Activity of the fragile X in heterozygous carriers.
Chromosome analyses with conventional stain, Q- and G-banding, and R-banding with 5-bromodeoxyuridine (BrdU) incorporation were performed on the lymphocytes of two sisters who are heterozygous for the fragile X chromosome and clinically diagnosed as slow learners. Two heterozygous relatives with normal intelligence were used as controls. The frequencies of the active fragile X for the "slow" females were 100/129 (77.5%) and 85/120 (70.8%) compared with 40/78 (51.3%) and 10/32 (31.3%) for controls, the difference being highly significant. These observations are consistent with the Lyon hypothesis: activity of the abnormal X could account for the reduction in mental ability of some heterozygous females. Similar to retarded males with the fragile X chromosome, our slow learners had verbal scores that were lower than performance scores.


Multiple surface plasmon modes for a colloidal solution of nanoporous gold nanorods and their comparison to smooth gold nanorods.
The paper represents a novel approach to investigating localized surface plasmon (LSP) resonance modes of nanoporous Au nanorods (NRs) in a solution phase with control over surface morphology. Au NRs, which have distinctive features such as nanopores and ligaments, showed interesting LSP resonance modes depending on the surface morphology and the total length of the structure. Compared with the analogous smooth surface NRs, the LSP modes of nanoporous NRs are red-shifted, which can be interpreted as a longer effective rod length and larger amplitude of plasmon oscillation.


Subjects develop tolerance to Pru p 3 but respiratory allergy to Pru p 9: A large study group from a peach exposed population.
Peach tree allergens are present in fruit, pollen, branches, and leaves, and can induce systemic, respiratory, cutaneous, and gastrointestinal symptoms. We studied the capacity of peach fruit/Pru p 1, Pru p 3, Pru p 4, Pru p 7 and peach pollen/Pru p 9 for inducing symptoms following oral or respiratory exposure in a large group of subjects. We included 716 adults (aged 21 to 83 y.o.) exposed to peach tree pollen and fruit intake in the study population. Participants completed a questionnaire and were skin tested with a panel of inhalant and food allergens, including peach tree pollen, Pru p 9 and peach fruit skin extract. Immunoglobulin E antibodies (SIgE) to Pru p 1, Pru p 3, Pru p 4 and Pru p 7 were quantified. Sensitised subjects underwent oral food challenge with peach fruit and nasal provocation test with peach tree pollen and Pru p 9. The prevalence of sensitisation to peach fruit was 5% and most of these had SIgE to Pru p 3, with a very low proportion to Pru p 4 SIgE and no SIgE to Pru p 1 and Pru p 7. In only 1.8%, anaphylaxis was the clinical entity induced. Cases with positive skin tests to peach and SIgE to Pru p 3 presented a good tolerance after oral challenge with peach fruit. The prevalence of skin sensitisation to peach tree pollen was 22%, with almost half recognising Pru p 9. This induced respiratory symptoms in those evaluated by nasal provocation. In a large population group exposed to peach fruit and peach tree pollen, most individuals were tolerant, even in those with SIgE to Pru p 3. A positive response to Pru p 9 was associated with respiratory allergy.


Mexican immigrants' explanatory model of latent tuberculosis infection.
This article reveals how the multiple and disparate explanations of latent tuberculosis infection (LTBI) from the U.S. and Mexico professional health sectors and the popular sector are used to inform the explanatory model (EM) of LTBI for Mexican immigrants residing in the U.S.-Mexico border region. Fourteen immigrants, nine diagnosed with LTBI (n = 9) and their spouses (n = 5) participated in this critical ethnographic study. Because care seeking and treatment decisions are influenced by EMs, the results indicate that it is imperative that interventions for Mexican immigrants with LTBI are built on an understanding of their illness experience and are contextually meaningful.


The primary practice physician program for chronic pain (© 4PCP): outcomes of a primary physician-pain specialist collaboration for community-based training and support.
One in 3 patients sees a primary care physician (PCP) for chronic pain yet most PCPs receive no training in this field. We evaluated the impact of 4PCP (© Primary Practice Physician Program for Chronic Pain) comprising of a specialist-PCP training collaboration integrated with clinical support. This prospective, controlled pilot study randomly assigned 31 physicians to receive a training program either immediately or after a 1-year control period. 4PCP includes: (1) an active learning arm, providing patient-focused, practice-based learning collaboration emphasizing the biopsychosocial pain model; (2) a PCP-led clinical support arm facilitating rehabilitative matrix style care by teams of pain-informed health providers. Main outcome measures included a 19-item chronic pain physician perspectives questionnaire, physician engagement through continuing medical education hours earned, and an array of established measures of patient pain and function. PCPs receiving the intervention reported improvements in diagnosing and managing chronic pain (P=0.023), especially its functional consequences (P=0.008), in treatment satisfaction, and in involving other disciplines. Mean visit time dropped from 20 to 11 minutes (P<0.03) with improved patient outcomes, which correlated with 4PCP physician engagement. Significant benefit began at 10 continuing medical education hours and proved durable 1 year after trial. This pilot study demonstrates successful interdisciplinary chronic pain management by PCPs with durability of training effect, improved patient outcomes, visit efficiency, and job satisfaction. 4PCP provides a promising framework to propel the national concept of PCP-specialist collaboration for chronic pain management.


Gram-scale enantioselective formal synthesis of morphine through an ortho-para oxidative phenolic coupling strategy.
A gram-scale catalytic enantioselective formal synthesis of morphine is described. The key steps of the synthesis involve an ortho-para oxidative phenolic coupling and a highly diastereoselective "desymmetrization" of the resulting cyclohexadienone that generates three of the four morphinan ring junction stereocenters in one step. The stereochemistry is controlled from a single carbinol center installed through catalytic enantioselective hydrogenation. These transformations enabled the preparation of large quantities of key intermediates and could support a practical and scalable synthesis of morphine and related derivatives.


Umbilical and paraumbilical veins in ligamentum teres. Their significance as collaterals in portal hypertension.
Twenty-two postmortem specimens of the liver (18 normal livers, three with liver metastases, and one with liver cirrhosis) with attached ligamenta teres were investigated using silicone rubber injection technique. In all cases, the paraumbilical veins were demonstrated. They were usually divided into 2 groups, one on the right and one on the left side of the ligamentum teres, and they terminated in a variable manner into small peripheral portal vein branches in the liver parenchyma. A patent segment of the umbilical vein was found in 7 of the 22 cases. Connections between the umbilical vein and paraumbilical veins were supposed to represent one of the collateral channels in portal hypertension.


The Society for Craniofacial Genetics and Developmental Biology 42nd Annual Meeting.
The Society for Craniofacial Genetics and Developmental Biology (SCGDB) 42nd Annual Meeting was held at the MD Anderson Cancer Center in Houston, Texas from October 14-15, 2019. The SCGDB meeting included scientific sessions on the molecular regulation of craniofacial development, cell biology of craniofacial development, signaling during craniofacial development, translational craniofacial biology, and for the first time, a career development workshop. Over a one hundred attendees from 21 states, and representing over 50 different scientific institutions, participated. The diverse group of scientists included cell and developmental biologists and clinical geneticists, promoting excellent discussions about molecular pathways guiding abnormal cell behaviors and the resultant morphological changes to craniofacial development. The results were high-quality science and a welcoming environment for trainees interested in craniofacial biology.


A Challenging Case of Acute Mercury Toxicity.
Mercury exists in multiple forms: elemental, organic, and inorganic. Its toxic manifestations depend on the type and magnitude of exposure. The role of colonoscopic decompression in acute mercury toxicity is still unclear. We present a case of acute elemental mercury toxicity secondary to mercury ingestion, which markedly improved with colonoscopic decompression. A 54-year-old male presented to the ED five days after ingesting five ounces (148 cubic centimeters) of elemental mercury. Examination was only significant for a distended abdomen. Labs showed elevated serum and urine mercury levels. An abdominal radiograph showed radiopaque material throughout the colon. Succimer and laxatives were initiated. The patient had recurrent bowel movements, and serial radiographs showed interval decrease of mercury in the descending colon with interval increase in the cecum and ascending colon. Colonoscopic decompression was done successfully. The colon was evacuated, and a repeat radiograph showed decreased hyperdense material in the colon. Three months later, a repeat radiograph showed no hyperdense material in the colon. Ingested elemental mercury can be retained in the colon. Although there are no established guidelines for colonoscopic decompression, our patient showed significant improvement. We believe further studies on this subject are needed to guide management practices.


Collagen-based fibrillar multilayer films cross-linked by a natural agent.
Surface functionalization plays an important role in the design of biomedical implants, especially when layer forming cells, such as endothelial or epithelial cells, are needed. In this study, we define a novel nanoscale surface coating composed of collagen/alginate polyelectrolyte multilayers and cross-linked for stability with genipin. This buildup follows an exponential growth regime versus the number of deposition cycles with a distinct nanofibrillar structure that is not damaged by the cross-linking step. Stability and cell compatibility of the cross-linked coatings were studied with human umbilical vein endothelial cells. The surface coating can be covered by a monolayer of vascular endothelial cells within 5 days. Genipin cross-linking renders the surface more suitable for cell attachment and proliferation compared to glutaraldehyde (more conventional cross-linker) cross-linked surfaces, where cell clumps in dispersed areas were observed. In summary, it is possible with the defined system to build fibrillar structures with a nanoscale control of film thickness, which would be useful for in vivo applications such as inner lining of lumens for vascular and tracheal implants.


No Impact of Omega-3 Fatty Acid Supplementation on Symptoms or Hostility Among Patients With Schizophrenia.
This study was aimed to explore the impact of fish oil (Omega-3 fatty acids) on hostility and psychopathology among patients with acute violent schizophrenia. Sixty seven acute hospitalized patients demonstrating violent behavior in the context of a schizophrenic illness, treated with antipsychotics, were randomly assigned to a supplement with either fish oil (N=32) or placebo (N=35) in a double-blind, placebo-controlled trial. Assessments were conducted at the baseline, week 4 and week 8. The symptoms and hostility decreased after treatment for 4 and 8 weeks in both groups, with no group differences. The current study did not find improvements in symptoms or hostility from the Omega-3 fatty acid supplementation in patients with schizophrenia. The implication is that Omega-3 fatty acids do not reduce psychopathology and hostility in acute patients with schizophrenia.


[Laparoscopic cholecystectomy in patients with liver cirrhosis].
Between 01. January 1994 and 31. December 1995 during 552 laparoscopic cholecystectomy the authors observed moderate or severe liver cirrhosis in 27 patients. They performed successful operations on all of the 27 patients with two conversions. None of the patients died. They discuss complications of the operations performed in liver cirrhosis, and state, that the existence of the cirrhosis does not contraindicate the laparoscopic cholecystectomy, moreover in the hands of a surgeon with great laparoscopic experience this method is more indulgent and has less complications than cholecystectomy performed with traditional methods.


[Evidence-based quality assessment of 10-year orthodontic clinical trials in 4 major dental journals].
To assess the quality of orthodontic clinical trials published in 4 major dental journals in the past 10 years and establish the reference standard for orthodontic clinical trials and quality control of dental journals. All the clinical trials published in Chinese Journal of Stomatology, West China Journal of Stomatology, Journal of Practice Stomatology and Chinese Journal of Orthodontics from 1999 to 2008 were searched. The demographic information of the papers was extracted and the quality of the clinical trials according to the consolidated standards of reporting trials (CONSORT) was assessed. Four hundred and ninety-four clinical trials were retrieved, and 21.3% (105/494) of them were supported by grants. For the study design, only 26.1% (129/494) were prospective studies, and 3.8% (19/494) were randomized clinical trials. It was hard to evaluate precisely due to the lack of information about the details of the study designs. For the randomized clinical trials, the lack of details for randomization, allocation concealment, blinding and intention to treat compromised the quality. The general quality of clinical trials in orthodontics is poor. It needs to be improved both in the clinical study design and the paper writing.


Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.
Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P < 0.01). When analyzed by real-time polymerase chain reaction, PdxR deficiency was found to drastically reduce expression of an apparent operon encoding a pyridoxal kinase (SMU865) and a pyridoxal permease (SMU866) of the salvage pathway of vitamin B6 biosynthesis. In addition, PdxR deficiency also altered the expression of genes for ClpL protease, glucosyltransferase B and adhesin SpaP, which are known to play important roles in stress tolerance and biofilm formation. Consistently, PdxR-deficiency affected the growth of the deficient mutant when grown in defined medium with and without vitamin B6 . Further studies revealed that although S. mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation.


Stereocomplex Crystallization of Linear Two-Armed Stereo Diblock Copolymers: Effects of Chain Directional Change, Coinitiator Moiety, and Terminal Groups.
Two-armed poly(l-lactide) (PLLA)-b-poly(d-lactide) (PDLA) (2-LD) copolymers with a wide-range of molecular weight were synthesized and the effect of coinitiator moiety, which functions as impurity and causes chain directional change in the middle of molecules (Effect A), and/or the additional effect of types of terminal groups (Effect B) on crystallization behavior of 2-LD copolymers were studied, in comparison with that reported for one-armed PLLA-b-PDLA (1-LD) copolymers. Formation of only stereocomplex (SC) crystallites in 2-LD and 1-LD copolymers indicates that neighboring PLLA and PDLA blocks facilitated SC crystallization and neither Effect A nor B affected the crystalline species. Effect A and/or B (both hydroxyl terminal groups) disturbed cold SC crystallization of 2-LD copolymers compared to that of 1-LD copolymers. Crystalline growth morphologies of 2-LD and 1-LD copolymers during cold SC crystallization were spherical and solid sheaf, respectively, exhibiting that crystalline growth morphology was influenced by Effects A and/or B. The melting temperature or crystalline thickness of SC crystallites were determined by number-average molecular weight per one block and not affected by Effect A or B. Maximum radial growth rates of spherulites of 2-LD copolymers compared to those of 1-LD copolymers were largely decreased by Effect A and/or B (both hydroxyl terminal groups).


Integration of Cot analysis, DNA cloning, and high-throughput sequencing facilitates genome characterization and gene discovery.
Cot-based sequence discovery represents a powerful means by which both low-copy and repetitive sequences can be selectively and efficiently fractionated, cloned, and characterized. Based upon the results of a Cot analysis, hydroxyapatite chromatography was used to fractionate sorghum (Sorghum bicolor) genomic DNA into highly repetitive (HR), moderately repetitive (MR), and single/low-copy (SL) sequence components that were consequently cloned to produce HRCot, MRCot, and SLCot genomic libraries. Filter hybridization (blotting) and sequence analysis both show that the HRCot library is enriched in sequences traditionally found in high-copy number (e.g., retroelements, rDNA, centromeric repeats), the SLCot library is enriched in low-copy sequences (e.g., genes and "nonrepetitive ESTs"), and the MRCot library contains sequences of moderate redundancy. The Cot analysis suggests that the sorghum genome is approximately 700 Mb (in agreement with previous estimates) and that HR, MR, and SL components comprise 15%, 41%, and 24% of sorghum DNA, respectively. Unlike previously described techniques to sequence the low-copy components of genomes, sequencing of Cot components is independent of expression and methylation patterns that vary widely among DNA elements, developmental stages, and taxa. High-throughput sequencing of Cot clones may be a means of "capturing" the sequence complexity of eukaryotic genomes at unprecedented efficiency.


Activity in chronic schizophrenic patients: comparison of pimozide with fluphenazine in a double blind trial.
A double-blind crossover trial was carried out comparing pimozide with fluphenazine. The effects of the drugs on the activity of 20 chronic inert male schizophrenic patients were measured using nursing observations, psychiatric rating, and an operant conditioning method. When activity was assessed in these different ways, no significant difference was found between the two drugs on any of the measures. It is concluded that pimozide does not effectively increase the activity in such patients. It is considered that the free operant conditioning method used was shown to be a useful measure for comparing therapy in chronic schizophrenic patients.


Babesia odocoilei infection in elk.
Two male North American elk from a commercial herd were evaluated because of a sudden onset of lethargy, anorexia, and voiding of red urine. These 2 elk were kept in the same pen as 4 other male elk that had died during the preceding 2 months. Laboratory analyses revealed anemia and intraerythrocytic parasites, later confirmed as Babesia odocoilei (a protozoal hemoparasite of cervids). Of the 240 elk remaining in the herd, 59 were screened for B odocoilei by microscopic evaluation of blood smears, protozoal culture of blood, and immunofluorescent antibody testing of serum. Of those 59 elk, 34 (58%) were infected with B odocoilei. Babesia odocoilei infection in elk can be fatal and should be considered in cases of sudden death or acute hemolytic anemia. Familiarity with the disease in elk is essential for practitioners because of the increasing popularity of commercial elk farming.


CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein.
Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into one-cell human embryos, we demonstrated efficient homologous recombination-mediated correction of point mutations in HBB and G6PD. However, our results also reveal limitations of this correction procedure and highlight the need for further research.


Loss and recovery of sound-evoked otoacoustic emissions in young chicks following acoustic trauma.
Young and adult chickens exhibit substantial inner-ear damage and post-exposure deterioration in cochlear nerve activity following exposure to intense sound. Both the structural and functional losses largely recover in both age groups within 2-4 weeks after exposure. However, some aspects of acoustic trauma differ between the young and adult chicken ear. Overstimulation in the young chick causes considerable post-exposure loss and then recovery of the steady-state endocochlear potential, while in the adult animal there is little post-exposure effect on this potential. Moreover, in adults there is post-exposure loss but little recovery in the distortion product otoacoustic emission (DPOAE). The present study explores the possibility of an age difference in the effects of overstimulation on the DPOAE by examining these emissions in young chicks following exposure to an intense pure tone. Chicks exposed to intense sound were formed into groups at 0 and 12 days of recovery, and these were complemented by two additional groups of age-matched controls. The cubic difference tone emission (the 2f(1)-f(2) DPOAE component) was measured at 9 levels for 13 frequencies in all groups. Shortly after the exposure, the DPOAE reliably declined with the maximum loss at or above the exposure tone frequency. The exposed chicks examined 12 days after exposure showed complete recovery of the DPOAE. It would appear that 12 days of recovery sufficiently repaired inner ear damage to completely restore DPOAE production. This result is different from that in adult chicken and may be related to the greater severity of acoustic damage in the adult ear, a reduced susceptibility of the young ear to acoustic trauma, or the ability of the young animal to more successfully repair the inner ear.


Sleep and physical activity: a survey of people with inflammatory arthritis and their engagement by health professionals in rheumatology in Ireland.
Sleep is important in maintaining the body's circadian rhythm and in maintaining health. Aim was to investigate sleep and physical activity among people who have inflammatory arthritis and their engagement with Health Professionals. Members from a national charitable organisation for patients with arthritis and a national rheumatology health professionals society were invited to participate in separate cross-sectional surveys hosted on SurveyMonkey(R)TM. Ninety people responded and report an average of 5.7 (SD 1.46) hours sleep per night. A majority (61%) report their sleep quality as bad, with 31% taking medications at least once a week to help sleep. There was a statistically significant association between longer years with symptoms, taking medication at least once a week and limited in their activities, when rating their sleep quality as bad. Twenty eight (65%) health professional's responded with 53% discussing sleep with their patients. People with inflammatory arthritis report low sleep with those having symptoms longer, taking medications regularly and having limitations with their activities, reporting poorer sleep quality. Only half of health professionals discuss sleep. More research is needed in investigating poor sleep quality, disturbances, and physical activity in order to promote health and well-being in this population. Implications for Rehabilitation People with inflammatory arthritis fall far below the National Sleep Foundations' "sleep needs spectrum", which is concerning as those who have reduced levels of sleep have been associated with decreased quality of life and physical function. Due to the importance of receiving sufficient sleep, there is a need to develop education and training for health professionals in the importance of engaging their patients in their sleep quality and disturbances. The effects of physical activity interventions on poor sleep need to be examined to show if it is a positive non-pharmacological treatment approach for the management of poor sleep in patients with inflammatory arthritis.


A microeconometric analysis of Canadian health care utilization.
Understanding health care utilization is important to design efficient and effective health systems. Toward this end, we develop a relatively simple and intuitively appealing microeconometric framework to analyse health care utilization and illustrate its use with recent Canadian microdata. We find that health care utilization consists of distinct stochastic processes requiring the use of two stochastic regression models. In particular, the latent class modelling framework is the superior statistical framework if the data permit modelling unobserved heterogeneity and overdispersion. In many instances, results differ for the classes of high and low users of health care services.


Production and downstream processing of (1→3)-β-D-glucan from mutant strain of Agrobacterium sp. ATCC 31750.
We isolated a mutant that produced higher levels of curdlan than the wild strain Agrobacterium sp. ATCC 31750 by chemical mutagenesis using N-methyl-N-nitro-nitrosoguanidine. The mutant strain produced 66 g/L of curdlan in 120 h with a yield of (0.88) while, the wild strain produced 41 g/L in 120 h with a yield of (0.62) in a stirred bioreactor. The mutant could not produce curdlan when the pH was shifted from 7.0 to 5.5 after nitrogen depletion as followed for wild strain. In contrast, pH optimum for cell growth and curdlan production for mutant was found to be 7.0. We optimized the downstream processing of curdlan by varying different volumes of NaOH and HCl for extraction and precipitation of curdlan. The molecular weight of the purified curdlan from the wild and mutant strain was 6.6 × 105 Da and 5.8 × 105 Da respectively. The monosaccharide analyses confirm that curdlan from both wild and mutant strain contains only glucose units. From the NMR and FTIR data, it has been confirmed that curdlan was exclusively composed of β (1 → 3)-D-glucan residues.


[Tuberculous spondylodiscitis with neurologic problems: results of surgical treatment].
The purpose of this study is to describe the outcome of surgical treatment for tuberculous spondylitis in 29 patients. These patients were part of an overall series of 67 cases of tuberculous spondylitis treated at the Traumatology and Orthopedic Department of the Yalgado-Ouedraogo National Hospital Center (YONHC) in Ouagadougou, Burkina Faso. Almost 90% of the 29 patients that underwent surgical treatment of tuberculous spondylitis associated with neurological manifestations were from poor rural areas. Mean age was 48 years and most patients were men. The procedure consisted of corporectomy via the anterolateral approach. Resection of variable extent was followed by replacement with forced insertion of a fibular graft. Intraoperative complications included non-fatal cardiovascular arrest (n = 1), inadvertent incision of the peritoneum (n = 3), and technical error in exposure of the damaged vertebrae (n = 1). Postoperative complications included emphysema (n = 2), massive pleurisy (n = 1), chylothorax (n = 1), pneumonia (n = 1), worsening of neurological manifestations (n = 1), and subacute peritonitis (n = 1). Surgical mortality was 10.3% (n = 3). Bone fusion was achieved in all patients. Functional recovery ranged from 50 to 60% after surgical treatment, which is comparable to rates in previous African reports. Choice of therapeutic modalities must take into account cost within the national health care context, duration of hospitalization and invasiveness. Surgical treatment should be used only when absolutely necessary.


A primary intervention program (pilot study) for Mexican American children at risk for type 2 diabetes.
Many chronic diseases that are leading causes of morbidity and mortality can be prevented or controlled by primary or secondary interventions. Type 2 diabetes with its complications constitutes a major health problem, especially among Mexican Americans. The purpose of this pilot study was to develop an age- and culturally appropriate primary intervention program for Mexican American children at risk of type 2 diabetes. The sample included 37 Mexican American children ages 7 to 12 years who had at least one parent or grandparent with type 2 diabetes. A health screen of physiologic risk factors, a nutritional assessment, and a diabetes knowledge test were administered before and after the program. The eight-session activity oriented educational program focused on nutrition, exercise, and diabetes knowledge. Due to small sample size and limited study time, changes in physiologic factors and diet were not analyzed for statistical significance. Analysis of individual factors showed a trend toward more normal values. Results of this pilot program indicated that health intervention projects may be effective in helping children at risk of type 2 diabetes adopt healthier lifestyles.


Intracranial arteriovenous malformation in a college football player and return-to-play considerations.
: The reported prevalence rates of arteriovenous malformations (AVMs) in the general population range from 0.001% to 0.50%. The following case describes the initial presentation of hemorrhage from an intracranial AVM in an 18-year-old college football player. It also discusses treatment of the AVM with stereotactic radiosurgery and successful return to football 17 months after radiosurgery (18.5 months after initial presentation). It is the first published description of return to contact sports after stereotactic radiosurgery for intracranial AVM.


A new ensemble-based targeted observational method and its application in the TPOS 2020.
Ensemble Kalman filter-based targeted observation is one of the best methods for determining the optimal observational array for oceanic buoy deployment. This study proposes a new algorithm suitable for a 'cross-region and cross-variable' approach by introducing a projection operator into the optimization process. A targeted observational analysis was conducted for El Niño-Southern Oscillation (ENSO) events in the tropical western Pacific for the Tropical Pacific Observation System (TPOS) 2020. The prediction target was at the Niño 3.4 region and the first 10 optimal observational sites detected reduced initial uncertainties by 70%, with the best observational array located where the Rossby wave signal dominates. At the vertical level, the most significant contribution was derived from observations near the thermocline. This study provides insights into understanding ENSO-related variability and offers a practical approach to designing an optimal mooring array. It serves as a scientific guidance for designing a TPOS observation network.


Anton's Syndrome associated with autotopagnosia.
We describe an unusual case of a 68-year-old male affected by cerebral amyloid angiopathy and cortical blindness associated with Anton's syndrome. In addition, our patient presented with autotopagnosia, a form of agnosia characterized by loss of body spatial representation. Neuropsychological assessment evidenced cognitive impairment. Magnetic Resonance Imaging showed hemorrhagic foci in the left occipital and right occipito-parietal lobe, paratrigonal white matter, and post-ischemic parenchymal gliosis. The pattern-reversal of visual evoked potentials were indicative bilateral visual pathway of integrity of the. After a neurological damage, patients could show a denial of their own deficit; however, the association between anosognosia and autotopagnosia represents a rare neurological condition. The simultaneous onset of unusual neuropsychological syndromes could be related to involvement of a complex brain network.


Gonioscopy: evaluation and interpretation.
Gonioscopy is the ocular health examination technique which offers to the practitioner the means to directly study the anterior chamber angle. Its uses are numerous and include glaucoma classification, predilation angle evaluation, and the presence of iris tumors, foreign bodies and anterior synechiae. Since a meaningful gonioscopic examination depends upon the examiner's recognition of the chamber landmarks, a detailed analysis of each structural element is presented. In addition, the techniques for performing gonioscopy with the popular lens types are viewed as is the system for interpretation and recording.


European Stroke Facilities Survey: the German and Austrian perspective.
The aim of this nested analysis was to identify the major components of stroke centers and other facilities actually available for acute stroke patients in hospitals of Germany and Austria. This analysis is part of a much larger European Stroke Facility Survey of 886 hospitals treating stroke patients all over Europe initiated by the European Stroke Initiative. Three levels of stroke care were predefined: comprehensive stroke centers (CSC), primary stroke centers (PSC) and a minimum level required for any hospital ward (AHW) admitting stroke patients. Hospitals providing even less than that were indicated in the 'none' category. The present survey was conducted in 178 (166 and 12) German and Austrian hospitals which returned the questionnaire (41% response rate). They treated a total of 54,257 acute stroke patients per year (25% of all strokes in Germany and Austria), with a mean of 376 patients per year per hospital. 2,168 patients were given recombinant tissue plasminogen activator (4.7%), a proportion much higher than the pan-European average, but strongly dependent on the level of the facility considered (range 7.5-1.3%). Criteria for CSC were met in 13 hospitals (7.3%), for PSC in 15 (8.4%) and for AHW in 85 (47.7%). The minimum level required for AHW was not met in 65 hospitals (36.5%). 15.7% of German and Austrian hospitals provide stroke center facilities at the CSC or PSC level, as compared with 8.5% in Europe. A 24-hour availability of a stroke-trained physician was met by 100% of CSC, 73% of PSC, 85% of AHW and by 62% at the 'none' level of care. At the levels of CSC and PSC, a 100% availability was achieved for multidisciplinary stroke team, stroke-trained nurses, in-house emergency department, physiotherapy and speech therapy within 2 days, 24-hour brain CT and CT or MR angiography, as well as for transesophageal echocardiography and automated 24-hour monitoring of vital parameters. Nearly all these hospitals had training programs, stroke pathways, thrombolysis protocols and prevention procedures in place for the acute care of stroke patients. This survey shows that the minimum level of care is met in Germany and Austria in 63% of hospitals treating stroke patients, whereas the European average is 48.6%. However, the lack of stroke center coverage should encourage health policy decision makers to further improve the infrastructure for acute stroke care in order to make stroke centers available to every stroke victim.


[Age and sex distribution of biliary lithiasis].
The authors analyze the age and sex distribution of cholelithiasis in 388 patients. Cholelithiasis in those patients is diagnosed by X-ray method and in 24 of them -- was verified at operation. The incidence of cholelithiasis patients increases with age advancing. The percentage of patients with cholithiasis in the age group from 21 to 30 is 8,2 per cent, to reach 24,7 per cent among the patients from the age group 61 to 70. After that age the incidence of cholelithiasis decreases and among patients over 80 - the percentage is 0,5 per cent. Females are more frequently affected than males. From all the patients examined 77,9 per cent are females and 22,1 per cent are males; the ratio is about 4:1. Younger females suffer more after than the young males and the ration ranges about 15:1.


Effect of calcium and light on the germination of Urochondra setulosa under different salts.
Urochondra setulosa (Trin.) C.E. Hubbard is a coastal halophytic grass thriving on the coastal dunes along the Pakistani seashore. This grass could be useful in coastal sand dune stabilization using seawater irrigation. The purpose of this investigation was to test the hypothesis that Ca(2+) (0.0, 2.5, 5.0, 10.0 and 50.0 mmol/L) alleviates the adverse effects of KCl, MgSO(4), NaCl and Na(2)SO(4) at 0, 200, 400, 600, 800 and 1000 mmol/L on the germination of Urochondra setulosa. Seed germination was inhibited with increase in salt concentration with few seeds germinated at and above 400 mmol/L concentration. No seed germinated in any of the KCl treatments. Inclusion of CaCl(2) substantially alleviated the inhibitory effects of all salts. Germination was higher under photoperiod in comparison to those seeds germinated under complete darkness. Among the CaCl(2) concentrations used, 10 mmol/L was most effective in alleviating salinity effects and allowing few seeds to germinate at 1000 mmol/L KCl, MgSO(4), NaCl and Na(2)SO(4) solution.


Wide-field optical coherence microscopy of the mouse brain slice.
The imaging capability of optical coherence microscopy (OCM) has great potential to be used in neuroscience research because it is able to visualize anatomic features of brain tissue without labeling or external contrast agents. However, the field of view of OCM is still narrow, which dilutes the strength of OCM and limits its application. In this study, we present fully automated wide-field OCM for mosaic imaging of sliced mouse brains. A total of 308 segmented OCM images were acquired, stitched, and reconstructed as an en-face brain image after intensive imaging processing. The overall imaging area was 11.2×7.0 mm (horizontal×vertical), and the corresponding pixel resolution was 1.2×1.2 μm. OCM images were compared to traditional histology stained with Nissl and Luxol fast blue (LFB). In particular, the orientation of the fibers was analyzed and quantified in wide-field OCM.


Phase I Study of MEDI3617, a Selective Angiopoietin-2 Inhibitor Alone and Combined with Carboplatin/Paclitaxel, Paclitaxel, or Bevacizumab for Advanced Solid Tumors.
Purpose: This first-in-human study aimed to determine the MTD and safety of MEDI3617, a selective anti-angiopoietin-2 (Ang2) mAb, alone and combined with bevacizumab or cytotoxic chemotherapy.Patients and Methods: This phase I/Ib, multicenter, open-label, dose-escalation and dose-expansion study evaluated patients with advanced solid tumors. Patients received intravenous MEDI3617 as monotherapy [5-1,500 mg every 3 weeks (Q3W)] or with bevacizumab every 2 weeks (Q2W) or Q3W, weekly paclitaxel, or carboplatin plus paclitaxel Q3W. Dose expansions included a monotherapy cohort in platinum-resistant ovarian cancer and a bevacizumab combination cohort in bevacizumab-refractory malignant glioma. Safety/tolerability, pharmacokinetics, pharmacodynamics, and clinical activity were assessed.Results: We enrolled 116 patients. No formal MTD was identified (monotherapy or combination therapy). MEDI3617 demonstrated linear pharmacokinetics and maximal accumulation of peripheral Ang2 binding at doses above 300 mg Q3W. MEDI3617 monotherapy safety profile was acceptable, except in advanced ovarian cancer [prolonged grade 3 edema-associated adverse events (AE) occurred]. Otherwise, MEDI3617 combined with chemotherapy or bevacizumab was well tolerated. The AE profiles of MEDI3617 and bevacizumab were largely non-overlapping. Overall response rates in ovarian cancer and glioma monotherapy dose-expansion arms were 6% and 0%, respectively.Conclusions: Recommended MEDI3617 monotherapy dosage is 1,500 mg Q3W or 1,000 mg Q2W, except in ovarian cancer. Although peripheral edema has occurred with other Ang2 inhibitors, the severity and duration seen here in ovarian cancer potentially identifies a new, clinically significant safety signal for this class of agents. On the basis of limited clinical activity, MEDI3617 development was discontinued. Clin Cancer Res; 24(12); 2749-57. ©2018 AACR.


Tuning Sn-Catalysis for Electrochemical Reduction of CO2 to CO via the Core/Shell Cu/SnO2 Structure.
Tin (Sn) is known to be a good catalyst for electrochemical reduction of CO2 to formate in 0.5 M KHCO3. But when a thin layer of SnO2 is coated over Cu nanoparticles, the reduction becomes Sn-thickness dependent: the thicker (1.8 nm) shell shows Sn-like activity to generate formate whereas the thinner (0.8 nm) shell is selective to the formation of CO with the conversion Faradaic efficiency (FE) reaching 93% at -0.7 V (vs reversible hydrogen electrode (RHE)). Theoretical calculations suggest that the 0.8 nm SnO2 shell likely alloys with trace of Cu, causing the SnO2 lattice to be uniaxially compressed and favors the production of CO over formate. The report demonstrates a new strategy to tune NP catalyst selectivity for the electrochemical reduction of CO2 via the tunable core/shell structure.


Impairment of sperm DNA methylation in male infertility: a meta-analytic study.
Considering the widespread use of assisted reproductive techniques (ART), DNA methylation of specific genes involved in spermatogenesis achieves increasingly clinical relevance, representing a possible explanation of increased incidence of syndromes related to genomic imprinting in medically assisted pregnancies. Several trials suggested a relationship between male sub-fertility and sperm DNA methylation, although its weight on seminal parameters alteration is still a matter of debate. To evaluate whether aberrant sperm DNA methylation of imprinted genes is associated with impaired sperm parameters. Meta-analysis of controlled clinical trials evaluating imprinted genes sperm DNA methylation comparing men with idiopathic infertility to fertile controls. Twenty-four studies were included, allowing a meta-analytic evaluation for H19, MEST, SNRPN, and LINE-1. When a high heterogeneity of the results was demonstrated, the random effect model was used. H19 methylation levels resulted significantly lower in 879 infertile compared with 562 fertile men (7.53%, 95% CI: 5.14-9.93%, p < 0.001), suggesting a 9.91-fold higher risk ratio to show aberrant sperm DNA methylation (95% CI: 5.55-17.70, p < 0.001, I2 = 19%) in infertile men. The mean MEST methylation level was significantly higher in 846 infertile compared with 353 fertile men (3.35%, 95% CI: 1.41-5.29%, p < 0.001), as well as for SNRPN comparing 301 infertile men with 124 controls (3.23%, 95% CI: 0.75-5.72%, p < 0.001). LINE-1 methylation levels did not differ between 291 infertile men and 198 controls (0.44%, 95% CI: -2.04-1.16%, p = 0.63). The meta-analytic approach demonstrated that male infertility is associated with altered sperm methylation at H19, MEST, and SNRPN. Although its role in infertility remains unclear, sperm DNA methylation could be associated with the epigenetic risk in ART. In this setting, before proposing this analysis in clinical practice, an accurate identification of the most representative genes and a cost-effectiveness evaluation should be assessed in ad hoc prospective studies.


Toolbox of Advanced Atomic Layer Deposition Processes for Tailoring Large-Area MoS2 Thin Films at 150 °C.
Two-dimensional MoS2 is a promising material for applications, including electronics and electrocatalysis. However, scalable methods capable of depositing MoS2 at low temperatures are scarce. Herein, we present a toolbox of advanced plasma-enhanced atomic layer deposition (ALD) processes, producing wafer-scale polycrystalline MoS2 films of accurately controlled thickness. Our ALD processes are based on two individually controlled plasma exposures, one optimized for deposition and the other for modification. In this way, film properties can be tailored toward different applications at a very low deposition temperature of 150 °C. For the modification step, either H2 or Ar plasma can be used to combat excess sulfur incorporation and crystallize the films. Using H2 plasma, a higher degree of crystallinity compared with other reported low-temperature processes is achieved. Applying H2 plasma steps periodically instead of every ALD cycle allows for control of the morphology and enables deposition of smooth, polycrystalline MoS2 films. Using an Ar plasma instead, more disordered MoS2 films are deposited, which show promise for the electrochemical hydrogen evolution reaction. For electronics, our processes enable control of the carrier density from 6 × 1016 to 2 × 1021 cm-3 with Hall mobilities up to 0.3 cm2 V-1 s-1. The process toolbox forms a basis for rational design of low-temperature transition metal dichalcogenide deposition processes compatible with a range of substrates and applications.


Fast multicomponent 3D-T1ρ relaxometry.
NMR relaxometry can provide information about the relaxation of the magnetization in different tissues, increasing our understanding of molecular dynamics and biochemical composition in biological systems. In general, tissues have complex and heterogeneous structures composed of multiple pools. As a result, bulk magnetization returns to its original state with different relaxation times, in a multicomponent relaxation. Recovering the distribution of relaxation times in each voxel is a difficult inverse problem; it is usually unstable and requires long acquisition time, especially on clinical scanners. MRI can also be viewed as an inverse problem, especially when compressed sensing (CS) is used. The solution of these two inverse problems, CS and relaxometry, can be obtained very efficiently in a synergistically combined manner, leading to a more stable multicomponent relaxometry obtained with short scan times. In this paper, we will discuss the details of this technique from the viewpoint of inverse problems.


High-mobility group box-1 contributes tumor angiogenesis under interleukin-8 mediation during gastric cancer progression.
Many soluble factors are involved in tumor angiogenesis. Thus, it is valuable to identify novel soluble factors for effective control of tumor angiogenesis in gastric cancer (GC). We investigated the role of extracellular high-mobility group box-1 (HMGB1) and its associated soluble factors in the tumor angiogenesis of GC. Clinically, we measured serum levels of HMGB1 and GC-associated cytokines/chemokines using GC serum samples (n = 120), and calculated microvessel density (MVD) by CD34 immunostaining using human GC tissues (n = 27). Then we analyzed the correlation of serum HMGB1 levels with MVD or that with cytokine/chemokine levels by linear regression. As in vitro angiogenesis assay for HMGB1, HUVEC migration and capillary tube formation assay were carried out using different histological types of human GC cells (N87 and KATOIII). CD34-positive microvessels were detected from early GC, but MVD increased according to GC stages, and were closely correlated with serum HMGB1 levels (R = 0.608, P = 0.01). The HUVECs cultured in conditioned media derived from rhHMGB1-treated or HMGB1-TF GC cells showed remarkably enhanced migration and tube formation activities. These effects were abrogated by anti-HMGB1 antibody or HMGB1 siRNA in both N87 and KATOIII cells (all P < 0.05). Among tested cytokines/chemokines, interleukin-8 (IL-8) was the most remarkable cytokine correlated with serum HMGB1 (P < 0.001), and enhanced HUVEC migration and tube formation activities by rhHMGB1 or HMGB1-TF were significantly reversed by IL-8 inhibition. These results indicate overexpressed HMGB1 contributes to tumor angiogenesis through IL-8 mediation, and combined targeting of HMGB1 and IL-8 can control tumor angiogenesis in GC.


Tricuspid valve endocarditis caused by a new species of actinomyces: Actinomyces funkei.
We present a case of tricuspid valve endocarditis in a 40-y-old woman with a history of heroin abuse. Blood cultures yielded a Gram-positive rod, preliminarily identified as "Actinomyces turicensis-like", but subsequently formally described as Actinomyces funkei sp. nov. The patient was cured by prolonged treatment with 10 weeks of i.v. antibiotics followed by oral antibiotic treatment for 12 weeks.


Neuroimaging, Genetics, and Clinical Data Sharing in Python Using the CubicWeb Framework.
In neurosciences or psychiatry, the emergence of large multi-center population imaging studies raises numerous technological challenges. From distributed data collection, across different institutions and countries, to final data publication service, one must handle the massive, heterogeneous, and complex data from genetics, imaging, demographics, or clinical scores. These data must be both efficiently obtained and downloadable. We present a Python solution, based on the CubicWeb open-source semantic framework, aimed at building population imaging study repositories. In addition, we focus on the tools developed around this framework to overcome the challenges associated with data sharing and collaborative requirements. We describe a set of three highly adaptive web services that transform the CubicWeb framework into a (1) multi-center upload platform, (2) collaborative quality assessment platform, and (3) publication platform endowed with massive-download capabilities. Two major European projects, IMAGEN and EU-AIMS, are currently supported by the described framework. We also present a Python package that enables end users to remotely query neuroimaging, genetics, and clinical data from scripts.


Nonischemic Priapism in Childhood: A Case Series and Review of Literature.
Nonischemic priapism (NIP) in childhood is a very rare affection. In the literature, patients with NIP are described mainly incidental after perineal trauma. Many of them underwent embolization of either internal pudendal artery or bulbocavernosal arteries. We report on six boys between 4 and 13 years of age with NIP, treated at our institution between 2008 and 2014. Color Doppler ultrasound (CDU) was performed in all patients as emergency diagnostic evaluation. Patients were treated conservatively, including bed rest, local cooling, and perineal compression. History, etiological factors, clinical findings, diagnostics, and follow-up are presented. Out of the six patients, only one boy had a history of perineal injury with subsequent arteriocavernosal fistula, revealed in CDU. Five patients were circumcised, and one of them suffered from thalassemia minor, but no other underlying disease or etiological factors could be found. In all patients, normal to high blood flow velocities were detected in the cavernosal arteries. Detumescence started with nonoperative treatment within 24 hours in five boys and in one patient with recurrent priapism after 1 week. All six patients remained painless without evidence for an ischemic priapism. None of them suffered from relapse and further erections were observed during follow-up from 3 to 87 months. In contrast to the literature, five out of six boys developed NIP without a previous perineal trauma. The etiology of idiopathic NIP in childhood remains unclear; however, circumcision may play a role as a conditional factor. One etiological thesis could be the release of the neurotransmitter nitric oxide after stimulation of the corpora cavernosa. Conservative treatment proved to be successful in all six patients. During a median follow-up of 55 months (3-87 months), none of the patients showed signs of erectile dysfunction.


Recombinant Mycobacterium smegmatis with a pMyong2 vector expressing Human Immunodeficiency Virus Type I Gag can induce enhanced virus-specific immune responses.
Recently, we have developed a novel Mycobacterium-Escherichia coli shuttle vector system using pMyong2, which can provide an enhanced expression of heterologous genes in recombinant Mycobacterium smegmatis (rSmeg). To investigate the usefulness of rSmeg using pMyong2 in vaccine application, we vaccinated M. smegmatis with pMyong2 system expressing Human Immunodeficiency Virus Type I (HIV-1) Gag p24 antigen (rSmeg-pMyong2-p24) into mice and examined its cellular and humoral immune responses against HIV gag protein. We found that rSmeg-pMyong2-p24 expressed higher levels of Gag protein in bacteria, macrophage cell line (J774A.1) and mouse bone marrow derived dendritic cells (BMDCs) compared to rSmeg strains using two other vector systems, pAL5000 derived vector (rSmeg-pAL-p24) and the integrative plasmid, pMV306 (rSmeg-pMV306-p24). Inoculation of mice with rSmeg-pMyong2-p24 elicited more effective immunity compared to the other two rSmeg strains, as evidenced by higher levels of HIV-1 Gag-specific CD4 and CD8 T lymphocyte proliferation, interferon gamma ELISPOT cell induction, and antibody production. Furthermore, rSmeg-pMyong2-p24 showed a higher level of cytotoxic T cell response against target cells expressing Gag p24 proteins. Our data suggest that Mycobacterium-Escherichia coli shuttle vector system with pMyong2 may provide an advantage in vaccine application of rSmeg over other vector systems.


Influence of ACE gene on differential response to sertraline versus fluoxetine in patients with major depression: a randomized controlled trial.
Extensive distribution of the different components of renin angiotensin system (RAS) in the brain, along with their roles in promoting anxiety, depression and brain inflammation, opposes RAS as a potential therapeutic target in major depression. Actions of angiotensin II, the main product of RAS, are reduced by antidepressants and this signifies the complex interplay of different mechanisms involved in response to therapy. Here, we hypothesized that genetic polymorphisms of RAS may affect the outcome of therapy in depressed patients. The frequencies of variants of genes encoding for angiotensin-converting enzyme (ACE) insertion/deletion (I/D), rs4291 and rs4343 polymorphisms were determined in extracted DNAs of 200 newly diagnosed depressed patients. Patients were randomly divided into two groups, one treated with fluoxetine and the other treated with sertraline for 12 weeks. Responsive patients were determined by psychiatrist using Hamilton questionnaire and were compared with regard to their genetic variants. Carriers of the D allele and patients with DD genotype responded significantly better to sertraline than to fluoxetine (P = 0.0006, odds ratio (OR) = 3.0, 95 % confidence interval (CI) = 1.80-5.08; P = 0.006, OR = 3.7, 95 % CI = 1.66-8.29, respectively). Mutant genotypes (GG and TT) of rs4343 and rs4291 polymorphisms were also more frequent in patients responding to sertraline, though not achieving the significance level (P = 0.162 and P = 0.256, respectively). These findings suggest that special genetic variants of RAS may influence or be an indicator for better response to sertraline.


Fusarium avenaceum -- the North European situation.
The Fusarium species complex found on small-grain cereals in Northern Europe is largely dominated by F. avenaceum, while other important species include F. tricinctum, F. poae, F. culmorum and F. graminearum. The dominance of F. avenaceum has in recent years initiated extensive analytical activity in Norway and Finland in order to gain insight into the contamination of grain with secondary metabolites related to the fungus. Of these, moniliformin is the most studied compound with regard to toxicity. However, the data from analytical surveys indicate that field conditions in Northern Europe do not favour production of the metabolite. Instead, enniatins are regularly found in ppm-concentrations in grain, especially wheat and barley, while the bio-production of a range of other F. avenaceum related metabolites has so far barely been investigated. This paper summarises the results from mycological and chemical analyses of grain samples from Norway and Finland for major Fusarium species and F. avenaceum-related secondary metabolites.


Effects of static magnetic fields on growth and membrane lipid composition of Salmonella typhimurium wild-type and dam mutant strains.
This study was carried out to explore the adaptive mechanisms of S. typhimurium particularly, the implication of the Dam methyltransferase in the remodelling of membrane lipid composition to overcome magnetic field stress. With this aim, we focused our analyses on the increase in viable numbers and membrane lipid modifications of S. typhimurium wild-type and dam mutant cells exposed for 10h to static magnetic fields (SMF; 200 mT). For the wild-type strain, exposure to SMF induced a significant decrease (p<0.05) of CFU at 6h, followed by an increase between 8 and 10h. Growth of the dam mutant was significantly affected (p<0.05) after 6h and no recovery was observed until 10h, highlighting a different behavior of SMF stressed wild-type and dam mutant strains. SMF significantly affected the phospholipid proportions in the two strains. The most affected were those of the acidic phospholipids, cardiolipins (CL). In the dam strain the phospholipid response to SMF followed a globally similar trend as in the wild-type with however lower effects, leading mainly to an unusual accumulation of CL. This would in part explain the different behavior of the wild-type and the dam strain. Results showed a significant increase of membrane cyclic fatty acids Cyc17 and Cyc19 in the wild-type strain but only the Cyc17 in the dam strain and a meaningful increase of the total unsaturated fatty acids (UFAs) to total saturated fatty acids (SFAs) ratios of the exposed cells compared to controls from 3 to 9h (p<0.05) for both strains. The net increase of the total UFAs to total SFAs ratios seemed to result mainly from the increase of (C18:1) proportion (p<0.05) and to a lower extent from that of (C16:1) (p<0.05). These modifications of cyclic and unsaturated fatty acid proportions constitute an adaptive response to SMF stress in S. typhimurium wild-type and dam mutants to maintain an optimum level of membrane fluidity under SMF.


High prevalence of pain in patients with cancer in a large population-based study in The Netherlands.
At present, no definite conclusions can be drawn about the real extent of the pain suffered by cancer patients. A population-based study was conducted to obtain reliable information about the prevalence and severity of pain in cancer patients (all phases) and about predictors of pain. A representative sample of cancer patients was recruited in the area from a cancer registry. Pain was assessed by the Brief Pain Inventory (BPI). Adequacy of pain treatment was assessed with the Pain Management Index (PMI). We found that 55% of the 1429 respondents had experienced pain past week; in 44% (n=351), the pain was moderate to severe (BPI score>or= 4). Total prevalence of pain/moderate to severe pain was present in 49%/41% in patients with curative treatment >or=6 months ago, 57%/43% in patients with current curative treatment or treatment <6 months ago, 56%/43% in patients with current palliative anti-cancer treatment and in 75%/70% in patients for whom treatment was no longer feasible. Positive predictors of the prevalence of pain were lower education level, more advanced disease and haematological (excluding (non)-Hodgkin lymphoma), gastro-intestinal, lung, or breast malignancies. According to the PMI, analgesic treatment was inadequate in 42% of the patients. Negative predictors of adequate treatment were current curative anti-cancer treatment and low education level. A substantial proportion of cancer patients does suffer from moderate to severe pain and does not receive adequate pain treatment.


Assessing the Use of PCR To Screen for Shedding of Salmonella enterica in Infected Humans.
Recovery from enteric bacterial illness often includes a phase of organismal shedding over a period of days to months. The monitoring of this process through laboratory testing forms the foundation of public health action to prevent further transmission. Regulations in most jurisdictions in the United States exclude individuals who continue to shed certain organisms from sensitive occupations and situations, such as food handling, providing direct patient care, or attending day care. The burden that this creates for recovering patients and their families/coworkers is great, so any effort to provide efficiency to the testing process would be of significant benefit. We sought to assess the ability of PCR for the detection of Salmonella enterica shedding and to compare that ability to culture-based testing. PCR would be faster than culture and would allow results to be generated more quickly. Herein, we show data that indicate that, while PCR and culture testing agree in the majority of cases, there are incidents of discordance between the two tests, whereupon PCR shows positive results when culture indicates lack of detectable viable organisms. Using culture-based testing as the standard, the negative predictive value of PCR was found to be 100%, while the positive predictive value was 79%. The nature of this discordance is briefly investigated. We found that it is possible that PCR may not only detect nonviable organisms in stool but also viable organisms that remain undetectable by standard culture methods.


A probe into the developmental pattern of public art education in colleges and universities from the perspective of new media.
The integration of public art education and new media in colleges and universities remains a trend which cannot be stopped. As new media has had a beneficial impact on teaching content, forms of teaching, and teaching effects, it has also created various challenges for public art education in colleges and universities. While investigating the current state of integrating new media with public art education in colleges and universities, it was found that the impact of new media benefits more than it harms, whether it be online, in-person, theoretical, or practical teaching. Based on the current state, future policy focus, the direction of new media's changes, and the depth of cultural and art resources, new media and public art education in colleges and universities will continue to deepen integration and show further improvement. Using a survey of more than a dozen universities in the Jiangsu Province and the results of a questionnaire survey of 116 college students, this paper probes into the changes in public art education in colleges and universities in the new media era and explores the future developmental pattern of public art education in colleges and universities both internally and externally.


Brenner tumors of the ovary: sonographic and computed tomographic imaging features.
The purpose of this study was to describe the sonographic appearance of ovarian Brenner tumors with computed tomographic (CT) correlation. Twenty-two female patients (age range, 32-78 years; mean, 58 years) with 25 ovarian Brenner tumors were identified from pathologic records from 1990 to 2005. Corresponding pathologic reports and images (17 sonographic and 14 CT) were reviewed independently. Tumors ranged in size from 0.3 to 12 cm (mean, 2.5 cm); all were benign. Sixteen (64%) of 25 were found incidentally. Eight (36%) of 22 patients had a total of 12 associated benign ovarian neoplasms (1 was contralateral); 3 patients had bilateral Brenner tumors. Eight (47%) of 17 tumors were not seen on sonography, and 5 (36%) of 14 were not seen on CT. Of the tumors seen on imaging, most were solid (67% on sonography and 78% on CT). Four tumors appeared at least partially cystic, of which 3 had coexistent cystic ovarian lesions. Brenner tumors are most often solid neoplasms found incidentally and frequently seen in association with other benign ovarian epithelial neoplasms.


[Differences among bisfosfonates--specificity of risedronate (Actonel)].
Bisphosphonates, a gold standard in therapeutic options for the management of osteoporosis, inhibit bone resorption with relatively few side effects. As a result, they are widely used for the prevention and treatment of osteoporosis. There are clear biochemical and pharmacological differences among bisfosfonates group. Risedronate has moderate mineral binding and has a higher inhibition of a key branch-point enzyme famesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Risedronate (Actonel) prevents vertebral and nonvertebral fractures as early as at 6 months of treatment. Clinical trials and observational trials have proved risk reduction of vertebral and hip fractures. Patients remarkably preferred therapy with a proven antifracture efficacy over a dosage frequency.


Rheumatic fever with severe carditis: still prevalent in the South West Pacific.
Rheumatic heart disease (RHD) has a worldwide prevalence of 33 million cases and 270 000 deaths annually, making it the most common acquired heart disease in the world. There is a disparate global burden in developing countries. This case report aims to address the minimal RHD coverage by the international medical community. A Tahitian boy aged 10 years was diagnosed with advanced heart failure secondary to RHD at a local clinic. Previous, subtle symptoms of changes in handwriting and months of fever had gone unrecognised. Following a rapid referral to the nearest tertiary centre in New Zealand, urgent cardiac surgery took place. He returned home facing lifelong anticoagulation. This case highlights the RHD burden in Oceania, the limited access to paediatric cardiac services in countries where the RHD burden is greatest and the need for improved awareness of RHD by healthcare professionals, and the general public, in endemic areas.


[Renal cell carcinoma in a horseshoe kidney: a case report].
A 69-year-old man presented for further examination for left renal mass. Computed tomography and magnetic resonance imaging revealed a heterogenous mass on the left side of a horseshoe kidney accompanied with renal vein thrombus. Aortography showed a hypervascular mass in the left kidney and aberrant arteries to the isthmus originating from the aorta. A left nephrectomy with the division of the isthmus was performed through an abdominal transperitoneal approach. Histological evaluation revealed grade 2, stage T3b, renal cell carcinoma. The patient was free of tumor, but died of intracerebral hemorrhage 5 months after the operation.


Functional genetic polymorphisms and female reproductive disorders: Part I: Polycystic ovary syndrome and ovarian response.
The identification of polymorphisms associated with a disease can help to elucidate its pathogenesis, and this knowledge can be used to improve prognosis for women with a particular disorder, such as polycystic ovary syndrome (PCOS). Since an altered response to ovarian stimulation is also a characteristic of the disease, further knowledge about its aetiology could help in defining the parameters that determine the response of an individual to ovarian stimulation. PubMed and EMBASE databases were systematically searched for gene association studies published until the end of August 2007, using search criteria relevant to PCOS and ovarian response to stimulation. Data from additional papers identified through hand searches were also included; 139 publications were reviewed. Several genes involved in ovarian function and metabolism are associated with increased susceptibility to PCOS, but none is strong enough to correlate alone with susceptibility to the disease, or response to therapy. A single-nucleotide polymorphism in exon 10 of the FSH receptor (FSHR) gene, FSHR p.N680S, was consistently identified as having a significant association with ovarian response to FSH. No consistent association between gene polymorphism and PCOS could be identified. The FSHR gene may play a significant role in the success of ovarian stimulation, and can be used as a marker to predict differences in FSHR function and ovarian response to FSH. Genotyping the FSHR p.N680S polymorphism may provide a means of identifying a population of poor responders before in vitro fertilization procedures are initiated.


Future immunosuppressive agents in solid-organ transplantation.
To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium, everolimus, and FTY720. Clinical trials and abstracts evaluating mycophenolate sodium, everolimus, and FTY720 in solid-organ transplantation were considered for evaluation. English-language studies and published abstracts were selected for inclusion. Mycophenolate sodium has recently been approved by the Food and Drug Adminstration for marketing in the United States; everolimus and FTY720 are immunosuppressive agents that may soon be available in the United States. These agents have proven efficacy in reducing the incidence of acute rejection in solid-organ transplantation. Clinical trials have shown that these newer agents are relatively well tolerated. The most common adverse events associated with these agents were gastrointestinal and hematologic effects (mycophenolate sodium); hyperlipidemia, increased serum creatinine, and hematologic effects (everolimus): and gastrointestinal effects, headache, and bradycardia (FTY720). Mycophenolate sodium has been approved in some European countries and the United States. Everolimus has been approved in some European countries and a new drug application has been submitted to the Food and Drug Administration. FTY720 is currently in phase III clinical trials and submission to the Food and Drug Administration for approval is a few years away. The approval of these agents will furnish the transplant practitioner with even more options for immunosuppression.


Genital Ulcer Disease: A Review of Pathogenesis and Clinical Features.
Genital ulcer disease can be caused by a wide variety of sources. Most commonly, genital ulcer disease is grouped into infectious and noninfectious causes. HSV, syphilis, lymphogranuloma venereum, and chancroid represent some common infectious ulcers. Noninfectious causes on the other hand can be inflammatory, noninflammatory, or malignant (eg, squamous cell carcinoma). Depending on the etiology, genital ulcers may present with unique features that can help clinicians identify the etiology and start treatment in a timely manner. The clinical presentation and management of infectious and noninfectious genital ulcers will be discussed in this review.


Complicated Fusobacterium Sinusitis: A Case Report.
Fusobacterium infections and Lemierre syndrome are traditionally associated with pharyngitis. We report 3 cases of Fusobacterium sinusitis that resulted in Pott puffy tumor. One of these cases also had Lemierre Syndrome. We encourage expansion of the clinical spectrum of Lemierre syndrome to include complicated Fusobacterium sinusitis.


African American Fathers' Occupational Participation: "Keeping the Mothers in a Positive Vibe".
Infant mortality is a major public health issue in the United States that disproportionally affects African Americans. Evidence suggests reducing stress on African American women and engaging African American fathers may improve health and social outcomes for families. This study sought to understand the experiences of African American fathers through a positivistic lens and to inform future interventions that support father engagement. A descriptive, qualitative study using the Person, Environment, Occupation-Performance (PEO-P) model as a framework for analysis was conducted involving 45 fathers participating in four focus groups and one member-checking group. An initial content analysis was followed by constant comparative methods to identify categories related to the PEO-P model. Transcripts revealed a range of factors that enable or inhibit fathers' occupational performance and engagement including environmental barriers such as societal expectations and perceptions. Occupational therapy practitioners may utilize population health approaches to support African American fathers' occupational engagement.


The context theory as applied to the decoding of the initiator tRNA by Escherichia coli ribosomes.
The involvement of nucleotides adjacent to the termination codons in tRNA during the suppression of termination has been formulated as the 'context theory' by Bossi and Roth (1980) [Nature (Lond.) 286, 123-127]. The finding that U-U-G functions as an initiator codon has revived the discussion on the participation of the nucleotides flanking the initiator triplet in the decoding of initiator tRNA (context theory of initiation by the ribosome). We compared the capacity of oligonucleotides cognate to the anticodon loop of formylmethionine tRNA, such as A-U-G, A-U-G-A and U-A-U-G-A, to enhance the formation of the 30-S and 70-S ribosomal initiation complexes. Three different methods were used to determine the apparent binding constants and the stoichiometries of the respective complexes: adsorption of the complexes to nitrocellulose filters, equilibrium dialysis, and velocity sedimentation. We found that in the 30-S ribosomal initiation complex and in the presence of initiation factor 2 and GTP, formylmethionyl-tRNA is preferentially decoded by more than three mRNA bases. With the 70-S ribosome, however, once initiation factor 2 had been released, A-U-G represented the most effective codon to direct the formylmethionyl-tRNA to the peptidyl site. An extended initiator sequence may either give additional stability to the 30-S initiation complex or may allow for an ambiguity by one base pair in the decoding of the initiator tRNA.


Production of age-related DNA strand breakage in brain cells of senescence-accelerated prone (SAMP1) mouse.
Amounts of DNA strand breaks were estimated by the proportion of cells without tails (PCWT) and the average lengths of tail momentum (ALTM) in comet images of tissue cells of senescence-accelerated prone (SAMP1) mouse and senescence-accelerated resistant (SAMR1) mouse. The PCWT and ALTM of brain cells from SAMR1 were unchanged from 4 to 15 months of age. In the case of SAMP1 brain cells, the PCWT decreased and the ALTM increased in an age-related manner from 8 to 15 months of age. In the cases of liver and kidney, the PCWT and the ALTM of both SAMP1 and SAMR1 cells showed constant values from 4 to 15 months of ages.


The Kollias legacy: Skin autofluorescence and beyond.
In a paper published at the J Invest Dermatol in 1998 Nik Kollias and coworkers described distinct changes in skin native fluorescence associated with skin aging and photoaging, using in vivo fluorescence excitation spectroscopy. The assignment of the 295 nm band to tryptophan fluorescence had a profound significance influencing many later studies from multiple groups. The reproducible changes in skin native fluorescence suggested that aging causes predictable alterations in both the epidermis and the dermis, whereas chronic UV exposure induces the appearance of new fluorophores. This seminal, but insufficiently widely appreciated work deserves re-examination as it points to important horizons in future experimental dermatology, such as cancer diagnostics, diabetes, wound healing, and understanding skin aging and photoaging mechanisms.


[Electronic processing of intravascular by measured blood pressure].
With the help of electronic processing of measurement values the possible information content of the dynamic blood pressure measured by means of the electromanometer is explained. Commericial writing systems and pressure changers are supplemented by self-constructed and especially dimensioned additional devices. Partly in connection with flow sizes by multiplication, division, addition, subtraction, differentiation and integration from pressure values special references to the behaviour of the haemodynamics of certain parts of the circulation are to be obtained. This is explained by examples. In addition to this the authors deal with the systolic and diastolic indication of blood pressure important for haemodynamic measuring programs, with the electronic mean value formation, with the limitaor connection for the indication of the enddiastolic ventricular pressure as well with the short-term accumulation. The electronic processing of the intravasally measured blood pressure as well as of flow values is necessary for analyses of the circulation.


Exploring the neuroanatomical bases of psychotic features in bipolar disorder.
Although bipolar disorder (BD) is traditionally conceptualised as one diagnostic entity, the heterogeneity of pathophysiological manifestations in BD suggests the need to classify the subtypes of the illness based on neural markers. Specifically, the presence of psychotic symptoms seems to be relevant for the clinical outcome and may have specific neuroanatomical bases. The main objective of the present review was to assess whether the distinction between psychotic BD (PBD) and non-psychotic BD (NPBD) can improve the identification of the neurobiological markers of this complex illness. To this end, we summarised the findings from the magnetic resonance imaging studies that explored the cerebral correlates of psychosis in BD in terms of grey matter volume (GMV). Overall, the results suggest the presence of peculiar GMV differences between PBD and NPBD. Specifically, psychosis in BD seems to be associated with cortical GMV deficits compared with both healthy controls and NPBD, mainly in the frontal region. Conversely, NPBD patients showed GMV deficits in selective regions of the basal ganglia when compared with the other groups. Taken together, this evidence confirms the importance to classify BD based on the psychotic dimension, which may have a specific neurobiological architecture that partially overlaps across multiple psychotic disorders.


A case report: Acute kidney injury with progression to chronicity in an eldery woman.
Acute renal failure in elderly patients can be caused by a wide spectrum of diseases that usually have a cause outside the kidney. The most common causes include renal impairment as part of ANCA vasculitis, another category includes clonal plasmatic cell disease with light chain cast nephropathy; and there also exists an increasing number of drug-induced tubulointerstial damage. We present a case of iatrogenic less common form of acute failure in a 73-year-old woman, who did not suffer from any serious disease until then. Although the biopsy helped to determine the cause of the failure and thus affect subsequent therapy, the function did not return to the previous state and the patient progressed to CKD G3bA1 with serum creatinine values of around 170-140 μmol/l.


[Experience in setting up a morbid anatomy bureau in the Gomel Region, Republic of Belarus].
A diversity of the clinical and morphological manifestations pf melanoma determines the great importance of each description of manifestation of this most malignant tumor. In this connection, there is a worldwide increasing rise in the number of patients with melanoma whose diagnosis present well-known difficulties, the authors describe a case of this tumor progression, which masked as uterine carcinoma.


CD47 Overexpression Is Associated with Epstein-Barr Virus Infection and Poor Prognosis in Patients with Nasopharyngeal Carcinoma.
Little is known about the clinical significance of CD47 expression and its association with Epstein-Barr virus (EBV) infection in patients with nasopharyngeal carcinoma (NPC). The aim of this study was to clarify the prognostic value and role of CD47 in EBV-associated NPC. Sixty-six cases of non-metastatic NPC were retrospectively reviewed. Tissues were collected for immunohistochemical staining of CD47 and the EBV-encoded oncoprotein latent membrane protein 1 (LMP1). Western blotting and quantitative real-time PCR were performed to determine the CD47 and LMP1 levels in common human NPC cell lines. Additionally, CD47 and LMP1 expression in a constructed EBV-positive human NPC cell (CNE-2-EBV+) and a stable cell line transfected with LMP1 plasmid (CNE-2-LMP1) was assessed. Next, we used Western blotting to assess the decrease in CD47 expression on CNE-2-LMP1 cells after transfecting them with small interfering RNA (siRNA)-targeting LMP1. In NPC patients, CD47 overexpression was significantly associated with disease recurrence (P=0.010), leading to poorer disease-free survival (DFS; P=0.002) and overall survival (P=0.021). Multivariate Cox proportional hazards models demonstrated that CD47 (HR=5.452, P=0.016) was an independent prognostic factor of DFS. Moreover, CD47 expression was associated with plasma EBV-DNA copy number and LMP1 tissue expression. Among the human NPC cell lines, CD47 and LMP1 expression was notably higher in the EBV-positive C666-1 cell line than in the EBV-negative cell lines. Furthermore, EBV infection upregulated CD47 expression via LMP1-mediated pathways in human NPC cells. This study indicated that CD47 is related to EBV infection in NPC patients, and it is a feasible biomarker.


Modification of relaxation of lipid protons by molecular oxygen and nitroxides.
Measurement of proton 1/T1 in model lipids from 0.00023 to 1.3 Tesla, at 5 degrees C and 37 degrees C, shows that both oxygen and nitroxides effectively enhance the relaxation rates of the protons of lipids. Equilibration with 1 atm of oxygen has a sixfold greater effect on lipid protons than on water protons, primarily because of the high lipid solubility of oxygen. The maximum relative relaxivity of oxygen for lipid protons occurs at 0.12-0.8 Tesla. Lipid soluble nitroxides have a four- to eightfold greater effect on lipid protons than on water protons. This high relaxivity, combined with the high lipid solubility possible with nitroxides, could lead to significant contrast in vivo in lipid environments.


Intracardiac Thrombosis and Heart Failure in a Patient with Hepatocellular Carcinoma and Cardiac Amyloidosis and an Implanted Cardiac Resynchronization Therapy Device.
BACKGROUND Intracardiac thrombosis has been known to be associated with not only hepatocellular carcinoma but also with amyloidosis and use of a cardiac implantable electronic device. We report a case of a continuous tumor thrombus with hepatocellular carcinoma from the portal vein and hepatic vein to the right atrium via the inferior vena cava in a patient with a cardiac amyloidosis and an implanted cardiac resynchronization therapy (CRT) device. CASE REPORT A 68-year-old female first admitted to our hospital because of heart failure with an AL type primary cardiac amyloidosis. After 3 years, she underwent an implantation of a CRT device for biventricular pacing following repeated episodes of heart failure and low left ventricular ejection fraction of 34% with NYHA class III. Again, she presented with symptoms of heart failure and cardiomegaly on chest x-ray at 7 years after the CRT device implantation. The echocardiography showed a huge echogenic mass occupying the right atrium, and 64 multi-detector computed tomography showed a lobulated heterogeneously enhancing mass of hepatocellular carcinoma in the right upper lobe of her liver and a continuous tumor thrombus from the portal vein and hepatic vein to the right atrium via the inferior vena cava. CONCLUSIONS Intracardiac thrombosis and heart failure occurred in a patient with hepatocellular carcinoma and cardiac amyloidosis, who had an implanted CRT device, which resulted not only in hypercoagulability by the hepatocellular carcinoma itself and the accumulation of various risk factors, but also the progression of myocardial damage with the development of amyloidosis.


A gait analysis of simulated knee flexion contracture to elucidate knee-spine syndrome.
Knee flexion contracture influences the physiological movements in lower extremities and may cause the kinematic changes of the trunk. Our purpose was to investigate static and dynamic changes in trunk kinematics with simulated knee flexion contracture. Ten healthy females averaged 62 years participated in our study. Unilateral knee flexion contractures of 15 degrees and 30 degrees were simulated with a knee brace. Relaxed standing and level walking were measured at our laboratory using a motion analysis system which consisted of five cameras, a force plate, and thirteen retro-reflective markers. Three-dimensional trunk kinematics and vertical knee forces (% Body Weight) with the contractures were compared with those without the contracture. The 15 degrees contracture did not significantly change trunk kinematics. However, the 30 degrees contracture significantly changed the kinematics in each of the following planes. In the coronal plane, the trunk tilted to the contracture side in standing and walking. In the sagittal plane, posterior inclination of the pelvis in standing significantly increased. In addition, anterior inclination of the trunk and pelvis during walking significantly increased. In the axial plane, trunk rotation to the unaffected side significantly decreased during walking. The vertical knee force in the contracture limb decreased, being accompanied by the increase of the force in the unaffected limb during standing and walking. Results of our study suggest that knee flexion contracture significantly influences three-dimensional trunk kinematics during relaxed standing and level walking, and will lead to spinal imbalance. These facts may explain the onset of the "Knee-Spine Syndrome".


Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or in combination with GHRH: comparison with the insulin tolerance test.
The diagnosis of GH deficiency in adults should be made using provocative testing of GH secretion. The insulin tolerance test (ITT) is recommended as the gold standard investigation. Because of the risk of serious complications, patients with epilepsy or known ischemic heart disease should not undergo this test. GHRP-6 is a synthetic hexapeptide that releases GH by binding to specific hypothalamic and pituitary receptors. We assessed the diagnostic capability of GH stimulation by GHRP-6 alone or in combination with GHRH in comparison to the results of an ITT. Twenty patients underwent an ITT for suspected pituitary or adrenal disease. Either GHRP-6 (1 microg/kg) alone, or GHRP-6 in combination with GHRH (1 microg/kg) were administered on different days. Blood samples were obtained during a subsequent 90-min period for measurement of GH. Ten patients had a GH peak response of less than 3 microg/l during ITT and were considered growth hormone deficient (GHD). The GH mean peak (+/-S.E.M., range) in this group was 0.7 microg/l (+/-0.3, 0.1-2.9) compared with 14.5 microg/l (+/-3.5, 3.8-40.8) in the group of patients with a GH peak response of more than 3 microg/l (growth hormone sufficient (GS)). For the GHRP-6 test, the GH mean peak was 1.3 microg/l (+/-0.6, 0.1-6.7) in the GHD group versus 25.7 microg/l (+/-5.5, 7.7-54.2) in the GS group. After GHRP-6+GHRH, the GH mean peaks were 4.0 microg/l (+/-1.3, 0.2-11.9) versus 54.7 microg/l (+/-11.1, 13.9-136.0) respectively. During administration of GHRP-6, the only side effects observed were flush symptoms. Peak GH levels below 7 microg/l for the GHRP-6 test and below 13 microg/l for the combined GHRP-6+GHRH test identified all patients with GH deficiency correctly as defined by ITT. The results suggest that testing with GHRP-6 or GHRP-6+GHRH is as sensitive and specific as an ITT for the diagnosis of adult GH deficiency.


Formulation development and process analysis of drug-loaded filaments manufactured via hot-melt extrusion for 3D-printing of medicines.
Three dimensional(3D)-printing via fused deposition modeling (FDM) allows the production of individualized solid dosage forms. However, for bringing this benefit to the patient, active pharmaceutical ingredient (API)-loaded filaments of pharmaceutical grade excipients are necessary as feedstock and have to be produced industrially. As large-scale production of API-loaded filaments has not been described in literature, this study presents a development of 3D-printable filaments, which can continuously be produced via hot-melt extrusion. Further, a combination of testing methods for mechanical resilience of filaments was applied to improve the prediction of their printability. Eudragit RL was chosen as a sustained release polymer and theophylline (30%) as thermally stable model drug. Stearic acid (7%) and polyethylene glycol 4000 (10%), were evaluated as suitable plasticizers for producing 3D-printable filaments. The two formulations were printed into solid dosage forms and analyzed regarding their dissolution profiles. This revealed that stearic acid maintained sustained release properties of the matrix whereas polyethylene glycol 4000 did not. Analysis of the continuous extrusion process was done using a design of experiments. It showed that powder feed rate and speed of the stretching device used after extrusion predominantly determine the diameter of the filament and thereby the mechanical resilience of a filament.


Economic impact of onabotulinumtoxinA for overactive bladder with urinary incontinence in Europe.
Overactive bladder (OAB) is a common condition that has a significant impact on patients' health-related quality-of-life and is associated with a substantial economic burden to healthcare systems. OnabotulinumtoxinA has a well-established efficacy and safety profile as a treatment for OAB; however, the economic impact of using onabotulinumtoxinA has not been well described. An economic model was developed to assess the budget impact associated with OAB treatment in France, Germany, Italy, Spain and the UK, using onabotulinumtoxinA alongside best supportive care (BSC)-comprising incontinence pads and/or anticholinergic use and/or clean intermittent catheterisation (CIC)-vs BSC alone. The model time horizon spanned 5 years, and included direct costs associated with treatment, BSC, and adverse events. Per 100,000 patients in each country, the use of onabotulinumtoxinA resulted in estimated cost savings of €97,200 (Italy), €71,580 (Spain), and €19,710 (UK), and cost increases of €23,840 in France and €284,760 in Germany, largely due to day-case and inpatient administration, respectively. Projecting these results to the population of individuals aged 18 years and above gave national budget saving estimates of €9,924,790, €27,458,290, and €48,270,760, for the UK, Spain, and Italy, respectively, compared to cost increases of €12,160,020 and €196,086,530 for France and Germany, respectively. Anticholinergic treatment and incontinence pads were the largest contributors to overall spending on OAB management when onabotulinumtoxinA use was not increased, and remained so in four of five scenarios where onabotulinumtoxinA use was increased. This decreased resource use was equivalent to cost offsets ranging from €106,110 to €176,600 per 100,000 population. In three of five countries investigated, the use of onabotulinumtoxinA, in addition to BSC, was shown to result in healthcare budget cost savings over 5 years. Scenario analyses showed increased costs in Germany and France were largely attributable to the treatment setting rather than onabotulinumtoxinA acquisition costs.


Multicentric Type 3 Gastric Neuroendocrine Tumors.
A 50-year-old woman with incidentally detected multiple gastric polyps and biopsy-proven neuroendocrine tumor (NET) was referred to our hospital. More than 10 polypoid lesions (less than 15 mm) with normal gastric mucosa were detected from the gastric body to the fundus. The serum level of gastrin was within the normal limits. There was no evidence of atrophic changes on endoscopy and serologic marker as pepsinogen I/II ratio. Computed tomography of the abdomen and pelvis revealed no evidence of metastatic lesions. She refused surgery, and we performed endoscopic polypectomy for almost all the gastric polyps that were greater than 5 mm. Although the histological examination revealed that all the removed polys were diagnosed as NET G1, three of them extended to the lateral or vertical resection margins, while two exhibited lymphovascular invasion. A follow-up upper endoscopy that was performed 6 months after the diagnosis showed multiple remnant gastric polyps that were suggestive of remnant gastric NET.


Subclinical ammonia toxicity in steers: effects on blood metabolite and regulatory hormone concentrations.
The effects of subclinical NH3 toxicity on circulating and regulatory hormone concentrations were investigated in seven Hereford steers. Ammonium chloride (NH4Cl) was infused via a right jugular vein catheter at a rate of 12 mumol NH4Cl.kg BW-1.min-1 for 240 min. This was preceded (PRE) and followed (POST) by saline infusions of 120 and 180 min, respectively. Blood samples were taken at 20-min intervals via a left jugular vein catheter. Metabolite and hormone concentrations during NH4Cl and POST periods were compared to PRE values using the Student's t-test procedure. Plasma NH3 was elevated rapidly (P less than .001) and peaked at 503 micrograms/dl 220 min into NH4Cl infusion. Plasma urea-N and glucose increased (P less than .001) 39 and 12%, respectively, during NH4Cl infusion and remained elevated 180 min POST. Whole blood L-lactate concentrations peaked (P less than .05) at 18% above PRE between 160 and 240 min into the NH4Cl infusion and gradually returned to PRE values, whereas pyruvate levels were not altered (P greater than .10). Plasma nonesterified fatty acids peaked (P less than .001) at 94% above PRE levels 40 min into NH4Cl infusion, thereafter declining to PRE concentrations. Whole blood acetoacetate and beta-hydroxybutyrate concentrations were not altered (P greater than .10) by NH4Cl administration. Plasma insulin concentration decreased (P less than .05) 26 to 46% during NH4Cl infusion and increased (P less than .05) 89 to 122% during POST. Plasma glucagon levels were not altered by NH4Cl infusion, so molar insulin:glucagon ratio changes resembled those of insulin. Plasma epinephrine, norepinephrine and dopamine did not vary (P greater than .10) with treatment. These results support the hypothesis that the hyperglycemia observed during hyperammonemia may result from an under-utilization of glucose by insulin-sensitive tissues.


Effect of Shi-Zhen-An-Shen herbal formula granule in the treatment of young people at ultra-high risk for psychosis: a pilot study.
To date, there is no conclusive evidence for early interventions on ultra-high risk (UHR) for psychosis. The Chinese herbal medicine is confirmed to be beneficial in improving psychiatric symptoms and cognitive impairments for schizophrenia patients. However, the effect of Chinese herbal medicine on treating UHR patients remains unknown. Eighty UHR patients were recruited from the outpatient department. They were randomly assigned to receive either Shi-Zhen-An-Shen herbal formula granule (SZAS-HFG) combined with aripiprazole placebo or aripiprazole combined with SZAS-HFG placebo for a 12-week treatment. The psychiatric symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). The Trail Making Test part A (TMT-A), Brief Visuospatial Memory Test (BVMT), Hopkins Verbal Learning Test (HVLT), and Continuous Performance Test (CPT) were used to assess cognitive functions. we also employed the Global Assessment of Functioning (GAF) to evaluate social functioning. The linear mixed-effects models were performed to detect the difference in effectiveness between the two groups. After 12-week treatment, both groups showed significant effects of time on SIPS, TMT-A, HVLT, BVMT, and GAF. There was a significant effect of group only on CPT. Moreover, we also found a significant interaction effect on GAF. SZAS-HFG can effectively alleviate psychosis symptoms, and improve cognitive impairments and overall functioning as well as aripiprazole.Clinical trial registration: Chinese Clinical Trial Registry, ChiCTR-IOR-17013513.


The safety of direct primary excision of low-grade chondral lesions based on radiological diagnosis alone.
The safety of treating low-grade chondral tumours by primary surgery without a pre- operative diagnostic needle biopsy was assessed by looking at the concordance between radiological and histological diagnoses. A retrospective review of the departmental histopathology registry from 2005 to 2009 was performed to identify cases of intramedullary chondral lesions in the appendicular skeleton. Cases with a pre-operative needle biopsy and with recurrence were excluded. Correlation between radiological and histological diagnosis was investigated with kappa analysis. Of 53 patients, bone expansion was seen in 18.4%, endosteal scalloping in 42.9% and extraosseous extension in 143%. Concordance was 100% between the radiological and histological diagnoses (Kappa score = 1.0). If a radiological diagnosis of an enchondroma or low-grade chondrosarcoma is made, then direct surgical treatment without needle biopsy is safe. A biopsy should be considered if any atypical radiological features suggesting a high-grade chondrosarcoma exist. This increases the certainty of diagnosis and allows planning of surgical treatment.


Enriching learning using Web and computer technologies: how not to throw caution to the wind.
Proponents of computer or web-based learning enthusiastically discuss its democratising potential in education whilst critics argue that the medium has many difficulties. Whilst acknowledging the need for caution in embracing this innovative technology, an Australian School of Nursing recently set about transforming an on-campus conventionally delivered nursing degree program into one which is web enhanced. This paper aims to describe the project as well as the teaching and learning approaches taken. Wh ilst our experience may not be universal, many of the ideas and lessons learned may be relevant to nursing educators interested in enhancing the quality and richness of their curriculum processes with computer and web-based activities.