Photoperiodism in higher vertebrates: an adaptive strategy in temporal environment.
Life on earth is subjected to strict regimen of cyclical changes. Of all geophysical changes, the most prominent are the daily changes between day and night and the regular succession of annual seasons. Synchronization to environmental day-night and seasonal cycles is key to survival. Night-time and day-time environments differ in illumination, temperature, food supplies and predators. Organisms have, therefore, developed highly specialized temporal programmes to get better adapted to activity either during night or during the day. Many species use annual cycle of changes in daylength as "calendar" to synchronize and/or to time their daily and seasonal physiological and behavioral functions. This is described as photoperiodism. The minimum daylength (photoperiod) that will induce a physiological response is the "critical daylength" (CD). CD requirement is quite stringent. CD is species-specific; CD may be response-specific as well. Switching 'on' and 'off' the seasonal responses in many species is regulated by the development of photorefractoriness-a phenomenon when organism remains no longer capable to continue its stimulatory response to a photoperiod. Photorefractoriness may be qualitatively different between species. Broadly, two categories of photorefractoriness are described: absolute refractoriness and relative refractoriness. What causes photorefractoriness and at what level in the brain photorefractoriness occurs are unknown. A photoperiodic response system has three principal components: a photoreceptor that interprets photic input, a clock that measures photic signal, and a neurosecretory system that translates photic signal into endocrine secretions. Both retinal and extra-retinal structures are involved in the photoperiodic photoreception. In insects, mollusks, crustaceans, fishes, amphibians, reptiles and birds, the photoreception occurs largely through extra-retinal photoreceptors (ERRs) localized in the hypothalamus. In adult mammals, brain photoreceptors are apparently absent and light input is only through eyes. Endogenous circa-rhythms believed to be involved in photoperiodism are synchronized to changes in illumination of the environment with either the time of day (circadian rhythm) or the season of the year (circannual rhythm). The Suprachiasmatic nuclei (SCN) of the hypothalamus in mammals function as the clock. The SCN monitors the photoperiodic message and decodes it by dictating the changes in rhythm in melatonin secretion in the pineal gland. The hypothalamic paraventricular nuclei (PVN) are also an integral component of the neural network mediating photoperiodism in mammals. The location of SCN homologue and the role of PVN in mediating photoperiodism in non-mammalian vertebrates is still unclear. Furthermore, how various components of photo-neuroendocrine circuitry are functionally linked together is unknown.


The phenotypic variability of amyotrophic lateral sclerosis.
Classic textbook neurology teaches that amyotrophic lateral sclerosis (ALS) is a degenerative disease that selectively affects upper and lower motor neurons and is fatal 3-5 years after onset--a description which suggests that the clinical presentation of ALS is very homogenous. However, clinical and postmortem observations, as well as genetic studies, demonstrate that there is considerable variability in the phenotypic expression of ALS. Here, we review the phenotypic variability of ALS and how it is reflected in familial and sporadic ALS, in the degree of upper and lower motor neuron involvement, in motor and extramotor involvement, and in the spectrum of ALS and frontotemporal dementia. Furthermore, we discuss some unusual clinical characteristics regarding presentation, age at onset and disease progression. Finally, we address the importance of this variability for understanding the pathogenesis of ALS and for the development of therapeutic strategies.


NMR spectroscopic studies of a TAT-derived model peptide in imidazolium-based ILs: influence on chemical shifts and the cis/trans equilibrium state.
NMR spectroscopy was used to study systematically the impact of imidazolium-based ionic liquid (IL) solutions on a TAT-derived model peptide containing Xaa-Pro peptide bonds. The selected IL anions cover a wide range of the Hofmeister series of ions. Based on highly resolved one- and two-dimensional NMR spectra individual 1H and 13C peptide chemical shift differences were analysed and a classification of IL anions according to the Hofmeister series was derived. The observed chemical shift changes indicate significant interactions between the peptide and the ILs. In addition, we examined the impact of different ILs towards the cis/trans equilibrium state of the Xaa-Pro peptide bonds. In this context, the IL cations appear to be of exceptional importance for inducing an alteration of the native cis/trans equilibrium state of Xaa-Pro bonds in favour of the trans-isomers.


The intraoperative gap difference (flexion gap minus extension gap) is altered by insertion of the trial femoral component.
A Tensor/Balancer device has been recently developed in order to assess soft tissue balancing in total knee arthroplasty (TKA) under more physiological conditions. This device allows us to measure the joint gap with a trial femoral component in place with the patella reduced. The purpose of this study was to clarify whether the placement of the component changes the intraoperative gap difference (flexion gap distance minus extension gap distance). We prospectively investigated the extension (0°) and flexion (90°) gaps in 73 posterior-stabilized TKAs under 30 lb of joint distraction force. Then, we compared the gap difference with and without the trial femoral component in place. Our results showed that the intraoperative gap difference with the trial femoral component in place was larger than the intraoperative gap difference without the trial component (p=0.00003; with the trial component: mean 4.7 mm (standard deviation (SD): 3.0mm); without the trial component: mean 2.7 mm (SD: 3.3mm)). We consider that the change in gap difference with or without femoral component was caused by a relative difference in the elasticity and/or tightness of the soft tissue in extension versus flexion. Surgeons should be aware of this effect of the femoral component when considering intraoperative soft tissue balancing which leads to postoperative stability of the knee joint consequently.


Cardiac Conduction Velocity, Remodeling and Arrhythmogenesis.
Cardiac electrophysiological disorders, in particular arrhythmias, are a key cause of morbidity and mortality throughout the world. There are two basic requirements for arrhythmogenesis: an underlying substrate and a trigger. Altered conduction velocity (CV) provides a key substrate for arrhythmogenesis, with slowed CV increasing the probability of re-entrant arrhythmias by reducing the length scale over which re-entry can occur. In this review, we examine methods to measure cardiac CV in vivo and ex vivo, discuss underlying determinants of CV, and address how pathological variations alter CV, potentially increasing arrhythmogenic risk. Finally, we will highlight future directions both for methodologies to measure CV and for possible treatments to restore normal CV.


Structure-activity relationships of C-terminal endothelin hexapeptide antagonists.
The discovery of selective endothelin (ET) receptor antagonists will facilitate identification of the physiological and pathological roles for ET and its isopeptides. Structure-activity studies of the C-terminal hexapeptide of ET have been carried out to elucidate those amino acids important for receptor binding and agonist or antagonist activity. Binding studies were performed in rat heart ventricle, rabbit renal artery vascular smooth muscle cells, and rat cerebellum. In addition, many of the compounds have been evaluated functionally for their effects on endothelin-1-induced arachidonic acid release and inositol phosphate accumulation in specific cell lines. Selected compounds have been evaluated in a functional bioassay in tissue preparations specifically expressing either ETA or ETB receptors. We have previously described the structure-activity relationships in the hydrophobic C-terminal hexapeptide of ET, a region known to be highly important for receptor recognition. A mono-D-amino acid scan of the ET[16-21] revealed that substitution at His gave rise to analogs with significantly enhanced binding affinity. We have further evaluated the C-terminal region and will describe the design, synthesis, and pharmacological evaluation of several novel and potent ET peptide receptor antagonists.


Statistical criteria for estimation of the cerebral autoregulation index (ARI) at rest.
The autoregulation index (ARI) can reflect the effectiveness of cerebral blood flow (CBF) control in response to dynamic changes in arterial blood pressure (BP), but objective criteria for its validation have not been proposed. Monte Carlo simulations were performed by generating 5 min long random input/output signals that mimic the properties of mean beat-to-beat BP and CBF velocity (CBFV) as usually obtained by non-invasive measurements in the finger (Finometer) and middle cerebral artery (transcranial Doppler ultrasound), respectively. Transfer function analysis (TFA) was used to estimate values of ARI by optimal fitting of template curves to the output (or CBFV) response to a step change in input (or BP). Two-step criteria were adopted to accept estimates of ARI as valid. The 95% confidence limit of the mean coherence function (0.15-0.25 Hz) ([Formula: see text]) was estimated from 15 000 runs, resulting in [Formula: see text] = 0.190 when using five segments of data, each with 102.4 s (512 samples) duration (Welch's method). This threshold for acceptance was dependent on the TFA settings and increased when using segments with shorter duration (51.2 s). For signals with mean coherence above the critical value, the 5% confidence limit of the normalised mean square error (NMSEcrit) for fitting the step response to Tieck's model, was found to be approximately 0.30 and independent of the TFA settings. Application of these criteria to physiological and clinical sets of data showed their ability to identify conditions where ARI estimates should be rejected, for example due to CBFV step responses lacking physiological plausibility. A larger number of recordings were rejected from acute ischaemic stroke patients than for healthy volunteers. More work is needed to validate this procedure with different physiological conditions and/or patient groups. The influence of non-stationarity in BP and CBFV signals should also be investigated.


Strabismus surgery before versus after completion of amblyopia therapy in children.
Normal visual development occurs when the brain is able to integrate the visual input from each of the two eyes to form a single three-dimensional image. The process of development of complete three-dimensional vision begins at birth and is almost complete by 24 months of age. The development of this binocular vision is hindered by any abnormality that prevents the brain from receiving a clear, similar image from each eye, due to decreased vision (e.g. amblyopia), or due to misalignment of the two eyes (strabismus or squint) in infancy and early childhood. Currently, practice patterns for management of a child with both strabismus and amblyopia are not standardized. To study the functional and anatomic (ocular alignment) outcomes of strabismus surgery before completion of amblyopia therapy as compared with surgery after completion of amblyopia therapy in children under seven years of age. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2014), EMBASE (January 1980 to July 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to July 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 24 July 2014. A manual search for articles from a review of the references of the selected publications and conference abstracts was completed to identify any additional relevant studies. We searched for randomized controlled trials (RCTs) that provided data on strabismus surgery in children less than seven years of age, performed after initiation of, but before completion of amblyopia therapy, as compared with strabismus surgery after completion of amblyopia therapy. Two authors independently assessed studies identified from the electronic and manual searches. There were no RCTs that fit our inclusion criteria and so no analysis was possible. As there are no RCTs currently available and the best existing evidence is only from non-randomized studies, there is a need for prospective RCTs to investigate strabismus surgery in the presence of strabismic amblyopia. The optimal timing of when to perform strabismus surgery in children with amblyopia is unknown.


An arginine to lysine substitution in the bZIP domain of an opaque-2 mutant in maize abolishes specific DNA binding.
The opaque-2 (o2) locus in maize encodes a transcription factor involved in the regulation of zein storage proteins. We have shown previously that the O2 protein contains a leucine zipper domain that binds to promoters of 22-kD zein genes. In this paper we characterize an EMS-induced o2 allele, o2-676, that causes a 50% reduction in zein. We have found that the o2-676 mutant protein does not show specific recognition of zein promoter fragments because of the substitution of a lysine residue for an arginine residue within the bZIP domain of o2-676. This particular arginine is conserved within the bZIP domains of all mammalian, fungal, and plant DNA binding proteins of this class. The correlation between this mutation in o2 and the altered pattern of zein expression strongly suggests that O2 regulates transcription of certain members of the zein multigene family through direct interaction with the zein promoters and not through the transcriptional activation of some other regulator of zein gene expression.


Interlaboratory comparison for the Filovirus Animal Nonclinical Group (FANG) anti-Ebola virus glycoprotein immunoglobulin G enzyme-linked immunosorbent assay.
The need for an efficacious vaccine against highly pathogenic filoviruses was reinforced by the devastating 2014-2016 outbreak of Ebola virus (EBOV) disease (EVD) in Guinea, Sierra Leone, and Liberia that resulted in over 28,000 cases and over 11,300 deaths. In addition, the 2018-2020 outbreak in the Democratic Republic of the Congo currently has over 3,400 cases and over 2,200 deaths. A fully licensed vaccine and at least one other investigational vaccine are being deployed to combat this EVD outbreak. To support vaccine development and pre-clinical/clinical testing a Filovirus Animal Nonclinical Group (FANG) human anti-EBOV GP IgG ELISA was developed to measure anti-EBOV GP IgG antibodies. This ELISA is currently being used in multiple laboratories. Reported here is a characterization of an interlaboratory statistical analysis of the human anti-EBOV GP IgG ELISA as part of a collaborative study between five participating laboratories. Each laboratory used similar method protocols and reagents to measure anti-EBOV GP IgG levels in human serum samples from a proficiency panel consisting of ten serum samples created by the differential dilution of a serum sample positive for anti-GP IgG antibodies (BMIZAIRE105) with negative serum (BMI529). The total assay variability (inter- and intra-assay variability) %CVs observed at each laboratory ranged from 12.2 to 30.6. Intermediate precision (inter-assay variability) for the laboratory runs ranged from 8.9 to 21.7%CV and repeatability (intra-assay variability) %CVs ranged from 7.2 to 23.7. The estimated slope for the relationship between log10(Target Concentration) and the log10(Observed Concentration) across all five laboratories was 0.95 with a 90% confidence interval of (0.93, 0.97). Equivalence test results showed that the 90% confidence interval for the ratios for the sample-specific mean concentrations at the five individual labs to the overall laboratory consensus value were within the equivalence bounds of 0.80 to 1.25 for each laboratory and test sample, except for six test samples from Lab D, two samples from Lab B1, and one sample from Lab B2. The mean laboratory concentrations for Lab D were less than those from the other laboratories by 20% on average across the serum samples. The evaluation of the proficiency panel at these laboratories provides a limited assessment of assay precision (intermediate precision, repeatability, and total assay variability), dilutional linearity, and accuracy. This evaluation suggests that the within-laboratory performance of the anti-EBOV GP IgG ELISA as implemented at the five laboratories is consistent with the intended use of the assay based on the acceptance criteria used by laboratories that have validated the assay. However, the assessment of between-laboratory performance revealed lower observed concentrations at Lab D and greater variability in assay results at Lab B1 relative to other laboratories.


Clinical applications of the hematopoietic growth factors.
Hematopoiesis occurs in a microenvironment containing a variety of growth factors. Normal hematopoietic cells require these growth factors for viability, proliferation, and differentiation. The purification and molecular cloning of human growth factors has permitted a detailed analysis of hematopoiesis. Furthermore, the commercial production of growth factors resulted in their widespread introduction into clinical practice to limit chemotherapy-induced neutropenia. Recently, clinical trials of growth factors have expanded to test their direct anticancer effects, to improve the efficacy of chemotherapy by stimulating cell division, and to use them as biological modulators to inhibit tumor growth. This review focuses on a few clinical uses of recombinant growth factors.


Nicotine Increases Activation to Anticipatory Valence Cues in Anterior Insula and Striatum.
Smoking is associated with significant morbidity and mortality. Understanding the neurobiology of the rewarding effects of nicotine promises to aid treatment development for nicotine dependence. Through its actions on mesolimbic dopaminergic systems, nicotine engenders enhanced responses to drug-related cues signaling rewards, a mechanism hypothesized to underlie the development and maintenance of nicotine addiction. We evaluated the effects of acute nicotine on neural responses to anticipatory cues signaling (nondrug) monetary reward or loss among 11 nonsmokers who had no prior history of tobacco smoking. In a double-blind, crossover design, participants completed study procedures while wearing nicotine or placebo patches at least 1 week apart. In each drug condition, participants underwent functional magnetic resonance imaging while performing the monetary incentive delay task and performed a probabilistic monetary reward task, probing reward responsiveness as measured by response bias toward a more frequently rewarded stimulus. Nicotine administration was associated with enhanced activation, compared with placebo, of right fronto-anterior insular cortex and striatal regions in response to cues predicting possible rewards or losses and to dorsal anterior cingulate for rewards. Response bias toward rewarded stimuli correlated positively with insular activation to anticipatory cues. Nicotinic enhancement of monetary reward-related brain activation in the insula and striatum in nonsmokers dissociated acute effects of nicotine from effects on reward processing due to chronic smoking. Reward responsiveness predicted a greater nicotinic effect on insular activation to salient stimuli. Previous research demonstrates that nicotine enhances anticipatory responses to rewards in regions targeted by midbrain dopaminergic systems. The current study provides evidence that nicotine also enhances responses to rewards and losses in the anterior insula. A previous study found enhanced insular activation to rewards and losses in smokers and ex-smokers, a finding that could be due to nicotine sensitization or factors related to current or past smoking. Our finding of enhanced anterior insula response after acute administration of nicotine in nonsmokers provides support for nicotine-induced sensitization of insular response to rewards and losses.


Expression of the bcl-2 gene in human multiple myeloma cell lines and normal plasma cells.
The bcl-2 gene, encoding a mitochondrial membrane protein suggested to play an important role in cell survival, is translocated into the Ig loci in about 80% of human follicular lymphomas, which results in a high level of expression. This report shows that bcl-2 was expressed in eight of eight human multiple myeloma cell lines and in normal lymph node and bone marrow plasma cells. In the majority of the myeloma lines, the level of expression was comparable with that observed in Karpas 422, a follicular lymphoma cell line carrying a 14;18 translocation of the bcl-2 gene. DNA rearrangements of the bcl-2 locus were evident in only one of the myeloma cell lines, U-266-1970. In this cell line, which exhibited the highest bcl-2 expression, a fourfold increased copy number of the bcl-2 gene was estimated by Southern analysis. This amplification was lost in cells of later passages (U-266-1984), suggesting that bcl-2 might possibly have played a role in the tumor development in vivo. Our results are in contrast to previous observations in murine plasmacytoma, in which bcl-2 was shown to be silent. The results also contradict the published observation that bcl-2 is not expressed at terminal stages of B-cell differentiation. It is at present unclear whether the high expression of bcl-2 in human myeloma is the result of a deregulated expression associated with the malignant phenotype or a mere reflection of the bcl-2 expression typical of normal plasma cells.


[Ischemic stroke, secondary to fibromuscular dysplasia: a case report].
Fibromuscular dysplasia is an infrequent angiopathy that occurs more often in young women. It consists in a series of heterogeneous histological changes that finally lead to the narrowing of arteries. Clinical manifestations depend on the vessel involved, but high blood pressure (renal artery involvement) and stroke (carotid artery involvement) are the most common. Little has been published about this process in recent years. A 30-year-old female with extensive infarction of the right middle cerebral artery caused by obstruction of the internal carotid artery. Arteriographical examination revealed the dissection of the four supra-aortic trunks together with alterations to the renal artery. The patient's age and the involvement of the four cerebral arteries with irregular stenoses led us to consider a fibromuscular dysplasia (FMD) as the first diagnostic option. A conservative attitude was adopted towards the vascular lesions and therapy was carried out with a view to rehabilitating the neurological deficits. Brain FMD can be asymptomatic and is often diagnosed by chance. The usual clinical presentation is a stenosis-related ischemic stroke, arterial obstruction or arterio-arterial thromboembolism. Arteriography or magnetic resonance angiography are useful for diagnosis; the involvement of different supra-aortic vessels is characteristic. Despite the good results shown by percutaneous transluminal angioplasty, there is still a need for prospective studies that determine the optimal treatment for this pathology.


Staphylococcal L-asparaginase: enzyme kinetics.
The ph optimum of purified staphylococcal L-asparaginase (EC 18.104.22.168) was found to be between 8.6 and 8.8. The temperature optimum was 30 degrees-32 degrees C and the highest reaction rate occurred at 30 degrees C. The KM of the enzyme calculated from Lineweaver-Burk plot was 3.71 x 10(-2) M. Besides L-asparaginase, the substrate specificity of enzyme was restricted to N-alpha-acetyl-L-asparagine. D-asparagine, L-aspartic acid and D-glutamic acid were competitive inhibitors. Hg2+ and Cu2+ cations strongly inhibited the enzyme while Na+ and K+ cations strongly stimulated activity. Two SH-groups could be detected after enzyme denaturation with guanidine.


Urban development patterns in Indonesia.
The author examines recent urban development in Indonesia. "Analysis of urban developments in Indonesia has been hampered in the past by weak data. Recently, the National Urban Development Strategy (NUDS) project has generated a set of improved data. This paper aims at elaborating and supplementing the NUDS study. After a discussion of definitional problems, an analysis is carried out of urban growth rates at the provincial level. Private investment is shown to be a principal determinant of urban growth rates. Other significant determinants are rural immigration and the present level of urbanisation. Private investment is shown to be strongly biased towards provinces with large urban areas. In addition, polarisation is studied at the level of individual cities. It is found that a period of rapidly increasing polarisation has come to an end during the last decade."


Directed mutagenesis of the Rhodobacter capsulatus puhA gene and orf 214: pleiotropic effects on photosynthetic reaction center and light-harvesting 1 complexes.
Rhodobacter capsulatus puhA mutant strains containing either a nonpolar, translationally in-frame deletion or a polar insertion of an antibiotic resistance cartridge were constructed and evaluated for their photosynthetic growth properties, absorption spectroscopy profiles, and chromatophore protein compositions. Both types of mutants were found to be incapable of photosynthetic growth and deficient in the reaction center (RC) and light-harvesting 1 (LH1) complexes. The translationally in-frame puhA deletion strains were restored to the parental strain phenotypes by complementation with a plasmid containing the puhA gene, whereas the polar puhA mutants were not. Analogous nonpolar and polar disruptions of orf 214 (located immediately 3' of the puhA gene) were made, and the resultant mutant strains were evaluated as described above. The strain containing the nonpolar deletion of orf 214 exhibited severely impaired photosynthetic growth properties and had greatly reduced levels of the RC and LH1 complexes. Complementation of this strain with a plasmid that expressed orf 214 from the nifHDK promoter restored photosynthetic growth capability, as well as the RC and LH1 complexes. The polar disruption of orf 214 yielded cells that were incapable of photosynthetic growth and had even lower levels of the RC and LH1 complexes, and complementation in trans with orf 214 only marginally improved these deficiencies. These results indicate that orf 214 and at least one additional gene located 3' of orf 214 are required to obtain the RC and LH1 complexes, and transcription read-through from the puhA superoperon is necessary for optimal expression of these new photosynthesis genes.


Hepatic histology in obese patients undergoing bariatric surgery.
Obesity is one of the most important clinical associations with non-alcoholic steatohepatitis (NASH). Our aim was to assess the prevalence of non-alcoholic fatty liver disease (NAFLD)/NASH in morbidly obese patients and the risk factors to more aggressive liver disease in this population. Review of available studies on prevalence of NAFLD/NASH in severely obese patients submitted to bariatric surgery. Twelve observational and transversal studies were included, with consecutive recruitment, and prospective evaluation of data, summing 1620 patients with severe obesity. Prevalence of steatosis and NASH was 91% (range: 85-98%) and 37% (24-98%), respectively, with unexpected cirrhosis in 1.7% (1-7%). NASH was not related with age or body mass index, but there was an association between male sex and NASH/hepatic fibrosis. Diabetes mellitus and insulin resistance were the conditions most frequently associated with NASH, and hypertension with advanced hepatic fibrosis. There is a very high prevalence of NAFLD in asymptomatic morbidly obese patients, more than one-third presenting histological criteria for NASH. This review underscores the large variations in prevalence of NASH between studies, calling for the need for a better agreement in the use of the histological criteria.


[Role of nitric oxide and hydrogen peroxide in the essential oil increasing of suspension cells from Atractylodes lancea induced by endophytic fungal Cunninghamella sp. AL4 elicitor].
Crude elicitor of one endophytic fungi (belong to Cunninghamella sp., named AL4) induced multiple responses in Atractylodes lancea suspension cells, including rapid generation of nitric oxide (NO) and hydrogen peroxide (H2O2), sequentially followed by enhancement of essential oil production. Adding NO-specific scavenger 2-4-carboxyphenyl-4,4,5, 5-tetramethylimidazol ine-1-oxyl-3-oxide (cPTIO) and H2O2 scavenger catalase (CAT) could block elicitor-induced NO and H2O2 generation respectively, but could all partly block elicitor-induced essential oil biosynthesis. Adding NO-donor sodium nitroprusside (SNP) and H2O2 could all promote essential oil accumulation in A. lancea cells, but the effect of both was different. These results strongly suggested that NO and H2O2 may all act as signaling molecule to mediate AL4 elicitor promoting essential oil accumulation in suspension cells of A. lancea. Furthermore, adding cPTIO and CAT contemporarily could not completely inhibit essential oil accumulation induced by AL4 elicitor. This result suggested that AL4 elicitor could also promote essential oil accumulation in suspension cells of A. lancea by other means.


Periodontal therapy reduces plasma levels of interleukin-6, C-reactive protein, and fibrinogen in patients with severe periodontitis and refractory arterial hypertension.
Recent epidemiologic studies suggest that inflammation is the link between periodontal diseases and cardiovascular complications. This study aimed to evaluate the effects of non-surgical periodontal treatment on plasma levels of inflammatory markers (interleukin [IL]-6, C-reactive protein [CRP], and fibrinogen) in patients with severe periodontitis and refractory arterial hypertension. Twenty-two patients were examined and randomly divided into two groups. The test group was composed of 11 patients (mean age, 48.9 +/- 3.9 years) who received periodontal treatment, whereas the control group had 11 patients (mean age, 49.7 +/- 6.0 years) whose treatment was delayed for 3 months. Demographic and clinical periodontal data were collected, and blood tests were performed to measure the levels of IL-6, CRP, and fibrinogen at baseline and 3 months later. The clinical results showed that the mean percentages of sites with bleeding on probing, probing depth (PD) 4 to 5 mm, PD > or =6 mm, clinical attachment loss (CAL) 4 to 5 mm, and CAL > or =6 mm were significantly reduced in the test group 3 months after periodontal treatment. There were no significant differences between the data at baseline and 3 months in the control group. Periodontal treatment significantly reduced the blood levels of fibrinogen, CRP, and IL-6 in the test group. Non-surgical periodontal therapy was effective in improving periodontal clinical data and in reducing the plasma levels of IL-6, CRP, and fibrinogen in hypertensive patients with severe periodontitis.


Ultrasonographic detection and guided biopsy of thoracic osteolysis.
Eighty-six osteolytic lesions of the rib cage were examined by means of conventional radiography and ultrasonography. The ultrasonographic criteria of osteolysis are described. Only 1 rib metastasis was missed by ultrasonography while 13 lesions were not detected by x-ray film. Of 63 ultrasonographically guided biopsies, 62 resulted in the final diagnosis; complications were not observed. The results recommend ultrasonographic examination combined with guided biopsy as the first diagnostic step, if a metastasis of the rib cage is suspected after physical examination or after a pathologic bone scan.


The value of interictal brain SPECT in epilepsy patients without mesial-temporal sclerosis.
Most of the literature concerning interictal SPECT brain scanning in patients with seizures has involved the evaluation of those with temporal lobe epilepsy. The authors' aim was to determine the utility of interictal SPECT in patients with neocortical epilepsy. Eighty-four patients with neocortical epilepsy were evaluated with 95 interictal SPECT scans and magnetic resonance imaging (MRI). Fifty-four percent of studies with normal MRI findings had SPECT images without regions of hypoperfusion. Sixty-one percent of patients with abnormal MRI results had matching defects visible on SPECT images. Fourteen scans (only 24%) had focal hypoperfusion by SPECT and no obvious matching MRI finding. Interictal SPECT, without a comparison ictal study, is of potentially limited value in localizing neocortical seizure foci. SPECT findings usually match MRI findings. Interictal SPECT, however, may still be of value in confirming abnormalities detected by ictal examination.


High-throughput screening of radioprotectors using rat thymocytes.
We invented a high-throughput screening method for the examination of radioprotective activity of chemical compounds using rat thymocytes. X-irradiation of the rat thymocytes induced apoptosis, leading to a significant cell shrinkage, which could be easily detected and directly quantified by the flow cytometry analysis. The protective effect of some natural antioxidants against radiation induced apoptosis in the rat thymocytes, as well as their toxicities without X-irradiation, was successfully evaluated using this method. This method provides a powerful tool to develop novel radioprotectors without toxicity and can also be widely used to estimate other oxidative stress except for radiation.


Medical professionalism and the clinical anatomist.
Medical professionalism has become an important issue for medical education and practice. The core attributes of professionalism derive from the roles and responsibilities of professions and from the nature of medicine as a healing profession. In medical education, most of the focus on professionalism has been directed to the clinical arena, yet it is critically important that the attributes of professionalism be manifested in basic science courses--especially anatomy--as well as in clinical experiences, because the transformation from medical student to physician begins at the outset of medical school. Throughout history, anatomists have exemplified many of the attributes and values of professionalism, and clinical anatomists today still have much to offer. Anatomy faculty have an important responsibility to nurture and exemplify professionalism.


Identification of ornithine decarboxylase as a trait gene for growth in replicated mouse lines divergently selected for lean body mass.
Studies of lines of mice selected for body mass have shown that there is a significant genetic component affecting this trait although the nature of the genes involved remains to be elucidated. Using replicate lines of mice, our studies have shown that two different variants of the mouse ornithine decarboxylase (ODCase) gene have been selected in replicate lines of mice selected for high and low lean body mass respectively. One variant is associated with an increased peak of ODCase activity in embryos (10-13 days of gestation) in all high mass lines and with a restriction fragment length polymorphism of the expressed gene. The increased ODCase activity coincides with increased ODCase mRNA levels in the high mass selected lines. These results provide evidence implicating ornithine decarboxylase as a major factor in cell growth, and as a candidate 'trait gene'.


Surgical outcome of Chiari I malformations--an experience sharing and literature review.
The Chiari malformations are a group of central nervous system defects that involve the posterior cranial fossa. The clinical complaints range from headache, sensory changes, vertigo, ataxia, and imbalance to hearing loss. In patients with Chiari malformation, only those with type I malformation were born grossly normal, the neurological dysfunction developing gradually as they grew up, which spurred our interest. From August 1990 to September 1998, seven patients received surgical intervention at Kaohsiung Medical College Hospital under the impression of Chiari malformations. There were 4 males and 3 females, with age ranging from 7 years to 41 years. All these patients were diagnosed via magnetic resonance imaging and surgical findings revealed a hypoplasic vermis. Among them, 4(57%) were cranial nerve plasy, 2(29%) nystagmus, 6(100%) syringomyelia, 7(100%) scoliosis and one (14%) with hydrocephalus. Cerebellar ataxia and upper limbs weakness was noted in 5(71%) patients. Our surgical interventions included suboccipital craniectomy and dural opening(7/7), C1 posterior arch decompression (7/7), C4,5 laminectomy (1/7), and syringostomy(4/7). There was one mortality in a 41 y/o male with progressively lower cranial nerve(V, VII, IX) impairment as well as poor lung compliance. Other patients improved in their symptoms after follow-up periods of 6 months to 6 years. Our study shows that 1) surgical decompression was indicated in all patients with brain stem and lower cranial nerve dysfunction as well as central cord syndrome caused by syringomyelia; 2) a better result was achieved in those patients who received adequate nervous system decompression; and 3) much attention should be payed to cases with lower cranial nerves XI, X, XII impairment, because complications such as choking and aspiration pneumonia can happen.


A review on techniques for tremor recording and quantification.
Tremor is the most common movement disorder and differs from other disorders by its repetitive, stereotyped movements, with regular frequency and amplitude. The three most frequent pathological forms of it are the essential tremor (ET), the Parkinson's disease (PD) tremor, and the enhanced physiological tremor. The ET and PD tremor affect the older population mostly. Although there are cases of tremor reported since ancient times, there is currently no consensus about its causes or about its main differential characteristics. In this article, we present a review of the methods more frequently used in measurement and analysis of tremor and the difficulties encountered in the research for the identification of methodologies that allow a significant advance in the study of tremor.


How do home health nurses spend their time?
Of critical importance to the financial viability of any home health agency are its productivity standards for staff. The authors discuss the results of a study that analyzed staff time spent in direct patient care, documentation of that care, travel, and other activities, and how the resulting data influenced agency operations.


Physical properties of addition silicones as a function of composition.
The effects of molecular weight of the base silicone, filler and copolymer concentrations on compression set, strain, creep and dynamic elastic modulus were determined. The molecular weight of the base silicone had the least effect on these properties although low molecular weights showed better properties. Chain extenders were detrimental to physical properties of creep, compression set and dynamic elastic modulus. Increased copolymer concentrations decreased compression set, strain and creep and increased the dynamic elastic modulus. The useful copolymer/base functional group ratio was from 1:1 to 3:1. Filler affected properties to a lesser extent than copolymer ratio. Compression set, strain, and creep decreased and the dynamic elastic modulus increased with increasing filler with the properties being directly proportional to the weight fraction. All properties were interrelated with ln strain linearly related to ln compression set, creep proportional to set, and the dynamic elastic modulus was inversely correlated with strain and creep.


Pediatric liver failure with massive sinusoidal infiltration of histiocytes.
Histiocytic neoplasms, such as Langerhans cell histiocytosis (LCH) and disseminated juvenile xanthogranuloma (JXG), can involve the liver and sometimes cause liver failure. We aimed to classify non-LCH histiocytic proliferating disorders that do not exhibit typical disseminated JXG histology. We examined four pediatric patients who presented with liver failure and splenomegaly. Two patients with liver cirrhosis without cholestasis underwent liver transplantation (LT). The other two patients presented with giant cell hepatitis causing neonatal/infantile acute liver failure (ALF). The infantile ALF patient also underwent LT. Liver dysfunction developed after LT in all three transplant cases and the grafts exhibited massive sinusoidal infiltration of histiocytes with hemophagocytosis, similar to the native liver. The neonatal ALF patient was treated with an LCH-type chemotherapy regimen, and is alive and well at 18 months. Infiltrating histiocytes were positive for CD68 and CD163, and negative for CD1a, CD207, and S-100 protein. The BRAF V600E mutation was not present. Liver histological findings were not consistent with conventional disseminated JXG or LCH, although the histological findings in other organs overlapped those of well-known histiocytic neoplasms. The histological and immunohistochemical findings of infiltrating histiocytes suggest that these four cases constituted a disseminated JXG-like systemic disease.


An Overview on Recent Progress in Electrochemical Biosensors for Antimicrobial Drug Residues in Animal-Derived Food.
Anti-microbial drugs are widely employed for the treatment and cure of diseases in animals, promotion of animal growth, and feed efficiency. However, the scientific literature has indicated the possible presence of antimicrobial drug residues in animal-derived food, making it one of the key public concerns for food safety. Therefore, it is highly desirable to design fast and accurate methodologies to monitor antimicrobial drug residues in animal-derived food. Legislation is in place in many countries to ensure antimicrobial drug residue quantities are less than the maximum residue limits (MRL) defined on the basis of food safety. In this context, the recent years have witnessed a special interest in the field of electrochemical biosensors for food safety, based on their unique analytical features. This review article is focused on the recent progress in the domain of electrochemical biosensors to monitor antimicrobial drug residues in animal-derived food.


The effects of prosodic prominence and serial position on duration perception.
This study addresses how prosodic expectations affect perceptual discrimination. Prosodic expectations were created using natural recordings of six-syllable sentences in dactylic, iambic, and trochaic metrical patterns at two speech rates, slow and quick. PSOLA resynthesis was used to lengthen target syllables located in three different serial positions in each of the three patterns. Subjects made forced-choice comparisons of durational structure in an AX task. Lengthening was detected significantly better for strong syllables than for weak ones in all metrical patterns, serial positions, and at speech rates. The result obtains even when absolute duration is eliminated as a potential confound. Results are interpreted in the light of prior research showing that prosodically strong syllables offer perceptual advantages in recognition and identification tasks, even when prosodic strength is cued only by the prior context (and not by any acoustic phonetic properties of the target syllables). In conclusion, metrical expectations cause listeners to focus their attention on metrically prominent syllables, with attentional focus leading to better performance in tasks tapping multiple levels of processing.


Assessment of Patient-Centered Outcomes When Treating Maxillary Constriction Using a Slow Removable Versus a Rapid Fixed Expansion Appliance in the Adolescence Period: A Randomized Controlled Trial.
Objective This study aimed to evaluate and compare the levels of pain, discomfort, and functional impairments between slow and rapid maxillary expansion (RME) in treating skeletal maxillary constriction in the adolescence period (i.e., between 12 and 16 years). Materials and methods The study sample consisted of 52 patients (21 males and 31 females) with maxillary skeletal constriction in the posterior region. The patients were randomly distributed into either RME (26 patients, with a mean age of 13.87 (± 1.31) years) or slow maxillary expansion group (SME, 26 patients, with a mean age of 14.31 (± 1.19) years). The levels of pain, discomfort, and functional difficulties were assessed after 24 hours (T1), 7 days (T2), 15 days (T3), one month (T4), and four months (T5) following the onset of the expansion procedure. Results Patients in the RME group encountered significantly greater levels of pain and discomfort than those in the SME group at T1, T2, and T3 (p>0.001). Chewing and swallowing difficulties were significantly greater in the RME group at T1, T2, T3, and T4 (P≤0.001). The pressure on soft tissue was greater in the RME group at T2 and T3 (p>0.001). After four months (T5), the levels of pain and discomfort decreased to their lowest levels, as well as the difficulties of chewing and swallowing, and the pressure on soft tissue were almost non-existent in both groups. Conclusion Patients treated with the removable slow maxillary expander reported lower levels of pain and discomfort, fewer chewing and swallowing difficulties, and less pressure on soft tissues than those treated with the bonded rapid maxillary expander. These difficulties gradually decreased over time in both groups. The lower levels of pain and discomfort may make the SME an effective and comfortable treatment alternative for adolescents with skeletal maxillary constriction.


Polymorphism in tumor necrosis factor-related apoptosis-inducing ligand receptor 1 is associated with poor viral response to interferon-based hepatitis C virus therapy in HIV/hepatitis C virus-coinfected individuals.
HIV/hepatitis C virus (HCV) coinfection causes accelerated liver disease compared to HCV monoinfection, and only 30-60% of HIV/HCV-coinfected individuals respond to HCV therapy with pegylated interferon and ribavirin. There are currently no biomarkers that predict treatment response in these coinfected patients. We investigated whether there is an association between HCV treatment response and SNPs of apoptosis-related genes during HIV/HCV coinfection. Genomic DNA from 53 HIV/HCV-coinfected individuals was analyzed for 82 SNPs of 10 apoptosis-related genes. We found that the presence of the rs4242392 SNP in tumor necrosis factor receptor superfamily, member 10a (TNFRSF10A), which encodes for tumor necrosis factor-related apoptosis-inducing ligand receptor 1, predicts poor outcome to HCV therapy, in HIV/HCV-co-infected patients [odds ratio 5.91 (95% confidence interval 1.63-21.38, P = 0.007)]. The rs4242392 SNP of the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 gene predicted poor interferon-based HCV treatment response in HIV/HCV-coinfected patients.


ThermoMutDB: a thermodynamic database for missense mutations.
Proteins are intricate, dynamic structures, and small changes in their amino acid sequences can lead to large effects on their folding, stability and dynamics. To facilitate the further development and evaluation of methods to predict these changes, we have developed ThermoMutDB, a manually curated database containing >14,669 experimental data of thermodynamic parameters for wild type and mutant proteins. This represents an increase of 83% in unique mutations over previous databases and includes thermodynamic information on 204 new proteins. During manual curation we have also corrected annotation errors in previously curated entries. Associated with each entry, we have included information on the unfolding Gibbs free energy and melting temperature change, and have associated entries with available experimental structural information. ThermoMutDB supports users to contribute to new data points and programmatic access to the database via a RESTful API. ThermoMutDB is freely available at: http://biosig.unimelb.edu.au/thermomutdb.


The allometric relationship between muscle mass and the main anthropometric variables in male and female elite athletes.
Muscle mass is estimated in athletes to measure the effects of training and determine if their muscle mass is optimized for their sport. The assessment depends on each subject's body size. The aim of the study was to analyze the most appropriate allometric relationship between muscle mass and the main size variables, as well as to define the most specific allometric indices for this population. The sample comprised 4651 elite athletes (65.3% male) from 41 sports. Muscle mass was estimated by Lee's equation using the anthropometric technique and correlated with nine anthropometric variables. Curvilinear regression was established according to an allometric model, y = a* xb, where y is the muscle mass, x are the size variables with the highest correlation coefficient, and b is the exponent of power. The powers obtained in males vs. females were: height, 1.7 vs. 1.5; sitting height, 2.0 vs. 1.7; arm span, 1.5 vs. 1.3; biacromial breadth, 1.7 vs. 1.4; and tibial height, 1.1 vs. 1.0. These new indices will allow the assessment of muscle mass, independent of the height or chosen size variable, and the calculation of muscle mass according to the subject's dimensions.


Epigenetic reprogramming of host genes in viral and microbial pathogenesis.
One of the key questions in the study of mammalian gene regulation is how epigenetic methylation patterns on histones and DNA are initiated and established. These stable, heritable, covalent modifications are largely associated with the repression or silencing of gene transcription, and when deregulated can be involved in the development of human diseases such as cancer. This article reviews examples of viruses and bacteria known or thought to induce epigenetic changes in host cells, and how this might contribute to disease. The heritable nature of these processes in gene regulation suggests that they could play important roles in chronic diseases associated with microbial persistence; they might also explain so-called 'hit-and-run' phenomena in infectious disease pathogenesis.


Pulsed Doppler in the diagnosis of small liver tumours.
Doppler ultrasound detection of the blood flow associated with liver tumours was studied in primary hepatocellular carcinoma as well as in metastatic liver cancer and haemangioma. Doppler signals were detected from 48 of 55 hepatocellular carcinomas (87.3%), seven of 25 metastatic liver cancers (28.0%) and four of 30 haemangiomas (13.3%). The waveforms of Doppler signals were divided into two types: the pulsatile wave, which was detected from hepatocellular carcinoma (in 35 of the 48 with Doppler signals) and metastatic liver cancer (in all seven with positive signals), and the continuous wave, which was seen from hepatocellular carcinoma (41 out of 48) and haemangioma (in all four with signals). In six patients with hepatocellular carcinoma who underwent transcatheter arterial embolization, the pulsatile wave detected before therapy disappeared immediately thereafter and it is possible that this type of wave originates from tumour vessels. In the study of small, hypoechoic, mass lesions appearing in liver cirrhosis, such signals were also demonstrated, even in eight of 10 small hepatocellular carcinomas less than 2 cm in diameter, whilst they were not detected from nine regenerative nodules related to cirrhotic change. In conclusion, the Doppler ultrasound method may be a useful technique in detecting blood flow within liver tumours and may offer the possibility of a differential diagnosis of small tumours.


SlCCD1A Enhances the Aroma Quality of Tomato Fruits by Promoting the Synthesis of Carotenoid-Derived Volatiles.
The loss of volatiles results in the deterioration of flavor in tomatoes. Volatiles are mainly derived from fatty acid, carotenoid, phenylpropane, and branched chain amino acids. In this study, the tomato accession CI1005 with a strong odor and accession TI4001 with a weak odor were analyzed. The volatile contents were measured in tomato fruits using gas chromatography-mass spectrometry. The scores of tomato taste and odor characteristics were evaluated according to hedonistic taste and olfaction. It was found that the content of fatty acid-derived volatiles accounted for more than half of the total volatiles that had grassy and fatty aromas. Phenylpropane-derived volatiles had irritation and floral aromas. Branched-chain amino acid-derived volatiles had a caramel aroma. Carotenoid-derived volatiles had floral, fruity, fatty, and sweet-like aromas, preferred by consumers. A lack of carotenoid-derived volatiles affected the flavor quality of tomato fruits. The accumulation of carotenoid-derived volatiles is regulated by carotenoid cleavage oxygenases (CCDs). A tissue-specific expression analysis of the SlCCD genes revealed that the expression levels of SlCCD1A and SlCCD1B were higher in tomato fruits than in other tissues. The expression levels of SlCCD1A and SlCCD1B were consistent with the trend of the carotenoid-derived volatile contents. The expression of SlCCD1A was higher than that for SlCCD1B. A bioinformatics analysis revealed that SlCCD1A was more closely linked to carotenoid metabolism than SlCCD1B. The overexpression of SlCCD1A indicated that it could cleave lycopene, α-carotene, and β-carotene to produce 6-methyl-5-hepten-2-one, geranylacetone, α-ionone, and β-ionone, increasing the floral, fruity, fatty, and sweet-like aromas of tomato fruits. The flavor quality of tomato fruits could be improved by overexpressing SlCCD1A.


[Prognostication of acute intraoperative bleeding in children with burn wounds undergoing tangential necrectomy and auto-dermatoplasty].
The aim of this study was to estimate the blood loss of children undergoing tangential necrectomies and skin grafting by using gravimetric methods. Also we had to estimate the influence of age upon the quantity of blood loss. We examined 50 cases. The body surface from which the intraoperative bleeding took place included the areas of tangential necrectomy and skin harvesting. The bleeding was controlled by electrocoagulation and wound dressing, soaked with epinephrine solution 1:50,000. The blood loss was estimated by weighing the material before and after the operation, excluding from the amount the quantity of the epinephrine solution. We divided the children into 3 groups according to their age: first--up to 1 year, second--1-3 year old, third--3-15 year old. By using the gravimetric method we found out that the mean blood loss from the areas of necrectomy and harvesting is 0.47 +/- 0.1 ml/cm2. The age of children does not influence the intensiveness of bleeding per square measure site of the necrectomy and harvesting area. The blood loss is a constant quantity and is equal to 0.47 +/- 0.1 ml/cm2. The blood loss that takes place from one percent of the necrectomy and harvesting areas is approximately equal to 2.05% of the circulating blood volume.


A long term study of pulmonary function among US refractory ceramic fibre workers.
Cross-sectional studies have shown declines in lung function among refractory ceramic fibre (RCF) workers with increasing fibre exposure. This study followed current and former workers (n=1396) for up to 17 years and collected 5243 pulmonary function tests. Cumulative fibre exposure and production years were categorised into exposure levels at five manufacturing locations. Conventional longitudinal models did not adequately partition age-related changes from other time-dependent variables. Therefore, a restricted cubic spline model was developed to account for the non-linear decline with age. Cumulative fibre >60 fibre-months/cc showed a significant loss in lung function at the first test. When results were examined longitudinally, cumulative exposure was confounded with age as workers with the highest cumulative exposure were generally older. A longitudinal model adjusted by age groups was implemented to control for this confounding. No consistent longitudinal loss in lung function was observed with RCF exposure. Smoking, initial weight and weight increase were significant factors. No consistent decline was observed longitudinally with exposure to RCF, although cross-sectional and longitudinal findings were discordant. Confounding and accelerated lung function declines with ageing and the correlation of multiple time-dependent variables should be considered in order to minimise error and maximise precision. An innovative statistical methodology for these types of data is described.


Aldehyde Dehydrogenase 2 as a Therapeutic Target in Oxidative Stress-Related Diseases: Post-Translational Modifications Deserve More Attention.
Aldehyde dehydrogenase 2 (ALDH2) has both dehydrogenase and esterase activity; its dehydrogenase activity is closely related to the metabolism of aldehydes produced under oxidative stress (OS). In this review, we recapitulate the enzyme activity of ALDH2 in combination with its protein structure, summarize and show the main mechanisms of ALDH2 participating in metabolism of aldehydes in vivo as comprehensively as possible; we also integrate the key regulatory mechanisms of ALDH2 participating in a variety of physiological and pathological processes related to OS, including tissue and organ fibrosis, apoptosis, aging, and nerve injury-related diseases. On this basis, the regulatory effects and application prospects of activators, inhibitors, and protein post-translational modifications (PTMs, such as phosphorylation, acetylation, S-nitrosylation, nitration, ubiquitination, and glycosylation) on ALDH2 are discussed and prospected. Herein, we aimed to lay a foundation for further research into the mechanism of ALDH2 in oxidative stress-related disease and provide a basis for better use of the ALDH2 function in research and the clinic.


Subcellular localization and topology of the p7 polypeptide of hepatitis C virus.
Although biological and biochemical data have been accumulated on most hepatitis C virus proteins, the structure and function of the 63-amino-acid p7 polypeptide of this virus have never been investigated. In this work, sequence analyses predicted that p7 contains two transmembrane passages connected by a short hydrophilic segment. The C-terminal transmembrane domain of p7 was predicted to function as a signal sequence, which was confirmed experimentally by analyzing the translocation of a reporter glycoprotein fused at its C terminus. The p7 polypeptide was tagged either with the ectodomain of CD4 or with a Myc epitope to study its membrane integration, its subcellular localization, and its topology. Alkaline extraction studies confirmed that p7 is an integral membrane polypeptide. The CD4-p7 chimera was detected by immunofluorescence on the surface of nonpermeabilized cells, indicating that it is exported to the plasma membrane. However, pulse-chase analyses showed that only approximately 20% of endoglycosidase H-resistant CD4-p7 was detected after long chase times, suggesting that a large proportion of p7 stays in an early compartment of the secretory pathway. Finally, by inserting a Myc epitope in several positions of p7 and analyzing the accessibility of this epitope on the plasma membrane of HepG2 cells, we showed that p7 has a double membrane-spanning topology, with both its N and C termini oriented toward the extracellular environment. Altogether, these data indicate that p7 is a polytopic membrane protein that could have a functional role in several compartments of the secretory pathway.


Measures of accuracy for active shoulder movements at 3 different speeds with kinesthetic and visual feedback.
Repeated-measures experiment. To compare measures of end point accuracy (EPA) for 2 feedback conditions: (1) visual and kinesthetic feedback and (2) kinesthetic feedback alone, during shoulder movements, at 3 different speeds. Shoulder joint kinesthesia is typically reported with EPA measures, such as constant error. Reporting multiple measures of EPA, such as variable error and absolute error, could provide a more detailed description of performance. Subjects were seated with the shoulder abducted 90 degrees in the scapular plane and externally rotated 75 degrees, with the forearm placed in a custom shoulder wheel. Subjects internally rotated the shoulder 27 degrees to a target position at 48 degrees of shoulder external rotation for both conditions. Motion analysis was used to determine peak angular velocity and 3 EPA measures for shoulder movements. Each EPA measure was compared between the 2 feedback conditions and among the 3 speeds with a separate 2-way analysis of variance. Movements performed with kinesthetic feedback alone, measured by constant error (P<.01), variable error (P<.01), and absolute error (P<.01), were less accurate than movements performed with visual and kinesthetic feedback. Faster movements were less accurate when measured by constant error (P = .01) and absolute error (P<.01) than slower movements. Subjects tended to overshoot the target in the absence of visual feedback; however, movement speed played minimal role in the overshooting. Multiple measures of EPA, such as constant, variable, and absolute error during simple restricted shoulder movements may provide additional information regarding the evaluation of a motor performance or identify different central nervous system control mechanisms for joint kinesthesia.


RNA-Seq and molecular docking reveal multi-level pesticide resistance in the bed bug.
Bed bugs (Cimex lectularius) are hematophagous nocturnal parasites of humans that have attained high impact status due to their worldwide resurgence. The sudden and rampant resurgence of C. lectularius has been attributed to numerous factors including frequent international travel, narrower pest management practices, and insecticide resistance. We performed a next-generation RNA sequencing (RNA-Seq) experiment to find differentially expressed genes between pesticide-resistant (PR) and pesticide-susceptible (PS) strains of C. lectularius. A reference transcriptome database of 51,492 expressed sequence tags (ESTs) was created by combining the databases derived from de novo assembled mRNA-Seq tags (30,404 ESTs) and our previous 454 pyrosequenced database (21,088 ESTs). The two-way GLMseq analysis revealed ~15,000 highly significant differentially expressed ESTs between the PR and PS strains. Among the top 5,000 differentially expressed ESTs, 109 putative defense genes (cuticular proteins, cytochrome P450s, antioxidant genes, ABC transporters, glutathione S-transferases, carboxylesterases and acetyl cholinesterase) involved in penetration resistance and metabolic resistance were identified. Tissue and development-specific expression of P450 CYP3 clan members showed high mRNA levels in the cuticle, Malpighian tubules, and midgut; and in early instar nymphs, respectively. Lastly, molecular modeling and docking of a candidate cytochrome P450 (CYP397A1V2) revealed the flexibility of the deduced protein to metabolize a broad range of insecticide substrates including DDT, deltamethrin, permethrin, and imidacloprid. We developed significant molecular resources for C. lectularius putatively involved in metabolic resistance as well as those participating in other modes of insecticide resistance. RNA-Seq profiles of PR strains combined with tissue-specific profiles and molecular docking revealed multi-level insecticide resistance in C. lectularius. Future research that is targeted towards RNA interference (RNAi) on the identified metabolic targets such as cytochrome P450s and cuticular proteins could lay the foundation for a better understanding of the genetic basis of insecticide resistance in C. lectularius.


Lipid-based surface engineering of PLGA nanoparticles for drug and gene delivery applications.
The use of poly(lactic-co-glycolic acid) (PLGA)-based nanocarriers presents several major challenges, including their synthetic hydrophobic surface, low transfection efficiency, short circulation half-life, and nonspecific tissue distribution. Numerous engineering strategies have been employed to overcome these problems, with lipid-based surface functionalization of PLGA nanoparticles (NPs) showing promising results in the development of PLGA-based clinical nanomedicines. Surface engineering with different lipids enhances the target specificity of the carrier and improves its physicochemical properties as well as NP-cell associations, such as cellular membrane permeability, immune responses, and long circulation half-life in vivo. This review focuses on recent advances in the lipid-based surface engineering of PLGA NPs for drug and gene delivery applications.


Medical Equipment and Healthcare Technology: Health Vision 2050.
To address the demands of worldwide demographic and epidemiologic changes and globalization, as well as their effects on population health, the Ministry of Health in Oman developed a long-term plan for its health system called Health Vision 2050. The plan was shaped by international consultants, who sought to augment the vision with up-to-date evidence and achieve alignment with international standards. The Health Vision 2050 main document was anchored by 24 separate strategic studies covering different dimensions and pillars of the health system, one of which was the strategic study of medical equipment and healthcare technology (MEHT). This study analyzed the current status of MEHT, highlighted the achievements and bottlenecks, anticipated future challenges, and determined the future vision through pragmatic, contextualized, and actionable objectives and strategies that will provide a platform for comprehensive MEHT planning. Of note, pharmacological technologies, pharmaceutical drugs, and information technology have not been covered under the scope of this vision. By shedding light on this important strategic study about MEHT, the aim of this article is to assist other countries that are seeking to improve their MEHT based on the latest international guidelines and standards.


[Cryostimulation as an antioxidative factor in sclerosis multiplex].
Cryostimulation is becoming popular in medicine and sport. However, changes that occur in the human body subjected to cryogenic temperatures are still not completely understood. Sclerosis multiplex (MS) is a complex disease with several pathophysiological processes: inflammation, demyelination, oxidative stress, axonal damage and repair mechanisms that participate in this disorder. These processes are not uniformly represented in patient populations but can selectively predominate in individual patients. Oxidative stress plays an important role in ptophysiology of MS. Currently approved therapies for relapse-remitting multiple sclerosis target only the onset of multiple sclerosis. There is a need for developing new therapies especially in progressive phase of MS that are more process-specific and can be used in specific patient subpopulations. Cryostimulation is a short term lasted 2-3 min cooling of whole body crotherapy with temperature between -110 degrees C and -160 degrees C. Currently studies suggested antioxidative role of cryostimulation in MS patients. The further studies of oxidative stress in MS patients are required to explain the role and antioxidative mechanisms of WBCT in MS patients treatment.


Publishing pilot intervention work.
Pilot intervention studies can be viewed as rehearsals for subsequent full-scale trials. They can help investigators fine-tune later larger studies as well as explore issues related to project management and budget. Pilot studies permit testing of sampling strategies, participant recruitment, intervention content, delivery methods, data collection, and analysis. They also allow researchers to experience the more practical aspects of implementing a study, such as determining the number of study staff members needed to handle recruitment and data collection or identifying special equipment needs. Because pilot study findings may be generalizable, publication is encouraged as long as the preliminary nature of the work is clearly indicated in both the abstract and the article. The present article provides an overview of the types of information that can be gleaned from pilot intervention studies that are suitable for publication.


Complementary and Alternative Medicine in Chronic Rhinosinusitis: A Systematic Review and Qualitative Analysis.
Complementary and alternative medicine (CAM) is frequently used in the treatment of chronic rhinosinusitis (CRS) in developed countries. With a plethora of CAM therapies available, their effectiveness and safety are poorly understood in the context of CRS. This article aims to critically appraise the evidence for CAM use in CRS through a systematic review of current literature that investigate the effects of CAM on symptoms and clinical status of adults with CRS. Systematic review and qualitative analysis. A comprehensive systematic review of the literature was conducted by the authors using 5 databases from inception to July 2017: CINAHL, Cochrane, Embase, PubMed, and SCOPUS. Inclusive medical subject headings and keywords consisted of, but were not limited to, sinusitis and complementary therapies, naturopathy, or traditional Chinese medicine. PRISMA guideline was followed. Using templates by Cochrane Public Health Group and Newcastle-Ottawa Scale, each author extracted data, assessed bias, and computed minimal clinically important difference. Any conflicts were resolved through discussion. In total, 7 of 7141 articles from 1995 to 2016 were included. Three randomized controlled trials and 4 observational studies were organized into 4 categories of CAM: naturopathy, Chinese medicine, homeopathy, and others. Limited evidence supported the use of Pimpinella anisum and crenotherapy for CRS. Data available on Chinese medicine, homeopathy, and liposomal therapy in CRS were inconclusive due to inherent flaws in the studies. Overall, there is very limited evidence to support the use of CAM in the treatment of CRS. No significant adverse effects have been found. Given its widespread use, more rigorous data from high-quality research are needed before it can be routinely recommended.


Stability of 0.5% Glucose-Containing Balanced Electrolyte Solutions for Patients on Ketogenic Diets: A Laboratory Study.
Ketogenic diets (KDs) are used to treat epilepsies resistant to pharmacotherapy or some inborn errors of metabolism. For prolonged anesthesia, use of balanced electrolyte solutions (BESs) supplemented with 0.5% glucose has been advocated to maintain ketosis while preventing hypoglycemia. Unfortunately, there is no BES containing 0.5% glucose available from pharmacies. In a laboratory study, we investigated the physical and chemical stability of different BES mixtures containing 0.5% glucose. In total, six approaches were chosen to create a BES with 0.5% glucose: three different glucose-free BESs were supplemented with glucose. Additionally, commercially available BES containing 1% glucose was diluted with three different glucose-free BESs to obtain a solution containing 0.5% glucose. Turbidity, pH, electrical conductivity, and macroscopic appearance of these solutions were measured immediately, at 24 hours, and after 7 days, and were compared with the original BES. Turbidity, pH, and electrical conductivity, as well as macroscopic appearance did not exceed the changes of the controls. No signs of incompatibility reactions could be observed in a 1-week time period. Our study supports the stability of the examined BES containing 0.5% glucose for prolonged anesthesia in patients on KD. Clinical studies are needed to evaluate if BES containing 0.5% glucose is superior in patients on KDs.


Aberration measurement and correction on a large field of view in fluorescence microscopy.
The aberrations induced by the sample and/or by the sample holder limit the resolution of optical microscopes. Wavefront correction can be achieved using a deformable mirror with wavefront sensorless optimization algorithms but, despite the complexity of these systems, the level of correction is often limited to a small area in the field of view of the microscope. In this work, we present a plug and play module for aberration measurement and correction. The wavefront correction is performed through direct wavefront reconstruction using the spinning-pupil aberration measurement and controlling a deformable lens in closed loop. The lens corrects the aberrations in the center of the field of view, leaving residual aberrations at the margins, that are removed by anisoplanatic deconvolution. We present experimental results obtained in fluorescence microscopy, with a wide field and a light sheet fluorescence microscope. These results indicate that detection and correction over the full field of view can be achieved with a compact transmissive module placed in the detection path of the fluorescence microscope.


In vitro tests of substitute lubricants for wear testing orthopaedic biomaterials.
Bovine serum is the lubricant recommended by several international standards for the wear testing of orthopaedic biomaterials; however, there are issues over its use due to batch variation, degradation, cost and safety. For these reasons, alternative lubricants were investigated. A 50-station Super-CTPOD (circularly translating pin-on-disc) wear test rig was used, which applied multidirectional motion to ultra-high-molecular-weight polyethylene test pins rubbing against cobalt chromium discs. Thirteen possible alternative lubricants were tested. The use of soy protein as a lubricant gave statistically higher wear, while soya oil, olive oil, Channel Island milk, whole milk, whey, wheatgerm oil, 11 mg/mL egg white, albumin/globulin mix and albumin/globulin/chondroitin sulphate mix all gave statistically lower wear than bovine serum. The lubricants giving the closest wear results to bovine serum were 20 and 40 mg/mL egg white solutions. A light absorbance assay found that these egg white solutions suffered from a high degradation rate that increased with increasing protein content. While egg white solutions offer the best alternative lubricant to bovine serum due to the wear volumes produced, cost-effectiveness and safety of handling, protein degradation will still occur, leading to the need for regular lubricant replacement. Of the lubricants tested in this study, none were found to be superior to bovine serum.


A tightly regulated expression system in Escherichia coli with SP6 RNA polymerase.
A tightly regulated gene-expression system was developed using SP6 RNA polymerase (RpoSP6). The RpoSp6-encoding gene (rpoSP6) was inserted into a mini-F plasmid (mini-F) and expression was controlled by the lactose promoter (P(lac)) and operator (O(lac)) on the plasmid. Therefore, a controlled expression system for the target genes can easily be constructed in various host strains by co-transformation of the system plasmid pFSP6 with other vector plasmids containing the genes linked to the SP6 promoters (P(SP6)). Using the lac gene linked to P(SP6) as a reporter, we evaluated the regulation of expression in this system in various host strains. Low-level expression of lac was detected in Escherichia coli harboring this expression system when RpoSP6 was uninduced, although very low activities of beta-galactosidase (beta-Gal) were observed which were independent of the presence of pFSP6. This basal level of beta-Gal activity was possibly derived, because the P(SP6) element has very weak activity for E. coli RNA polymerase (Rpo). These results showed that RpoSP6 seemed to be produced at very low levels in uninduced cells. Beta-GAl activity increased about 18-32-fold when the expression of rpoSP6 was induced, as compared with the beta-Gal activity when uninduced. The tight regulation of this system is superior to that of other known systems and it has a considerable advantage for gene expression in E. coli.


Sensory perception is related to the rate of change of volatile concentration in-nose during eating of model gels.
The relationship between perceived aroma and the volatile concentration measured in-nose was investigated during eating of a model food. Sensory ranking and time-intensity analysis (TI) were used to measure perceived aroma, while in-nose volatile concentration was monitored by atmospheric pressure ionization mass spectrometry, which produced time release data. A gelatine-sucrose gel with a range of gelatine concentrations (2-8% w/w) and flavoured with furfuryl acetate was used as the model food. Sensory scaling showed decreased flavour intensities and TI showed a decrease in the flavour perceived over time, as the gelatine concentration increased. Studies in model systems and in people demonstrated that the different rates of release observed for different gelatine concentrations were not due to binding of volatile to protein in the gel, nor to mucous membranes, but were due to different rates of gel breakdown in-mouth. There were no significant differences in the maximum in-nose volatile concentrations for the different gelatine concentrations, so the amount of volatile present did not correlate well with the sensory analysis. However, the rates of volatile release were different for the different gels and showed a good correlation with sensory data.


Automated detection of harm in healthcare with information technology: a systematic review.
To improve patient safety, healthcare facilities are focussing on reducing patient harm. Automated harm-detection methods using information technology show promise for efficiently measuring harm. However, there have been few systematic reviews of their effectiveness. To perform a systematic literature review to identify, describe and evaluate effectiveness of automated inpatient harm-detection methods. Data sources included MEDLINE and CINAHL databases indexed through August 2008, extended by bibliographic review and search of citing articles. The authors included articles reporting effectiveness of automated inpatient harm-detection methods, as compared with other detection methods. Two independent reviewers used a standardised abstraction sheet to extract data about automated and comparison harm-detection methods, patient samples and events identified. Differences were resolved by discussion. From 176 articles, 43 articles met inclusion criteria: 39 describing field-defined methods, two using natural language processing and two using both methods. Twenty-one studies used automated methods to detect adverse drug events, 10 detected general adverse events, eight detected nosocomial infections, and four detected other specific adverse events. Compared with gold standard chart review, sensitivity and specificity of automated harm-detection methods ranged from 0.10 to 0.94 and 0.23 to 0.98, respectively. Studies used heterogeneous methods that often were flawed. Automated methods of harm detection are feasible and some can potentially detect patient harm efficiently. However, effectiveness varied widely, and most studies had methodological weaknesses. More work is needed to develop and assess these tools before they can yield accurate estimates of harm that can be reliably interpreted and compared.


Bringing juvenile justice and public health systems together to meet the sexual and reproductive health needs of justice-involved youth.
Constitutional mandates require access to medical testing and treatment in correctional settings, including sexual and reproductive health (SRH) care services. These same mandates do not apply to youth supervised in the community, who represent the majority of justice-involved youth. Waiting until youth are in detention settings to provide access to SRH services misses an opportunity to improve health outcomes for youth who have earlier points of contact with the system. This mixed-methods study explored structural intervention development and policy geared toward increasing access to and uptake of SRH prevention, treatment, care, and support services for court-involved, nonincarcerated (CINI) youth. Data were collected from a nationwide survey (N = 226) and qualitative interviews (N = 18) with juvenile justice (JJ) and public health (PH) system stakeholders between December 2015 and January 2017. Results suggest both PH and JJ stakeholders perceive CINI youth as having substantial, largely unmet SRH care needs due to a lack of services, policies, or procedures to address these needs. Barriers to implementing programs and policies to improve SRH services for this population include limited resources (e.g., staffing, time); perceived irrelevance for juvenile court, probation, or other community supervision settings; and concerns about confidentiality, privacy, and information sharing. Recommendations for effective intervention included colocating services, justice-to-community referrals, and service linkages (e.g., through a community health navigator), and staff education around youth SRH confidentiality and information-sharing practices. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


[Neoadjuvant chemotherapy and concurrent radiochemotherapy for advanced esophageal carcinoma potentially invading adjacent structures].
Advanced esophageal carcinoma invades adjacent structures, and its resection without residual tumor is difficult. Preoperative chemotherapy and combined modality therapy are being tried to improve survival in patients with T4 esophageal carcinoma. For these cases, chemotherapy with 5-fluorouracil and cisplatin (FP) is known to be not so effective. For 17 patients with T4 esophageal carcinoma in 2 institutes, treated primarily with chemotherapy with 5-fluorouracil, cisplatin and adriamycin (FAP), the response rate was 76%. Operation was performed in all of them after 2-3 courses of FAP, and curative resection without resection of adjacent structure was carried out in 14 cases (82%). Treatment with FP concurrent with more than 50Gy of radiation (CRT) was effective for patients with T4 esophageal carcinoma, its response rate was 72.80% in Japanese literature, and resectability rate was 37-48% after treatment. All of our 3 cases had partial response, but resection was not performed because patients refused surgery. Phase II trial of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy was carried out for 45 patients with clinical stage T1-4N0-1M0 in an attempt to improve the result of concurrent chemoradiation in America (RTOG), and the overall median survival was 20 months. But this treatment will not be used, because treatment-related death was seen in 10%. We think that FAP and CRT are the most effective neoadjuvant therapy in patients with T4 esophageal carcinoma. If curative resection is possible after treatment, operation should be done to improve prognosis.


Depressive symptoms in men aged 50 years and older and their relationship to genetic androgen receptor polymorphism and sex hormone levels in three different samples.
Depression in aging men has been related to low sex hormone concentrations; the putatively modulating effects of the genetically determined androgen receptor (AR) cytosine-adenosine-guanine (CAG) repeat polymorphism are often not taken into account. The aim of this study was to determine how sex hormone levels and the AR polymorphism relate to depressive symptoms in aging men. This cross-sectional study of men aged 50 years and older included 120 consecutive patients of the Department of Psychosomatics and Psychotherapy, 76 consecutive patients of the Andrologic Clinic, and 100 participants from the community sample (CS); all participants completed the Patient Health Questionnaire. Morning blood samples were analyzed for total and free testosterone, estradiol, and the AR CAG polymorphism. Patients on hormone substitution or other medication known to influence testosterone levels were excluded. The two clinical samples had significantly longer AR CAG repeats and higher depression levels compared with the CS. When controlling for possible confounders, depression scores were positively correlated with CAGn (r = 0.20, df: 107, p ≤ 0.038) in psychosomatic patients and with CAGn (r = 0.27, df: 55, p ≤ 0.043) and estradiol (r = 0.31, df: 55, p ≤ 0.019) in andrologic patients, whereas the CS showed no significant correlations between depression scores, CAGn, and sex hormones. CAGn did not correlate significantly with testosterone in the three samples. Regression analysis confirmed association of CAGn with depression. Conclusions from these data must be considered to be preliminary and need to be replicated. However, our results point to associations between the genetic AR polymorphism and vulnerability to depressive symptomatology.


Conversion of taxane glycosides to 10-deacetylbaccatin III.
10-Deacetylbaccatin III (10-DAB III) (2) was obtained by a series of treatment of a mixture of taxane glycosides (3, 4, and 5) without isolation before treatment. Since the taxane glycosides are isolated with paclitaxel from yew trees and can be found during the process of the production of paclitaxel, their conversion to 10-DAB III improves the total yield of paclitaxel (1) and docetaxel.


Calcification associated with terminal defects of the upper extremity.
Four children who had calcifications associated with terminal defects of the upper extremity are reported. A review of the literature has revealed no previous report. Moreover, an examination of the radiographs of 65 children who had terminal defects of the upper limb failed to show any such calcifications. The exact cause of this association remains unknown.


Stapling instruments for intestinal anastomosis in colorectal surgery.
The circular stapling instrument has had a major impact in the practice of colorectal surgery. Stapling technology was pioneered in the early part of this century and subsequently modified. Russian initiatives led to development of the original circular stapling instrument and further progress has resulted in instruments that are widely available, reliable and totally disposable. Mechanical failure is now rare and malfunction is generally due to operator error. Complications related to the stapling technique are uncommon, although anastomotic stricture may be more frequent than when handsewn anastomosis is performed. A stapling instrument facilitates and may expedite a surgical procedure but it is an adjunct to, and not a substitute for, meticulous surgical technique.


[Practice of antidiabetic therapy in Hungary].
Type 2 diabetes is one of the biggest public health problems of our age. In the present study the authors analyse the development of the therapy of type 2 diabetic patients. National antidiabetic consumption data and data of National Health Insurance Fund Administration (OEP) were used. From OEP database definite method were used to choose 1002 type 2 diabetic patients. The Hungarian therapeutic practice develops according to guidelines of multi centered studies, and the consumption of antidiabetics dynamically increases. Increasing the number of patients who get insulin therapy and among patients who get oral antidiabetics more of them get insulin resistance decreasing therapy. However the out-of-date drugs (non-micronized glibenclamide, buformin) are still in daily therapy. The authors revealed the ratio of diet and drug (monotherapy, combination therapy) therapy, the higher use of Sulfanylurea monotherapy than recommended and the use of unreasonable combinations.


Identification of Novel and Potent Indole-Based Benzenesulfonamides as Selective Human Carbonic Anhydrase II Inhibitors: Design, Synthesis, In Vitro, and In Silico Studies.
In recent decades, human carbonic anhydrase inhibitors (hCAIs) have emerged as an important therapeutic class with various applications including antiglaucoma, anticonvulsants, and anticancer agents. Herein, a novel series of indole-based benzenesulfonamides were designed, synthesized, and biologically evaluated as potential hCAIs. A regioisomerism of the sulfonamide moiety was carried out to afford a total of fifteen indole-based benzenesulfonamides possessing different amide linkers that enable the ligands to be flexible and develop potential H-bond interaction(s) with the target protein. The activity of the synthesized compounds was evaluated against four hCA isoforms (I, II, IX and, XII). Compounds 2b, 2c, 2d, 2f, 2h and 2o exhibited potent and selective profiles over the hCA II isoform with Ki values of 7.3, 9.0, 7.1, 16.0, 8.6 and 7.5 nM, respectively. Among all, compound 2a demonstrated the most potent inhibition against the hCA II isoform with an inhibitory constant (Ki) of 5.9 nM, with 13-, 34-, and 9-fold selectivity for hCA II over I, IX and XII isoforms, respectively. Structure-activity relationship data attained for various substitutions were rationalized. Furthermore, a molecular docking study gave insights into both inhibitory activity and selectivity of the target compounds. Accordingly, this report presents a successful scaffold hoping approach that reveals compound 2a as a highly potent and selective indole-based hCA II inhibitor worthy of further investigation.


The positive inotropic effect of alpha 1A-adrenoceptor stimulation is inhibited by 4-aminopyridine.
This study was designed to determine if 4-aminopyridine, a reported inhibitor of the transient outward K+ current (Ito), alters the inotropic actions elicited via stimulation of WB4101- or chloroethylclonidine-sensitive receptors in rat myocardium. WB4101 (N-[2-(2, 6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin-2-m ethanamine) is a competitive antagonist that is selective for alpha 1A- and alpha 1C-adrenoceptors, while chloroethylclonidine is an irreversible blocker that is reported to antagonize alpha 1B-, alpha 1C-, and alpha 1D-adrenoceptor binding. Inotropic effects of the alpha 1-adrenoceptor agonist phenylephrine were examined in isolated left atrial and papillary muscle before and after addition of 4-aminopyridine, and before and after addition of 4-aminopyridine in preparations pretreated with chloroethylclonidine or WB4101. In addition, effects of phenylephrine were examined before and after treatment with staurosporine (an inhibitor of protein kinase C) in chloroethylclonidine-pretreated preparations. Phenylephrine (10 microM) elicited a sustained positive inotropic response in left atria and a triphasic inotropic action in papillary muscle (transient positive and negative inotropic components preceding a sustained positive inotropic response). 4-Aminopyridine (1.0, 1.7, 3.0 mM) reduced the sustained positive inotropic responses in the absence of antagonists and in chloroethylclonidine-pretreated preparations. However, in the presence of 10 nM WB4101, 4-aminopyridine had no effect on the remaining inotropic actions of phenylephrine. The sustained positive inotropic response to the alpha 1-agonist in chloroethylclonidine-pretreated preparations was not inhibited by 100 nM staurosporine. These data suggest that the sustained positive inotropic actions of alpha 1A-adrenoceptor stimulation in rat atrial and ventricular myocardium are mediated via non-protein kinase C-associated reductions in Ito.


Delayed diagnosis of lymphogranuloma venereum-associated colitis in a man first suspected to have rectal cancer.
Lymphogranuloma venereum-associated colitis is a diagnosis that should not be missed. The following case represents the importance of a thorough history, including the importance of the sexual history to prevent the misdiagnosis of these patients.


Prospective analysis of mannose-binding lectin genotypes and coronary artery disease in American Indians: the Strong Heart Study.
Mannose-binding lectin (MBL) is a circulating immune factor responsible for opsonization of pathogens and directly activating complement. Common variations in the MBL gene are responsible for an opsonic deficiency that affects 5% to 7% of whites and are associated with increased susceptibility to infections. After a preliminary report associating these variations with coronary artery disease (CAD), we determined MBL genotypes in 3 American Indian communities experiencing an increased mortality and morbidity from CAD. We examined DNA from 434 participants in a population-based cohort, the Strong Heart Study. Genotypes for 3 common MBL coding variations and 1 promoter polymorphism were determined. The frequency of a composite genotype that conferred low MBL levels was 20.7% in 217 cases and 11.1% in matched controls without CAD. A conditional logistic regression model indicated a univariate OR for CAD of 2.3 (95% CI 1.3 to 4.2, P=0.005) for the variant genotypes. After adjustment for demographic and CAD risk factors, including type 2 diabetes mellitus, fibrinogen, triglycerides, and hypertension, the OR was 3.2 (95% CI 1.5 to 7.0, P=0.004). Variant MBL genotypes coding for markedly diminished levels of MBL are predictive of CAD. After adjustment for multiple traditional risk factors for ischemic heart disease, this association remains significant. A high prevalence of variant MBL alleles and CAD in this population suggests that potentially important public health benefits may accrue from future interventions based on these genotypes.


[Palliative surgical treatment of cancer of the esophagus].
Palliative surgery, including cleaning resection, colon or stomach bypass, intubation or fistula is all one can offer to the majority of patients suffering from oesophageal carcinoma due to an usually advanced tumor stage at the time of diagnosis. The primary goal is to prevent or resolve dysphagia. A prolongation of survival time can - with the exception of cleaning resection - not be expected by these procedures. The average survival time was 9.4 months after cleaning resection and 4.7 months after other palliative procedures in our series. If a cleaning resection is not possible, the endoscopic implantation of an endotube is the treatment of choice because of its low mortality and morbidity.


A bimetallic aluminum(salen) complex for the synthesis of 1,3-oxathiolane-2-thiones and 1,3-dithiolane-2-thiones.
The combined use of the bimetallic aluminum(salen) complex [Al(salen)](2)O and tetrabutylammonium bromide (or tributylamine) is found to catalyze the reaction between epoxides and carbon disulfide. In most cases, at 50 °C, the reaction produces 1,3-oxathiolane-2-thiones, while at 90 °C, 1,3-dithiolane-2-thiones are the main product. The structure and stereochemistry of three of the 1,3-dithiolane-2-thiones is unambiguously determined by X-ray crystallographic analysis, and this is used to correct errors in the literature concerning the synthesis of cyclic di- and trithiocarbonates. The kinetics of 1,3-oxathiolane-2-thione synthesis are determined, and the resulting rate equation, along with a stereochemical analysis of the reaction and catalyst modification studies, is used to determine a mechanism for the synthesis of 1,3-oxathiolane-2-thiones which contrasts with the mechanism previously determined for cyclic carbonate synthesis using the same bimetallic aluminum(salen) complex.


Pro (With Caution): Extended oncologic indications in liver transplantation.
The success of liver transplantation (LT) in curing cancer (particularly hepatocellular carcinoma and hepatic metastases from neuroendocrine tumors) is based on the augmented oncologic potentials of the total hepatectomy and on restrictive criteria applied to patient selection. Consensus on the grade of expansion of conventional limits and implementation of alternative indications to LT (cholangiocarcinoma and metastases from colorectal cancer) has not been reached. On top of regional/local conditions for wait-list dynamics and organ availability, expanded cancer indications for LT should be explored with caution. Prospective investigations should rely on staging protocols predicting the exclusive hepatic location of cancer; restrictions on clinical conditions, tumor biology, and molecular profile, including the response to neoadjuvant therapies; confirmed tumor nonresectability with curative intent; sufficient life span of the transplant candidates to assess survival and transplant benefit; and use of marginal and extended criteria donors. In conclusion, the arguments supporting moderately loosened criteria for cancer seem more valid today than in the past. Transplant oncology is likely to represent a leading field in the near future, also because comorbidities and transplant-related causes of death are better managed and often eliminated. Liver Transplantation 24 98-103 2018 AASLD.


Power spectral analysis of heart rate variability in healthy young women during the normal menstrual cycle.
This study investigated the fluctuations of autonomic nervous activities during the menstrual cycle. Twenty college females were tested for cardiovascular reactivity to mental challenge during both follicular and luteal phases across two menstrual cycles. Power spectral analysis of heart rate variability (HRV) was used to examine the autonomic nervous activities. At baseline, although heart rate and blood pressure did not differ across the menstrual cycle, the low-frequency (LF) component in the HRV was higher and the high-frequency (HF) component in the HRV was lower during the luteal phase than during the follicular phase. The LF/HF ratio was also significantly greater in the luteal phase. These data suggest that sympathetic nervous activities are predominant in the luteal phase as compared with follicular phase. In addition, the power spectral analysis of HRV has more sensitivity than heart rate or blood pressure in assessing the slight fluctuations of autonomic nervous activities during the menstrual cycle.