[Structural and enzymatic disorganization of biological membranes in rat liver cells in thermal burns].
Permeability of hepatocyte cell membrane was studied from the release into blood of hepatospecific enzymes and from 5'-nucleotidase activity in plasma membranes. A study was also made of membrane permeability of mitochondria, lysosomes and microsomes in liver cells of burnt rats from the level of non-sedimented activity and activity of malate dehydrogenase, succinate dehydrogenase, cathepsin D and glucose-6-phosphatase in appropriate organelles. Permeability of cell and lysosomal membranes was demonstrated to be disordered within the first hours after burn. One day after burn generalized disturbance of membrane permeability in the cell was observed, followed by the release into cytosol of organelles template enzymes and a decrease in the activity of membrane-bound enzymes in these organelles. The alterations persisted during 7 days of observation.


Addressing a gap: a qualitative analysis of Scotland's Drowning and Incident Review process.
Drowning is a leading cause of fatalities worldwide and Scotland carries a disproportionate number of drownings compared with its UK neighbours. Drowning data captured in Scotland are often incomplete and the Drowning and Incident Review (DIR) is a new process designed to help improve the capture of data and help inform future preventative measures. The aim of this study was to explore the perspectives and views of key stakeholders on the facilitators and barriers of implementing the DIR as well as areas for its future sustainability. A qualitative approach was used with in-depth interviews using key participants. Participants were identified using purposive sampling, through use of a stakeholder analysis. Participants watched a hypothetical DIR and then participated in a semistructured interview. Questions focused on DIR facilitators, barriers and areas for future sustainability. Qualitative data were then analysed using thematic analysis. A total of 14 participants took part in the study. Results found: three facilitator themes (addresses a gap, design of DIR, safe space), four barrier themes (representation, resource, legal concerns, control concerns) and four areas for future sustainability (the voluntary nature, framework agreement, political prioritisation and the human element). These themes were then discussed within this paper in relation to findings from research on similar review processes. The research was the first of its kind and the findings are therefore extremely important to provide a first exploration and insight into facilitators and barriers of the DIR as well as areas for its future sustainability.


[Sulfonylurea-induced hypoglycemia. An iatrogenic and potentially fatal condition].
Sulfonylureas are the most frequently used peroral antidiabetic drugs in Norway. Five cases of serious sulfonylurea-induced hypoglycemia are described. In one of these cases glibenklamid-induced hypoglycemia was thought to be the direct cause of death. A review of the literature indicates that glibenclamide induces more frequent and serious hypoglycemias than other sulfonylureas do. The author discusses the possible mechanisms behind these differences, and the conditions predisposing to sulfonylurea-induced hypoglycemia. It is recommended to check blood glucose whenever a patient's diagnosis has not been adequately clarified.


A patient with Werner's syndrome and erythroleukemia: just coincidence?
Werner's syndrome is a rare clinical entity and approximately 150 cases have been reported in the medical literature. Werner's syndrome, inherited by autosomal recessive transmission, is characterized primarily by a short stature, premature greying and balding, trophic ulceration of the legs, diabetes mellitus and hypogonadism. These features combine to present a picture of adult progeria. In this brief report we describe a 51-year-old Bedouin male with Werner's syndrome, diagnosed as erythroleukemia (AML-6), and presenting as acute pancytopenia. The patient died two months after diagnosis. This is a rare case of erythroleukemia in a patient with Werner's syndrome. We survey current knowledge of the cytogenetic pathogenesis of Werner's syndrome and erythroleukemia, and attempt to explain the possible link between these two rare syndromes.


Exploring Host-Microbiome Interactions using an in Silico Model of Biomimetic Robots and Engineered Living Cells.
The microbiome's underlying dynamics play an important role in regulating the behavior and health of its host. In order to explore the details of these interactions, we created an in silico model of a living microbiome, engineered with synthetic biology, that interfaces with a biomimetic, robotic host. By analytically modeling and computationally simulating engineered gene networks in these commensal communities, we reproduced complex behaviors in the host. We observed that robot movements depended upon programmed biochemical network dynamics within the microbiome. These results illustrate the model's potential utility as a tool for exploring inter-kingdom ecological relationships. These systems could impact fields ranging from synthetic biology and ecology to biophysics and medicine.


Selection of high-avidity CD8 T cells correlates with control of hepatitis C virus infection.
Both strong antigenic avidity and acquisition of proper effector functions contribute to the efficacy of antiviral T cell responses. To correlate these parameters with the outcome of hepatitis C virus (HCV) infection, we characterized HCV-specific CD8 T cell lines isolated after immunomagnetic sorting of peripheral blood mononuclear cells from human leukocyte antigen A*02 (HLA-A*02) individuals with various HCV serological statuses, using recombinant HLA-A*0201 multimers loaded with three immunodominant HCV genotype 1-derived epitopes. CD8 T cells specific for these three epitopes were derived from most HLA-A*0201 individuals, regardless of their HCV serology or clinical outcome. Donors recovered from genotype 1 HCV infection were enriched for high-avidity T cells with enhanced interferon gamma (IFN-gamma), tumor necrosis factor alpha, and cytotoxic T lymphocyte responses, when compared with seronegative donors and seropositive patients infected with irrelevant HCV genotypes. Patients chronically infected with genotype 1 strain yielded almost exclusively low-avidity T cells, whose hyporesponsiveness was primarily attributable to low T cell receptor (TCR) avidity rather than intrinsic functional defects. This study suggests that strong IFN-gamma responses associated with efficient viral clearance primarily result from Ag-driven selection/survival of HCV-specific T cells expressing high-avidity TCR. It also suggests a link between the quality of the initial HCV-specific T cell repertoire and susceptibility to chronic infection.


Locomotor characteristics of horses with navicular disease.
To determine whether force-plate evaluation of horses with navicular disease would reveal an abnormal gait that persists despite loss of sensation to the palmar foot region, which may predispose such horses to navicular disease. 17 clinically normal Thoroughbreds and 8 Thoroughbreds with navicular disease. Data on ground reaction forces were obtained in trotting horses, using a force plate. Force-time curve variables for clinically normal horses were derived from 4 points at the beginning and 4 points at the end of the vertical and craniocaudal horizontal plots. Principal component analysis was undertaken separately on beginning-of-stride and end-of-stride data, and the first 2 components were represented graphically. Rotation matrices were applied to equivalent data for horses with navicular disease before and after disruption of sensation by administration of a palmar digital nerve blockade. Prior to nerve block, horses with navicular disease differed significantly from normal horses for beginning-of-stance phase and end-of-stance phase variables. After nerve block, horses with navicular disease maintained the same significant differences from clinically normal horses only for variables at the beginning-of-stance phase. Horses with navicular disease have abnormal limb-loading force patterns that are not altered by loss of sensation in the palmar region. These abnormal patterns were detected in a horse without navicular disease. Some horses are predisposed to navicular disease as a result of an inherent abnormal gait pattern. Analysis of gait patterns could be used for detection and appropriate management of horses susceptible to development of navicular disease.


Opioid prescribing habits of physicians in Kwara State, Nigeria.
Although opioid analgesics are effective in the treatment of moderate to severe acute, cancer and chronic non-malignant pains, they are under-prescribed in Nigeria. The objective of this study was to assess the prescription pattern of opioids among physicians in a north central State, Nigeria.. This was a descriptive cross sectional study. The study was conducted at the International Association for the Study of Pain (IASP)-sponsored workshops on pain and palliative care at the University of Ilorin Teaching Hospital, Ilorin, Nigeria. These were physicians at the monthly workshops organized by the Pain and Palliative Care Unit of the hospital between August 2011 and July, 2012. Pre-tested semi-structured questionnaires were used to obtain responses to questions on pain management including opioids utilization in the various hospitals of the 114 participants. The main outcome measure was opioid prescription by the participants. Out of the 114 questionnaires distributed, 113 were returned with complete information giving a response rate of 99.1%. The mean age of the respondents was 42.0±10.8 years. Although 97.3% of the respondents reported that pain was a frequent complaint in their practice, 69.5% of those who reported seeing patients with moderate to severe pain on a daily basis rarely or never prescribed opioid analgesics. The reasons given for poor opioid prescription were fear of respiratory depression (86.8%), fear of addiction (85.1%) and non-availability (28.9%). Opioid prescription rate for patients with moderate-severe pain is low possibly due to myths and misconceptions about their adverse effects. International Association for the Study of Pain (IASP) Initiative for Improving Pain Education Grant awarded to Dr. K.W. Wahab in 2011.


Optimal green (red-free) digital imaging of conjunctival vasculature.
Green illumination is commonly used to image vessels of the retina and conjunctiva. The purpose was to derive the best optical set-up for imaging vessels of the conjunctiva. The concept of exposure density was used to predict a digital camera response to imaging vessels on a scleral background. Practical verification was performed to verify vessel contrast because of the difficulties in measuring the spectral components of the imaging system, such as the spectral reflectivity of vessels and sclera. Images of the same conjunctiva were repetitively taken through different coloured filters, using the Nikon FS-2 photo slit-lamp and recorded on different coloured channels of the Kodak DCS 100 digital camera. Gaussian blurred tubular models were fitted to densitometric profiles across three vessels from each image, allowing vessel contrast and width to be objectively measured. These measures were compared using different optical set-ups. Optimal exposure density calculations and vessel contrast was obtained with the xenon light source filtered with Wratten 99 (green) and Wratten 96 (neutral density, 0.2 log units) gelatine absorption filters using the green channel of the digital camera. This image set-up was associated with a 46% (99% CI 43-51%) to 64% (99% CI 58-72%) increase in contrast compared with vessels imaged without filtration, using the combined colour channel of the digital camera. Although differences in vessel widths resulted, absolute differences were marginal. With the increased use of digital imaging, and the need for image processing of vascular networks, image optimisation is beneficial. This study verified the optimal set-up for non-invasively imaging vessels of the bulbar conjunctiva.


Long term outcomes of cataract surgery in severe and end stage primary angle closure glaucoma with controlled IOP: a retrospective study.
To investigate the long term surgical outcomes of cataract surgery in severe and end stage glaucoma patients with preoperative intraocular pressure less than 21 mmHg, and to detect the associated factors. A retrospective study of primary angle closure glaucoma patients was conducted on who underwent cataract surgery or combined with goniosynechialysis from March 2015 to April 2018. Main outcome measures were visual acuity, intraocular pressure, number of glaucoma medications and complications. Sixteen patients (19 eyes) were included. The mean age was 64.89 ± 11.68 years and the mean followed up duration was 21.89 ± 7.85 months. The final visual acuity was significantly improved from 0.69 ± 0.55 to 0.46 ± 0.52 logMAR, within 12 (63.2%) eyes improved, 4 (21.1%) eyes kept unchanged, and 3 (15.8%) eyes reduced. Linear regression analysis indicated that higher mean deviation, higher visual field index and lower glaucoma stage associated with better final visual acuity (r = - 0.511, r = - 0.493, r = 0.537 respectively). Moreover, the final number of medications were reduced from 1.26 ± 0.99 to 0.26 ± 0.56 (p < 0.01). The mean intraocular pressure was not significantly reduced with the final IOP of 14.48 ± 3.74 mmHg (p = 0.97). While the eyes with intraocular pressure above 15 mmHg was decreased to 6 (31.6%) eyes compared to 10 (52.6%) eyes at baseline. Moreover, the number of eyes free of medications was increased from 4 (21.1%) preoperatively to 15 (78.9%) eyes postoperatively. Final visual acuity was significantly improved in the severe and end stage primary angle closure glaucoma patients and the number of eyes came off medications increased by 57.8% after cataract surgery. Preoperatively, the glaucoma stage, mean deviation and visual field index are important parameters to predict the final visual acuity after cataract surgery.


An overview of the perspectives on experimental models and new therapeutic targets in giant cell arteritis.
Giant cell arteritis (GCA) is the most frequent systemic vasculitis occurring in adults older than 50 years, and aortitis is described in 40% to 80% of patients. The treatment relies on corticosteroids, but it is complicated by high rates of relapses and adverse effects and may be unable to completely inhibit aortic inflammation. Moreover, most of the current data regarding the pathophysiology of GCA have been obtained from bioassays using blood and temporal arteries, as well as histological analyses of temporal arteries and very few aortic aneurysms from patients with GCA. The limitations of these analyses prevent researchers from determining the implications of specific targets and studying the effects of targeted treatments. Several experimental models have been developed, but to date, a perfect model is not available for GCA, particularly for studies of large-vessel vasculitis. The review focuses on the perspectives on experimental models and new therapeutic targets in giant cell arteritis.


Analysis of synaptic proteins in the cerebrospinal fluid as a new tool in the study of inborn errors of neurotransmission.
In a few rare diseases, specialised studies in cerebrospinal fluid (CSF) are required to identify the underlying metabolic disorder. We aimed to explore the possibility of detecting key synaptic proteins in the CSF, in particular dopaminergic and gabaergic, as new procedures that could be useful for both pathophysiological and diagnostic purposes in investigation of inherited disorders of neurotransmission. Dopamine receptor type 2 (D2R), dopamine transporter (DAT) and vesicular monoamine transporter type 2 (VMAT2) were analysed in CSF samples from 30 healthy controls (11 days to 17 years) by western blot analysis. Because VMAT2 was the only protein with intracellular localisation, and in order to compare results, GABA vesicular transporter, which is another intracellular protein, was also studied. Spearman's correlation and Student's t tests were applied to compare optical density signals between different proteins. All these synaptic proteins could be easily detected and quantified in the CSF. DAT, D2R and GABA VT expression decrease with age, particularly in the first months of life, reflecting the expected intense synaptic activity and neuronal circuitry formation. A statistically significant relationship was found between D2R and DAT expression, reinforcing the previous evidence of DAT regulation by D2R. To our knowledge, there are no previous studies on human CSF reporting a reliable analysis of these proteins. These kinds of studies could help elucidate new causes of disturbed dopaminergic and gabaergic transmission as well as understanding different responses to L-dopa in inherited disorders affecting dopamine metabolism. Moreover, this approach to synaptic activity in vivo can be extended to different groups of proteins and diseases.


Selected socio-economic features and the prevalence of peptic ulcer among Polish rural population.
The aim of the study was to determine the relationship between the prevalence of peptic ulcer and the occurrence of selected socio-economic features among Polish rural population. The study was conducted based on the all- Polish representative study of the state of health of rural population, and covered a group of 6,512 rural inhabitants aged 20-64 -- 3,107 males and 3,405 females selected by two-stage stratified sampling. Peptic ulcer was diagnosed in 348 people in the study (5.3%): 250 males (8.0%) and 98 females (2.9%). Duodenal ulcer occurred in 3.2% of people examined, followed by gastric ulcer -- 1.2%, duodenal and gastric ulcer -- 0.2%, and 0.9% of patients underwent surgical procedures due to peptic ulcer. Peptic ulcer occurred more frequently among people with a lower education level (lack of education -- 7.8%, elementary school education -- 5.8%), compared to those with higher education categories (elementary vocational -- 4.9%, secondary school and college -- 3.7%). The disease was more often diagnosed among respondents who described their material standard as poor (7.7%), compared to those who described this standard as good (4.0%). Among people who considered their material standard as poor, gastric ulcer was noted more frequently than duodenal ulcer. A correlation was observed between the prevalence of peptic ulcer and such socio-economic features of Polish rural population as the level of education and material standard.


Referral patterns of children with glaucoma and their caretakers in Northern Tanzania.
To describe the referral patterns of children with primary childhood glaucoma (PCG) or secondary childhood glaucoma (SCG) and their presenting symptoms in Northern Tanzania. A retrospective observational study of children <17y with PCG or SCG who were referred to Kilimanjaro Christian Medical Centre (KCMC) Eye Department between 2000 and 2013 was conducted. Presenting symptoms, age at presentation, place of origin, distance to hospital, type of glaucoma, visual acuity, optic disc appearance (vertical cup-to-disc ratio) and type of referral were described. Seventy patients with PCG and 27 patients with SCG were included in the study. Median age at first presentation was 1y in the PCG group (range 0-16y) and 9y in the SCG group (range 1-15y). In both groups around 87% of the children presented already with low vision (logMAR>0.48, better eye). Most of the children (60%) and their caretakers presented on their own initiative, while 24% were sent by different general health cadres and 16% by eye care professionals. Buphthalmos was the main symptom mentioned as a trigger for presentation. The study shows that most of the children presented late resulting in advanced stages of glaucoma at the time of initiation of treatment. The majority attended the referral eye department on their own initiative with buphthalmos being the most commonly described symptom. Awareness creation among caretakers of children, general health and eye care providers, ideally embedded in general child health promotion activities, is needed to increase and accelerate referrals.


Cooperative photoredox catalysis.
Visible-light photoredox catalysis has been experiencing a renaissance in response to topical interest in renewable energy and green chemistry. The latest progress in this area indicates that cooperation between photoredox catalysis and other domains of catalysis could provide effective results. Thus, we advance the concept of cooperative photoredox catalysis for organic transformations. It is important to note that this concept can bridge the gap between visible-light photoredox catalysis and other types of redox catalysis such as transition-metal catalysis, biocatalysis or electrocatalysis. In doing so, one can take advantage of the best of both worlds in establishing organic synthesis with visible-light-induced redox reaction as a crucial step.


Molecular dynamics simulations of SrTiO3 thin-film growth from cluster deposition.
We use classical molecular dynamics simulations to examine the deposition of SrTiO(3) stoichiometric clusters on (001) SrTiO(3). The simulations consider the deposition of clusters that consist of one, two, three or four stoichiometric units that have incident energies of 1.0 eV/atom. Two types of beam compositions are considered: those that are comprised of mono-sized clusters and those that are comprised of mixed-sized clusters along with individual SrO and TiO(2) particles. The results are analyzed to determine the effect of surface termination layer (SrO versus TiO(2)), cluster size and beam composition on the resulting thin-film structure. The simulations indicate that termination layer and beam composition have an impact on the resulting film structure with mixed-beam composition and TiO(2) termination yielding films with a structure similar to that of bulk STO.


Cancer informatics analysis indicates high CHAC2 associated with unfavorable prognosis in breast cancer.
Breast cancer remains the most commonly diagnosed cancer worldwide and exhibits a poor prognosis. The induction of genetic changes deregulates several genes that increase the disposal towards this life-threatening disease. CHAC2, a member of the glutathione degrading enzyme family has been shown to suppress gastric and colorectal cancer progression, however, the expression of CHAC2 in breast cancer has not been reported. We did an analysis of CHAC2 expression in breast cancer patients from various online tools like UALCAN, GEPIA2, GENT2, TIMER2, and bcGenExminer v4.8. Further, we used the Kaplan-Meier plotter to establish the significance of CHAC2 in BC patient survival and prognosis while TISIDB and TIMER databases were used to investigate the filtration of immune cells. The results showed that CHAC2 levels were high in breast cancer patients and elevated CHAC2 was associated with low overall survival. Taken together, the results of the present study show that like its paralog CHAC1, CHAC2 may also be an important biomarker and could have a potential therapeutic implication in breast cancer.


Nanovaccines for Advancing Long-Lasting Immunity against Infectious Diseases.
Infectious diseases, particularly life-threatening pathogens such as small pox and influenza, have substantial implications on public health and global economies. Vaccination is a key approach to combat existing and emerging pathogens. Immunological memory is an essential characteristic used to evaluate vaccine efficacy and durability and the basis for the long-term effects of vaccines in protecting against future infections; however, optimizing the potency, improving the quality, and enhancing the durability of immune responses remains challenging and a focus for research involving investigation of nanovaccine technologies. In this review, we describe how nanovaccines can address the challenges for conventional vaccines in stimulating adaptive immune memory responses to protect against reinfection. We discuss protein and nonprotein nanoparticles as useful antigen platforms, including those with highly ordered and repetitive antigen array presentation to enhance immunogenicity through cross-linking with multiple B cell receptors, and with a focus on antigen properties. In addition, we describe how nanoadjuvants can improve immune responses by providing enhanced access to lymph nodes, lymphnode targeting, germinal center retention, and long-lasting immune response generation. Nanotechnology has the advantage to facilitate vaccine induction of long-lasting immunity against infectious diseases, now and in the future.


Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger's disorder: a 14-week, prospective, open-label study.
The aim of this study was to determine the effectiveness and tolerability of aripiprazole for irritability in pervasive developmental disorder not otherwise specified (PDD-NOS) and Asperger's disorder. This is a 14-week, prospective, open-label investigation of aripiprazole in 25 children and adolescents diagnosed with PDD-NOS or Asperger's disorder. Primary outcome measures included the Clinical Global Impressions-Improvement (CGI-I) scale and the Irritability subscale of the Aberrant Behavior Checklist (ABC-I). Twenty-five subjects, ages 5-17 years (mean 8.6 years) received a mean final aripiprazole dosage of 7.8 mg/day (range 2.5-15 mg/day). Full-scale intelligence quotient (IQ) scores ranged from 48 to 122 (mean 84). Twenty-two (88%) of 25 subjects were responders in regard to interfering symptoms of irritability, including aggression, self-injury, and tantrums, with a final CGI-I of 1 or 2 (very much or much improved) and a 25% or greater improvement on the ABC-I. The final mean CGI-I was 1.6 (p <or= 0.0001). ABC-I scores ranged from 18 to 43 (mean 29) at baseline, whereas scores at week 14 ranged from 0 to 27 (mean 8.1) (p <or= 0.001). Aripiprazole was well tolerated. Mild extrapyramidal symptoms (EPS) were reported in 9 subjects. Age- and sex-normed body mass index (BMI) increased from a mean value of 20.3 at baseline to 21.1 at end point (p <or= 0.04). Prolactin significantly decreased from a mean value of 9.3 at baseline to 2.9 at end point (p <or= 0.0001). No subject exited the study due to a drug-related adverse event. These preliminary data suggest that aripiprazole may be effective and well tolerated for severe irritability in pediatric patients with PDD-NOS or Asperger's disorder. Larger-scale placebo-controlled studies are needed to elucidate the efficacy and tolerability of aripiprazole in this understudied population.


Protocol for the development and validation procedure of the managing the link and strengthening transition from child to adult mental health care (MILESTONE) suite of measures.
Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017.


Herbivory enhances the resistance of mangrove forest to cordgrass invasion.
The biotic resistance hypothesis proposes that biotic interactions, such as competition and herbivory, resist the establishment and spread of non-native species. The relative and interactive role of competition and herbivory in resisting plant invasions, however, remains poorly understood. We investigated the interactive role of competition and herbivory (by the native rodent Rattus losea) in resisting Spartina alterniflora (cordgrass) invasions into mangrove forests. In southern China, although exotic cordgrass numerically dominates intertidal mudflats and open gaps in mangrove forests, intact forests appear to be highly resistant to cordgrass invasion. A field transplant and rodent exclusion experiment showed that while the impact of rodent grazing on cordgrass was weak on mangrove forest edges and open mudflats, rodent grazing strongly suppressed cordgrass in mangrove understory habitats. A greenhouse experiment confirmed a synergistic interaction between grazing and light availability (a proxy for mangrove shading and light competition) in suppressing cordgrass establishment, with the strongest impacts of grazing in low light conditions that likely weakened cordgrass to survive and resprout. When both were present, as in mangrove understory habitats, grazing and low light acted in concert to eliminate cordgrass establishment, resulting in resistance of mangrove forests to cordgrass invasion. Our results reveal that grazing by native herbivores can enhance the resistance of mangrove forests to cordgrass invasion in southern China, and suggest that investigating multifactor interactions may be critical to understanding community resistance to exotic invasions.


Sleep-disordered breathing in cystic fibrosis.
Sleep-disordered breathing (SBD) is an under recognized comorbidity in the cystic fibrosis (CF) population across the lifespan. Nocturnal hypoxemia, obstructive sleep apnea, and nocturnal hypoventilation are respiratory abnormalities that occur commonly during sleep in patients with lung disease, and have deleterious consequences to the quality of life in people with CF. Effective screening for these abnormalities is needed to allow for timely initiation of treatment, which has been reported to be efficacious. Lack of treatment leads to worsened pulmonary, cardiovascular, and metabolic outcomes in patients. In this review, we give an overview of SBD for the CF clinician, including prevalence, treatment, and suggestions for future research. We strongly encourage the CF community to incorporate evaluation for SBD in CF clinical care so that outcomes for the subset of the CF patients with comorbid SBD improve.


Strategic allocation of ejaculates by male Adélie penguins.
Sperm competition theory suggests that males should strategically allocate sperm to those females that will bring them the best possible genetic returns. Although males of a number of species of insects and fishes have been shown to allocate sperm strategically, we provide, to our knowledge, the first evidence that an avian species is also capable of allocating ejaculates. Male Adélie penguins (Pygoscelis adeliae) are more likely to transfer sperm during extra-pair copulations (EPCs) than during pair copulations. We investigated the question of how males allocate ejaculates within the constraints of limited sperm availability and found (i) that males that engaged in EPC attempts ejaculated less often when copulating with their social partner than males that made no EPC attempts, and (ii) that there was no difference between males that were involved in failed EPC attempts and those that were involved in successful EPCs in the proportion of copulations that resulted in sperm transfer. These results indicate that males achieve strategic allocation of sperm within the constraints of limited sperm availability by withholding ejaculates from their social partners.


The Madrid triple classification of dry eye.
From the clinical point of view, there are many etiologic causes, several combinations of anatomo-pathologic manifestations, and different grades of severity of Dry Eye diseases in the dysfunctional tear film syndrome. The dacryologist doctor must recognize these three parameters, quantify them, and establish the most appropriate treatment. The present triple classification has been elaborated for this purpose. First, there is an etiologic distribution in ten groups: age-related, hormonal, pharmacologic, immunopathic, hyponutritional, dysgenetic, inflammatory, traumatic, neurodeprivative, and tantalic. Each of these groups comprise many variants. Second, there is an anatomo-pathologic classification named ALMEN classification from the acronym of aquodeficiency, lipodeficiency, mucodeficiency, epitheliopathy, and non-ocular exocrine affectations. Finally, there is a severity classification in five grades: subclinical (symptoms only when overexposure), mild (habitual symptoms), moderate (symptoms plus reversible signs), severe (symptoms plus permanent signs), and disabling (all the above, plus visual discapacity).


The influence of dietary inositol on glyceride composition and synthesis in livers of rats fed different fats.
The effect of inositol supplementation on the composition and biosynthesis of glycerides in the livers of rats fed diets containing fats with differing fatty acid composition was investigated. The dietary fats employed in these studies included corn oil, Tower rapeseed oil (RSO), partially hydrogenated soybean oil (SBO), and tallow. No significant influence of inositol on hepatic triglyceride levels was found in animals fed corn oil and SBO whereas inositol deficiency caused a two-and four-fold elevation in triglyceride concentrations in the RSO and tallow groups, respectively. The level of total fatty acids in phospholipid (mg/g liver) was slightly decreased in all fat groups and included a notable decrease in the concentration of monoenoic (18:1) and dienoic (18:2) acids in the RSO and tallow groups. Dietary inositol had a minor effect on the weight % of individual fatty acids in hepatic triglycerides. Inositol-deficient animals showed an increased rate of glyceride synthesis from glycerol-3-phosphate (glycerol-3-P) regardless of the type of fat that was fed. The results indicate that triglyceride accumulation in liver under conditions of inositol deficiency is not only produced with highly saturated fats since the most unsaturated of all the fats tested, Tower RSO, also gave the syndrome. The results further suggested that the accumulation of hepatic lipid due to the feeding of inositol-deficient diets likely arises from their effect on specific metabolic site(s) other than the conversion of glycerol-3-P into lipid.


SOD mimetics: a novel class of androgen receptor inhibitors that suppresses castration-resistant growth of prostate cancer.
Advanced prostate cancer is the second leading cause of cancer-related deaths among American men. The androgen receptor (AR) is vital for prostate cancer progression, even in the face of castrate levels of serum testosterone following androgen ablation therapy, a mainstay therapy for advanced prostate cancer. Downregulation of superoxide dismutase 2 (SOD2), a major intracellular antioxidant enzyme, occurs progressively during prostate cancer progression to advanced states and is known to promote AR activity in prostate cancer. Therefore, this study investigated the effects of SOD mimetics on AR expression and function in AR-dependent LNCaP, CWR22Rv1, and LAPC-4AD prostate cancer cells. Treatment with Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), a SOD mimetic, not only lowered cellular superoxide levels but also concomitantly attenuated AR transcriptional activity and AR target gene expression in a dose- and time-dependent manner, in the presence and absence of dihydrotestosterone, the major endogenous AR agonist. Inhibition of AR by Tempol was mediated, in large part, by its ability to decrease AR protein via increased degradation, in the absence of any inhibitory effects on other nuclear receptors. Inhibitory effects of Tempol on AR were also reproducible with other SOD mimetics, MnTBAP and MnTMPyP. Importantly, effects of Tempol on AR function were accompanied by significant in vitro and in vivo reduction in castration-resistant prostate cancer (CRPC) survival and growth. Collectively, this study has shown for the first time that SOD mimetics, by virtue of their ability to suppress AR function, may be beneficial in treating the currently incurable CRPC, in which SOD2 expression is highly suppressed.


[Antibiotic-associated colitis--the dark side of antibiotic therapy].
Intestinal side effects after antibiotic therapy are frequent. Mostly, harmless diarrhea disappears after cessation of therapy without inducing colitis; however, changing of the intestinal flora sometimes leads to colonization of the colon by toxin-producing strains of Clostridium difficile, inducing sometimes severe pseudomembranous colitis. A rapid correct diagnosis by anamnesis, clinical signs, endoscopical aspect and demonstration of toxin in the stool allows an efficient treatment. The therapeutic modalities, especially in recurrency, are delineated. In addition, the unusual and etiologically still unknown illness of penicillin-induced segmental hemorrhagic colitis will be discussed as well.


Molecular pathology in basal cell cancer with p53 as a genetic marker.
Human basal cell cancer (BCC) has unique growth characteristics with virtual inability to metastasize. We investigated clonality and genetic progression using p53 mutations as marker. Sampling was done through microdissection of frozen immunohistochemically stained 16 microm slices of tumors. From 11 BCC tumors 78 samples were analysed. Direct DNA sequencing of exons 5-8 was performed, haplotypes were determined after cloning of p53 exons and loss of heterozygosity (LOH) ascertained by microsatellite analysis. All tumors had p53 mutations and in a majority both p53 alleles were affected, commonly through missense mutations. Microdissection of small parts (50-100 cells) of individual tumors showed BCC to be composed of a dominant cell clone and prone to genetic progression with appearance of subclones with a second and even third p53 mutation. Samples from normal immunohistochemically negative epidermis always showed wild type sequence, except for a case of previously unknown germline p53 mutation. Our analysis also included p53 immunoreactive patches i.e. morphologically normal epidermis with a compact pattern of p53 immunoreactivity. Mutations within those were never the same as in the adjacent BCC. This detailed study of only one gene thus uncovered a remarkable heterogeneity within a tumor category famous for its benign clinical behavior.


Study of the carbohydrate content of mucus glycoproteins from normal and diseased colons.
1. Mucus samples obtained from colectomy colons from 10 patients with ulcerative colitis and four patients with Crohn's disease of the colon, together with samples from 10 normal postmortem colons, have been studied. 2. Two glycoprotein fractions were isolated from mucosal scrapings by gel-permeation chromatography. The high-molecular-weight fraction consisted largely of mucus glycoproteins and was further purified to the glycopolypeptides. The low-molecular-weight fraction contained a glycoprotein with a high mannose content. The carbohydrate content of both the mucus glycoprotein and glycopolypeptide fractions were significantly reduced in active colitis. 3. Oligosaccharides were prepared from the mucus glycoprotein material. In the normal material more than half the units contained eight or more monosaccharide residues, whereas in the disease material the bulk of the units were smaller than this.


Clinical outcome and predictive factors of recurrence among patients with Kikuchi's disease.
To evaluate the clinical outcome and predictive factors of recurrence among patients with Kikuchi's disease. Between January 2001 and December 2006, all patients with Kikuchi's disease were included in the study. Data were collected on co-morbidities, clinical manifestations, and ultrasound/laboratory findings, and the differences were compared between recurrent disease and non-recurrent disease groups. The study included 102 patients with a mean age of 26.7 years. Among these patients, three developed systemic lupus erythematosus during the follow-up period, while two cases were later associated with tuberculosis. Eight patients (7.8%) experienced early relapse and 13 (12.7%) showed late recurrence. Patients with recurrent episodes were more likely to have fever and fatigue with extranodal involvement. Compared to the non-recurrent cases, recurrent cases remained symptomatic for a rather longer duration. The positive rate of the fluorescence anti-nuclear antibody (FANA) test was significantly higher in the recurrent disease group compared to the non-recurrent disease group. Kikuchi's disease took a self-limiting clinical course in most cases, but the recurrence rate found in the present study was higher than that of previous reports. Kikuchi's disease might be a phenotype of diverse disease entities. The prognosis is different according to the underlying cause. The FANA test would be useful in predicting recurrence.


Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma.
Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. The efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma require further assessment. We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients (12 to 80 years of age) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The primary end point was the annualized rate of asthma exacerbations over a period of 52 weeks. This end point was also assessed in patients with baseline blood eosinophil counts of less than 300 cells per microliter. Secondary end points included the forced expiratory volume in 1 second (FEV1) and scores on the Asthma Control Questionnaire-6 (ACQ-6; range, 0 [no impairment] to 6 [maximum impairment]), Asthma Quality of Life Questionnaire (AQLQ; range, 1 [maximum impairment] to 7 [no impairment]), and Asthma Symptom Diary (ASD; range, 0 [no symptoms] to 4 [worst possible symptoms]). Overall, 1061 patients underwent randomization (529 were assigned to receive tezepelumab and 532 to receive placebo). The annualized rate of asthma exacerbations was 0.93 (95% confidence interval [CI], 0.80 to 1.07) with tezepelumab and 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; P<0.001). In patients with a blood eosinophil count of less than 300 cells per microliter, the annualized rate was 1.02 (95% CI, 0.84 to 1.23) with tezepelumab and 1.73 (95% CI, 1.46 to 2.05) with placebo (rate ratio, 0.59; 95% CI, 0.46 to 0.75; P<0.001). At week 52, improvements were greater with tezepelumab than with placebo with respect to the prebronchodilator FEV1 (0.23 vs. 0.09 liters; difference, 0.13 liters; 95% CI, 0.08 to 0.18; P<0.001) and scores on the ACQ-6 (-1.55 vs. -1.22; difference, -0.33; 95% CI, -0.46 to -0.20; P<0.001), AQLQ (1.49 vs. 1.15; difference, 0.34; 95% CI, 0.20 to 0.47; P<0.001), and ASD (-0.71 vs. -0.59; difference, -0.12; 95% CI, -0.19 to -0.04; P = 0.002). The frequencies and types of adverse events did not differ meaningfully between the two groups. Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo. (Funded by AstraZeneca and Amgen; NAVIGATOR ClinicalTrials.gov number, NCT03347279.).


TSG-6 produced by hMSCs delays the onset of autoimmune diabetes by suppressing Th1 development and enhancing tolerogenicity.
Genetic and immunological screening for type 1 diabetes has led to the possibility of preventing disease in susceptible individuals. Here, we show that human mesenchymal stem/stromal cells (hMSCs) and tumor necrosis factor-α-stimulated gene 6 (TSG-6), a protein produced by hMSCs in response to signals from injured tissues, delayed the onset of spontaneous autoimmune diabetes in NOD mice by inhibiting insulitis and augmenting regulatory T cells (Tregs) within the pancreas. Importantly, hMSCs with a knockdown of tsg-6 were ineffective at delaying insulitis and the onset of diabetes in mice. TSG-6 inhibited the activation of both T cells and antigen-presenting cells (APCs) in a CD44-dependent manner. Moreover, multiple treatments of TSG-6 rendered APCs more tolerogenic, capable of enhancing Treg generation and delaying diabetes in an adoptive transfer model. Therefore, these results could provide the basis for a novel therapy for the prevention of type 1 diabetes.


Shared features in the pathobiology of babesiosis and malaria.
The pathobiology of malaria has been extensively studied in humans but many questions remain, especially regarding fulminant disease associated with Plasmodium falciparum infection. Babesiosis, recognized since biblical times as an important disease of livestock and more recently as an emerging health problem in humans, is caused by related intraerythrocytic protozoa with a similar pathogenesis and clinical course. Recent studies of cytokine activation and erythrocyte cytoadherence in babesiosis and malaria have exploited these similarities to provide new insights into malaria pathobiology. Continued investigation of similarities and differences in the pathogenesis of babesiosis and malaria should lead to additional fundamental insights for both conditions.


An empirical examination of the environmental sustainability-influencing mechanisms of renewable energy: contextual evidence from Next Eleven countries.
Recognizing the environmental development-related commitments made by the Next Eleven countries at 26th Conference of Parties (COP26), this study scrutinizes the repercussions accompanying good democratic governance, renewable energy transition, economic growth, and the ratification of the Kyoto Protocol on carbon emission figures of these emerging nations. In this regard, the period of analysis considered spans from 1990 to 2018 while the econometric analyses involve application of both parametric and non-parametric panel data estimators. Among the key findings, firstly, the outcomes from the parametric estimation methods verify that establishing better democratic governance and undergoing renewable energy transition, both independently and jointly, curb carbon emission levels, while higher economic growth and the signing of the Kyoto Protocol are responsible for boosting emissions the Next Eleven countries. Secondly, the findings derived using the non-parametric methods reveal a great deal of heterogeneity when compared with the results obtained from the parametric analysis. Notably, better democratic governance is seen to reduce carbon emissions in less and moderately polluted. Next Eleven nations, while renewable energy transition curbs emissions only in the moderately and highly polluted ones. Additionally, these variables jointly inhibit emissions only in the Next Eleven nations that are moderately polluted. Besides, better democratic governance is observed to mediate the renewable energy transition-carbon emissions nexus only for the less-polluted Next Eleven nations, while the environmental impacts of economic growth and the signing of the Kyoto Protocol vary across different emission quantiles. Accordingly, relevant policies are recommended for helping the Next Eleven countries to comply with their pledges made at the COP26.


Estrogenic and cholinergic properties of the methanol extract of Ruellia praetermissa Sceinf. ex. Lindau (Acanthaceae) in female rats.
In search for alternative drugs with pharmacological profile to replace hormone replacement therapy, the effects of MeOH extract of Ruellia praetermissa on the uterus and gestation in rats was investigated. 350 mg/kg/day of extract from days 1-9, 1-17 and 9-17 respectively, resulted in increase of the number of implantation sites (56 to 64) and the percentage of implantation (68.6 +/- 2.7 to 90.5 +/- 0.5%). There was also an increase in body weight (1-9 and 1-17) followed by a slight decrease (154 +/- 15.5 to 125 +/- 10) in the body weight at term. The number and the mean value of corpora lutea per female decreased from 25.4 +/- 1.6 to 14.00 +/- 1.6. The extract produced dose-related contraction of the isolated uterine muscle in vitro comparable to ACh. Atropine in doses from 3.4 x 10(-6) to 3 x 10(-3) microM antagonized the response of the uterus to ACh at 2 microM. It induced an increase (0.03 +/- 0.002 to 0.34 +/- 0.001 g) of the uterine weight comparable to that produced by using 3 microM estradiol (0.03 +/- 0.001 to 0.35 +/- 0.005 g). It could therefore be postulated that this extract possesses estrogenic and possible cholinergic effects. The estrogenic effect could have been generated by plant sterols (beta-sitosterol and stigmasterol) and flavonoids (luteolin and apigenin) while cholinergic effect could be due to iridoid glycosides.


Platelet and leukocyte antibodies in autoimmune hemolytic anemia.
Platelet and leukocyte counts and leukocytotoxic and platelet antibodies were studied in 32 patients with autoimmune hemolytic anemia (AHA). Leukopenia was present in 59.4%, thrombocytopenia in 59.4% and leuko-thrombocytopenia in 40.5% of the cases. Specific antibodies for granulocytes were found in 81.3%, platelet antibodies in 90.6%. The AHA, leukopenia and thrombocytopenia generally presented a dissociated evolution and a different response to immunosuppressive treatment. The leukopenia of 2 and the thrombocytopenia of 6 patients appeared at variable time intervals after the AHA or the detection of leukocyte and platelet antibodies. Thrombocytopenic purpura was present in 6 patients, and in 2 of these since infancy. AHA may thus be a comples autoimmune syndrome that may involve leukocytes and platelets as well as erythrocytes, with synthesis of autoantibodies specific for different blood cells.


Range expansion and hybridization in Round Island petrels (Pterodroma spp.): evidence from microsatellite genotypes.
Historical records suggest that the petrels of Round Island (near Mauritius, Indian Ocean) represent a recent, long-distance colonization by species originating from the Atlantic and Pacific Oceans. The majority of petrels on Round Island appear most similar to Pterodroma arminjoniana, a species whose only other breeding locality is Trindade Island in the South Atlantic. Using nine microsatellite loci, patterns of genetic differentiation in petrels from Round and Trindade Islands were analysed. The two populations exhibit low but significant levels of differentiation in allele frequencies and estimates of migration rate between islands using genetic data are also low, supporting the hypothesis that these populations have recently separated but are now isolated from one another. A second population of petrels, most similar in appearance to the Pacific species P. neglecta, is also present on Round Island and observations suggest that the two petrel species are hybridizing. Vocalizations recorded on the island also suggest that hybrid birds may be present within the population. Data from microsatellite genotypes support this hypothesis and indicate that there may have been many generations of hybridization and back-crossing between P. arminjoniana and P. neglecta on Round Island. Our results provide an insight into the processes of dispersal and the consequences of secondary contact in Procellariiformes.


A Free-Market Environmentalist Enquiry on Spain's Energy Transition along with Its Recent Increasing Electricity Prices.
This paper analyzes the Spanish energy transition's general situation and its increasing electricity prices in recent years from a free-market environmentalist (FME) approach. We hypothesize and argue that high taxes, high government subsidies, and government industrial access restrictions breach private property rights, hindering Spain's renewable energy (RE) development. Our paper discovers that Spain's state-interventionist policies have increased the cost of the energy and power industries, leading to electricity prices remaining relatively high before and after the outbreak of the COVID-19 pandemic. After reviewing the literature on the FME approach and Spain's case, a Box-Jenkins (ARIMA) model is used to clarify the economic performance of the Spanish electricity industry with a proposal for forecasting electricity prices. It is observed that Spain fails the EU and its national goal of providing an affordable energy price as a part of the green energy transition. Finally, free-market environmental solutions and policy reforms are proposed to facilitate Spain's energy transition.


Review of the ecology of malaria vectors in the WHO Eastern Mediterranean Region.
On the basis of published records and unpublished reports to WHO, the author reviews the information available on the ecology of 15 anopheline malaria vectors occurring in areas of the WHO Eastern Mediterranean Region where attack measures are being applied. The information, which is still incomplete, relates chiefly to the period since 1956, the year when the malaria eradication programme in the Region was launched. An attempt is made to evaluate the control measures undertaken so far, and to provide data on the sensitivity to insecticides, behaviour, and mortality of vector populations.


Experimental Characterization of the Torsional Damping in CFRP Disks by Impact Hammer Modal Testing.
Composite materials are widely used for their peculiar combination of excellent structural, mechanical, and damping properties. This work presents an experimental study on the dissipation properties of disk-shaped composite specimens exploiting vibration tests. Two different polymer matrix composites with the same number of identical laminae, but characterized by different stacking sequences, namely unidirectional and quasi-isotropic configurations, have been evaluated. An ad-hoc steel structure was designed and developed to reproduce an in-plane torsional excitation on the specimen. The main idea of the proposed approach relies on deriving the damping properties of the disks by focusing on the modal damping of the overall vibrating structure and, in particular, using just the first in-plane torsional deformation mode. Experimental torsional damping evaluations were conducted by performing vibrational hammer excitation on the presented setup. Two methods were proposed and compared, both relying on a single-degree-of-freedom (SDOF) approximation of the measured frequency response function (FRF).


Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone.
The p62 protein (also known as SQSTM1) mediates diverse cellular functions including control of NFkappaB signaling and transcriptional activation. p62 binds non-covalently to ubiquitin and co-localizes with ubiquitylated inclusions in a number of human protein aggregation diseases. Mutations in the gene encoding p62 cause Paget's disease of bone (PDB), a common disorder of the elderly characterized by excessive bone resorption and formation. All of the p62 PDB mutations identified to date cluster within the C-terminal region of the protein, which shows low sequence identity to previously characterized ubiquitin-associated (UBA) domains. We report the first NMR structure of a recombinant polypeptide that contains the C-terminal UBA domain of the human p62 protein (residues 387-436). This sequence, which confers multiubiquitin chain binding, forms a compact three-helix bundle with a structure analogous to the UBA domains of HHR23A but with differences in the loop regions connecting helices that may be involved in binding accessory proteins. We show that the Pro392 --> Leu PDB substitution mutation modifies the structure of the UBA domain by extending the N terminus of helix 1. In contrast to the p62 PDB deletion mutations that remove the UBA domain and ablate multiubiquitin chain binding, the Pro392 --> Leu substitution does not affect interaction of the UBA domain with multiubiquitin chains. Thus, phenotypically identical substitution and deletion mutations do not appear to predispose to PDB through a mechanism dependent on a common loss of ubiquitin chain binding by p62.


Toward elimination of perinatal human immunodeficiency virus transmission in the United States: effectiveness of funded prevention programs, 1999-2001.
The objective of the study was to assess the effectiveness of federal funds in preventing perinatal human immunodeficiency virus (HIV) transmission in the United States. We used surveillance data from 1999 and 2001 in 6 funded areas to estimate the proportion of HIV-infected women prescribed perinatal prophylaxis and whose infants were HIV infected. We compared outcomes with 5 unfunded areas in which surveillance data were available. The proportion of funded-area women prescribed prophylaxis increased from 80.1% to 85.9% (P < .01), compared with a decline in unfunded areas from 95.1% to 86.7% (P < .01); the difference in trends between groups was P < .01. The perinatal HIV transmission rate for funded areas declined from 6.5% (105 cases) in 1999 to 3.4% (46 cases) in 2001 (P < .01), compared with a decline in unfunded areas from 4.3% (19 cases) to 3.4% (13 cases) (P = .59); the difference in trends between groups was P = .24). The number of perinatal HIV infections in the funded areas decreased by 56%, achieving the Centers for Disease Control and Prevention's goal of a 50% reduction in incidence by 2005.


Electrical stimulation therapy for dysphagia: descriptive results of two surveys.
Given the paucity of objective information on neuromuscular electrical stimulation approaches to dysphagia therapy, and the expanding utilization of this clinical approach, we designed and conducted two surveys to gather large-scale information regarding reported practice patterns, outcomes, complications, and professional perceptions associated with electrical stimulation approaches to dysphagia therapy. Self-administered questionnaires were mailed to 1000 randomly selected speech-language pathologists in each of two groups: (1) clinicians who had completed a formal electrical stimulation training course and were actively using these techniques, and (2) clinicians who were members of Special Interest Division 13 of the American Speech-Language and Hearing Association. Survey responses were anonymous and no incentive to respond was included. Acceptable response rates were achieved for both surveys (47% and 48%). Both groups of respondents were demographically similar and reported similar practice patterns. Stroke was the most common etiology of dysphagia treated with this approach. The majority of respondents identified no specific dysphagia criteria for application of electrical stimulation, used varied behavioral treatment methods, and did not follow patients beyond therapy. Clinicians reported positive outcomes with no treatment-related complications. Satisfaction with this approach was reported to be high among patients and professionals. Clinicians who did not report using these techniques indicated that they were waiting for more objective information on clinical outcomes and safety. Results of these surveys form an initial description of practice patterns and outcomes associated with electrical stimulation approaches to dysphagia therapy.


Total knee arthroplasty conversion after a failed lateral closing wedge high tibial osteotomy with knee hyperextension and secondary ankle degeneration: A case report.
High tibial osteotomy (HTO) has been used widely for medial compartment knee osteoarthritis to correct the deformity and relieve symptoms, especially in young patients who are willing to maintain the high activity level. However, the change of bone morphology, ligament imbalance, limb malalignment, and other complications may influence the short-term outcomes of HTO. Some cases may even require conversion to TKA shortly after HTO because of the loss of correction or pain due to accelerated osteoarthritis. A 43-year-old female patient presented with persistent pain of both the left knee and the ankle. She underwent a lateral closing wedge HTO two years ago. Radiographies showed The Kellgren-Lawrence (K-L) grade IV osteoarthritic change and hyperextension (HE) of the left knee and the degeneration of the left ankle. A failed lateral closing wedge high tibial osteotomy with knee hyperextension and secondary ankle degeneration. A posterior-stabilized TKA conversion and postoperative rehabilitation were performed. The operation corrected the HE deformity and relieved the pain at the level of the left knee. However, the secondary change of the left ankle was irreversible. A failed lateral closing wedge HTO might speed up the degeneration of the knee and increase extra technical issues in the following TKA. What is more, the secondary osteoarthritis and deformity of the ankle cannot be ignored.


Reduced pancreatic volume in hepatocyte nuclear factor 1A-maturity-onset diabetes of the young.
There are interplays between the endocrine and exocrine pancreas. We recently reported an increased frequency of exocrine dysfunction in HNF1A-maturity-onset diabetes of the young (MODY3) patients, compared with controls. Reduced pancreatic volume is seen in HNF1B-MODY (MODY5) and diabetes types 1 and 2. The aim of this study was to investigate whether HNF1A mutation carriers have reduced pancreatic volume or abnormal pancreatic structure and whether any changes are associated with exocrine dysfunction. Fifteen HNF1A mutation carriers recruited from the Norwegian MODY Registry, 31 subjects with type 1 diabetes, 10 subjects with type 2 diabetes, and 11 controls underwent computed tomography of the pancreas. We measured pancreatic volume and X-ray attenuation. Pancreatic volume index was defined as pancreatic volume divided by body surface area. Pancreatic volume index was reduced in subjects with HNF1A-MODY (34.5 ml/m2; P < 0.02) and type 1 diabetes (21.4 ml/m2; P < 0.001) as compared with nondiabetic controls (45.7 ml/m2), and was reduced in subjects with diabetes in combination with fecal elastase deficiency (P = 0.03). Subjects with type 1 diabetes had smaller pancreatic volume index, compared with HNF1A mutation carriers (P < 0.001). Reduced pancreatic volume index was associated with increasing duration of diabetes. Pancreatic X-ray attenuation in HNF1A mutation carriers was not significantly different from that of nondiabetic controls. HNF1A mutation carriers have reduced pancreatic volume but less reduced than in patients with type 1 diabetes. Insulinopenia could explain both the pancreatic volume reduction and the associated pancreatic dysfunction.


Acute Management of Pediatric Cyclic Vomiting Syndrome: A Systematic Review.
To synthesize quantitative and qualitative data on pharmacologic interventions of pediatric cyclic vomiting syndrome and their effectiveness in disease management in the acute care setting. Using keywords, 799 studies published up from December 1954 to February 2018 were extracted from MEDLINE via Pubmed, Embase via OVID, CINAHL via EBSCO, and Cochrane Controlled Trials Registry. Studies were evaluated for inclusion and exclusion by 2 independent reviewers using predetermined inclusion and exclusion criteria. The search yielded 84 studies for full review, of which 54 were included in the systematic review. Studies were subsequently separated into 1 group of 6 case series studies containing quantitative data on sumatriptan, ondansetron, phenothiazines, prokinetic agents, carbohydrate, isometheptene, and aprepitant; 1 one group consisting only of qualitative studies containing expert recommendations. Ondansetron has the most quantitative and qualitative evidence to support its inclusion in pediatric emergency department protocols as a rescue therapy. Sumatriptan and aprepitant are potential candidates for inclusion as abortive therapies. Qualitative data from retrospective studies and case reports are not applicable to a larger patient population. This report informs a need for controlled, prospective cohort studies and randomized, controlled trials to optimize current management protocols and to develop new medical interventions.


Psychometric properties of the revised conscientiousness dimension of Inventário Dimensional Clínico da Personalidade (IDCP).
This study investigated the psychometric properties of the revised scale of conscientiousness of a clinical personality inventory (Inventário Dimensional Clínico da Personalidade, IDCP). One hundred and twenty participants (68 women; 56.7%) aged 18 to 53 years (mean = 22.58, standard deviation = 6.19) were recruited by convenience and answered the IDCP and the NEO Personality Inventory - Revised. The analysis of internal structure, association with external variables and reliability of the dimension under review confirmed its validity. The psychometric characteristics of the revised dimension seem to be more adequate than those of the original version and more focused on pathological functioning, which was expected and desirable.


[Synchronization of plasmapheresis and pulse therapy in the complex treatment of children with highly active glomerulonephritis].
To suppress the activity of glomerulonephritis, lupus and primary chronic mixed one, 13 children received plasmapheresis synchronously with pulse therapy with cyclophosphamide or prednisolone. Plasmapheresis was carried out daily for 3 days. Six hours after the last session and on days 4 and 5 of the treatment pulse therapy was provided, followed by conventional intake of prednisolone per os in combination with azathioprine or cyclophosphamide. Beneficial therapeutic results were obtained in 10 patients within 3 to 6 weeks. The effect turned out insufficient in a patient with associated systemic lupus erythematosus, and rapid-progressing nephritis and in a child with primary chronic glomerulonephritis of the mesangiocapillary type with fibroplastic transformation and persistent nephrotic syndrome. No therapeutic effect was attained in a patient with focal segmental glomerulosclerosis running its course with long persistent nephrotic syndrome.


A practical approach to wound care in patients with complex enterocutaneous fistulas.
A practical, low cost method for controlling high output enterocutaneous fistulas is presented herein. The technique is advantageous because it provides for excellent protection of the skin, is low in cost and is constructed from readily available materials. It is applicable to all fistulas which do not readily accept prefabricated base plate appliances. Its components are so simple that minimal time for wound care on the part of the surgeon, nursing staff or stomal therapist is required.


Evidence that serum calcium oxalate supersaturation is a consequence of oxalate retention in patients with chronic renal failure.
Serum oxalate rises in uremia because of decreased renal clearance, and crystals of calcium oxalate occur in the tissues of uremic patients. Crystal formation suggests that either uremic serum is supersaturated with calcium oxalate, or local oxalate production or accumulation causes regional supersaturation. To test the first alternative, we ultrafiltered uremic serum and measured supersaturation with two different methods previously used to study supersaturation in urine. First, the relative saturation ratio (RSR), the ratio of the dissolved calcium oxalate complex to the thermodynamic calcium oxalate solubility product, was estimated for 11 uremic (before and after dialysis) and 4 normal serum samples using a computer program. Mean ultrafiltrate oxalate predialysis was 89 +/- 8 microM/liter (+/- SEM), 31 +/- 4 postdialysis, and 10 +/- 3 in normals. Mean RSR was 1.7 +/- 0.1 (predialysis), 0.7 +/- 0.1 (postdialysis), and 0.2 +/- 0.1 (normal), where values greater than 1 denote supersaturation, less than 1, undersaturation. Second, the concentration product ratio (CPR), the ratio of the measured calcium oxalate concentration product before to that after incubation of the sample with calcium oxalate monohydrate crystal, was measured in seven uremic and seven normal serum ultrafiltrates. Mean oxalate was 91 +/- 11 (uremic) and 8 +/- 3 (normal). Mean CPR was 1.4 +/- 0.2 (uremic) and 0.2 +/- 0.1 (normal). Predialysis, 17 of 18 uremic ultrafiltrates were supersaturated with respect to calcium oxalate. The degree of supersaturation was correlated with ultrafiltrate oxalate (RSR, r = 0.99, r = 29, P less than 0.001; CPR, r = 0.75, n = 11, P less than 0.001). A value of ultrafiltrate oxalate of 50 microM/liter separated undersaturated from supersaturated samples and occurred at a creatinine of approximately 9.0 mg/dl.


Evidence of an antimicrobial-immunomodulatory role of Atlantic salmon cathelicidins during infection with Yersinia ruckeri.
Cathelicidins are a family of antimicrobial peptides that act as effector molecules of the innate immune system with broad-spectrum antimicrobial properties. These evolutionary conserved cationic host-defence peptides are integral components of the immune response of fish, which are generally believed to rely heavily on innate immune defences to invading pathogens. In this study we showed that Atlantic salmon cathelicidin 1 and 2 (asCATH1 and asCATH2) stimulated peripheral blood leukocytes increasing the transcription of the chemokine interleukin-8. Further, functional differences were identified between the two cathelicidins. In the presence of serum, asCATH1 displayed greatly diminished host haemolytic activity, while the constitutively expressed asCATH2 had no haemolytic activity with or without serum. These findings support our hypothesis that fish cathelicidins exert their primary antimicrobial action at the site of pathogen invasion such as epithelial surfaces. Further, we hypothesise that like their mammalian counterparts in the presence of serum they act as mediators of the innate and adaptive immune response via the release of cytokines thus indirectly protecting against a variety of pathogens. We highlight the importance of this immunomodulatory role from the involvement of asCATHs during an infection with the fish pathogen Yersinia ruckeri. While we were able to demonstrate in vitro that asCATH1 and 2, possessed direct microbicidal activity against the fish pathogen, Vibrio anguillarum, and a common gram negative bacterium, Escherichia coli, little or no bactericidal activity was found against Y. ruckeri. The contribution of either asCATH in the immune response or as a potential virulence factor during yersiniosis is highlighted from the increased expression of asCATH1 and 2 mRNA during an in vivo challenge with Y. ruckeri . We propose that Atlantic salmon cathelicidins participate in the interplay between the innate and adaptive immune systems via the release of cytokines enabling a more effective response to invading pathogens.


Assessing hospital performance for acute myocardial infarction: how should emergency department transfers be attributed.
The Centers for Medicare and Medicaid Services publicly reports risk-standardized mortality rates (RSMRs) to assess quality of care for hospitals that treat acute myocardial infarction patients, and the outcomes for inpatient transfers are attributed to transferring hospitals. However, emergency department (ED) transfers are currently ignored and therefore attributed to receiving hospitals. New York State administrative data were used to develop a statistical model similar to the one used by Centers for Medicare and Medicaid Services to risk-adjust hospital 30-day mortality rates. RSMRs were calculated and outliers were identified when ED transfers were attributed to: (1) the transferring hospital and (2) the receiving hospital. Differences in hospital outlier status and RSMR tertile between the 2 attribution methods were noted for hospitals performing and not performing percutaneous coronary interventions (PCIs). Although both methods of attribution identified 3 high outlier non-PCI hospitals, only 2 of those hospitals were identified by both methods, and each method identified a different hospital as a third outlier. Also, when transfers were attributed to the referring hospital, 1 non-PCI hospital was identified as a low outlier, and no non-PCI hospitals were identified as a low outlier with the other attribution method. About one sixth of all hospitals changed their tertile status. Most PCI hospitals (89%) that changed status moved to a higher (worse RSMR) tertile, whereas the majority of non-PCI hospitals (68%) that changed status were moved to a lower (better) RSMR tertile when ED transfers were attributed to the referring hospital. Hospital quality assessments for acute myocardial infarction are affected by whether ED transfers are assigned to the transferring or receiving hospital. The pros and cons of this choice should be considered.


A short measure of balance in multiple sclerosis: validation through Rasch analysis.
Ambulatory patients with multiple sclerosis (MS) frequently present with poor balance. Neither static nor dynamic posturography explore balance during self-paced movements in real-life activities, when fall is most probable. Behavioural item-response scales can easily represent these activities. However, testing many items can easily cause fatigue in MS patients, thus distorting their scores. On the other hand, the lower the number of items, the lower the precision of the cumulative score and its reliability. A new short instrument was derived from existing ones (the Tinetti and the Berg balance scales). A preliminary 10-item version encompassed sit/stand manoeuvres, standing with eyes open and closed, standing with eyes closed and head extended, leaning forward while standing, picking up an object from floor, resisting nudges on the sternum, turning around, tandem stance. The instrument was administered 1-3 times to 55 MS patients (103 observations overall), all of them able to walk autonomously for at least 20 metres. The Rasch Analysis was adopted to explore the psychometric validity of the scale. Two items (Stand-to-sit and Standing with eyes open) were deleted, as they were too easy and thus uninformative. The remaining 8 items made up a scale (called EQUI-SCALE) complying with the requirements of unidimensionality and reliability. The item scores remained stable in a sub-sample of 24 patients tested before and after ten 1-hour exercise sessions, thus supporting the homogeneity of the items.


Functional morphology of the gills of the shortfin mako, Isurus oxyrinchus, a lamnid shark.
This study examines the functional gill morphology of the shortfin mako, Isurus oxyrinchus, to determine the extent to which its gill structure is convergent with that of tunas for specializations required to increase gas exchange and withstand the forceful branchial flow induced by ram ventilation. Mako gill structure is also compared to that of the blue shark, Prionace glauca, an epipelagic species with lower metabolic requirements and a reduced dependence on fast, continuous swimming to ventilate the gills. The gill surface area of the mako is about one-half that of a comparably sized tuna, but more than twice that of the blue shark and other nonlamnid shark species. Mako gills are also distinguished from those of other sharks by shorter diffusion distances and a more fully developed diagonal blood-flow pattern through the gill lamellae, which is similar to that found in tunas. Although the mako lacks the filament and lamellar fusions of tunas and other ram-ventilating teleosts, its gill filaments are stiffened by the elasmobranch interbranchial septum, and the lamellae appear to be stabilized by one to two vascular sacs that protrude from the lamellar surface and abut sacs of adjacent lamellae. Vasoactive agents and changes in vascular pressure potentially influence sac size, consequently effecting lamellar rigidity and both the volume and speed of water through the interlamellar channels. However, vascular sacs also occur in the blue shark, and no other structural elements of the mako gill appear specialized for ram ventilation. Rather, the basic elasmobranch gill design and pattern of branchial circulation are both conserved. Despite specializations that increase mako gill area and efficacy relative to other sharks, the basic features of the elasmobranch gill design appear to have limited selection for a larger gill surface area, and this may ultimately constrain mako aerobic performance in comparison to tunas.


A new training method to improve deep microsurgical skills using a mannequin head.
Neurosurgeons need fine and special microsurgical techniques, such as the ability to suture deep microvasculature. Intensive training is required to perform microsurgery, especially in deep microvascular anastomosis. There have been many previous reports of training methods for typical microsurgical techniques, including suturing of surgical gloves, Silastic tubes, living animals, and chicken wing arteries. However, there have been no reports of training methods to improve deep microsurgical skills under the various hand positions specific to neurosurgical operation. Here, we report a new training method using a mannequin head, water balloons, and clay to mimic actual deep microsurgery in the brain. This method allows trainees to experience microsurgery under various hand positions to approach the affected areas located at various depths in the brain from various angles.


What serious video games can offer child obesity prevention.
Childhood obesity is a worldwide issue, and effective methods encouraging children to adopt healthy diet and physical activity behaviors are needed. This viewpoint addresses the promise of serious video games, and why they may offer one method for helping children eat healthier and become more physically active. Lessons learned are provided, as well as examples gleaned from personal experiences.


A Rare Case of a Distal Humerus Pathological Fracture from Klebsiella Pneumoniae Osteomyelitis: A Case Report.
Klebsiella pneumoniae is one of the leading causative organisms in pyogenic liver disease. It can cause disseminated infections, but rarely to bone, and rarely in healthy hosts. We report an unusual case of a distal humerus fracture from osteomyelitis secondary to dissemination in a non-immuno-compromised patient. The patient was surgically managed with external fixation and insertion of anti-biotic beads, in conjunction with medical therapy via culture direct antibiotics. This report highlights the diagnostic approach and treatment options for these atypical cases.


Methodologic issues in a population-based health survey of Gulf War veterans.
This report describes the principal methods used in the development, conduct, and analysis of the research study "Health Assessment of Persian Gulf War Veterans from Iowa" (Iowa Gulf War Study). The methods presented include an outline of the organizational structure, study timeline, hypotheses, outcome definitions, and study design. Adhering to a strict timeline, the study protocol and instruments were developed, and a stratified sample of 3,695 military personnel (76% participation) was located and surveyed by structured telephone interview. The study tracked personnel from all service branches residing nationally and internationally, including those discharged from service. This study required development and implementation of methods appropriate to analysis of data collected in a complex sampling framework and methodological procedures to ensure scientific rigor in a highly public and politicized environment. Statistical analyses were conducted on a priori health outcomes and required development of methods to compute Cochran-Mantel-Haenszel adjusted rate differences. This environment facilitated rapid implementation, critique by scientific and public advisors, a high participation rate, and rapid publication.


Efficient lymphocyte migration across high endothelial venules of mouse Peyer's patches requires overlapping expression of L-selectin and beta7 integrin.
Lymphocyte migration into lymphoid organs is regulated by adhesion molecules including L-selectin and the beta7 integrins. L-selectin and alpha4beta7 are predominantly hypothesized to direct the selective migration of lymphocytes to peripheral lymph nodes and the gut-associated lymphoid tissues, respectively. To further characterize interactions between L-selectin and beta7 integrins during lymphocyte recirculation, mice deficient in both receptors (L-selectin/beta7 integrin-/-) were generated. The simultaneous loss of L-selectin and beta7 integrin expression prevented the majority of lymphocytes (>95% inhibition) from attaching to high endothelial venules (HEV) of Peyer's patches and other lymphoid tissues during in vitro binding assays. Moreover, the inability to bind HEV eliminated the vast majority of L-selectin/beta7 integrin-/- lymphocyte migration into Peyer's patches during short-term and long-term in vivo migration assays (>99% inhibition,p < 0.01). The lack of lymphocyte migration into Peyer's patches correlated directly with the dramatically reduced size and cellularity (99% reduced) of this tissue in L-selectin/beta7 integrin-/- mice. High numbers of injected L-selectin/beta7 integrin-/- lymphocytes remaining in the blood of wild-type mice correlated with markedly increased numbers of circulating lymphocytes in L-selectin/beta7 integrin-/- mice. Loss of either L-selectin or the beta7 integrins alone resulted in significant but incomplete inhibition of Peyer's patch migration. Collectively, the phenotype of L-selectin/beta7 integrin-/- mice demonstrates that these two receptors primarily interact along the same adhesion pathway that is required for the vast majority of lymphocyte migration into Peyer's patches.


Exploring variability in the diet of depredating sperm whales in the Gulf of Alaska through stable isotope analysis.
Sperm whales interact with commercially important groundfish fisheries offshore in the Gulf of Alaska (GOA). This study aims to use stable isotope analysis to better understand the trophic variability of sperm whales and their potential prey, and to use dietary mixing models to estimate the importance of prey species to sperm whale diets. We analysed tissue samples from sperm whales and seven potential prey (five groundfish and two squid species). Samples were analysed for stable carbon and nitrogen isotope ratios, and diet composition was estimated using Bayesian isotopic mixing models. Mixing model results suggest that an isotopically combined sablefish/dogfish group, skates and rockfish make up the largest proportion of sperm whale diets (35%, 28% and 12%) in the GOA. The top prey items of whales that interact more frequently with fishing vessels consisted of skates (49%) and the sablefish/dogfish group (24%). This is the first known study to provide an isotopic baseline of adult male sperm whales and these adult groundfish and offshore squid species, and to assign contributions of prey to whale diets in the GOA. This study provides information to commercial fishermen and fisheries managers to better understand trophic connections of important commercial species.


Parents' Willingness to Vaccinate Their Children Against Seasonal Influenza After the COVID-19 Pandemic in Saudi Arabia: A Retrospective Cross-Sectional Survey.
To explore the impact of the novel coronavirus (COVID-19) pandemic on caregivers' willingness to vaccinate their children against influenza in 2021 in Saudi Arabia and the factors influencing this decision. An online survey of 2501 caregivers in Saudi Arabia with children aged 6 months-18 years was conducted between July 15, 2021, and August 2, 2021. A convenience sample of participants that met the inclusion criteria was used as the study sample. Social Science Package Statistical (SPSS) was used for the statistical analysis. Categorical variables were reported as frequencies and percentages. The Chi-square test was used for categorical variables to assess the difference between the variables and the parents' willingness to vaccinate their children against seasonal influenza after the COVID-19 pandemic. Of the 2501 respondents to the survey, 1185 (47.3%) parents plan to give their children the influenza vaccine next year, which is an increase from 745 (29.8%) in the previous year. The following were the main reasons for not giving children the vaccine: children were less likely to get seasonal flu (617, 24.7%), fear of side effects (491, 19.6%), and fear of needles and syringes (484, 19.4%). Among the parents, 1222 (48.9%) were more likely to receive the seasonal flu vaccine themselves the following year, and 1361 (54.4%), which is more than half, were concerned about their children contracting seasonal influenza. Parents' decision-making to vaccinate their children against seasonal influenza has been influenced by the COVID-19 pandemic. Numerous factors including a caregiver who had received the seasonal influenza vaccine themselves, who had vaccinated or planned to vaccinate their children during the previous or current seasonal influenza season, and/or who had a higher education level were associated with increased willingness to receive the flu vaccine.


Role of QN1 protein in cell proliferation arrest and differentiation during the neuroretina development.
In this report, we describe the involvement of the quail neuroretina 1 (QN1) protein in retinal development. The Qn1 cDNA was isolated as a gene specifically expressed at the onset of neuronal cell cycle withdrawal (Bidou et al., Mech. Dev. 43 (1993) 159). Qn1 is located in the cytoplasm in proliferating cells during the early stages of the development. Its distribution changes, becoming predominantly nuclear, in neurons during establishment of the quiescent state upon the differentiation. We decreased the amount of QN1 protein by an antisense strategy in vitro or in vivo. This decrease of the amount of QN1 protein results in additional mitosis and in severe abnormalities such as retinal dysplasia. Our results suggest that QN1 plays a key role at the onset of neuronal cell cycle withdrawal.


An association between infantile haemangiomas and erythropoietin treatment in preterm infants.
Infantile haemangiomas are benign vascular neoplasms that occur frequently in premature infants. The authors hypothesised that in addition to gestational age and birth weight, erythropoietin therapy may influence the incidence of these soft tissue tumours in preterm infants. 2563 infants born prematurely and admitted to the Division of Neonatology, University of Heidelberg Medical School were investigated in a retrospective analysis. Hospital charts for all infants were reviewed for clinical data. The primary endpoint was the percentage of infants who had received erythropoietin treatment and were diagnosed with a haemangioma. Haemangiomas were diagnosed in 4.3% (n=110) of the 2563 preterm infants. These 110 infants had a median gestational age of 29 weeks (IQR 27-33 weeks) and the female:male ratio was 1.8:1. A higher incidence of haemangiomas (12-15%) was detected in premature infants with a lower gestational age (<31 weeks). Erythropoietin therapy was shown to be an independent risk factor after adjusting for all other known factors and oxygen therapy in multivariable analysis (HR 2.82, 95% CI 1.55 to 5.12). Subgroup analysis revealed that the effect was more pronounced in male than female infants (HR 3.61, 95% CI 1.52 to 8.57). This retrospective study demonstrates that erythropoietin treatment is associated with an increase in the incidence of these benign vascular tumours after adjusting for all other factors.


Three-layer sandwich gel electrophoresis: a method of salt removal and protein concentration in proteome analysis.
Sample preparation plays a critical role in successful proteomic applications. Features of electrospray mass spectrometry impose limits on the types of buffers, detergents and other reagents that can be used in sample preparation. Unfortunately, many of these mass spectrometry incompatible reagents significantly enhance protein recoveries from complex matrices. This problem prompted our search for a better cleanup protocol. Our data suggest that the Three-layer Sandwich Gel Electrophoresis (TSGE) protocol can solve this problem and provide near quantitative recovery of extremely low concentration proteins from harsh solutions, a feature not available from other cleanup protocols. The hallmark of the TSGE protocol is the combination of the properties of agarose gels (that serve as the matrix to immobilize the proteins of interest) with low- and high-percentage polyacrylamide gels (that serve as the concentration and sealing layers, respectively). By electrophoretically driving the proteins of interest from the agarose matrix into the concentration layer, the TSGE protocol simultaneously concentrates the sample in the concentration layer and provides an environment amenable to downstream buffer exchange and proteolytic digestion. In combination with 2D-LC-MS/MS, the TSGE protocol was evaluated in the analysis of a whole cell extract from the protozoan parasite Toxoplasma gondii. Comparison of our experimental proteomic results with in silico predictions from gene data indicated that TSGE did not bias the protein identification.


Hypertrophic pyloric stenosis: volumetric measurement of nasogastric aspirate to determine the imaging modality.
The authors postulated that volumetric measurement of residual gastric aspirate in neonates and infants with nonbilious projectile vomiting could enable differentiation between patients with hypertrophic pyloric stenosis (HPS) and those with gastroesophageal reflux (GER) and help to determine whether ultrasound (US) or fluoroscopy of the upper gastrointestinal tract would best confirm the diagnosis. In the 38 patients (all but two of whom had been fasting for 3-4 hours), 10 mL or more of nasogastric aspirate was considered indicative of obstruction. HPS occurred in 91.7% of patients with 10 mL of aspirate or more, whereas GER occurred in 85.7% of patients with less than 10 mL. The differences between the two groups were statistically significant. Solely on the basis of residual volume (greater than or equal to 10 mL), the cause of vomiting could be differentiated, prior to standard radiologic studies, 89.4% of the time. It is concluded that patients with projectile vomiting who have 10 mL or more of residual aspirate in the stomach should undergo US for confirmation of HPS; those with less than 10 mL should undergo fluoroscopy for confirmation of GER.


Expression of DNA methyltransferases in adult dorsal root ganglia is cell-type specific and up regulated in a rodent model of neuropathic pain.
Neuropathic pain is associated with hyperexcitability and intrinsic firing of dorsal root ganglia (DRG) neurons. These phenotypical changes can be long lasting, potentially spanning the entire life of animal models, and depend on altered expression of numerous proteins, including many ion channels. Yet, how DRGs maintain long-term changes in protein expression in neuropathic conditions remains unclear. DNA methylation is a well-known mechanism of epigenetic control of gene expression and is achieved by the action of three enzymes: DNA methyltransferase (DNMT) 1, 3a, and 3b, which have been studied primarily during development. We first performed immunohistochemical analysis to assess whether these enzymes are expressed in adult rat DRGs (L4-5) and found that DNMT1 is expressed in both glia and neurons, DNMT3a is preferentially expressed in glia and DNMT3b is preferentially expressed in neurons. A rat model of neuropathic pain was then used to determine whether nerve injury may induce epigenetic changes in DRGs at multiple time points after pain onset. Real-time RT PCR analysis revealed robust and time-dependent changes in DNMT transcript expression in ipsilateral DRGs from spared nerve injury (SNI) but not sham rats. Interestingly, DNMT3b transcript showed a robust upregulation that appeared already 1 week after surgery and persisted at 4 weeks (our endpoint); in contrast, DNMT1 and DNMT3a transcripts showed only moderate upregulation that was transient and did not appear until the second week. We suggest that DNMT regulation in adult DRGs may be a contributor to the pain phenotype and merits further study.


Seasonality of births and abortions in New South Wales, Australia.
Complex seasonal variations in abortions and seasonal trends have been reported worldwide, but there are no data from Australia. Hospital morbidity and birth data were modelled using time series and regression techniques to describe seasonal changes in births and abortions (1989-99) in NSW, Australia. Data were also analysed to determine demographic predictors of abortions. A higher proportion of births in NSW were recorded in March and September-October. Irrespective of the nuptiality the lowest seasonal indices were recorded in February and November. For married women aged 20-49 years, voluntary abortions were significantly higher in February (t=0.04) and significantly lower in April (t<0.001) and June (t=0.03) and non-voluntary abortions were significantly higher in February (t=0.002) and March (t=0.006). There was seasonality in voluntary abortions (F=4.3, p<0.001) and no seasonality in non-voluntary abortions (F=2.4, p=0.01) for never married women aged 20-49 years. As similar to married women, voluntary abortions among never married women were significantly higher in February (t<0.001) and significantly low in April (t=0.009). The lowest number of abortions were in April. Non-voluntary abortions occurred mostly in March for married women. The average number of voluntary abortions were significantly higher for never married women than for married women. There was a significant seasonality of births and abortions in NSW, Australia, with a peak of conceptions in December/January. Abortions were lowest in April and non-voluntary abortions were peaked in March. These data suggest that the human reproductive behaviour has a close relationship with environmental factors.


Chemical composition and evaluation of modulatory of the antibiotic activity from extract and essential oil of Myracrodruon urundeuva.
The combination of antibiotics with natural products has demonstrated promising synergistic effects in several therapeutic studies. The aim of this study was to determine the effect of a combination of an ethanol extract of Myracrodruon urundeuva Fr. All. (Anacardiaceae) (aroeira plant) and its essential oil with six antimicrobial drugs against multiresistant strains of Staphylococcus aureus and Escherichia coli from clinical isolates. After identification of the chemical components by GC-MS, the antibacterial activity of the natural products and antibiotics was assessed by determining the minimal inhibitory concentration (MIC) using the microdilution method and concentrations ranging 8-512 μg/mL and 0.0012-2.5 mg/mL, respectively. Assays were performed to test for a possible synergistic action between the plant products and the antimicrobials, using the extract and the oil at a sub-inhibitory concentration (128 μg/mL) and antibiotic at concentrations varying between 8 and 512 μg/mL. The GC-MS analysis identified the main compound as δ-carene (80.41%). The MIC of the natural products was >1024 μg/mL, except against S. aureus ATCC25923. Only the combinations of the natural products with gentamicin, amikacin and clindamycin were effective against S. aureus 358, enhancing the antibiotic activity by reducing the MIC. The extract from aroeira showed a higher antibacterial activity and the oil was more effective in potentiating the activity of conventional antibiotics.


Recurrent vulvovaginal candidiasis.
Recurrent vulvovaginal candidiasis (RVVC) is a common cause of significant morbidity in women in all strata of society affecting millions of women worldwide. Previously, RVVC occurrence was limited by onset of menopause but the widespread use of hormone replacement therapy has extended the at-risk period. Candida albicans remains the dominant species responsible for RVVC, however optimal management of RVVC requires species determination and effective treatment measures are best if species-specific. Considerable progress has been made in understanding risk factors that determine susceptibility to RVVC, particularly genetic factors, as well as new insights into normal vaginal defense immune mechanisms and their aberrations in RVVC. While effective control of RVVC is achievable with the use of fluconazole maintenance suppressive therapy, cure of RVVC remains elusive especially in this era of fluconazole drug resistance. Vaccine development remains a critical challenge and need.


I-spline Smoothing for Calibrating Predictive Models.
We proposed the I-spline Smoothing approach for calibrating predictive models by solving a nonlinear monotone regression problem. We took advantage of I-spline properties to obtain globally optimal solutions while keeping the computational cost low. Numerical studies based on three data sets showed the empirical evidences of I-spline Smoothing in improving calibration (i.e.,1.6x, 1.4x, and 1.4x on the three datasets compared to the average of competitors-Binning, Platt Scaling, Isotonic Regression, Monotone Spline Smoothing, Smooth Isotonic Regression) without deterioration of discrimination.