients on the liver transplant waiting list for decompensated cirrhosis, negative for hepatocellular carcinoma, between February 2014 and June 2015 were treated with DAA therapy and were prospectively followed up. Forty-four patients (30.9%) were delisted following clinical improvement. This percentage was higher than in the original study because of a number of patients being delisted long after starting DAAs. The median Child-Pugh and MELD score of delisted patients was 5.5 and 9 respectively. Four patients were relisted, because of HCC diagnosis in 1 case and 3 patients developed ascites. One further patient died (2.4%) because of rapidly progressing hepatocellular carcinoma twenty-two months after delisting. Of the 70 patients who received a liver graft, 9 died (13%). Antiviral therapy allows for a long-term improvement of liver function and the delisting of one-third of treated patients with risk of liver-related complications after delisting being very low.


High-dimensional optimization under nonconvex excluded volume constraints.
We consider high-dimensional random optimization problems where the dynamical variables are subjected to nonconvex excluded volume constraints. We focus on the case in which the cost function is a simple quadratic cost and the excluded volume constraints are modeled by a perceptron constraint satisfaction problem. We show that depending on the density of constraints, one can have different situations. If the number of constraints is small, one typically has a phase where the ground state of the cost function is unique and sits on the boundary of the island of configurations allowed by the constraints. In this case, there is a hypostatic number of marginally satisfied constraints. If the number of constraints is increased one enters a glassy phase where the cost function has many local minima sitting again on the boundary of the regions of allowed configurations. At the phase transition point, the total number of marginally satisfied constraints becomes equal to the number of degrees of freedom in the problem and therefore we say that these minima are isostatic. We conjecture that by increasing further the constraints the system stays isostatic up to the point where the volume of available phase space shrinks to zero. We derive our results using the replica method and we also analyze a dynamical algorithm, the Karush-Kuhn-Tucker algorithm, through dynamical mean-field theory and we show how to recover the results of the replica approach in the replica symmetric phase.


Comparison of milk production of dairy cows vaccinated with a live double deleted BVDV vaccine and non-vaccinated dairy cows cohabitating in commercial herds endemically infected with BVD virus.
Daily milk production and reproductive performance of cows vaccinated with a live double-deleted Bovine Viral Diarrhoea Virus (BVDV) vaccine were compared to those of non-vaccinated cows, cohabitating in endemic BVDV herds. All animals in the treatment group were vaccinated on study day 0 irrespective of lactation or gestation status, while control animals did not receive any treatment. 1463 animals were enrolled in the study from four different farms in three different countries (UK, Italy, France). Endemic presence of BVDV in study herds was demonstrated by the detection of BVDV in the bulk tank milk, and seroconversion was evaluated at the beginning of the study. For individual animals, the day of calving was taken to be the start of lactation for the calculation of days in milk (DIM). The standard lactation period of 305 days was divided into three periods: early lactation (EL, from DIM 8 to DIM 102), mid lactation (ML, from DIM 103 to DIM 204 and late lactation (LL, from DIM 205 to DIM 305). For each farm and each lactation period, a mixed model statistical analysis was performed with daily milk production as response, and group, day as well as the interaction between those two factors as fixed factors. Chi-square test was used to compare abortion rate and prolonged inter-oestrous interval rate between treatment and control groups. A significant increase in milk production in the vaccinated group was observed in farms 1 (1.023 L/day) and 3 (0.611 L/day) during EL (p<0.001) and in farm 2 (1.799 L/day) during ML (P<0.001). In addition, at farm 2, vaccinated cows produced more milk than non-vaccinated cows starting from 80 DIM. No differences were found between groups in abortion rates or prolonged inter-oestrous interval rates. Data demonstrate that cows in herds endemically infected with BVDV and vaccinated with live double-deleted BVDV vaccine produce more milk; the difference in milk production occurs during early lactation.


Vitamin D requirements during pregnancy.
Adequate vitamin D concentrations during pregnancy are necessary to ensure appropriate maternal responses to the calcium demands of the fetus and neonatal handling of calcium. The purpose of this report is to review studies that investigated maternal and neonatal outcomes of vitamin D deficiency or supplementation during pregnancy. Most studies reported included women at high risk of vitamin D deficiency, because of low vitamin D and calcium intake or decreased ability to synthesize endogenous vitamin D (attributable to lack of sun exposure or to heavily pigmented skin). Overall, vitamin D supplementation in these populations leads to improved neonatal handling of calcium. Results concerning benefits for fetal growth and bone development are inconclusive. There is no evidence of a benefit of supplementation during pregnancy above amounts routinely required to prevent vitamin D deficiency.


A soybean mapping population specific to the early soybean production system.
The objective of this research was to create a soybean [Glycine max (L.) Merr] genetic resource in the form of a publicly available, well-characterized mapping population specific to maturity groups (MG) used in the early soybean production system. A total of 568 simple sequence repeat (SSR) markers were tested for polymorphism between soybean breeding line DS97-84-1 (MG IV) and germplasm line DT97-4290 (MG IV). A 90-genotype subset of an F2 population from a cross between these lines was evaluated for genetic linkage using 162 polymorphic SSRs, plant height, pod color (L2/l2), flower color (W1/w1) and stem termination (Dt1/dt1). A 1514 cM (Kosambi) genetic map covering 65% of the soybean genome based on 157 linked SSR markers was created. Comparison with the composite soybean genetic map was used to verify map order. Loci for pod color, flower color and stem termination fell in the expected position on the map indicating this is a normally segregating mapping population. Loci for height were identified on linkage groups C2, D1a, D1b, H, L, M and O. MG IV and V soybean genotypes are critical for the early soybean production system widely used in the midsouthern US. However, only two mapping populations have been reported in Soybase for MG IV and V genotypes. Additionally, the parents used in this cross are known to differ in their response to soybean cyst nematode and charcoal rot, which constitute two major pathology threats to Midsouth soybean production. The population and map reported herein represent an important genetic resource for the early soybean production system.


Multiple-Choice Questions in Small Animal Medicine: An Analysis of Cognitive Level and Structural Reliability, and the Impact of these Characteristics on Student Performance.
Students entering the final year of the veterinary curriculum need to integrate information and problem solve. Assessments used to document competency prior to entry to the clinical environment should ideally provide a reliable measurement of these essential skills. In this study, five internal medicine specialists evaluated the cognitive grade (CG) and structural integrity of 100 multiple-choice questions (MCQs) used to assess learning by third-year students at a United States (US) veterinary school. Questions in CG 1 tested factual recall and simple understanding; those in CG 2 required interpretation and analysis; CG 3 MCQs tested problem solving. The majority (53%) of questions could be answered correctly using only recall or simple understanding (CG 1); 12% of MCQs required problem solving (CG 3). Less than half of the questions (43%) were structurally sound. Overall student performance for the 3 CGs differed significantly (92% for CG 1 vs. 84% for CG 3; p = .03. Structural integrity did not appear to impact overall performance, with a median pass rate of 90% for flawless questions versus 86% for those with poor structural integrity (p = .314). There was a moderate positive correlation between individual student outcomes for flawless CG 1 versus CG 3 questions (rs = 0.471; p = < .001), although 13% of students failed to achieve an aggregate passing score (65%) on the CG 3 questions. These findings suggest that MCQ-based assessments may not adequately evaluate intended learning outcomes and that instructors may benefit from guidance and training for this issue.


Reducing i.v. waste to under 2.25 percent.
Reduction of IV waste is of extreme importance in the maintenance of cost-effective, quality pharmacy services. This report describes the methods undertaken by a large community hospital to decrease IV waste to under 4%. The program uses several techniques including: "status sheets", IV reminder labels, commercial partial fill containers, extensive recycling procedures and close communication between the central IV service, pharmacy satellites and nursing units.


Heterologous challenge in the presence of maternally-derived antibodies results in vaccine-associated enhanced respiratory disease in weaned piglets.
Control of influenza A virus (IAV) in pigs is done by vaccination of females to provide maternally-derived antibodies (MDA) through colostrum. Our aim was to evaluate if MDA interfere with IAV infection, clinical disease, and transmission in non-vaccinated piglets. In the first study, naïve sows were vaccinated with H1N2-δ1 whole inactivated virus (WIV) vaccine. In a follow-up study seropositive sows to 2009 pandemic H1N1 (H1N1pdm09) were boosted with H1N1pdm09 WIV or secondary experimental infection (EXP). MDA-positive pigs were challenged with homologous or heterologous virus, and MDA-negative control groups were included. WIV-MDA piglets were protected from homologous infection. However, piglets with WIV-derived MDA subsequently challenged with heterologous virus developed vaccine associated enhanced respiratory disease (VAERD), regardless of history of natural exposure in the sows. Our data indicates that although high titers of vaccine-derived MDA reduced homologous virus infection, transmission, and disease, MDA alone was sufficient to induce VAERD upon heterologous infection.


Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5.
Description of 8 new ANO5 mutations and significant expansion of the clinical phenotype spectrum associated with previously known and unknown mutations to improve diagnostic accuracy. DNA samples of 101 patients in 95 kindreds at our quaternary referral center in Finland, who had undetermined limb-girdle muscular dystrophy (LGMD), calf distal myopathy, or creatine kinase (CK) elevations of more than 2,000 IU/L, were selected for ANO5 genetic evaluation, and the clinical findings of patients with mutations were retrospectively analyzed. A total of 25 patients with muscular dystrophy caused by 11 different recessive mutations in the ANO5 gene were identified. The vast majority of mutations, 8 of 11, proved to be previously unknown new mutations. The most frequent mutation, c.2272C>T (p.R758C), was present in 20 patients. The phenotypes associated with this and the common European mutation, c.191dupA, varied from nearly asymptomatic high hyperCKemia to severe LGMD with consistently milder phenotypes in female patients. Mutations in ANO5 are a frequent cause of undetermined muscular dystrophy, with both distal and proximal presentation. Other types include high hyperCKemia, myalgia, or calf hypertrophy over decades without significant weakness, especially in female patients. Mutations are distributed all over the gene, indicating that muscular dystrophy caused by ANO5 can be expected to occur in all populations.


Operando vibrational spectroscopy for electrochemical biomass valorization.
Electrocatalysis is a promising route to generate fuels and value-added chemicals from abundant feedstocks powered by renewable electricity. The field of electrocatalysis research has made great progress in supplementing electrocatalyst development with operando vibrational spectroscopic techniques, those carried out simultaneously as the reaction is occurring. Such experiments unveil reaction mechanisms, structure-activity relationships and consequently, accelerate the development of next generation electrocatalytic systems. While operando techniques have now been extensively applied to water electrolysis and CO2 reduction, their application to the emerging area of biomass valorization is rather nascent. The electrocatalytic conversion of biomass can provide an alternate, environmentally friendly route to the chemicals which power our society, but this field still requires much growth before the envisioned technologies are economically competetive with thermochemical routes. Within this context, a growing body of work has begun to translate the methodology and concepts from water/CO2 electrolysis to biomass valorization to elucidate links between catalyst structure, adsorbed surface intermediates, and the resultant catalytic performance. The reactions of interest here include the upgrading of biomass platforms such a 5-hydroxymethylfurfural or glycerol to value-added chemicals. In this feature article we highlight these efforts and provide a critical view on the steps necessary to take to further progress the field. We further show how the knowledge derived from these studies can be translated to a plethora of other organic transformations to forge new avenues in renewable energy electrocatalysis.


Formulation of time-resolved counting statistics based on a positive-operator-valued measure.
We propose a derivation of the full counting statistics of electronic current based on a positive-operator-valued measure. Our approach justifies the Levitov-Lesovik formula in the long-time limit, but can be generalized to the detection of finite-frequency noise correlations. The combined action of the projection postulate and the quantum formula for current noise at high frequencies imply an additional white noise. Estimates for this additional noise are in accordance with known experiments. We propose an experimental test of our conjecture by a simultaneous measurement of high- and low-frequency noise.


ImageNet-trained deep neural networks exhibit illusion-like response to the Scintillating grid.
Deep neural network (DNN) models for computer vision are capable of human-level object recognition. Consequently, similarities between DNN and human vision are of interest. Here, we characterize DNN representations of Scintillating grid visual illusion images in which white disks are perceived to be partially black. Specifically, we use VGG-19 and ResNet-101 DNN models that were trained for image classification and consider the representational dissimilarity (\(L^1\) distance in the penultimate layer) between pairs of images: one with white Scintillating grid disks and the other with disks of decreasing luminance levels. Results showed a nonmonotonic relation, such that decreasing disk luminance led to an increase and subsequently a decrease in representational dissimilarity. That is, the Scintillating grid image with white disks was closer, in terms of the representation, to images with black disks than images with gray disks. In control nonillusion images, such nonmonotonicity was rare. These results suggest that nonmonotonicity in a deep computational representation is a potential test for illusion-like response geometry in DNN models.


Using genetic variants to evaluate the causal effect of cholesterol lowering on head and neck cancer risk: A Mendelian randomization study.
Head and neck squamous cell carcinoma (HNSCC), which includes cancers of the oral cavity and oropharynx, is a cause of substantial global morbidity and mortality. Strategies to reduce disease burden include discovery of novel therapies and repurposing of existing drugs. Statins are commonly prescribed for lowering circulating cholesterol by inhibiting HMG-CoA reductase (HMGCR). Results from some observational studies suggest that statin use may reduce HNSCC risk. We appraised the relationship of genetically-proxied cholesterol-lowering drug targets and other circulating lipid traits with oral (OC) and oropharyngeal (OPC) cancer risk using two-sample Mendelian randomization (MR). For the primary analysis, germline genetic variants in HMGCR, NPC1L1, CETP, PCSK9 and LDLR were used to proxy the effect of low-density lipoprotein cholesterol (LDL-C) lowering therapies. In secondary analyses, variants were used to proxy circulating levels of other lipid traits in a genome-wide association study (GWAS) meta-analysis of 188,578 individuals. Both primary and secondary analyses aimed to estimate the downstream causal effect of cholesterol lowering therapies on OC and OPC risk. The second sample for MR was taken from a GWAS of 6,034 OC and OPC cases and 6,585 controls (GAME-ON). Analyses were replicated in UK Biobank, using 839 OC and OPC cases and 372,016 controls and the results of the GAME-ON and UK Biobank analyses combined in a fixed-effects meta-analysis. We found limited evidence of a causal effect of genetically-proxied LDL-C lowering using HMGCR, NPC1L1, CETP or other circulating lipid traits on either OC or OPC risk. Genetically-proxied PCSK9 inhibition equivalent to a 1 mmol/L (38.7 mg/dL) reduction in LDL-C was associated with an increased risk of OC and OPC combined (OR 1.8 95%CI 1.2, 2.8, p = 9.31 x10-05), with good concordance between GAME-ON and UK Biobank (I2 = 22%). Effects for PCSK9 appeared stronger in relation to OPC (OR 2.6 95%CI 1.4, 4.9) than OC (OR 1.4 95%CI 0.8, 2.4). LDLR variants, resulting in genetically-proxied reduction in LDL-C equivalent to a 1 mmol/L (38.7 mg/dL), reduced the risk of OC and OPC combined (OR 0.7, 95%CI 0.5, 1.0, p = 0.006). A series of pleiotropy-robust and outlier detection methods showed that pleiotropy did not bias our findings. We found limited evidence for a role of cholesterol-lowering in OC and OPC risk, suggesting previous observational results may have been confounded. There was some evidence that genetically-proxied inhibition of PCSK9 increased risk, while lipid-lowering variants in LDLR, reduced risk of combined OC and OPC. This result suggests that the mechanisms of action of PCSK9 on OC and OPC risk may be independent of its cholesterol lowering effects; however, this was not supported uniformly across all sensitivity analyses and further replication of this finding is required.


Suppressive effects of vitamin C-treated induced-regulatory T cells on heart allograft rejection under vitamin C-deficient or -sufficient conditions.
Foxp3 stability of vitamin C-treated induced-regulatory T cells (V-iTregs) is superior to that of conventional iTregs (C-iTregs). However, the role of V-iTregs in allograft rejection under vitamin C-deficient conditions, such as those seen in humans, remains unclear. We aimed to elucidate the role of vitamin C treatment on generation and maintenance of iTregs from gulo knockout (Gulo-KO) mice as well as wild type (WT) mice, and in vitro and in vivo suppressive effects of V-iTregs on heart allograft rejection in either Gulo-KO or WT recipient mice. Conversion efficiency of iTregs was similar between C- and V-iTregs in both WT and Gulo-KO mice. V-iTregs from WT or Gulo-KO mice showed better in vitro Foxp3 stability than C-iTregs, although there was no difference between WT V-iTregs and Gulo-KO V-iTregs. Furthermore, V-iTregs from WT or Gulo-KO mice suppressed in vitro T cell proliferation better than C-iTregs. Heterotrophic heart transplantation from BALB/c mice to WT or vitamin C-deficient Gulo-KO C57BL/6J mice was performed following adoptive transfer of C- or V-iTregs. V-iTregs as well as C-iTregs prolonged heart allograft survival in WT and Gulo-KO mice. However, there was no difference between the C- and V-iTreg groups. Supplementation of low- or high-dose vitamin C did not induce significant changes in heart allograft survival in Gulo-KO recipients that had received V-iTregs. In conclusion, V-iTregs do not exert better suppressive effects on heart allograft survival than C-iTregs in either WT or vitamin C-deficient recipients.


A 2-year longitudinal study of eating attitudes, BMI, perfectionism, asceticism and family climate in adolescent girls and their parents.
The aim of this longitudinal study of 383 Swedish adolescent girls (11 and 13 years old at year 1) and their parents was to examine changes in eating attitudes over a two-year period, and to investigate the predictive value of eating attitudes, perfectionism, asceticism, family climate and body mass index (BMI) for the development of disturbed eating attitudes. The following self-report questionnaires were used: Children's Eating Attitudes test, Eating Attitudes Test, Eating Disorder Inventory for Children, Eating Disorder Inventory 2, I Think I Am and The Family Climate. The frequency of disturbed eating attitudes increased with increased age in the girls. Children's eating attitudes, higher BMI than peers, the girls rating of a less healthy relation to family and their fathers' eating attitudes at year 1 contributed most to the prediction of disturbed eating attitudes for the girls 2 years later. The results suggest that early signs of disturbed eating attitudes and higher BMI than peers may be important predictors for the development of more serious eating disturbances among adolescent girls.


Leber hereditary optic neuropathy presenting as bilateral visual loss and white matter disease.
Leber hereditary optic neuropathy (LHON) is a rare maternally inherited mitochondrial disorder that typically affects young male adults in their second and third decades of life. It usually manifests as painless, subacute, progressive, bilateral vision loss, with more than 90% of affected individuals losing their vision before age 50. Compared with other diseases that cause optic neuritis (multiple sclerosis or neuromyelitis optica spectrum disorders), LHON has worsening visual function in the first 6-12 months of disease progression, is predominantly male, the optic nerve is affected bilaterally from onset, there is no gadolinium enhancement on MRI, no response to disease-modifying therapy, and there is a family history of mutation in mitochondrial DNA. In this article, we describe an interesting and challenging case of LHON due to a homoplasmic variant in the MT -CO3 gene that was initially misdiagnosed as a monophasic demyelinating disorder (clinically isolated syndrome vs acute disseminated encephalomyelitis vs neuromyelitis optica spectrum disorders).


[Indicators of phagocytic activity of neutrophils in patients with diabetes mellitus before and after treatment using the "Biostator"].
Phagocytic function of polymorphonuclear leukocytes was studied in patients with insulin-dependent and insulin-independent diabetes. A total of 52 patients were examined; the patients were mainly young, suffering from insulin-dependent diabetes with or without angiopathies. The leukocyte phagocytic activity was studied with the use of the direct method developed by G. I. Podoprigora and V. N. Andreev in 1976. All phagocytosis parameters were shown to be reduced, the relationship between these parameters distorted, and digestion impaired, especially in patients with diabetic functional angiopathy and with the Kimmelstiel-Wilson syndrome. A trial is described of correcting phagocytosis disorders by means of a Biostator apparatus (an artificial pancreas, functioning according to the feedblack principle). Such investigation was the first attempted in this country, no data on the leukocyte phagocytic activity before and after treatment with the use of an artificial pancreas apparatus were reported in foreign literature. Clinical application of the method is described.


Quercetin differently regulates insulin-mediated glucose transporter 4 translocation under basal and inflammatory conditions in adipocytes.
Quercetin is the most abundant dietary flavonol with beneficial regulation of glucose homeostasis, but its regulation of insulin action remains uncertain. This study aims to investigate the effects of quercetin on insulin-mediated glucose transporter 4 (GLUT4) translocation under basal and inflammatory conditions as well as the molecular mechanisms in adipocytes. The effects of quercetin on insulin-mediated GLUT4 translocation in 3T3-L1 cells under basal and insulin resistant conditions were investigated. Meanwhile, we investigated the effect of quercetin on AMP-activated protein kinase (AMPK) activation implicated in regulation of insulin action. Quercetin inhibited insulin-mediated GLUT4 translocation by inhibiting AS160 phosphorylation. Differently, when inflammatory challenge impaired insulin action in 3T3-L1 cells, quercetin inhibited IκB kinase β (IKKβ) phosphorylation and facilitated insulin signaling, leading to the restoration of insulin-mediated AS160 phosphorylation and downstream GLUT4 translocation. AMPK inhibitor Compound C or knockdown of AMPKα by small interfering RNA (siRNA) abolished both actions of quercetin. Results from mice adipose tissue (AT) further confirmed its positive regulation of AMPK phosphorylation and opposite effects on AS160 phosphorylation in vivo. Quercetin demonstrated divergent effects on insulin-mediated GLUT4 translocation in adipocytes under basal and insulin resistant conditions, which were related to its regulation of AMPK activity.


New PHA products using unrelated carbon sources.
Polyhydroxyalkanoates (PHA) are natural polyesters stored by a wide range of bacteria as carbon source reserve. Due to its chemical characteristics and biodegradability PHA can be used in chemical, medical and pharmaceutical industry for many human purposes. Over the past years, few Burkholderia species have become known for production of PHA. Aside from that, these bacteria seem to be interesting for discovering new PHA compositions which is important to different industrial applications. In this paper, we introduce two new strains which belong either to Burkholderia cepacia complex (Bcc) or genomovar-type, Burkholderia cepacia SA3J and Burkholderia contaminans I29B, both PHA producers from unrelated carbon sources. The classification was based on 16S rDNA and recA partial sequence genes and cell wall fatty acids composition. These two strains were capable to produce different types of PHA monomers or precursors. Unrelated carbon sources were used for growth and PHA accumulation. The amount of carbon source evaluated, or mixtures of them, was increased with every new experiment until it reaches eighteen carbon sources. As first bioprospection experiments staining methods were used with colony fluorescent dye Nile Red and the cell fluorescent dye Nile Blue A. Gas chromatography analysis coupled to mass spectrometry was used to evaluate the PHA composition on each strain cultivated on different carbon sources. The synthesized polymers were composed by short chain length-PHA (scl-PHA), especially polyhydroxybutyrate, and medium chain length-PHA (mcl-PHA) depending on the carbon source used.


The effects of toluene on the central nervous system.
In recent decades the organic solvent toluene (methylbenzene) has emerged as one of the best-studied neurotoxins. Long-term and intense exposure to toluene vapors in humans who abuse spray paint and related substances has led to the recognition that toluene has a severe impact on central nervous system myelin. Chronic toluene abuse produces a devastating neurological disorder, of which dementia is the most disabling component. The clinical syndrome, toluene leukoencephalopathy, can be detected by a combination of characteristic symptoms and signs, detailed neurobehavioral evaluation, and brain magnetic resonance imaging. In this paper, we consider the impact of toluene abuse on our society, describe the specific neurobehavioral deficits in toluene leukoencephalopathy, review the spectrum of neuroimaging findings in patients with this disorder, summarize the teratogenic effects of toluene in both humans and animal models, and offer possible explanations for the range of neuropathological damage seen in brains of individuals who chronically abuse toluene.


Magnetic biomaterials and nano-instructive tools as mediators of tendon mechanotransduction.
Tendon tissues connect muscle to bone allowing the transmission of forces resulting in joint movement. Tendon injuries are prevalent in society and the impact on public health is of utmost concern. Thus, clinical options for tendon treatments are in demand, and tissue engineering aims to provide reliable and successful long-term regenerative solutions. Moreover, the possibility of regulating cell fate by triggering intracellular pathways is a current challenge in regenerative medicine. In the last decade, the use of magnetic nanoparticles as nano-instructive tools has led to great advances in diagnostics and therapeutics. Recent advances using magnetic nanomaterials for regenerative medicine applications include the incorporation of magnetic biomaterials within 3D scaffolds resulting in mechanoresponsive systems with unprecedented properties and the use of nanomagnetic actuators to control cell signaling. Mechano-responsive scaffolds and nanomagnetic systems can act as mechanostimulation platforms to apply forces directly to single cells and multicellular biological tissues. As transmitters of forces in a localized manner, the approaches enable the downstream activation of key tenogenic signaling pathways. In this minireview, we provide a brief outlook on the tenogenic signaling pathways which are most associated with the conversion of mechanical input into biochemical signals, the novel bio-magnetic approaches which can activate these pathways, and the efforts to translate magnetic biomaterials into regenerative platforms for tendon repair.


An interplay of Progesterone, Leukemia Inhibitor Factor and Interleukin-6 in the window of implantation; Impact on fertility.
The process of implantation is crucial for the initiation of conception and hence fertility. In addition to a number of factors, it is regulated by a cross talk of gonadotrophins [Luteinizing Hormone (LH), Follicle Stimulatory Hormone (FSH)], ovarian steroids [Estrogen (Et), Progesterone (Pt)] and cytokines [Leukemia inhibitory factor (LIF) and Interleukin 6 (IL6)]. These biomarkers are chief players of implantation. We aimed to explore the role of gonadotrophins (LH, FSH, LH/FSH ratio), ovarian steroids (Et, Pt) and cytokines (LIF, IL6) in the implantation process. This aim was achieved by comparing these hormones and cytokines in the fertile and infertile groups [Polycystic ovaries (PCOs), endometriosis, unexplained infertility (Uex-IF)] and finding their association in all study groups. A case control study conducted from October 2020-March 2023. A total of 135 infertile women (with PCOs, Uex-IF, and endometriosis) and 177 fertile women (matched for age and BMI) were selected. Levels of 'Et', 'Pt', 'LIF' and, 'IL6' were estimated using Enzyme Linked Immunosorbent Assay (ELISA). LH and FSH values were obtained from hospital desk records. The Independent Student'st-test was used to compare fertile and infertile groups. One-way ANOVA test was used to compare more than two groups, and Pearson's chi-square (χ2) test was employed to compare percentages of variables. Pearson correlation analysis was performed to assess the associations and correlations. A p value < 0.05 was considered statistically significant. Significantly higher levels of LIF and IL6 were observed in fertile women compared to infertile women. Pt levels were significantly greater in the fertile group than in the infertile group. The FSH/LH ratio was significantly higher in the fertile group. Among infertile women, PCOs (71%) and Uex-IF (91%) exhibited lower Pt levels than the fertile controls (p < 0.01), but these levels remained within the reference range (RR). Among the fertile group (81%), levels of LIF within the RR were significantly higher compared to those with Uex-IF (49%) and females with endometriosis (37%). Moreover, the highest number of participants (57%) with Uex-IF exhibited IL6 levels significantly below the RR in comparison to the fertile group and infertile groups (PCOS and endometriosis). However, lower levels of IL6 were observed in women with Uex-IF. In the control group, LIF exhibited a significant positive correlation with IL6 (r = 0.370), Pt (r = 0.496), Et (r = 0.403), and LH (r = 0.428). Among women with PCOs, LIF showed a significant positive correlation with IL6 (r = 0.443), Pt (r = 0.607), and LH (r = 0.472). In cases of Uex-IF, LIF demonstrated a significant positive correlation with IL6 (r = 0.727). Females with endometriosis displayed a significant positive correlation between LIF and IL6 (r = 0.535) as well as Pt (r = 0.605). In fertile women, a positive correlation was observed between LH and IL6 (r = 0.197, p = 0.009), LIF (r = 0.428, p = 0.000), Pt (r = 0.238, p = 0.001), and Et (r = 0.356, p = 0.000). Furthermore, a positive correlation was found between LH and LIF (r = 0.472, p = 0.000) in women with PCOs. Elevated levels of Pt were found to increase the production of LIF in fertile females. However, infertile females with PCOs and Uex-IF exhibited deficient levels of Pt, supporting its role as a biomarker for successful implantation in infertile women. These females showed decreased levels of gonadotropins as well as reduced LH/FSH ratio and diminished secretion of receptivity marker LIF, in addition to reduced Pt secretion. This suggests that reduced gonadotropin levels contribute to a lower LH/FSH ratio, resulting in decreased Pt secretion and ultimately leading to low levels of LIF, thereby causing impaired implantation in women with PCOs and Uex-IF. The exploration of low levels of LIF in patients with endometriosis requires further investigation. The significantly low levels of IL6 in the Uex-IF group elucidate the role of this cytokine in association with decreased Pt and LIF synthesis within this group.


Planning an objective and need based curriculum: the logistics with reference to the undergraduate medical education in biochemistry.
The medical education is recently being transformed into several domains in order to adapt to the need and the value based academics which is required for the quality doctors who serve the community. Presently, the biochemistry curricula for the graduate students of medicine have been questioned by as many experts, because of their multiple lacunae. In this review, we would like to highlight the scenario which is related to the existing biochemistry curricula for graduate medical students, which have been followed in several medical schools and universities and we also hope to share our ideas for implementing objective and pragmatic curricula. Evidence based research, wherein the articles which are related to innovative teaching-learning tools are collected and the pros and cons which are related to the different methods analyzed in biochemistry point of view. Rapid changes in the content of the curriculum may not be required, but a gradual introduction of the novel approach and the methods of teaching biochemistry can be adopted into the curriculum.


Precordial exercise mapping: improved diagnosis of coronary artery disease.
Surface mapping of the exercise electrocardiogram (ECG) provides a measure of the precordial area, severity, and time course of ST-segment changes occurring after exercise. Sixteen-lead isopotential surface maps were recorded before and after exercise in 109 patients with probable angina who subsequently underwent coronary arteriography. In addition, exercise ECGs with three orthogonal leads were obtained in 53 of these patients, and with a single unipolar chest lead in all 109. Of the 109 patients, 85 had significant (greater than or equal to 70%) narrowing of at least one major coronary artery. The sensitivities of the precordial surface mapping, orthogonal leads, and single chest lead (V5) when compared with the findings at coronary arteriography were 95%, 68%, and 64% respectively, while the specificities of the three lead systems did not differ significantly. The technique of precordial surface mapping after exercise may easily be applied in clinical practice and requires only conventional equipment available in most hospitals. It effectively aids diagnosis of coronary artery disease.


Effect of primary language on developmental testing in children born extremely preterm.
The aim of this study was to better understand the impact of non-English language spoken in the home on measures of cognition, language and behaviour in toddlers born extremely preterm. Eight hundred and fifty children born at <28 weeks of gestational ages were studied. 427 male and 423 female participants from three racial/ethnic groups (White, Black and Hispanic) were evaluated at 18-22 months adjusted for age using the Bayley Scales of Infant Development third edition and the Brief Infant Toddler Social Emotional Assessment (BITSEA). Children whose primary language was Spanish (n = 98) were compared with children whose primary language was English (n = 752), using multivariable regression adjusted for medical and psychosocial factors. Cognitive scores were similar between groups; however, receptive, expressive and composite language scores were lower for children whose primary language was Spanish. These differences remained significant after adjustment for medical and socio-economic factors. Spanish-speaking children scored worse on the BITSEA competence and problem scores using univariate analysis, but not after adjustment for medical and socio-economic factors. Our finding that preterm children whose primary language was Spanish had similar cognitive but lower language scores than those whose primary language was English suggests that using English language-based testing tools may introduce bias against non-English-speaking children born preterm.


The Impact of Mode of Birth on Childbirth-Related Post Traumatic Stress Symptoms beyond 6 Months Postpartum: An Integrative Review.
(1) Background: A traumatic birth can lead to the development of childbirth-related posttraumatic stress symptoms or disorder (CB-PTS/D). Literature has identified the risk factors for developing CB-PTS/D within the first six months postpartum thoroughly. However, the impact of mode of birth on CB-PTS/D beyond 6 months postpartum is scarcely studied. (2) Methods: A systematic search of the literature was conducted in the databases PubMed, Embase and CINAHL and PRISMA guidelines were followed. Studies were included if they reported the impact of mode of birth on CB-PTS/D beyond 6 months postpartum. (3) Results: In total, 26 quantitative and 2 qualitative studies were included. In the quantitative studies the percentage of women with CB-PTS/D ranged from 0.7% to 42% (between six months and five years postpartum). Compared with vaginal birth, operative vaginal birth, and emergency caesarean section were associated with CB-PTS/D beyond 6 months postpartum. Qualitative studies revealed that some women were suffering from CB-PTS/D as long as 18 years after birth. (4) Conclusions: Long- term screening of women for PTSD in the postnatal period could be beneficial. More research is needed on models of care that help prevent CB-PTS/D, identifying women at risk and factors that maintain CB-PTS/D beyond 6 months postpartum.


Tiotropium and exercise training in COPD patients: effects on dyspnea and exercise tolerance.
Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD). Tiotropium 18 microg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients. To determine whether tiotropium enhances the effects of exercise training in patients with COPD. Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study. Twelve Italian Pulmonary Units practicing pulmonary rehabilitation. Two hundred thirty four COPD patients (196 males; mean age: 67.4 +/- 7.6; forced expiratory volume at 1 second (FEV1): 41.4 +/- 13.0% predicted) were randomised to tiotropium 18 microg or placebo inhalation capsules taken once daily. Both groups underwent a 8 week pulmonary rehabilitation program (PR) consisting of 3 exercise training session per week. Baseline, at the end of PR and after 12 weeks, patients completed pulmonary function testing, six minute walking test (6MWT), the Baseline and Transition Dyspnea Index (BDI and TDI), and the St. George's Respiratory Questionnaire (SGRQ). Relative to placebo, tiotropium had larger trough and post-study drug FEV1 responses on all test days. At the end of and 12 weeks following PR, patients on tiotropium showed no statistically significant differences in 6MWT compared to patients on placebo. Compared to the period immediately prior to PR, the mean improvement in 6MWT was only 29.7 meters (7.1%) for the combined cohort. Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo (p < 0.01). At 12 weeks after PR, TDI focal scores were 2.71 for tiotropium and 2.11 for placebo (p = 0.16). Reduction in all four SGRQ component scores, indicating an improvement in health-related quality of life, was observed for the tiotropium group over the duration of the study compared to placebo but the differences were not statistically significant. During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group. Although significant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT.


Effects of extradural anaesthesia on umbilical and uteroplacental arterial flow velocity waveforms.
Flow velocity waveforms were recorded from the umbilical artery and uteroplacental arterial circulations of 15 women undergoing elective Caesarean section under extradural anaesthesia. The systolic: diastolic ratios of the flow velocity waveform were determined before and after extradural block. Extradural block did not alter fetal or maternal heart rates; however, umbilical artery systolic:diastolic ratio decreased from a mean (SD) of 2.4 (0.42) to 2.26 (0.38) (P = 0.049). There were no significant changes in the uteroplacental systolic:diastolic ratios. These results were compared with those from a control group in which no statistically significant changes in maternal and fetal systolic:diastolic ratios or heart rates were observed. The application of a pulse correction factor to standardize the data to fixed maternal and fetal heart rates had little effect on the significance of the findings. Extradural block in normal pregnant women during late gestation was associated with a small reduction in umbilical artery systolic:diastolic ratios, suggesting a decrease in downstream fetoplacental vascular resistance.


Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications.
Advanced liver fibrosis is an important predictor of liver disease progression and mortality, and current guidelines recommend screening for complications of cirrhosis once patients develop F3 fibrosis. Our study compared liver disease progression and survival in patients with stage 3 (F3) and stage 4 (F4) fibrosis on liver biopsy. Retrospective study of patients with F3 or F4 on liver biopsy followed for development of liver disease complications (variceal bleeding, ascites, and hepatic encephalopathy); hepatocellular carcinoma, and survival (overall and transplant free survival). Of 2488 patients receiving liver biopsy between 01/02 and 12/12, a total of 294 (171 F3) were analyzed. Over a median follow up period of 3 years, patients with F4 (mean age 53 years, 63% male) compared to F3 (mean age 49 years, 43% male) had higher five year cumulative probability of any decompensation (38% vs. 14%, p<0.0001), including variceal bleed (10% vs. 4%, p = 0.014), ascites (21% vs. 9%, p = 0.0014), and hepatic encephalopathy (14% vs. 5%, p = 0.003). F4 patients also had lower overall 5-year survival (80% vs. 93%, p = 0.003) and transplant free survival (80% vs. 93%, p = 0.002). Probability of hepatocellular carcinoma in 5 years after biopsy was similar between F3 and F4 (1.2% vs. 2%, p = 0.54). Compared to F4 stage, patients with F3 fibrosis have decreased risk for development of liver disease complications and better survival. Prospective well designed studies are suggested with large sample size and overcoming the limitations identified in this study, to confirm and validate these findings, as basis for modifying guidelines and recommendations on follow up of patients with advanced fibrosis and stage 3 liver fibrosis.