Semen collection and polymerase chain reaction-based sex determination of black-headed and straw-necked ibis.
This study aimed to develop a polymerase chain reaction (PCR)-based sexing and effective semen collection methods for black-headed and straw-necked ibis species. However, most birds are not sexually dimorphic, that is, the sexes appear similar. Therefore, the gender should be determined before semen collection. DNA was extracted from the blood samples of 11 black-headed and 4 straw-necked ibis. The sex was determined after PCR amplification of the EE0.6 region of W-chromosome. The PCR products were separated using gel electrophoresis. A single band indicated the presence of the EE0.6 region and that the individual was a female, while no band indicated that the individual was a male. Further, the single bands from seven specimens were amplified. Semen collection was performed by massage or a combination of massage with electro-ejaculation and was attempted during all four seasons. The semen was successfully collected in March from male straw-necked ibis using the massage method. Limited motility, viability and concentration of straw-necked ibis sperm were observed. The sperm length was 180 μm and that of the nucleus was 30 μm with acrosome located at the tip of the nucleus. Thus, the PCR-based sexing proved to be an accurate molecular sexing method for black-headed and straw-necked ibis. Furthermore, we successfully collected semen and observed the stained sperm nucleus and acrosome of the straw-necked ibis sperm. We propose that the use of this PCR methodology can be applied as a routine method for sex determination and semen collection in ibis species for future ecological research. However, considering our limited success, further studies on semen collection method are required.


Use of calcitonin in psychotic agitation or mania.
Synthetic salmon calcitonin was administered subcutaneously to 12 inpatients with several primary psychotic diagnoses. Increases in serum total calcium and inorganic phosphorus levels and decreases in CSF calcium level had earlier been observed during periodic psychotic agitation or mania. By contrast, calcitonin, which decreased serum calcium and phosphorus levels and increased CSF calcium level, appeared to produce transient (24-hour) increases in depression and decreases in arousal in this double-blind placebo-controlled trial. Quantitative activity monitoring confirmed the rater's impression that this agent had tranquilizing or depressant effects in such patients. When given in the evening, this polypeptide also appeared to delay sleep onset, as demonstrated both by nurses' 30-minute sleep checks and by the same longitudinal activity record. A decreased hypocalcemic response to calcitonin was noted in the agitated patients, which might explain the increases in serum calcium level described at the "switch".


Evaluation of Photosynthetic Efficiency in Photorespiratory Mutants by Chlorophyll Fluorescence Analysis.
Photosynthesis and photorespiration represent the largest carbon fluxes in plant primary metabolism and are necessary for plant survival. Many of the enzymes and genes important for photosynthesis and photorespiration have been well studied for decades, but some aspects of these biochemical pathways and their crosstalk with several subcellular processes are not yet fully understood. Much of the work that has identified the genes and proteins important in plant metabolism has been conducted under highly controlled environments that may not best represent how photosynthesis and photorespiration function under natural and farming environments. Considering that abiotic stress results in impaired photosynthetic efficiency, the development of a high-throughput screen that can monitor both abiotic stress and its impact on photosynthesis is necessary. Therefore, we have developed a relatively fast method to screen for abiotic stress-induced changes to photosynthetic efficiency that can identify uncharacterized genes with roles in photorespiration using chlorophyll fluorescence analysis and low CO2 screening. This paper describes a method to study changes in photosynthetic efficiency in transferred DNA (T-DNA) knockout mutants in Arabidopsis thaliana. The same method can be used for screening ethyl methanesulfonate (EMS)-induced mutants or suppressor screening. Utilizing this method can identify gene candidates for further study in plant primary metabolism and abiotic stress responses. Data from this method can provide insight into gene function that may not be recognized until exposure to increased stress environments.


Guidance for biostatisticians on their essential contributions to clinical and translational research protocol review.
Rigorous scientific review of research protocols is critical to making funding decisions, and to the protection of both human and non-human research participants. Given the increasing complexity of research designs and data analysis methods, quantitative experts, such as biostatisticians, play an essential role in evaluating the rigor and reproducibility of proposed methods. However, there is a common misconception that a statistician's input is relevant only to sample size/power and statistical analysis sections of a protocol. The comprehensive nature of a biostatistical review coupled with limited guidance on key components of protocol review motived this work. Members of the Biostatistics, Epidemiology, and Research Design Special Interest Group of the Association for Clinical and Translational Science used a consensus approach to identify the elements of research protocols that a biostatistician should consider in a review, and provide specific guidance on how each element should be reviewed. We present the resulting review framework as an educational tool and guideline for biostatisticians navigating review boards and panels. We briefly describe the approach to developing the framework, and we provide a comprehensive checklist and guidance on review of each protocol element. We posit that the biostatistical reviewer, through their breadth of engagement across multiple disciplines and experience with a range of research designs, can and should contribute significantly beyond review of the statistical analysis plan and sample size justification. Through careful scientific review, we hope to prevent excess resource expenditure and risk to humans and animals on poorly planned studies.


[Hemodynamic mechanism of the hypotensive action of beta-phenyl-GABA esters (phenibut)].
It was established in acute and chronic experiments on cats that phenibut ethers are 7-10 times more potent than phenibut itself as regards hypotensive activity and produce inconsistent effects on the cardio- and hemodynamics. Of these ethers, methyl ether of phenibut is the most powerful agent. It causes lasting hypotension when given in doses of 1/50 and 1/30 of the LD50 at the cost of a decrease in the general peripheral resistance. At the same time, apart from raising the blood inflow to the heart and cardiac output, the drug has a compensated adverse ino- and chronotropic action on the heart.


Phosphatidylinositol-3-phosphate regulates sorting and processing of amyloid precursor protein through the endosomal system.
Defects in endosomal sorting have been implicated in Alzheimer's disease. Endosomal traffic is largely controlled by phosphatidylinositol-3-phosphate, a phosphoinositide synthesized primarily by lipid kinase Vps34. Here we show that phosphatidylinositol-3-phosphate is selectively deficient in brain tissue from humans with Alzheimer's disease and Alzheimer's disease mouse models. Silencing Vps34 causes an enlargement of neuronal endosomes, enhances the amyloidogenic processing of amyloid precursor protein in these organelles and reduces amyloid precursor protein sorting to intraluminal vesicles. This trafficking phenotype is recapitulated by silencing components of the ESCRT (Endosomal Sorting Complex Required for Transport) pathway, including the phosphatidylinositol-3-phosphate effector Hrs and Tsg101. Amyloid precursor protein is ubiquitinated, and interfering with this process by targeted mutagenesis alters sorting of amyloid precursor protein to the intraluminal vesicles of endosomes and enhances amyloid-beta peptide generation. In addition to establishing phosphatidylinositol-3-phosphate deficiency as a contributing factor in Alzheimer's disease, these results clarify the mechanisms of amyloid precursor protein trafficking through the endosomal system in normal and pathological states.


Birefringence of the central cornea in children assessed with scanning laser polarimetry.
Corneal birefringence is a well-known confounding factor with all polarization-sensitive technology used for retinal scanning and other intraocular assessment. It has been studied extensively in adults, but little is known regarding age-related differences. Specifically, no information is available concerning corneal birefringence in children. For applications that are geared towards children, such as retinal birefringence scanning for strabismus screening purposes, it is important to know the expected range of both corneal retardance and azimuth in pediatric populations. This study investigated central corneal birefringence in children (ages three and above), by means of scanning laser polarimetry (GDx-VCC™, Carl Zeiss Meditec, Inc.). Children's measures of corneal retardance and azimuth were compared with those obtained in adults. As with previous studies in adults, corneal birefringence was found to vary widely in children, with corneal retardance ranging from 10 to 77 nm, and azimuth (slow axis) ranging from -11° to 71° (measured nasally downward). No significant differences in central corneal birefringence were found between children and adults, nor were significant age-related differences found in general. In conclusion, establishing knowledge of the polarization properties of the central cornea in children allows better understanding, exploitation, or bypassing of these effects in new polarization-sensitive pediatric ophthalmic applications.


Discoveries on the Genetics of ADHD in the 21st Century: New Findings and Their Implications.
The 21st century has witnessed the discovery of multiple rare and common gene variants associated with attention deficit hyperactivity disorder (ADHD), and these discoveries have already provided a starting point for the investigation of the biology of the disorder and novel treatments. The purpose of this selective review is to examine genetic findings from the past 5 years and consider their implications for the conceptualization of ADHD and future clinical practice. Recent discoveries reveal the strong genetic overlaps between ADHD and autism spectrum disorder (ASD) as well as intellectual disability. Thus, the removal of the previous diagnostic exclusion criteria for ADHD in the presence of ASD is a welcome change in DSM-5. However, ADHD also shows substantial genetic correlations with a much broader group of neuropsychiatric disorders as well as with nonpsychiatric conditions (e.g., lung cancer). Investigating potential explanations for these links is an important next step. ADHD, while usefully conceptualized as a disorder in clinical practice, can be viewed as a trait. Recent genome-wide association study findings, consistent with twin studies, highlight that ADHD lies at the extreme end of a continuously distributed dimension, akin to hypertension along the continuum of blood pressure. Although ADHD levels typically decline with age, twin and molecular genetic studies suggest that a persistent trajectory is associated with higher genetic loading. Routine testing for rare mutations in ADHD is not yet recommended, although guidelines in many countries recommend testing individuals with mild intellectual disability or ASD, so practice could change. Common gene variants for ADHD are only weakly predictive and therefore have limited clinical value at present, as does pharmacogenomics. [AJP at 175: Remembering Our Past As We Envision Our Future November 1938: Electroencephalographic Analyses of Behavior Problem Children The electroencephalogram was the first biological technique to be applied to childhood behavioral disorders. Jasper, Solomon, and Bradley reported that "the electroencephalogram has succeeded in revealing a definite abnormality of brain function in over one half of a group of childhood behavior disorders which had been previously considered as largely psychogenic." (Am J Psychiatry 1938; 95:641-658 )].


Lipophilicity, antifungal and antioxidant properties of persilben.
The lipophilicity of persilben, an important parameter influencing the penetration of the compound through biological membranes, was determined experimentally by dynamic method and was theoretically calculated according to the fragmentation methods introduced by Crippen, Broto and Viswanadhan. The higher value of partition coefficient (log P = 3.89) obtained for persilben than that for resveratrol points to potentially higher ease of penetration of persilben into cells of living organism. Antimicrobial and antioxidant activities of persilben were tested. The obtained data suggest that this compound possesses some antioxidant activity. Persilben appears to have also some inhibitory effect against some species of dermatophytes from Tnichophyton genus but only at high concentrations.


Biosynthesis and function of tRNA modifications in Archaea.
tRNA modifications are important for decoding, translation accuracy, and structural integrity of tRNAs. Archaeal tRNAs contain at least 47 different tRNA modifications, some of them, including archaeosine, agmatidine, and mimG, are specific to the archaeal domain. The biosynthetic pathways for these complex signature modifications have recently been elucidated and are extensively described in this review. Archaeal organisms still lag Escherichia coli and Saccharomyces cerevisiae in terms of genetic characterization and in vivo function of tRNA modifications. However, recent advances in the model Haloferax volcanii, described here, should allow closing this gap soon. Consequently, an update on experimental characterizations of archaeal tRNA modification genes and proteins is given to set the stage for future work in this field.


Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways.
Cystic renal diseases are caused by mutations of proteins that share a unique subcellular localization: the primary cilium of tubular epithelial cells. Mutations of the ciliary protein inversin cause nephronophthisis type II, an autosomal recessive cystic kidney disease characterized by extensive renal cysts, situs inversus and renal failure. Here we report that inversin acts as a molecular switch between different Wnt signaling cascades. Inversin inhibits the canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for degradation; concomitantly, it is required for convergent extension movements in gastrulating Xenopus laevis embryos and elongation of animal cap explants, both regulated by noncanonical Wnt signaling. In zebrafish, the structurally related switch molecule diversin ameliorates renal cysts caused by the depletion of inversin, implying that an inhibition of canonical Wnt signaling is required for normal renal development. Fluid flow increases inversin levels in ciliated tubular epithelial cells and seems to regulate this crucial switch between Wnt signaling pathways during renal development.


The accuracy of using last menstrual period to determine gestational age for first trimester medication abortion: a systematic review.
We sought to evaluate the accuracy of assessing gestational age (GA) prior to first trimester medication abortion using last menstrual period (LMP) compared to ultrasound (U/S). We searched Medline, Embase and Cochrane databases through October 2013 for peer-reviewed articles comparing LMP to U/S for GA dating in abortion care. Two teams of investigators independently evaluated data using standard abstraction forms. The US Preventive Services Task Force and Quality Assessment of Diagnostic Accuracy Studies guidelines were used to assess quality. Of 318 articles identified, 5 met inclusion criteria. Three studies reported that 2.5-11.8% of women were eligible for medication abortion by LMP and ineligible by U/S. The number of women who underestimated GA using LMP compared to U/S ranged from 1.8 to 14.8%, with lower rates found when the sample was limited to a GA <63 days. Most women (90.5-99.1%) knew their LMP, 70.8-90.5% with certainty. Our results support that LMP can be used to assess GA prior to medication abortion at GA <63 days. Further research looking at patient outcomes and identifying women eligible for medication abortion by LMP but ineligible by U/S is needed to confirm the safety and effectiveness of providing medication abortion using LMP alone to determine GA.


[Morphofunctional state of the rat male reproductive system after chronic low intensity irradiation at a dose of 1.0 Gy].
It was studied the morphofunctional state of rat male reproductive system after chronically exposure to low intensive gamma-irradiation in early ontogenesis. After radiation with a total dose of 1.0 Gy it was revealed the decrease of the testes and epididymis weight, dysbalance in the ratio of different spermatogenic cells, changes in nucleic acid content and discoordination of bioenergetic metabolism in testes. Disturbance in rat male reproductive system retained in remote period (180 days after irradiation).


Evaluating Successful Aging in Older People Who Participated in Computerized or Paper-and-Pencil Memory Training: The Memoria Mejor Program.
Background. The evaluation of successful aging includes objective criteria to measure cognitive function and psychological well-being and levels of functional capacity needed to perform daily activities related to the preservation of autonomy. In addition, the emergence of computerized cognitive training programs has allowed us to use a new class of tools to verify the theoretical postulates of neural plasticity in aging. Objective. The present study investigates subjective and objective criteria of successful aging in healthy older adults participating in a memory training program offered as two versions: computer and paper-and-pencil. Method. Fifty-four healthy older adult participants recruited for the study were organized into two training groups. Group 1 (G1) used the computer program and Group 2 (G2) used the paper-and-pencil program. Results. The analysis revealed no significant differences in psychological well-being between the two training groups. However, the groups did differ significantly in objective evaluations of successful aging, as measured by attention and everyday memory, and brain activity as measured by sLORETA, with G1 outperforming G2 on both measures. Conclusion. Computerized memory training programs show promise for restoring cognitive and cerebral functioning in older adults, and consequently, may be better suited to achieving the objective criteria of successful aging than paper-and-pencil memory training programs. However, this conclusion should be taken with caution since differences in age and educational level may have influenced the results.


Evaluating the translation process of an Internet-based self-help intervention for prevention of depression: a cost-effectiveness analysis.
Depression is common and treatable with cognitive behavior therapy (CBT), for example. However, access to this therapy is limited. Internet-based interventions have been found to be effective in reducing symptoms of depression. The International Society for Research on Internet Interventions has highlighted the importance of translating effective Internet programs into multiple languages to enable worldwide dissemination. The aim of the current study was to determine if it would be cost effective to translate an existing English-language Internet-based intervention for use in a non-English-speaking country. This paper reports an evaluation of a trial in which a research group in Norway translated two English-language Internet-based interventions into Norwegian (MoodGYM and BluePages) that had previously been shown to reduce symptoms of depression. The translation process and estimates of the cost-effectiveness of such a translation process is described. Estimated health effect was found by using quality-adjusted life years (QALY). Conservative estimates indicate that for every 1000 persons treated, 16 QALYs are gained. The investment is returned 9 times and the cost-effectiveness ratio (CER) is 3432. The costs of the translation project totaled to approximately 27% of the estimated original English-language version development costs. The economic analysis shows that the cost-effectiveness of the translation project was substantial. Hopefully, these results will encourage others to do similar analyses and report cost-effectiveness data in their research reports.


Bad medicine: low-dose dopamine in the ICU.
Low-dose dopamine administration (ie, doses < 5 microg/kg/min) has been advocated for 30 years as therapy in oliguric patients on the basis of its action on dopaminergic renal receptors. Recently, a large, multicenter, randomized, controlled trial has demonstrated that low-dose dopamine administered to critically ill patients who are at risk of renal failure does not confer clinically significant protection from renal dysfunction. In this review, we present the best evidence and summarize the effects of low-dose dopamine infusion in critically ill patients. We review the history and physiology of low-dose dopamine administration and discuss the reasons why dopamine is not clinically effective in the critically ill. In addition to the lack of renal efficacy, we present evidence that low-dose dopamine administration worsens splanchnic oxygenation, impairs GI function, impairs the endocrine and immunologic systems, and blunts ventilatory drive. We conclude that there is no justification for the use of low-dose dopamine administration in the critically ill.


Transanal Total Mesorectal Excision: A Novel Approach to Rectal Surgery.
Less invasive approaches continue to be explored and refined for diseases of the colon and rectum. The current gold standard for the surgical treatment of rectal cancer, total mesorectal excision (TME), is a technically precise yet demanding procedure with outcomes measured by both oncologic and functional outcomes (including bowel, urinary, and sexual). To date, the minimally invasive approach to rectal cancer has not yet been perfected, leaving ample opportunity for rectal surgeons to innovate. Transanal TME has recently emerged as a safe and effective technique for both benign and malignant diseases of the rectum. While widespread acceptance of this surgical approach remains tempered at this time due to lack of long-term oncologic outcome data, short-term outcomes are promising and there is great excitement surrounding the promise of this technique.


Effect of pre-treatment and extraction conditions on the antioxidant properties of persimmon (Diospyros kaki) leaves.
Persimmon is a very delicious fruit and the leaves of this tree are used as a traditional drug. This study aimed to investigate the effects of drying method (hot air and freeze-drying), extraction temperature (80, 90 and 100 °C) and extraction time (10, 30, 60 and 120 min) and harvest stage (flowering and fruiting) on the antioxidant contents and antioxidant activity of persimmon leaves. The results showed that the highest antioxidants were obtained in both methods of drying. Also, 100 °C for 120 min of extraction gave the highest antioxidant contents, but with no significant difference compared to 90 °C for 60 min of extraction. Persimmon leaves collected during flowering stage had the maximum amount of antioxidants compared to the fruiting stage. Finally, it can be said that persimmon leaves harvested during flowering stage and treated by hot air drying with these extraction conditions (90 °C for 60 min) are richer in bioactive compounds.


Efficient Alkaline Hydrogen Evolution Reaction Using Superaerophobic Ni Nanoarrays with Accelerated H2 Bubble Release.
Despite the adverse effects of H2 bubbles adhering to catalyst's surface on the performance of water electrolysis, the mechanisms by which H2 bubbles are effectively released during the alkaline hydrogen evolution reaction (HER) remain elusive. In this study, a systematic investigation on the effect of nanoscale surface morphologies on H2 bubble release behaviors and HER performance by employing earth-abundant Ni catalysts consisting of an array of Ni nanorods (NRs) with controlled surface porosities is performed. Both aerophobicity and hydrophilicity of the catalyst's surface vary according to the surface porosity of catalysts. The Ni catalyst with the highest porosity of ≈52% exhibits superaerophobic nature as well as the best HER performance among the Ni catalysts. It is found that the Ni catalyst's superaerophobicity combined with the effective open pore channels enables the accelerated release of H2 bubbles from the surface, leading to a significant improvement in geometric activities, particularly at high current densities, as well as intrinsic activities including both specific and mass activities. It is also demonstrated that the superaerophobicity enabled by highly porous Ni NRs can be combined with Pt and Cr having optimal binding abilities to further optimize electrocatalytic performance.


Establishment of digital cutoff values for intraepithelial lymphocytes in biopsies from colonic mucosa with lymphocytic colitis.
Lymphocytic colitis (LC) and the incomplete form (LCi) are common causes of chronic watery diarrhea. Endoscopy is often inconspicuous, and the diagnosis relies on histopathological assessment of colonic biopsies. Digital Image Analysis (DIA) eliminates interobserver variation. The aim of this study was to establish digital cutoff values for LC and LCi on CD3 stained slides. One hundred and six patients with a hematoxylin and eosin (HE) diagnosis of normal colonic mucosa (N = 19), non-specific reactive changes (N = 24), LCi (N = 23) and LC (N = 40) were eligible for analysis. The number of intraepithelial lymphocytes (IELs) reached by DIA in the total surface epithelium and in hot spots of the biopsies was compared with the diagnostic category assigned by the pathologists based on HE stained slides. The digitalized slides were analyzed for number of IELs using Visiopharm Quantitative Digital Pathology software. All digitalized slides were examined manually to identify differences in the approach to the evaluation of the biopsies by the pathologists and DIA. The median IEL counts and interquartile range in the total surface epithelium were 3.6 (3.2-4.3), 4.4 (3.4-5.3), 19.8 (16.6-30.0) and 41.3 (37.0-47.8) in normal colon mucosa, mucosa with non-specific reactive changes, LCi and LC, respectively. Discrimination between normal mucosa and non-specific reactive changes was not possible. Digital cutoff values with the best separation between non-LC, LCi and LC were > 13 IELs/100 epithelial cells for LCi and > 36 IELs/100 epithelial cells for LC. These cutoff values resulted in an agreement between the pathologist's and DIA that was very good with a kappa value of 0.90. Despite differences among the approach of DIA and the pathologist's assessment of IELs in colonic mucosa DIA is able discriminate between the HE based diagnoses of the three subgroups non-LC, LCi and LC with high accuracy.


A hexanuclear gold carbonyl cluster.
The hexanuclear gold carbonyl cluster [PPh4]2[Au6(CF3)6Br2(CO)2] (4) has been obtained by spontaneous self-assembly of the following independent units: CF3AuCO (1) and [PPh4][Br(AuCF3)2] (3). The cyclo-Au6 aggregate 4, in which the components are held together by unassisted, fairly strong aurophilic interactions (Au···Au ∼310 pm), exhibits a cyclohexane-like arrangement with chair conformation. These aurophilic interactions also result in significant ν(CO) lowering: from 2194 cm-1 in the separate component 1 to 2171 cm-1 in the mixed aggregate 4. Procedures to prepare the single-bridged dinuclear component 3 as well as the mononuclear derivative [PPh4][CF3AuBr] (2) are also reported.


Advanced magnetic resonance strategies for the elucidation of nanostructured soft matter.
An overview is given on advanced magnetic resonance strategies and techniques, both nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR), as applied to nanostructured soft matter. In addition, the combination of the two forms of spectroscopy to enhance signal intensity in NMR by means of dynamic nuclear polarization (DNP) is described. It is shown how these techniques can provide unique information on the structure of soft matter as well as the local dynamics of the constituents. Examples of recent applications are described, including dendronized and thermoresponsive polymers, hydrogels, synthetic and bio-inspired polymers, as well as polypeptides and biopolymers.


Munchausen's syndrome.
Munchausen's syndrome is a chronic condition in which patients with factitious illness present with dramatic and sometimes self-inflicted signs and symptoms. Much investigation is needed to delineate the etiology and psychodynamics of this disorder. After other causes for the patient's condition have been ruled out and a firm diagnosis is made, cautious confrontation with long-term psychotherapy, if the patient is amenable, is thought to be the best approach.


Endobronchial Ultrasound Transbronchial Needle Aspiration for the Diagnosis of Paratracheal and Peribronchial Central Parenchymal Lesions.
Obtaining qualitative, sufficient material for the diagnosis of malignancies in cases with normal endoscopic findings in patients with suspected lung cancer and hilar and mediastinal lymphadenopathy is challenging. Endobronchial ultrasound (EBUS) was used to control a transbronchial needle biopsy (ТBNA) for the first time in our country. From 2015 to 2018, TBNA with a convex probe EBUS was performed on 57 patients [41 men, 16 women, mean age 56.10 (range 37-77 years)] with mediastinal lesions found on CT scan. We used the Hitachi Aloka - ProSound Alpha 7 and BF-UC180F (Olympus) 21G and 22G needles Ultrasound System. In 22 of the cases, we performed a biopsy of hilum lesions (9 on the left and 13 on the right), in 13 - of subcarinal lesions, and in 4 - of lesions located on the right paratracheal lymphatic chain. EBUS-TBNA confirmed lung cancer in 48 patients (84.2%). In 33 of them, it was non-small cell lung cancer: spinocellular in 13 cases and adenocarcinoma in 17 cases; three cases were without accurate verification. Small cell lung cancer was found in 15 cases. In two cases, the biopsies were negative for tumor (3.5%), and in seven - non-specific inflammatory process (12.3%). This study confirms the high diagnostic success rate of EBUS-TBNA reported in similar studies developed on a daily routine basis without adhering to a specific protocol. EBUS-TBNA is an interventional procedure with high sensitivity in diagnosing hilar and mediastinal lesions in negative conventional bronchoscopy and thus is useful in patients with paratracheal and peribronchial lesions. The results could be improved with training and experience.


Physicochemical, bioactive, and sensory properties of persimmon-based ice cream: technique for order preference by similarity to ideal solution to determine optimum concentration.
In the present study, persimmon puree was incorporated into the ice cream mix at different concentrations (8, 16, 24, 32, and 40%) and some physicochemical (dry matter, ash, protein, pH, sugar, fat, mineral, color, and viscosity), textural (hardness, stickiness, and work of penetration), bioactive (antiradical activity and total phenolic content), and sensory properties of samples were investigated. The technique for order preference by similarity to ideal solution approach was used for the determination of optimum persimmon puree concentration based on the sensory and bioactive characteristics of final products. Increase in persimmon puree resulted in a decrease in the dry matter, ash, fat, protein contents, and viscosity of ice cream mix. Glucose, fructose, sucrose, and lactose were determined to be major sugars in the ice cream samples including persimmon and increase in persimmon puree concentration increased the fructose and glucose content. Better melting properties and textural characteristics were observed for the samples with the addition of persimmon. Magnesium, K, and Ca were determined to be major minerals in the samples and only K concentration increased with the increase in persimmon content. Bioactive properties of ice cream samples improved and, in general, acetone-water extracts showed higher bioactivity compared with ones obtained using methanol-water extracts. The technique for order preference by similarity to ideal solution approach showed that the most preferred sample was the ice cream containing 24% persimmon puree.


Iodixanol and iohexol in cardioangiography. A comparative vectorcardiographic study.
The non-ionic dimeric contrast medium (CM) iodixanol is isotonic with blood through the addition of electrolytes. In this study, we evaluated computerised dynamic vectorcardiography (VCG) as a tool in CM research by comparing the electrophysiological effects of iodixanol with those of the low-osmolar CM iohexol. A total of 119 patients referred for cardioangiography were included in this double-blind, randomised, parallel comparison of iodixanol (320 mg I/ml) and iohexol (350 mg I/ml). VCG was recorded and different VCG parameters were analysed. General tolerability, safety and radiographic efficacy were also assessed. Iodixanol induced less changes than iohexol in all VCG parameters and the sensation of warmth was significantly milder after iodixanol, but both CM were well tolerated. VCG might be useful in future studies to analyse electrophysiological effects caused by CM.


Cervical spondylotic myelopathy. Approaches to surgical treatment.
Cervical spondylotic myelopathy is the leading cause of spinal cord dysfunction in older patients. This review article looks at the natural history of the condition and examines the role of different surgical treatments for it. Anterior and posterior surgical approaches have a role in the treatment of cervical spondylotic myelopathy dependent on the number of levels involved and the alignment of the spine. Anterior decompression and fusion is useful in patients who have disease at three or fewer levels or in patients with kyphotic alignment. In more extensive disease, a posterior decompression and fusion is usually best. Canal expansive laminoplasty is useful in the treatment of myelopathy without radiculopathy in a patient with lordotic alignment. With the exception of laminoplasty, nonfusion procedures have little role in the treatment of cervical spondylotic myelopathy.


Localization of the human NCAM gene to band q23 of chromosome 11: the third gene coding for a cell interaction molecule mapped to the distal portion of the long arm of chromosome 11.
cDNA clones containing sequences coding for the murine neural cell adhesion molecule (N-CAM) were used in Southern hybridizations on human genomic DNA and demonstrated approximately 90% homology between human and murine NCAM genes. In situ hybridization with one of these clones was performed on human metaphase chromosomes and allowed the localization of the human NCAM gene to band q23 of chromosome 11. The genes for two other cell surface molecules believed to be involved in cell-cell interactions, Thy-1 and the delta chain of the T3-T cell receptor complex, have recently been localized to the same region of chromosome 11 in man. Moreover, this region of the human chromosome 11 appears to be syntenic to a region of murine chromosome 9 that also contains the staggerer locus: staggerer mice show abnormal neurological features which may be related to abnormalities in the conversion of the embryonic to the adult forms of the N-CAM molecule.


Complete nucleotide sequence of the fumarase gene fumA, of Escherichia coli.
The nucleotide sequence of a 2.41 kb fragment of E. coli DNA containing the fumA gene encoding fumarase was determined using the dideoxy chain termination method. The initiation and termination sites of fumA transcription were located using RNA:DNA hybridisation with single-stranded M13 probes. The length of the fumA transcript was estimated as 1760 +/- 15 nucleotides and the fumA coding region of 1647 base pairs (549 codons) was identified. The deduced molecular weight of the fumarase protein (Mr = 60163) is in good agreement with that of the protein identified by the maxicell procedure. The DNA fragment also contains the 5' end of the manA gene encoding mannose 6-phosphate isomerase, which is transcribed with the opposite polarity to fumA .


Molecular architecture and assembly principles of Vibrio cholerae biofilms.
In their natural environment, microbes organize into communities held together by an extracellular matrix composed of polysaccharides and proteins. We developed an in vivo labeling strategy to allow the extracellular matrix of developing biofilms to be visualized with conventional and superresolution light microscopy. Vibrio cholerae biofilms displayed three distinct levels of spatial organization: cells, clusters of cells, and collections of clusters. Multiresolution imaging of living V. cholerae biofilms revealed the complementary architectural roles of the four essential matrix constituents: RbmA provided cell-cell adhesion; Bap1 allowed the developing biofilm to adhere to surfaces; and heterogeneous mixtures of Vibrio polysaccharide, RbmC, and Bap1 formed dynamic, flexible, and ordered envelopes that encased the cell clusters.


The effect of nitrate and different substrates on enhanced biological phosphorus removal in sequencing batch reactors.
Enhanced biological phosphorus removal (EBPR) requires an anaerobic-aerobic sequence and short chain fatty acids, namely acetate. It is also known that the presence of nitrate in the anaerobic phase inhibits EBPR. This study describes a lab-scale experimentation carried out to study the effect of different substrates on EBPR and behaviour of PAOs under anoxic conditions in a sequencing batch reactor operated using synthetic wastewater. Experimental data show that the EBPR performance is significantly affected by glucose rich influent. Low COD/TKN ratios caused lower phosphorus removal performance since nitrate entering the anaerobic zone consumes substrate for denitrification. The results also show that anoxic phosphate uptake took place together with nitrate reduction when there was no external substrate. However, the uptake rate under anoxic conditions was lower than that under aerobic conditions.


Phylogenetic Analysis of Belgian Small Ruminant Lentiviruses Supports Cross Species Virus Transmission and Identifies New Subtype B5 Strains.
Small ruminant lentiviruses (SRLV) are a group of highly divergent viruses responsible for global and fatal infections in sheep and goats. Since the current phylogenetic classification of these viruses was proposed in 2004, it nowadays consists out of 5 genotypes and 28 subtypes. In support of our national SRLV control program, we performed the genetic characterization of SRLV strains circulating in the Belgian sheep and goat population. Fourteen sheep and 9 goat strains were sequenced in the gag-pol and pol regions using the method described by Shah. Most SRLV strains from sheep and goats belonged to prototype A1 and B1 subtypes, respectively. We, however, also found indications for cross-species transmission of SRLV strains between sheep and goats and vice versa, and identified a new subtype designated as B5. An in-depth analysis of the current SRLV phylogeny revealed that many subtypes have been defined over the years based on limited sequence information. To keep phylogeny as a useful tool, we advocate to apply more rigorous sequencing standards to ensure the correct classification of current and new emerging strains. The genetic characterization of Belgian SRLV strains will help in the development of appropriate diagnostic tools to assist the national control program.


Plasma amino acids in ecstasy users.
Recreational use of the illegal drug "ecstasy" has increased dramatically in recent years. We have measured 33 different plasma amino acids in ecstasy users and controls. Significant differences were found for phosphoserine, glutamate, citrulline, methionine, tyrosine and histidine. Resembling changes in the plasma amino acids have been described in acute transient polymorphous psychosis. Thus, alterations in plasma - methionine and phosphoserine or other amino acids could be involved in the psychical symptoms produced by MDMA.


Pattern recognition receptor expression is not impaired in patients with chronic mucocutanous candidiasis with or without autoimmune polyendocrinopathy candidiasis ectodermal dystrophy.
Patients with chronic mucocutaneous candidiasis (CMC) have an unknown primary immune defect and are unable to clear infections with the yeast Candida. CMC includes patients with AIRE gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, suggesting that defective expression of pattern recognition receptors (PRRs) may underlie disease pathogenesis. In 29 patients with CMC (13 with APECED) and controls, we assessed dendritic cell (DC) subsets and monocyte Toll-like receptor (TLR) expression in blood. We generated and stimulated monocyte-derived (mo)DCs with Candida albicans, TLR-2/6 ligand and lipopolysaccharide and assessed PRR mRNA expression by polymerase chain reaction [TLR-1-10, Dectin-1 and -2, spleen tyrosine kinase (Syk) and caspase recruitment domain (CARD) 9] in immature and mature moDCs. We demonstrate for the first time that CMC patients, with or without APECED, have normal blood levels of plasmocytoid and myeloid DCs and monocyte TLR-2/TLR-6 expression. We showed that in immature moDCs, expression levels of all PRRs involved in anti-Candida responses (TLR-1, -2, -4, -6, Dectin-1, Syk, CARD9) were comparable to controls, implying that defects in PRR expression are not responsible for the increased susceptibility to Candida infections seen in CMC patients. However, as opposed to healthy controls, both groups of CMC patients failed to down-regulate PRR mRNA expression in response to Candida, consistent with defective DC maturation, as we reported recently. Thus, impaired DC maturation and consequent altered regulation of PRR signalling pathways rather than defects in PRR expression may be responsible for inadequate Candida handling in CMC patients.


The mechanism of Sanzi Yangqin decoction for asthma treatment based on network pharmacology and experimental verification.
Asthma is a chronic airway inflammatory disease characterized by airway inflammation, mucus hypersecretion, airway hyper-reactivity. Sanzi Yangqin Decoction (SZYQD) is widely prescribed for asthma treatment. Its anti-asthma activities have been reported in animal model, but the exact mechanism and targets of SZYQD in asthma treatment have not been fully elucidated. A network pharmacological approach was used to predict the active components, targets, and signalling pathways of SZYQD in asthma, including potential target prediction, protein‒protein interaction (PPI) network construction and analysis, and Gene Ont (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The active ingredients were identified from the SZYQD, and were molecular docked according to the results of network pharmacology. A mouse model of asthma induced by ovalbumin (OVA) and lipopolysaccharide (LPS) was constructed to evaluate the therapeutic effect of SZYQD. Furthermore, the effects of SZYQD and its active ingredients were tested in vitro for regulating inflammation and MUC5AC expression (two main pathophysiologic abnormalities of asthma) in macrophages and airway epithelial cells by using Real-time PCR and western blotting. A total of 28 active ingredients and 111 HUB genes were screened in the relevant databases, including three key ingredients (luteolin, β-carotene, and Sinapine) and nine core target genes (JUN, CTNNB1, IL10, TP53, AKT1, STAT3, TNF, IL6 and EGFR). KEGG and GO analysis indicated that the potential anti-asthmatic mechanisms of SZYQD were related to PI3K-Akt signalling pathway and response to lipopolysaccharide, etc. In the in vivo asthmatic model, our findings demonstrated that SZYQD exerted a protective effect against asthmatic mice induced by OVA and LPS through the inhibition of inflammation and mucus overproduction. Consistently, cell experiments showed that the SZYQD extract or the key active ingredients luteolin significantly decreased lipopolysaccharide (LPS)-induced IL-6 expression and activation of the NF-κB pathway in macrophages. In addition, SZYQD extract or luteolin inhibited activation of the AKT pathway and expression of MUC5AC induced by EGF in airway epithelial cells. The anti-asthmatic mechanism of SZYQD might be associated with inhibiting inflammation and airway mucus hypersecretion by regulating the NF-κB and AKT signalling pathways as predicted by network pharmacology, which provides more evidence for the application of SZYQD in asthma treatment.


Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes.
Rab GTPases regulate discrete steps in vesicular transport pathways. Rabs require activation by specific guanine nucleotide exchange factors (GEFs) that stimulate the exchange of GDP for GTP. Rab27a controls motility and regulated exocytosis of secretory granules and related organelles. In melanocytes, Rab27a regulates peripheral transport of mature melanosomes by recruiting melanophilin and myosin Va. Here, we studied the activation of Rab27a in melanocytes. We identify Rab3GEP, previously isolated as a GEF for Rab3a, as the non-redundant Rab27a GEF. Similar to Rab27a-deficient ashen melanocytes, Rab3GEP-depleted cells show both clustering of melanosomes in the perinuclear area and loss of the Rab27a effector Mlph. Consistent with a role as an activator, levels of Rab27a-GTP are decreased in cells lacking Rab3GEP. Recombinant Rab3GEP exhibits guanine nucleotide exchange activity against Rab27a and Rab27b in vitro, in addition to its previously documented activity against Rab3. Our results indicate promiscuity in Rab GEF action and suggest that members of related but functionally distinct Rab subfamilies can be controlled by common activators.


Sensing antimonite and arsenite at the subattomole level with genetically engineered bioluminescent bacteria.
A highly sensitive and selective optical sensing system for antimonite has been developed using genetically engineered bacteria. The basis of this system is the ability of certain bacteria to survive in environments that are contaminated with antimonite, arsenite, and arsenate. The survival is conferred to the bacteria by the ars operon, which consists of five genes that code for three structural proteins, ArsA, ArsB, and ArsC, and two regulatory proteins, ArsD and ArsR. ArsA, ArsB, and ArsC form a protein pump system that extrudes antimonite, arsenite, and arsenate once these anions reach the cytoplasm of the bacterium. A method was developed for monitoring antimonite and arsenite by using a single plasmid that incorporates the regulatory gene of the extrusion system, arsR, and the genes of bacterial luciferase, luxA and luxB. In the designed plasmid, ArsR regulates the expression of bacterial luciferase in a manner that is dependent on the concentration of antimonite and arsenite in the sample. Thus, the bioluminescence emitted by luciferase can be related to the concentration of antimonite and arsenite in the sample. Concentrations for antimonite and arsenite in the order of 10(-5) M, which corresponds to subattomole levels, can be detected. This bacterial-based sensing system is highly selective for antimonite and arsenite.


Cytokine dichotomy in peripheral nervous system influences the outcome of experimental allergic neuritis: dynamics of mRNA expression for IL-1 beta, IL-6, IL-10, IL-12, TNF-alpha, TNF-beta, and cytolysin.
Experimental autoimmune neuritis (EAN) is a T-cell-mediated autoimmune disease of the peripheral nervous system (PNS) that can be actively induced in Lewis rats by immunization with bovine PNS myelin and Freund's complete adjuvant. EAN is used as an animal model of the Guillain-Barré syndrome (GBS) in humans. To study the potential role of cytokines in EAN, we used in situ hybridization to detect mRNA expression of interleukin 1 beta (IL-1 beta), IL-6, IL-10, IL-12, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, and cytolysin in sciatic nerve sections over the course of EAN. Cells expressing IL-1 beta and IL-6 mRNA appeared early and peaked on Day 7 postimmunization (p.i.), i.e., at onset of clinical signs of EAN, consistent with a role of these cytokine in an early immune response leading to autoaggressive immunity in EAN. TNF-alpha, TNF-beta, and IL-12 mRNA expression was maximally upmodulated on Day 14 p.i., i.e., at height of clinical EAN, favoring a role for these cytokines in disease development. On the contrary, transcription of cytolysin and IL-10 in sciatic nerves reached maxima during clinical improvement of EAN. The data argue for a major proinflammatory role for IL-1 beta, IL-6, TNF-alpha, TNF-beta, and IL-12 and a disease downregulating function for both cytolysin and IL-10 at the target site in EAN. These findings have relevance for future studies on pathogenesis and treatment of GBS in humans.


Multivariable Logistic Regression And Back Propagation Artificial Neural Network To Predict Diabetic Retinopathy.
Monitoring and prediction of diabetic retinopathy (DR) is necessary in patients with diabetes for early discovery and timely treatment of disease. We aimed to analyze the association between DR and biochemical and metabolic parameters, and develop a predictive model for DR. A total of 530 Chinese residents including 423 with type 2 diabetes (T2D) aged 18 years or older participated in this study. The association between DR and biochemical and metabolic parameters was analyzed by the univariate and multivariable logistic regression (MLR). According to the MLR results, we developed a back propagation artificial neural network (BP-ANN) model by selecting tan-sigmoid as the transfer function of the hidden layers nodes, and pure-line of the output layer nodes, with training goal of 0.5×10-5. There were 51 (9.6%) diabetic participants with DR. After univariate and MLR analysis, duration of diabetes, waist to hip ratio, HbA1c and family history of diabetes were independently associated with the presence of DR (all P < 0.05). Based on these parameters, the area under the receiver operating characteristic (ROC) curve for the BP-ANN model was significantly higher than that by MLR (0.84 vs. 0.77, P < 0.001). Our evaluation demonstrated the potential role of BP-ANN model to identify DR in screening practice. The presence of DR was well predictable using the proposed BP-ANN model based on four related parameters (duration of diabetes, waist to hip ratio, HbA1c and family history of diabetes).


Changes in maximal and explosive strength, electromyography, and muscle thickness of lower and upper extremities induced by combined strength and endurance training in soldiers.
The purpose of present study was to examine to what extent an 8-week endurance-based military training period interferes with muscle strength development in the conscripts (n = 72) compared with that caused by sport-related military training with added strength training (ST) or endurance training (ET). More specifically, we examined the effects of these 3 training modes on maximal isometric force, maximal rate of force development (RFD), electromyography (EMG), and muscle thickness of the lower and upper extremities. The measurements included isometric force-time parameters of leg and arm extensors and EMG activity from the vastus lateralis, vastus medialis, rectus femoris, and triceps brachii muscles. The 8-week basic training period combined with added ST and ET significantly improved maximal bilateral isometric force of the arm extensors in ST by 11.8% (p < 0.001), ET by 13.9% (p < 0.001), and normal training (NT) by 7.8% (p < 0.05). Strength training and ET showed significant increases in maximal EMG activity of the trained arm muscles. A significant increase was observed in maximal RFD of the upper extremities only in ST by 28.1% (p < 0.05). Both ST and ET increased their maximal leg extension strength by 12.9% (p < 0.01) and 9.1% (p < 0.05), respectively, whereas no significant change occurred in NT (5.2%, p = 0.45). No significant changes were observed in the shape of the force-time curves of leg extensors. No increases occurred in muscle thickness either in the lower or upper extremities. The present BT training with a large amount of endurance-based military training interfered with strength development, and especially, explosive power development of the lower extremities in the ST group. The optimal improvements in neuromuscular characteristics may not be possible without some decreases in the amount of the endurance-based military training and/or some increases in the amount of the maximal/explosive strength training during the BT.


AUF1 contributes to Cryptochrome1 mRNA degradation and rhythmic translation.
In the present study, we investigated the 3' untranslated region (UTR) of the mouse core clock gene cryptochrome 1 (Cry1) at the post-transcriptional level, particularly its translational regulation. Interestingly, the 3'UTR of Cry1 mRNA decreased its mRNA levels but increased protein amounts. The 3'UTR is widely known to function as a cis-acting element of mRNA degradation. The 3'UTR also provides a binding site for microRNA and mainly suppresses translation of target mRNAs. We found that AU-rich element RNA binding protein 1 (AUF1) directly binds to the Cry1 3'UTR and regulates translation of Cry1 mRNA. AUF1 interacted with eukaryotic translation initiation factor 3 subunit B and also directly associated with ribosomal protein S3 or ribosomal protein S14, resulting in translation of Cry1 mRNA in a 3'UTR-dependent manner. Expression of cytoplasmic AUF1 and binding of AUF1 to the Cry1 3'UTR were parallel to the circadian CRY1 protein profile. Our results suggest that the 3'UTR of Cry1 is important for its rhythmic translation, and AUF1 bound to the 3'UTR facilitates interaction with the 5' end of mRNA by interacting with translation initiation factors and recruiting the 40S ribosomal subunit to initiate translation of Cry1 mRNA.


A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas.
Glioblastoma Multiforme (GBM), the most common and lethal primary human brain tumor, exhibits multiple molecular aberrations. We report that loss of the transcription factor GATA4, a negative regulator of normal astrocyte proliferation, is a driver in glioma formation and fulfills the hallmarks of a tumor suppressor gene (TSG). Although GATA4 was expressed in normal brain, loss of GATA4 was observed in 94/163 GBM operative samples and was a negative survival prognostic marker. GATA4 loss occurred through promoter hypermethylation or novel somatic mutations. Loss of GATA4 in normal human astrocytes promoted high-grade astrocytoma formation, in cooperation with other relevant genetic alterations such as activated Ras or loss of TP53. Loss of GATA4 with activated Ras in normal astrocytes promoted a progenitor-like phenotype, formation of neurospheres, and the ability to differentiate into astrocytes, neurons, and oligodendrocytes. Re-expression of GATA4 in human GBM cell lines, primary cultures, and brain tumor-initiating cells suppressed tumor growth in vitro and in vivo through direct activation of the cell cycle inhibitor P21(CIP1), independent of TP53. Re-expression of GATA4 also conferred sensitivity of GBM cells to temozolomide, a DNA alkylating agent currently used in GBM therapy. This sensitivity was independent of MGMT (O-6-methylguanine-DNA-methyltransferase), the DNA repair enzyme which is often implicated in temozolomide resistance. Instead, GATA4 reduced expression of APNG (alkylpurine-DNA-N-glycosylase), a DNA repair enzyme which is poorly characterized in GBM-mediated temozolomide resistance. Identification and validation of GATA4 as a TSG and its downstream targets in GBM may yield promising novel therapeutic strategies.


[Contemporary refractive surgical procedures].
Ocular surgery has progressed a great deal these last decades thanks to technological progress. The aim of this article is to describe different contemporary endocular surgical procedures such as cataract surgery, vitreoretinal surgery and corneal grafts. The main indications of the surgeries will be discussed, as well as the type of anaesthesia, the practical issues of every surgical technique and the type and rates of the different complications.


Creating and Using Minimizer Sketches in Computational Genomics.
Processing large data sets has become an essential part of computational genomics. Greatly increased availability of sequence data from multiple sources has fueled breakthroughs in genomics and related fields but has led to computational challenges processing large sequencing experiments. The minimizer sketch is a popular method for sequence sketching that underlies core steps in computational genomics such as read mapping, sequence assembling, k-mer counting, and more. In most applications, minimizer sketches are constructed using one of few classical approaches. More recently, efforts have been put into building minimizer sketches with desirable properties compared with the classical constructions. In this survey, we review the history of the minimizer sketch, the theories developed around the concept, and the plethora of applications taking advantage of such sketches. We aim to provide the readers a comprehensive picture of the research landscape involving minimizer sketches, in anticipation of better fusion of theory and application in the future.


Post-operative nausea and vomiting: update on predicting the probability and ways to minimize its occurrence, with focus on ambulatory surgery.
Postoperative nausea and vomiting "the little big problem" after surgery/anaesthesia is still a common side-effect compromising quality of care, delaying discharge and resumption of activities of daily living. A huge number of studies have been conducted in order to identify risk factors, preventive and therapeutic strategies. The Apfel risk score and a risk based multi-modal PONV prophylaxis is advocated by evidence based guidelines as standards of care but is not always followed. Tailored anaesthesia and pain management avoiding too liberal dosing of anaesthetics and opioid analgesics is also essential in order to reduce risk. Thus multi-modal opioid sparing analgesia and a risk based PONV prophylaxis should be provided in order to minimise the occurrence. There is however still no way to guarantee an individual patient that he or she should not experience any PONV. Further studies are needed trying to identify risk factors and ways to tailor the individual patient prevention/therapy are warranted. The present paper provides a review around prediction, factors influencing the occurrence and the management of PONV with a focus on the ambulatory surgical patient.


Subclinical hypothyroidism and the risk of chronic kidney disease in T2D subjects: A case-control and dose-response analysis.
Evidence indicated a positive association between subclinical hypothyroidism (SCH) and cardiovascular diseases. But the relationship between SCH and chronic kidney diseases (CKD) remains unclear. A case-control study was performed to ascertain this relationship followed by a meta-analysis. In this hospital-based, case-control study, we recruited 3270 type 2 diabetic patients with euthyroidism and 545 type 2 diabetic patients with SCH. All English studies were searched upon the relationship between SCH and CKD up to October 2016. Meta-analysis was performed using STATA 13.0 software. Our case-control study indicated an association between SCH and CKD in patients with type 2 diabetes [OR (95% CI): 1.22 (1.09-1.36)]. Five observational studies reporting risk of CKD in SCH individuals were enrolled. A significant relationship between SCH and CKD was shown [pooled OR 1.80, (95% CI) 1.38-2.35]. Among normal TSH range, individuals with TSH ≥3.0 μIU/ml had a significantly higher rate of CKD (Fisher exact test, P = 0.027). Dose-response linear increase of CKD events was explored [pooled OR 1.09 (95% CI): 1.03-1.16 per1 mIU/L increase of TSH]. The present evidence suggests that SCH is probably a significant risk factor of CKD in T2D. Linear trend is shown between TSH elevation and CKD in T2D. This relationship between serum TSH and renal impairment in type 2 diabetic patients needs further studies to investigate.


Eliminating lymphatic filariasis: a view from the field.
Among infections closely associated with poverty, lymphatic filariasis (LF) is a study in contrasts. It is both a consequence of and a contributor to poverty. Although rarely fatal, it is recognized as a leading global cause of lifelong disability as well as significant personal, social, and economic burdens coincident with disease. Infection is often considerably more prevalent in communities than the number of cases of overt pathology for which LF is best known (lymphedema, elephantiasis, and hydrocele). With an estimated 120 million to 130 million affected persons in 83 countries and 1.25 billion persons living in areas at risk, in some countries LF may be expanding its range, whereas in others, with economic development, it has disappeared with little if any targeted intervention. The transmission cycle is relatively inefficient, yet an association with pockets of deepest poverty remains tenacious. Thanks to scientific advances in diagnostic tools, and particularly in control strategies focused on large-scale drug donation and mass drug distribution programs, scientists and policy makers now consider LF eliminable. Together with new approaches for morbidity control, a hopeful tone surrounds a disease problem that as recently as two decades ago could easily have been categorized as among the most neglected of neglected diseases. Continued progress toward global LF elimination will require solutions to potential obstacles in the most challenging--that is, the poorest--endemic settings. This chapter reviews progress toward LF elimination and some of the remaining challenges from a perspective in Haiti, the only least developed country of the Americas.


Ascaris and eosinophil. II. Isolation and characterization of eosinophil chemotactic factor and neutrophil chemotactic factor of parasite in Ascaris antigen.
In the previous study, we found an eosinophil chemotactic factor of the parasite (ECF-P) in extracts from the body cavity fluid of the Ascaris species. In this study, the physiochemical characteristics of ECF-P were determined in order to elucidate the relationship between ECF-P and Ascaris antigens. ECF-P was active in both in vivo and in vitro chemotactic assay systems and was found to be heat labile, nondialyzable, and stable to lyophilization. The estimated m.w. was approximately 30,000 daltons. The isoelectric point of ECF-P was 8.5. It was quite different from the Ascaris antigen in the same extract, or various Ascaris allergens that had been reported previously by other researchers. Furthermore, ECF-P did not show any activity in eliciting a guinea pig passive cutaneous anaphylaxis (PCA) reaction. From these experimental results, we concluded that ECF-P is not identical to Ascaris antigens. In addition, we found that the neutrophil chemotactic factor of the parasite (NCF-P), with at least two components, is present in the Ascaris extract, and is also heat labile and resistant to dialysis and lyophilization, but separable from coexistent ECF-P by reason of their different physiochemical properties.


A mortality risk prediction model for older adults with lymph node-positive colon cancer.
Clinicians are less likely to recommend adjuvant chemotherapy for older adults based on their age alone. This study aimed to develop a mortality risk model to assist treatment decision making by identifying patients who are unlikely to live to benefit from chemotherapy. All lymph node-positive colon cancer patients ≥65 years who received surgery in New South Wales, Australia in 2007/2008 were identified using a linked population-based dataset (n = 1550). A model predicting 1-year all-cause mortality was built using multilevel logistic regression. Risk scores derived from model factors were summed for each patient. One-year mortality was 11.5%. The risk model consisted of 14 factors, including comorbidities, hospital admission factors and other markers of frailty or health status. People with a total score of 0, 1 or 2 were considered at low risk (predicted 1-year mortality of 2.9%), those scoring 3 to 8 at medium risk (7.4% mortality) and those scoring 9 or above at high risk (24.7% mortality). The model had good discrimination (area under the receiver operating characteristic curve = 0.788, 95% confidence interval: 0.752-0.825) and calibration (P = 0.46). The risk model accurately predicts mortality for this cohort and could be useful in shifting the emphasis in chemotherapy decision making from chronological age to the identification of those of any age who will benefit.


Effect of Cerebellar Stimulation on Gait and Balance Recovery in Patients With Hemiparetic Stroke: A Randomized Clinical Trial.
Gait and balance impairment is associated with poorer functional recovery after stroke. The cerebellum is known to be strongly implicated in the functional reorganization of motor networks in patients with stroke, especially for gait and balance functions. To determine whether cerebellar intermittent θ-burst stimulation (CRB-iTBS) can improve balance and gait functions in patients with hemiparesis due to stroke. This randomized, double-blind, sham-controlled phase IIa trial investigated efficacy and safety of a 3-week treatment of CRB-iTBS coupled with physiotherapy in promoting gait and balance recovery in patients with stroke. Thirty-six patients with consecutive ischemic chronic stroke in the territory of the contralateral middle cerebral artery with hemiparesis were recruited from a neuro-rehabilitation hospital. Participants were screened and enrolled from March 2013 to June 2017. Intention-to-treat analysis was performed. Patients were randomly assigned to treatment with CRB-iTBS or sham iTBS applied over the cerebellar hemisphere ipsilateral to the affected body side immediately before physiotherapy daily during 3 weeks. The primary outcome was the between-group difference in change from baseline in the Berg Balance Scale. Secondary exploratory measures included the between-group difference in change from baseline in Fugl-Meyer Assessment scale, Barthel Index, and locomotion assessment with gait analysis and cortical activity measured by transcranial magnetic stimulation in combination with electroencephalogram. A total of 34 patients (mean [SD] age, 64 [11.3] years; 13 women [38.2%]) completed the study. Patients treated with CRB-iTBS, but not with sham iTBS, showed an improvement of gait and balance functions, as revealed by a pronounced increase in the mean (SE) Berg Balance Scale score (baseline: 34.5 [3.4]; 3 weeks after treatment: 43.4 [2.6]; 3 weeks after the end of treatment: 47.5 [1.8]; P < .001). No overall treatment-associated differences were noted in the Fugl-Meyer Assessment (mean [SE], baseline: 163.8 [6.8]; 3 weeks after treatment: 171.1 [7.2]; 3 weeks after the end of treatment: 173.5 [6.9]; P > .05) and Barthel Index scores (mean [SE], baseline: 71.1 [4.92]; 3 weeks after treatment: 88.8 [2.1]; 3 weeks after the end of treatment: 92.2 [2.4]; P > .05). Patients treated with CRB-iTBS, but not sham iTBS, showed a reduction of step width at the gait analysis (mean [SE], baseline: 16.8 [4.8] cm; 3 weeks after treatment: 14.3 [6.2] cm; P < .05) and an increase of neural activity over the posterior parietal cortex. Cerebellar intermittent θ-burst stimulation promotes gait and balance recovery in patients with stroke by acting on cerebello-cortical plasticity. These results are important to increase the level of independent walking and reduce the risk of falling. ClinicalTrials.gov Identifier: NCT03456362.


Employment status and temporal patterns of energy intake: Nutrition and Health Survey in Taiwan, 2005-2008.
To (i) identify the major temporal patterns of energy intake among adults; (ii) examine the association between employment status and the patterns; and (iii) examine the association between dietary quality and the patterns. Secondary analysis based on the cross-sectional population-based nutrition survey in Taiwan, 2005-2008. Based on energy intake levels at six time intervals of a day derived from 24 h recall data, we applied cluster analysis to identify major temporal patterns of energy intake. Self-reported employment status was categorized into six groups: full-time, part-time, no job, student, homemaker and retired. Multinomial logistic regression models were fitted to test the association between temporal patterns of energy intake and employment groups. Non-institutionalized community dwellers. Non-pregnant adults (≥19 years old) with total energy intake between 2092 and 20920 kJ/d (500 and 5000 kcal/d; n 4508). Five major patterns were identified, which can be seen as the traditional meal pattern and its variants. About 20 % of adults had the traditional pattern. The most prevalent pattern was the delayed morning meal pattern (33 %), which had lower Ca and P intakes than the traditional pattern. About 14 % of adults had the delayed lunchtime pattern, which had lower protein, PUFA, fibre, Ca, P, vitamin D and vitamin E intakes than the traditional. Adjusted prevalence of the delayed lunchtime pattern was highest among full-time students (34 %), followed by part-time workers (24 %), and was lower in retired (8 %), homemakers (11 %) and full-time employed adults (12 %). Adults' temporal patterns of energy intake, which varied with their employment status, affected their dietary quality.


The effects of trinucleotide repeats found in human inherited disorders on palindrome inviability in Escherichia coli suggest hairpin folding preferences in vivo.
Unusual DNA secondary structures have been implicated in the expansion of trinucleotide repeat tracts that are associated with several human inherited disorders. We present evidence consistent with the folding of these trinucleotide repeats into hairpin loops at the center of a long DNA palindrome in vivo. Our assay utilizes a palindrome in bacteriophage lambda, the center of which determines its ability to inhibit plaque formation in a manner that is consistent with folding into a hairpin or cruciform structure. We show that central inserts of even numbers of d(CAG).d(CTG) repeats inhibit plaque formation more than do odd numbers. Both d(CAG)2.d(CTG)2 and d(CGG)2.d(CCG)2 central sequences behave like DNA sequences known to form two-base loops in vitro, suggesting that they may also form compact and stable loops. By contrast, repeats of d(GAC).d(GTC) do not show any evidence consistent with unusual loop stability. These results agree with in vitro evidence that the unstable repeats can form hairpin secondary structures and suggest a favored position of folding. We discuss the potential roles of secondary structures, DNA replication and recombination in models of repeat tract expansion.


Dexmedetomidine for Refractory Intracranial Hypertension.
Dexmedetomidine (DEX) is a selective α2 adrenergic agonist that is commonly used for sedation in the intensive care unit (ICU). The role of DEX for adjunctive treatment of refractory intracranial hypertension is poorly defined. The primary objective of this study was to determine the effect of DEX on the need for rescue therapy (ie, hyperosmolar boluses, extraventricular drain [EVD] drainages) for refractory intracranial hypertension. Secondary objectives included the number of intracranial pressure (ICP) excursions, bradycardic, hypotensive, and compromised cerebral perfusion pressure episodes. This retrospective cohort study evaluated patients admitted to the neurosurgical ICU from August 1, 2009, to July 29, 2015, and who received DEX for refractory intracranial hypertension. The objectives were compared between the 2 time periods-before (pre-DEX) and during therapy (DEX). Twenty-three patients with 26 episodes of refractory intracranial hypertension met the inclusion criteria. The number of hyperosmolar boluses was decreased after DEX therapy was initiated. Mannitol boluses required were statistically reduced (1 vs 0.5, P = .03); however, reduction in hypertonic boluses was not statistically significant (1.3 vs 0.9, P = .2). The mean number of EVD drainages per 24 hours was not significantly different between the time periods (15.7 vs 14.0, P = .35). The rate of ICP excursions did not differ between the 2 groups (24.3 vs 22.5, P = .62). When compared to pre-DEX data, there was no difference in the median number of hypotensive (0 vs 0), bradycardic (0 vs 0), or compromised cerebral perfusion pressure episodes (0.5 vs 1.0). Dexmedetomidine may avoid increases in the need for rescue therapy when used as an adjunctive treatment of refractory intracranial hypertension without compromising hemodynamics.


The roles of noncatalytic ATP binding and ADP binding in the regulation of dynein motile activity in flagella.
The regulation of dynein activity to produce microtubule sliding in flagella has not been well understood. To gain more insight into the roles of ATP and ADP in the regulation, we examined the effects of fluorescent ATP analogues and fluorescent ADP analogues on the ATPase activity and motile activity of dynein. 21S dynein purified from the outer arms of sea urchin sperm flagella hydrolyzed BODIPY(R) FL ATP (FL-ATP) at 78% of the rate for ATP hydrolysis. FL-ATP at 0.1-1 mM, however, induced neither microtubule translocation on a dynein-coated glass surface nor sliding disintegration of elastase-treated axonemes. Direct observation of single molecules of the fluorescent analogues showed that both the ATP and ADP analogues were stably bound to dynein over several minutes (dissociation rates = 0.0038-0.0082/s). When microtubule translocation on 21S dynein was induced by ATP, the initial increase of the mean velocity was accelerated by preincubation of the dynein with ADP. Similar increase was also induced by the preincubation with the ADP analogues. Even after preincubation with ADP, FL-ATP did not induce sliding disintegration of elastase-treated axonemes. After preincubation with a nonhydrolyzable ATP analogue, AMPPNP (adenosine 5'-(beta:gamma-imido)triphosphate), however, FL-ATP induced sliding disintegration in approximately 10% of the axonemes. These results indicate that both noncatalytic ATP binding and stable ADP binding, in addition to ATP hydrolysis, are involved in the regulation of the chemo-mechanical transduction in axonemal dynein.


Beyond Anesthesia Toxicity: Anesthetic Considerations to Lessen the Risk of Neonatal Neurological Injury.
Infants who undergo surgical procedures in the first few months of life are at a higher risk of death or subsequent neurodevelopmental abnormalities. Although the pathogenesis of these outcomes is multifactorial, an understanding of the nature and pathogenesis of brain injury in these infants may assist the anesthesiologist in consideration of their day-to-day practice to minimize such risks. This review will summarize the main types of brain injury in preterm and term infants and their key pathways. In addition, the review will address key potential pathogenic pathways that may be modifiable including intraoperative hypotension, hypocapnia, hyperoxia or hypoxia, hypoglycemia, and hyperthermia. Each of these conditions may increase the risk of perioperative neurological injury, but their long-term ramifications are unclear.


circKMT2E Protect Retina from Early Diabetic Retinopathy through SIRT1 Signaling Pathway via Sponging miR-204-5p.
To explore the changes of circRNAs in the retina of diabetic patients without diabetic retinopathy (DR) to screen latent protective factor. The sequencing data of the retina from three diabetic donors that possess no noticeable pathological feature of the retina at ultimate eye inspection and three healthy donative samples were involved in this study. Herein, we carried out bioinformatics analysis to disclose the expression pattern and characteristics of circRNAs on the basis of Gene Ontology as well as KEGG pathway analyses. Then, sequencing data were applied to infer the interaction between selected circRNAs and miR-204-5p. The potential miRNA response elements for the annotated circRNAs and their target gene were speculated using TargetScan as well as miRanda. RNA sequencing detected 28,978 alternative circRNAs. Thereinto, 1063 were expressed with significant difference. circKMT2E was upregulated more than two folds in alloxan-induced diabetic retinal tissues compared with normal retinal tissues, exhibiting an expression trend opposite to miR-204-5p. Bioinformatics analysis showed that circKMT2E have four seed sequences on hsa-miR-204-5p. Thus, circKMT2E was speculated to have function on the basis of sponging miR-204-5p in order to participate in the pathogenetic process of DR. Besides, miR-204-5p was speculated to be able to bind SIRT1, which can interact with its target proteins, and adjusts various cell functions including cellular inflammatory responses, proliferation, as well as apoptosis. The upregulation of circKMT2E in the early stage of DR may be involved in its pathogenesis and may activate the SIRT1 signaling pathway to protect the retina by the sponge function to miR-204-5p.


Optimized performances of tetrapod-like ZnO nanostructures for a triode structure field emission planar light source.
Tetrapod-like ZnO (T-ZnO) nanostructures were synthesized by a simple vapor phase oxidation method without any catalysts or additives. We optimized the performances of T-ZnO nanostructures by adjusting the partial pressure of Zn vapour in the total pressure of the quartz chamber and obtained T-ZnO nanostructure materials of high purity, uniform morphology and size and high aspect ratio with a low turn-on electric field of 2.75 V μm(-1), a large field enhancement factor of 3410 and good field emission stability for more than 70 hour continuous emission. Besides, based on the optimized T-ZnO, we developed metal grid mask-assisted water-based electrostatic spraying technology, and fabricated a large-scale, pollution-free, hole-shaped array T-ZnO nanostructure cathode used in a triode structure field emission planar light source. The controllable performances of the triode device were intensively investigated and the results showed that the triode device uniformly illuminated with a luminous intensity as high as 8000 cd m(-2) under the conditions of 200 V grid voltage and 3300 V anode voltage. The research in this paper will benefit the development of a high performance planar light source based on T-ZnO nanostructures.


Sleep disturbances in patients with major depressive disorder: incongruence between sleep log and actigraphy.
Depression has become a severe global health problem, and sleeping difficulties are typically associated with depression. The purpose of this study was to investigate the relationships among subjective sleep quality, objective sleep quality, and the sleep hygiene practices of hospitalized patients with major depressive disorder. Daily sleep logs and actigraphy were used to obtain subjective and objective sleep data. Thirty patients were recruited from a regional teaching hospital in Taipei and completed the Hamilton Rating Scale for Depression and the Sleep Hygiene Practice Scale. Significant differences were found between subjective and objective sleep data in patients with major depressive disorder (MDD). For patients with more severe depression, subjective measurements obtained using sleep logs, such as total sleep time and sleep efficiency, were significantly lower than those obtained using actigraphy by controlling for demographics. The results regarding the differences between subjective and objective sleep data can be a reference for care providers when comforting depression patients who complain of sleep disturbance.


Mitogen-activated protein kinases, inhibitory-kappaB kinase, and insulin signaling in human omental versus subcutaneous adipose tissue in obesity.
MAPKs and inhibitory-kappaB kinase (IKK) were suggested to link various conditions thought to develop in adipose tissue in obesity (oxidative, endoplasmic reticulum stress, inflammation) with insulin resistance. Yet whether in obesity these kinases are affected in a fat-depot-differential manner is unknown. We assessed the expression and phosphorylation of these kinases in paired omental and abdominal-sc fat biopsies from 48 severely obese women (body mass index > 32 kg/m(2)). Protein and mRNAs of p38MAPK, ERK, c-Jun kinase-1, and IKKbeta were increased 1.5-2.5-fold in omental vs. sc fat. The phosphorylated (activated) forms of these kinases were also increased to similar magnitudes as the total expression. However, phosphorylation of insulin receptor substrate-1 on Ser312 (equivalent of murine Ser307) was not increased in omental, compared with sc, fat. Consistently, fat tissue fragments stimulated with insulin demonstrated that tyrosine phosphorylation and signal transduction to Akt/protein kinase B in omental fat was not inferior to that observable in sc fat. Comparison with lean women (body mass index 23.2 +/- 2.9 kg/m(2)) revealed similar ERK2 and IKKbeta expression and phosphorylation in both fat depots. However, as compared with lean controls, obese women exhibited 480 and 270% higher amount of the phosphorylated forms of p38MAPK and c-Jun kinase, respectively, in omental, but not sc, fat, and this expression level correlated with clinical parameters of glycemia and insulin sensitivity. Increased expression of stress-activated kinases and IKK and their phosphorylated forms in omental fat occurs in obesity, potentially contributing to differential roles of omental and sc fat in the pathophysiology of obesity.


Identification of an ovarian voltage-activated Na+-channel type: hints to involvement in luteolysis.
An endocrine type of voltage-activated sodium channel (eNaCh) was identified in the human ovary and human luteinized granulosa cells (GC). Whole-cell patch-clamp studies showed that the eNaCh in GC is functional and tetrodotoxin (TTX) sensitive. The luteotrophic hormone human CG (hCG) was found to decrease the peak amplitude of the sodium current within seconds. Treatment with hCG for 24-48 h suppressed not only eNaCh mRNA levels, but also mean Na+ peak currents and resting membrane potentials. An unexpected role for eNaChs in regulating cell morphology and function was indicated after pharmacological modulation of presumed eNaCh steady-state activity in GC cultures for 24-48 h using TTX (NaCh blocker) and veratridine (NaCh activator). TTX preserved a highly differentiated cellular phenotype. Veratridine not only increased the number of secondary lysosomes but also led to a significantly reduced progesterone production. Importantly, endocrine cells of the nonhuman primate corpus luteum (CL), which represent in vivo counterparts of luteinized GC, also contain eNaCh mRNA. Although the mechanism of channel activity under physiological conditions is not clear, it may include persistent Na+ currents. As observed in GC in culture, abundant secondary lysosomes were particularly evident in the regressing CL, suggesting a functional link between eNaCh activity and this form of cellular regression in vivo. Our results identify eNaCh in ovarian endocrine cells and demonstrate that their expression is under the inhibitory control of hCG. Activation of eNaChs in luteal cells, due to loss of gonadotropin support, may initiate a cascade of events leading to decreased CL function, a process that involves lysosomal activation and autophagy. These results imply that ovarian eNaChs are involved in the physiological demise of the temporary endocrine organ CL in the primate ovary during the menstrual cycle. Because commonly used drugs, including phenytoin, target NaChs, these results may be of clinical relevance.


Selective loss of PMA-stimulated expression of matrix metalloproteinase 1 in HaCaT keratinocytes is correlated with the inability to induce mitogen-activated protein family kinases.
Many cell types, including fibroblasts and primary keratinocytes, increase matrix metalloproteinase 1 (MMP-1) production in response to agonists such as growth factors and phorbol esters. However, the spontaneously transformed human keratinocyte cell line HaCaT, although it increases MMP-1 production in response to epidermal growth factor (EGF), does not respond similarly to stimulation with PMA. This phenomenon occurs even though HaCaT cells remain proliferatively responsive to both agonists, suggesting a HaCaT-specific defect in a PMA-mediated signal transduction pathway. Using an inside-out approach to elucidate the source of this defect, we found that EGF, but not PMA, stimulated MMP-1 promoter activity in transiently transfected HaCaT keratinocytes. In addition, an assessment of fibroblast and HaCaT c-fos and c-jun gene expression after exposure to EGF and PMA showed that although both agonists increased the expression of c-fos and c-jun mRNA in fibroblasts, only EGF did so in HaCaT keratinocytes. Finally, we looked at the activation of mitogen-activated protein (MAP) family kinases after stimulation with EGF or PMA and found that both agonists increased the phosphorylation and activation of fibroblast extracellular signal-regulated protein kinase and c-Jun N-terminal kinase, but only EGF activated the same kinase activities in HaCaT cells. Further, the EGF-mediated increase in MMP-1 gene expression was inhibited by the MAP kinase/ERK kinase (MEK)-specific inhibitor PD98059 and the p38 kinase-specific inhibitor SB203580. Our evidence indicates that although HaCaT MAP kinases are functional, they are not properly regulated in response to the activation of protein kinase C, and that the defect that bars HaCaT MMP-1 expression in response to stimulation with PMA lies before MAP kinase activation.


Biochemical and immunocytochemical analysis of a histone H1 variant from the mouse testis.
An H1 histone variant, H1a, has been isolated and purified from the mouse testis. Biochemical and amino acid analyses indicate its similarity with the rat testis H1a. Specific antibodies against the purified H1a have been generated in rabbits and used to study its tissue and species distribution using protein blotting procedures. We have also used the immunocytochemical technique to determine in situ distribution of H1a in spermatogenic cells and somatic tissues of the mouse. A non-random distribution of H1a has been noted in the nuclei of certain somatic cell types such as Sertoli cells, Leydig cells and neurons. By contrast, hepatocyte nuclei lacked detectable levels of H1a. In adult seminiferous tubules, the early primary spermatocyte nuclei displayed a greater level of immunoreactivity relative to other cell types. Developmental studies indicate its initial expression in the 7-day-old mouse testis concomitant with the appearance of intermediate and type B spermatogonia.


Potential positive and negative consequences of ZnT8 inhibition.
SLC30A8 encodes the zinc transporter ZnT8. SLC30A8 haploinsufficiency protects against type 2 diabetes (T2D), suggesting that ZnT8 inhibitors may prevent T2D. We show here that, while adult chow fed Slc30a8 haploinsufficient and knockout (KO) mice have normal glucose tolerance, they are protected against diet-induced obesity (DIO), resulting in improved glucose tolerance. We hypothesize that this protection against DIO may represent one mechanism whereby SLC30A8 haploinsufficiency protects against T2D in humans and that, while SLC30A8 is predominantly expressed in pancreatic islet beta cells, this may involve a role for ZnT8 in extra-pancreatic tissues. Consistent with this latter concept we show in humans, using electronic health record-derived phenotype analyses, that the 'C' allele of the non-synonymous rs13266634 SNP, which confers a gain of ZnT8 function, is associated not only with increased T2D risk and blood glucose, but also with increased risk for hemolytic anemia and decreased mean corpuscular hemoglobin (MCH). In Slc30a8 KO mice, MCH was unchanged but reticulocytes, platelets and lymphocytes were elevated. Both young and adult Slc30a8 KO mice exhibit a delayed rise in insulin after glucose injection, but only the former exhibit increased basal insulin clearance and impaired glucose tolerance. Young Slc30a8 KO mice also exhibit elevated pancreatic G6pc2 gene expression, potentially mediated by decreased islet zinc levels. These data indicate that the absence of ZnT8 results in a transient impairment in some aspects of metabolism during development. These observations in humans and mice suggest the potential for negative effects associated with T2D prevention using ZnT8 inhibitors.


Nontraumatic Descemet Membrane Detachment with Tear in Osteogenesis Imperfecta.
We report the first case of unilateral spontaneous Descemet membrane detachment (DMD) with tear occurring in a patient with osteogenesis imperfecta (OI). A 20-year-old male patient with OI presented with a history of recent primary repair (2 weeks prior) of left globe rupture following local finger trauma to the left eye. The patient had no history of other ocular surgery or trauma. The examination revealed a best corrected visual acuity of 20/40 in the right and no light perception in the left eye. Slit-lamp examination showed an oval giant Descemet tear extending from the 12 o'clock to the 5 o'clock area and a large DMD involving the upper and nasal quadrants in the right cornea. It was thought that monitoring the patient without intervention and only considering a surgical procedure if the disorder progressed was the best option, taking into account the patient's reasonable visual acuity and the risks of keratoplasty. The dimensions of the DMD and tear had remained the same at 1-year follow-up period. We believe that follow-up without intervention should be considered for non-progressive DMD with a giant tear if the patient has a single functional eye.


[The influence of tobacco-smoke toxic components on glucosaminoglycans in biologic tissues].
The aim of the work is detailed analysis of glucosaminoglikans and glukuronic acid in chisel tooth and molars of tobacco-smokers and non-smokers. The total number of 140 patients (tobacco-smokers - 60) by acute serous pulpit is investigated. The conducted quantative and qualitative analyzes show that tobacco-smokers tooth contains les glucosaminoglikans (chondroitinsulfats A and C) and more glucuronic acid than non-smokers individuals. The chisel tooth pulp contained considerably more glucuronic acid as compared with molars. These studies support the hypothesis of important role of cigarette smoke toxical components in the tooth support mechanisms. The studies are necessary to be held in different directions.


An historical and critical review of the articles on blood pressure published in Psychosomatic Medicine between 1939 and 1997.
Between 1939 and 1997, there have been 59 volumes of Psychosomatic Medicine. Over this period there were 200 articles dealing with blood pressure. About 90% of these were concerned with high blood pressure. This article reviews all of these papers both from an historical perspective and critically. Although there has been a significant growth in the rate of articles published since 1939, there has always been a strong interest in the nature of hypertension, particularly the roles of affects and emotions in the natural history of the disease. For example, volume 1, number 1 of the Journal includes a symposium on high blood pressure in which Franz Alexander stated his well-known hypothesis that the chronic inhibition of rage plays a causal role in the production of hypertension. In various forms, the notion that anger is an important mediator of hypertension has neither been proved nor abandoned. One major conclusion drawn from this review is that the current research on high blood pressure is drifting somewhat aimlessly. It has become preoccupied with demonstrations that various stimuli or situations (usually characterized as stresses) can acutely raise blood pressure. Despite this focus, neither the necessary nor the sufficient conditions for labeling a stimulus as stress has ever been agreed upon. Likewise, there have been many demonstrations of an iatrogenic effect on blood pressure, but neither the behavioral mechanisms underlying this effect nor the strategies for eliminating it have been explicated. Finally, this article identifies several areas where it would be useful to review and integrate current knowledge. Hopefully, such integrations could play a significant role in focusing and shaping future research and clinical practice.


Traumatic pulmonary artery pseudoaneurysm.
Traumatic pulmonary artery pseudoaneurysm is an uncommon cause of a solitary nodule on a chest radiograph. Consideration of this abnormality is important as the lesion can cause fatal hemorrhage. We report a patient with a traumatic segmental pulmonary artery pseudoaneurysm detected by computed tomography and confirmed by intravenous digital subtraction angiography.


Recombinational Repair of Nuclease-Generated Mitotic Double-Strand Breaks with Different End Structures in Yeast.
Mitotic recombination is the predominant mechanism for repairing double-strand breaks in Saccharomyces cerevisiae Current recombination models are largely based on studies utilizing the enzyme I-SceI or HO to create a site-specific break, each of which generates broken ends with 3' overhangs. In this study sequence-diverged ectopic substrates were used to assess whether the frequent Pol δ-mediated removal of a mismatch 8 nucleotides from a 3' end affects recombination outcomes and whether the presence of a 3' vs. 5' overhang at the break site alters outcomes. Recombination outcomes monitored were the distributions of recombination products into crossovers vs. noncrossovers, and the position/length of transferred sequence (heteroduplex DNA) in noncrossover products. A terminal mismatch that was 22 nucleotides from the 3' end was rarely removed and the greater distance from the end did not affect recombination outcomes. To determine whether the recombinational repair of breaks with 3' vs. 5' overhangs differs, we compared the well-studied 3' overhang created by I-SceI to a 5' overhang created by a ZFN (Zinc Finger Nuclease). Initiation with the ZFN yielded more recombinants, consistent with more efficient cleavage and potentially faster repair rate relative to I-SceI. While there were proportionally more COs among ZFN- than I-SceI-initiated events, NCOs in the two systems were indistinguishable in terms of the extent of strand transfer. These data demonstrate that the method of DSB induction and the resulting differences in end polarity have little effect on mitotic recombination outcomes despite potential differences in repair rate.


Morphometric analysis of the corneal endothelium of Yacare caiman (Caiman yacare) using scanning electron microscopy.
The objective of this study was to examine the endothelial surface morphology and to perform morphometric analysis of the corneal endothelial cells of Yacare caiman (Caiman yacare) using scanning electron microscopy. Morphometric analysis with regard to polygonality, mean cell area, cell density and coefficient of variation of mean cell area was performed. Cell areas were measured using image analysis software. The normal corneal endothelium of Yacare caiman consisted of polygonal cells of uniform size and shape with interdigitations of the cell borders. Microvilli appeared as protrusions on the cellular surface. The average cell area was 270 +/- 24 microm(2) and the endothelial cell density was 3704 +/- 324 cells/mm(2). The coefficient of variation of cell area was 0.22. This study demonstrates that the Yacare caiman corneal endothelium is similar to those described in other vertebrates.


First report on two-fold classification of Plasmodium falciparum carbonic anhydrase inhibitors using QSAR modeling approaches.
Quantitative structure-activity relationship (QSAR)-based classification approach is one of the important chemometric tools in drug discovery process for categorizing the target protein inhibitors into more active and less active classes. In this background, we have presented here a novel approach of two-fold QSAR-based classification modeling for the Plasmodium falciparum carbonic anhydrase (PfCA) inhibitors using 2D-QSAR and linear discriminant analysis (LDA) methods. The logic of applying this concept is to ensure more accurate classification of compounds and to draw some concrete conclusion about structure-activity relations for further work, in absence of 3D-protein structure and lack of sufficient experimental data using the PfCA target. The 2D-QSAR modeling analysis suggested the importance of electrotopological, electronic, extended topochemical atom, and spatial (Jurs) indices for modeling the inhibitory activity against PfCA. The LDA model analysis showed that spatial (Jurs), electrotopological and thermodynamic indices were the discriminating features to differentiate the inhibitors into more active and less active groups. The classification ability of both the models for training and test sets was checked by different qualitative validation parameters such as sensitivity, specificity, accuracy, recall, precision, F-measure and G-means. The classification results revealed that the developed models were significant in classifying the more active inhibitors as compared to the less active inhibitors of both training and test sets. The structural features unveiled from these two models could be utilized for the selection of more active compounds against PfCA in the database screening process.