Influence of cardiopulmonary bypass on nitroglycerin clearance.
The effect of cardiopulmonary bypass on the clearance of nitroglycerin (NTG) was studied in seven patients scheduled for coronary artery bypass graft surgery. Intravenous NTG was administered through nonadsorbing tubing at a starting dosage of 5-10 micrograms/min and was adjusted as needed. Blood samples were obtained from the radial artery and antecubital vein before bypass and from the arterial outlet of the oxygenator during bypass at least 30 minutes apart during a constant dosage or at least 30 minutes after a dosage change. Serum concentrations were analyzed for NTG by gas chromatography. Venous NTG concentrations were always lower than concurrent arterial concentrations, with an average arteriovenous extraction of 67.2%. Serum concentrations of NTG were generally within the range associated with a therapeutic response in congestive heart failure patients. Consistent with other reports, NTG concentrations varied widely among patients and considerable intrasubject fluctuations in drug concentrations were seen. The mean +/- SD apparent clearance of NTG before bypass of 0.044 +/- 0.02 L/kg/min increased 20% to 0.052 +/- 0.02 L/kg/min during bypass (P = .05). These results suggest that cardiopulmonary bypass increases the clearance of NTG; however, the magnitude appears to be small and only partially explains the reported increased dosage needed during cardiopulmonary bypass.


Recombinant adeno-associated virus type 8-mediated extensive therapeutic gene delivery into skeletal muscle of alpha-sarcoglycan-deficient mice.
Autosomal recessive limb-girdle muscular dystrophy type 2D (LGMD 2D) is caused by mutations in the alpha-sarcoglycan gene (alpha-SG). The absence of alpha-SG results in the loss of the SG complex at the sarcolemma and compromises the integrity of the sarcolemma. To establish a method for recombinant adeno-associated virus (rAAV)-mediated alpha-SG gene therapy into alpha-SG-deficient muscle, we constructed rAAV serotypes 2 and 8 expressing the human alpha-SG gene under the control of the ubiquitous cytomegalovirus promoter (rAAV2-alpha-SG and rAAV8-alpha-SG). We compared the transduction profiles and evaluated the therapeutic effects of a single intramuscular injection of rAAVs into alpha-SG-deficient (Sgca(-/-)) mice. Four weeks after rAAV2 injection into the tibialis anterior (TA) muscle of 10-day-old Sgca(-/-) mice, transduction of the alpha-SG gene was localized to a limited area of the TA muscle. On the other hand, rAAV8-mediated alpha-SG expression was widely distributed in the hind limb muscle, and persisted for 7 months without inducing cytotoxic and immunological reactions, with a reversal of the muscle pathology and improvement in the contractile force of the Sgca(-/-) muscle. This extensive rAAV8-mediated alpha-SG transduction in LGMD 2D model animals paves the way for future clinical application.


Dying in Australian hospitals: will a separate national clinical standard improve the delivery of quality care?
While it is commonly stated that for most people the preferred place of death is their own homes, the actual reality is that most people will die in hospitals. This is both by choice and necessity. However, for many, the care that they receive would not necessarily align with their expectations. The need to improve the quality of health care at the end of life has been acknowledged by the Australian Commission for Safety and Quality in Healthcare with the release of a recent discussion paper. It is presumed this is a prelude to the release of another quality standard specifically for end of life care. The aim of this paper is to question whether such a standard is likely to result in the hoped for improvements in care.


The effects of partial wrist denervation in wrist osteoarthritis: patient-reported outcomes and objective function.
This prospective longitudinal study aimed to analyse the effect of partial wrist denervation on patient-reported outcomes, quality of life and objective function in symptomatic wrist osteoarthritis during the first year after surgery. Sixty consecutive patients underwent an anterior and posterior interosseous neurectomy during 2018-2020. Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation, EuroQol-5D-3L, pain at rest and on load, and objective function were assessed preoperatively and 3, 6 and 12 months postoperatively. Generalized estimating equations were used to analyse the effect on the outcome variables. Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation and pain scores improved significantly postoperatively with no decline over time, but no patient reported outcome measure reached the minimal clinically important difference. Quality of life, strength and range of motion did not improve. We found no complications. Seventeen patients needed further surgery during the study period. More studies are needed to evaluate whether denervation is truly effective or not.Level of evidence: II.


Soluble sperm extract triggers inositol 1,4,5-trisphosphate-induced Ca2+ release in the oocytes of the sea urchin, Anthocidaris crassispina.
The substance in sperm which induces the activation of eggs at fertilization has yet to be elucidated. Osawa et al. reported that the soluble extract of sperm (spex) causes inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release (IICR) in fertilized eggs of sea urchins when externally applied [Osawa et al., (1992). Zool. Sci. 9: 1206a]. This paper reports that spex also caused IICR in immature oocytes of Anthocidaris crassispina at their germinal vesicle stage and induced a transient increase in their intracellular Ca2+ concentration (Cai-transient). The peak value of this Cai-transient was 160 +/- 16 nM, a small increase by about 60 nM from the basal intracellular Ca2+ concentration, [Ca2+]i, of 96 +/- 12 nM. This reaction was completely blocked by heparin, an IICR inhibitor. Furthermore, the active factor in spex was resistant to pronase and did not show species specificity. It was found that Cai-transient can also be induced in oocytes by sperm. The peak value of the Cai-transient in this case was dependent on sperm concentration and was a maximum of approximately 250 nM, which was significantly lower than that at normal fertilization, i.e., 941 +/- 136 nM. The Cai-transient induced by sperm in oocytes was not suppressed, though its time course was delayed, by heparin.


The 50 Most-cited Articles in Gastroenterology and Hepatology from Mainland China.
To identify and analyze the 50 most-cited gastroenterology and hepatology articles originating from mainland China. We utilized the 2015 edition of Journal Citation Reports and PubMed to determine the 50 most-cited gastroenterology and hepatology articles from 75 professional journals and four leading journals in clinical medicine, which are The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The British Medical Journal. Then we excluded the articles written outside mainland China and collected the basic information, including the title, authors, year of publication, source journal, city, institution, number of citations, and topic of the research. The number of citations for the top 50 papers ranged from 279 to 89 (mean, 129). These articles were published between 2005 and 2012, in which 2009 was the year with the largest number of highly cited papers(13). All articles were published in 15 journals. The journal Hepatology published the largest number of articles(21), followed by Journal of Gastroenterology and Hepatology(4), Journal of Hepatology(4) and World Journal of Gastroenterology(4). The top 50 articles originated mainly from Shanghai(20), Guangzhou(13) and Beijing(6). Sun Yat-sen University produced most highly cited papers(10). The number of basic research was far more than clinical research, of which the ratio was about 1.78(32:18). In all these articles, hepatocellular carcinoma was the most-discussed topic(19), followed by hepatitis B virus(8) and endoscopic(5). Although a large gap remains between mainland China and the global community, the gastroenterology and hepatology research from China is gradually recognized by the world.


[TGFbeta, activin and SMAD signalling in thyroid cancer].
TGFbeta and activin are members of the TGFbeta superfamily and play a wide role in development, proliferation and apoptosis. These growth factors exert their biological effects by binding to the type I and II membrane receptors to transduce their signalling through the nucleus by phosphorylation of R-SMADs (SMAD 2/3) and co-SMADs (Smad 4). The proper control of TGFbeta/activin pathway is negatively regulated by inhibitory SMAD (SMAD7) and by E3 ubiquitination enzymes (Smurfs). Physiologically, TGFbeta and activin act as potent growth inhibitors in thyroid follicular cell. Thus, alterations in the receptors and components of SMAD signalling pathway are associated with several types of tumors. Since TGFbeta and activin generate their intracellular signalling through the same components of the SMAD pathway, the unbalance of this pathway impairs both of anti-mitogenic signals in the cell. This review addresses aspects of the molecular mechanisms in the understanding of resistance to the growth inhibitory effects of TGFbeta and activin due to the disequilibrium in the SMAD inhibitory pathway in thyroid neoplasia.


Effect of epidural spinal cord stimulation on the activity of lateral vestibular nucleus neurons in the cat.
The activity of neurons in Deiters' lateral vestibular nucleus was recorded in decerebrate cats before, during and after spinal cord stimulation. An almost equal number of units were inhibited and excited early during stimulation. Later during stimulation the majority of units was inhibited. Early after cessation of stimulation an ever larger number of units were inhibited to an even larger extent (for about 2 imp/s on the average). Later after stimulus cessation the predominant inhibitory effect could still be noted, as well as excitation in some units. The results could support the hypothesis that the inhibition of Deiters' neurons during and for some time after epidural cord stimulation may play a part in the decrease of limb spasticity. The mechanism of inhibitory and excitatory unitary responses, side effects during stimulation and differences between the experimental model and human state are discussed.


THE QUANTITATIVE GENETICS OF SEXUAL DIMORPHISM IN SILENE LATIFOLIA (CARYOPHYLLACEAE). I. GENETIC VARIATION.
It is widely recognized that there are basic conflicts between the resource needs of a plant for paternal versus maternal functions. In dioecious species, these divergent demands, and the selection pressures they impose, can lead to the evolution of sexual dimorphism. The present study was conducted to assess the potential for the evolution of sexual dimorphism in Silene latifolia by evaluating the genetic variation and genetic correlation between characters and between the sexes for a range of growth and reproductive characters. Sexual dimorphism is largely restricted to reproductive characters, particularly flower number and flower size. A canonical correlation analysis revealed considerable intercorrelation between growth characters, such as germination date, height, and leaf size, and reproductive characters; plants that grow fast early on also flower earlier, and plants that produce big leaves also produce big flowers. There was genetic variation for several sexually dimorphic characters; much of the focus in this analysis was on flower size, particularly calyx diameter. Finally, genetic correlations within and between the sexes were found that limit the rate of evolutionary divergence between the sexes. The genetic results suggest that S. latifolia has been subject to divergent selection on the two sexes for a long period of time, bringing about a gradual fixation of sex-limited gene effects, so that the remaining genetic effects are expressed in both sexes. Genetic correlations between the sexes that arise from this residual variation impose limits on further evolutionary change.


Ferrocene-based nitroheterocyclic sulfonylhydrazones: design, synthesis, characterization and trypanocidal properties.
A series of new ferrocenyl nitroheterocyclic sulfonylhydrazones (1a-4a and 1b-2b) were prepared by the reaction between formyl (R = H) or acetyl (R = CH3) nitroheterocyclic precursors [4/5-NO2(C5H2XCOR), where X = O, S)] and ferrocenyl tosyl hydrazine [(η5-C5H5)Fe(η5-C5H4SO2-NH-NH2)]. All compounds were characterized by conventional spectroscopic techniques. In the solid state, the molecular structures of compounds 1a, 2b, and 3a were determined by single-crystal X-ray diffraction. The compounds showed an E-configuration around the C=N moiety. Evaluation of trypanocidal activity, measured in vitro against the Trypanosoma cruzi and Trypanosoma brucei strains, indicated that all organometallic tosyl hydrazones displayed activity against both parasite species with a higher level of potency toward T. brucei than T. cruzi. Moreover, the biological evaluation showed that the 5-nitroheterocyclic derivatives were more efficient trypanocidal agents than their 4-nitroheterocyclic counterparts.


Atropine increases inspiratory flow during enflurane anaesthesia after pethidine premedication.
The effects of atropine i.v. on inspired volume and occlusion pressure were measured in three groups of patients. Group PE received premedication with pethidine 50 mg and promethazine 12.5 mg i.m., and anaesthesia was provided by 2% enflurane in 67% nitrous oxide. Group TE received temazepam 20 mg orally for premedication and similar anaesthesia. Group TH received temazepam premedication and 1% halothane in 67% nitrous oxide. Atropine 0.02 mg kg-1 i.v. increased significantly the inspiratory flow in the first 1 s of inspiration, and this effect was greater in the group that received pethidine (9% increase in flow). However, occlusion pressure did not change, and minute volume was not altered. The results suggest that atropine increases inspiratory flow after pethidine premedication without increasing the force developed during inspiration, possibly by bronchodilatation.


Ex Vivo Tracer Efficacy in Optical Imaging of Staphylococcus Aureus Nuclease Activity.
The key to effective treatment of bacterial infections is a swift and reliable diagnosis. Current clinical standards of bacterial diagnosis are slow and laborious. There are several anatomical imaging modalities that can detect inflammation, but none can distinguish between bacterial and sterile inflammation. Novel tracers such as smart activatable fluorescent probes represent a promising development that allow fast and specific testing without the use of ionizing radiation. Previously, a smart activatable probe was developed that is a substrate for the micrococcal nuclease as produced by Staphylococcus aureus. In the present study, the function of this probe was validated. Practical applicability in terms of sensitivity was assessed by incubation of the probe with 26 clinical S. aureus isolates, and probe specificity was verified by incubation with 30 clinical isolates and laboratory strains of various bacterial pathogens. The results show that the nuclease-specific probe was activated by all tested S. aureus isolates and laboratory strains with a threshold of ~106-107 cells/mL. The probe was also activated by certain opportunistic staphylococci. We therefore propose that the studied nuclease probe represents a significant step forward to address the need for a rapid, practical, and precise method to detect infections caused by S. aureus.


Secondary transfer of organic gunshot residues: Empirical data to assist the evaluation of three scenarios.
The present study aimed at providing data to assess the secondary transfer of organic gunshot residues (OGSR). Three scenarios were evaluated in controlled conditions, namely displacing a firearm from point A to point B, a simple handshake and an arrest involving handcuffing on the ground. Specimens were collected from the firearm, the hands of the shooter and the non-shooter undergoing the secondary transfer in order to compare the amounts detected. Secondary transfer was observed for the three scenarios, but to a different extent. It was found that displacing a firearm resulted in secondary transfer in <50% of the experiments. The firearm also had an influence, as contrary to the pistol, no secondary OGSR were detected using the revolver. Shaking the hand of the shooter also transferred OGSR to the non-shooter's hand. In that case, the amount of OGSR was generally higher on the shooter than on the non-shooter. Finally, the largest secondary transfer was observed after the arrest with handcuffing with positive results in all cases using the pistol. In that scenario, the amounts on the shooter and the non-shooter were in the same range. This study highlights that the secondary transfer must be taken into account in the interpretation of OGSR. Indeed, an individual's hands might be contaminated by handling a firearm or having physical contact with a shooter.


Estimation of individual axon bundle properties by a Multi-Resolution Discrete-Search method.
A stable, accurate and robust-to-noise method for the estimation of the intra-voxel bundle-wise diffusion properties for diffusion-weighted magnetic resonance imaging is presented. The proposed method overcomes some of the limitations of most of the multi-fiber algorithms in the literature and extends them to estimate the diffusion profiles, improving the estimation of the intra-voxel geometry at challenging microstructure configurations, that is to say: relatively small crossing angles, different voxel-wise anisotropic diffusion profiles and low SNR. The proposed methodology is based on four key novel ideas: (i) A Multi-Resolution Discrete-Search determines the orientation of the fiber bundles accurately and naturally constrains the sparsity on the recovered solutions; (ii) the determination of the number of fiber bundles using the F-test combined with a Rician bias correction; (iii) a Simultaneous Denoising and Fitting procedure that exploits the spatial redundancy of the axon bundles to achieve robustness with respect to noise; and (iv) a general framework for the estimation of the axial and radial diffusivity parameters independently for each voxel. A new useful evaluation metric is also proposed, which combines the information of the success rate in the estimated number of bundles and the angular error, avoiding in this way, some of the limitations these metrics have individually. A novel methodology for the evaluation of the methods on in-vivo data is also proposed. This work presents an extensive evaluation: the proposed methodology has been tested on state-of-the-art biophysical synthetic data for a variety of conditions, on the challenging spatially coherent phantom used on the HARDI reconstruction Challenge 2012, and on the recently released in-vivo MASSIVE data-set. Our results present significant improvements on the estimation of the number and orientation of the fiber bundles over the Spherical Deconvolution algorithm for multi-shell data, which is one of the most widely used multi-fiber algorithm. The results also show that, by the voxel-wise estimation of the diffusion profiles, the axial and radial diffusivity parameters are robustly estimated, being this essential for a better understanding of the individual bundle diffusion properties at challenging structural configurations.


Chemical risk factors and childhood leukaemia: a review of recent studies.
The search for chemical risks factors as determinants of childhood leukaemia has been ongoing for over two decades. Results of epidemiological studies, published from 1998 to the present, evaluating parental smoking, outdoor sources of pollution, indoor contaminants and chemicals from drinking water are reported. Overall, results were mostly negative. This may be due to the relatively small study sizes to detect environmental effects, usually measured imprecisely. Another reason may be that such effects, which may be revealed among the genetically susceptible, have rarely accounted for genetic susceptibility. The few studies that have are also reported here. Suggestions are made for work in the immediate future, which include pooling of data and of analyses, as well as carrying out in-depth reviews of studies with the goal of understanding the reasons for discrepant results.


Palliative care for respiratory disease: An education model of care.
That palliative care improves quality of life for seriously ill patients and their families is well known - but how can healthcare providers ensure that the palliative needs of all patients are being assessed and addressed? A growing number of curricula in core palliative care practices have been developed to ensure that clinicians from all specialties and disciplines have the necessary training to manage pain and symptoms and discuss care goals with patients and families. Through broad-based training in core palliative care skills, combined with referral to specialty palliative care for high-need patients, providers can improve quality of life for their patients with respiratory disease.


Gender stereotype susceptibility.
Gender affects performance on a variety of cognitive tasks, and this impact may stem from socio-cultural factors such as gender stereotyping. Here we systematically manipulated gender stereotype messages on a social cognition task on which no initial gender gap has been documented. The outcome reveals: (i) Stereotyping affects both females and males, with a more pronounced impact on females. Yet an explicit negative message for males elicits a striking paradoxical deterioration in performance of females. (ii) Irrespective of gender and directness of message, valence of stereotype message affects performance: negative messages have stronger influence than positive ones. (iii) Directness of stereotype message differentially impacts performance of females and males: females tend to be stronger affected by implicit than explicit negative messages, whereas in males this relationship is opposite. The data are discussed in the light of neural networks underlying gender stereotyping. The findings provide novel insights into the sources of gender related fluctuations in cognition and behavior.


Effectiveness of 8- or 12-weeks of ledipasvir and sofosbuvir in real-world treatment-naïve, genotype 1 hepatitis C infected patients.
Treatment of genotype 1 hepatitis C virus (HCV) infection with combination direct acting anti-virals is associated with very high rates of sustained virological response (SVR). Daily combination of ledipasvir and sofosbuvir for 12 weeks is approved for the treatment of genotype 1 HCV patients, though noncirrhotic patients who are naïve to treatment with a baseline HCV RNA <6 million IU/mL can be treated for 8 weeks. This guidance stemmed from a post hoc analysis of the ION 3 clinical trial, which demonstrated similar SVR for patients treated with ledipasvir and sofosbuvir with or without ribavirin for 8 or 12 weeks. To compare the SVR for 8 weeks vs 12 weeks of ledipasvir and sofosbuvir in HCV infected patients in a real-world setting. We performed an observational real-world cohort study of treatment success following 8 or 12 weeks of ledipasvir and sofosbuvir for treatment-naïve genotype 1 HCV patients. A total of 826 patients were treated for either 8 (n=252) or 12 weeks (n=574) with ledipasvir and sofosbuvir and achieved SVR rate of 95.3% and there was no statistical difference in SVR rates in the two groups irrespective of any clinical or virological variables. In treatment-naïve HCV genotype 1 patients, SVR was 95% in those treated for either 8 weeks or 12 weeks with ledipasvir and sofosbuvir. 8 week ledipasvir and sofosbuvir can reduce costs without compromising outcomes for those patients who qualify for such regimen.


Late adult-onset spinal muscular atrophy with lower extremity predominance (SMALED).
An elderly man in his early 80s presented with a 6-month history of worsening lower limb weakness on a background of a longer-standing waddling gait. Examination revealed bilateral scapular winging, and weakness in his proximal and distal lower limbs. Electromyography showed widespread chronic partial denervation changes, while sensory and motor nerve conduction parameters were preserved. After little progression over the course of 18 months, motor neuron disease was deemed less likely. Genetic testing revealed BICD2-related spinal muscular atrophy with lower extremity dominance (SMALED2), a disease that is usually of earlier onset. He is the oldest patient in the literature to be diagnosed with SMALED2 while maintaining ambulation, suggesting the milder spectrum of BICD2-related disease.


[Bilateral adrenal hemorrhage due to adrenal metastasis of lung cancer].
A 58-year-old man presented with nausea and left flank pain. The patient was referred to our hospital based on clear detection of anemia and computed tomography findings of bilateral adrenal tumors with hemorrhage and a mass in the apex of the left lung. Right adrenal artery embolization had no effect on enlargement of the right adrenal hematoma or advanced anemia. Right adrenalectomy was then performed in an attempt to control hemorrhaging and make a definitive diagnosis, and the patient's anemia improved following the operation. Histopathological diagnosis suggested adrenal metastasis of lung adenocarcinoma, which was subsequently diagnosed given similarities in transbronchial biopsy findings to those in the right adrenal gland. Adrenal hemorrhage due to metastasis of lung cancer is an extremely rare condition; indeed, to our knowledge, the present case is only the 26th reported worldwide. However, prognosis for this mortal condition may be improved should patients receive adrenalectomy followed by an appropriate treatment regimen.


Characterization of high-affinity receptors for interleukin 5 on interleukin 5-dependent cell lines.
Interleukin 5 (IL-5) is a glycosylated polypeptide that acts as a key factor for B-cell growth and differentiation. We demonstrated previously that there are two classes (high and low affinity) of IL-5 receptors on murine chronic B-cell leukemic cells (BCL1-B20). Treatment of surface-bound radiolabeled IL-5 with bivalent crosslinkers identified a polypeptide of Mr 92,500. In this study, we analyzed characteristics of high-affinity IL-5 receptors on IL-5-dependent early B-cell lines (T-88 and T88-M), mouse myeloma cells (MOPC-104E), and BCL1-B20 cells. All cell lines had two classes of IL-5 binding sites, but T88-M cells bore the highest number of high-affinity receptors. The number of high-affinity IL-5 receptors on BCL1-B20 cells could be up-regulated 3-fold by lipopolysaccharide and down-regulated by IL-5. Disuccinimidyl tartarate crosslinking of 35S-labeled IL-5 to the receptors on the T88-M and lipopolysaccharide-stimulated BCL1-B20 cells revealed two major 35S-labeled components of Mr 92,500 and Mr 160,000, even when the binding of 35S-labeled IL-5 was carried out under high-affinity conditions (100 pM 35S-labeled IL-5). The Mr 92,500 component, but not the Mr 160,000 component, was detected in the lysates of MOPC-104E and T-88 cells, both of which bore a large number of low-affinity receptors and a limited number of high-affinity receptors. The results suggest that the Mr 92,500 component represents the complex of IL-5 with the low-affinity Mr 46,500 receptor, whereas the high-affinity receptor consists of the Mr 46,500 peptide and an additional peptide.


Ferrihydrite Formation: The Role of Fe13 Keggin Clusters.
Ferrihydrite is the most common iron oxyhydroxide found in soil and is a key sequester of contaminants in the environment. Ferrihydrite formation is also a common component of many treatment processes for cleanup of industrial effluents. Here we characterize ferrihydrite formation during the titration of an acidic ferric nitrate solution with NaOH. In situ SAXS measurements supported by ex situ TEM indicate that initially Fe13 Keggin clusters (radius ∼ 0.45 nm) form in solution at pH 0.12-1.5 and are persistent for at least 18 days. The Fe13 clusters begin to aggregate above ∼ pH 1, initially forming highly linear structures. Above pH ∼ 2 densification of the aggregates occurs in conjunction with precipitation of low molecular weight Fe(III) species (e.g., monomers, dimers) to form mass fractal aggregates of ferrihydrite nanoparticles (∼3 nm) in which the Fe13 Keggin motif is preserved. SAXS analysis indicates the ferrihydrite particles have a core-shell structure consisting of a Keggin center surrounded by a Fe-depleted shell, supporting the surface depleted model of ferrihydrite. Overall, we present the first direct evidence for the role of Fe13 clusters in the pathway of ferrihydrite formation during base hydrolysis, showing clear structural continuity from isolated Fe13 Keggins to the ferrihydrite particle structure. The results have direct relevance to the fundamental understanding of ferrihydrite formation in environmental, engineered, and industrial processes.


Correlation of Serum CysC, IMA, and LP-PLA2 Levels With Type 2 Diabetes Mellitus Patients With Lower Extremity Atherosclerotic Occlusive Disease.
To investigate the serum level of cystatin C (CysC), ischemia-modified albumin (IMA), and lipoprotein-associated phospholipase A2 (LP-PLA2) in patients with type 2 diabetes mellitus (T2DM) and with lower extremity atherosclerotic occlusive disease (LEASOD) and their correlation. From March 2017 to December 2019, 110 patients with T2DM with LEASOD, who were treated in our hospital, were selected as the observation group. One hundred ten healthy persons who received medical examination in our hospital during the same period were selected as the control group. Serum CysC, IMA, LP-PLA2, and ankle-brachial index (ABI) were detected in each group. According to the ABI index, the observation group was divided into three subgroups, namely, the mild group (n = 45), the moderate group (n = 42), and the severe group (n = 23). Pearson correlation analysis was used to analyze the relationship between serum CysC, IMA, and LP-PLA2 levels in patients with T2DM with LEASOD and their condition. The receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of serum CysC, IMA, and LP-PLA2 levels in patients with T2DM with LEASOD. The serum levels of CysC, IMA, and LP-PLA2 in the observation group were higher than those in the control group (p < 0.05). The serum levels of CysC, IMA, and LP-PLA2 in the severe and the moderate group were higher than those in the mild group, and the serum levels of CysC, IMA, and LP-PLA2 in the severe group were higher than those in the moderate group (p < 0.05). Pearson correlation analysis showed that CysC, IMA, and LP-PLA2 levels were all negatively correlated with ABI (r = -0.802, r = -0.757, r = -0.764, p < 0.001). The ROC curve results showed that the area under the curve (AUC) of serum CysC in the diagnosis of T2DM with LEASOD was 0.806, and the best cut-off value was 1.74 mg/L. The AUC of serum IMA for diagnosis of T2DM with LEASOD was 0.772, and the best cut-off value was 92.58 g/L. The AUC of serum LP-PLA2 in the diagnosis of T2DM with LEASOD was 0.781, and the best cut-off value was 544.86 ng/L. The AUC of the three combined diagnoses of T2DM with LEASOD was 0.863. Serum levels of CysC, IMA, and LP-PLA2 were increased in patients with T2DM with LEASOD. Serum CysC, IMA, and LP-PLA2 are closely related to the severity of the disease. The higher the serum levels of CysC, IMA, and LP-PLA2, the more serious the degree of lower extremity arteriosclerosis occlusion, which can be used as an important serum marker to monitor the severity of T2DM with LEASOD. The combined detection of serum CysC, IMA, and LP-PLA2 has good diagnostic value for patients with T2DM with LEASOD.


Peripheral arterial disease of the lower extremities.
Persons with peripheral arterial disease (PAD) are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Smoking should be stopped and hypertension, dyslipidemia, diabetes mellitus, and hypothyroidism treated. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. The serum low-density lipoprotein cholesterol should be reduced to < 70 mg/dl. Antiplatelet drugs such as aspirin or clopidogrel, angiotensin-converting enzyme inhibitors, and statins should be given to persons with PAD. β-Blockers should be given if coronary artery disease is present. Cilostazol improves exercise time until intermittent claudication. Exercise rehabilitation programs should be used. Revascularization should be performed if indicated.


Cyclic electron flow provides acclimatory plasticity for the photosynthetic machinery under various environmental conditions and developmental stages.
Photosynthetic electron flow operates in two modes, linear and cyclic. In cyclic electron flow (CEF), electrons are recycled around photosystem I. As a result, a transthylakoid proton gradient (ΔpH) is generated, leading to the production of ATP without concomitant production of NADPH, thus increasing the ATP/NADPH ratio within the chloroplast. At least two routes for CEF exist: a PROTON GRADIENT REGULATION5-PGRL1-and a chloroplast NDH-like complex mediated pathway. This review focuses on recent findings concerning the characteristics of both CEF routes in higher plants, with special emphasis paid on the crucial role of CEF in under challenging environmental conditions and developmental stages.


Individualized right ventricular outflow tract reconstruction using autologous pulmonary tissue in situ for the treatment of pulmonary atresia with ventricular septum defect.
The study aims to evaluate the feasibility and effectiveness of an individualized procedure for right ventricular outflow tract (RVOT) reconstruction in pulmonary atresia with ventricular septal defect (PA-VSD). RVOT was reconstructed using autologous pulmonary artery tissue preserved in situ as the posterior wall and a bovine jugular vein patch (BJVP) as the anterior wall in patients with PA-VSD (observation group). The size of the BJVP made from a bovine jugular vein conduit (BJVC) was individually calculated using a formula based on the child's weight and the size of the autologous pulmonary artery (the diameter of BJVC DBJVC = Dtheoretical-Wz^-4π). Its effect was then compared with the conventional modified Rastelli procedure based on the BJVC (control group). A total of 22 patients that underwent the new procedure were simultaneously compared with the 25 patients in the control group. No deaths occurred in both groups. Notably, there were no significant differences in mechanical ventilation, ICU and postoperative residence, cardiopulmonary bypass, and aortic cross-clamp time. In the follow-up, which spanned for 8-12 years (mean 9.2 years), only four cases with moderate regurgitation were noted in the observation group without obstruction. In the control group, two patients had a conduit replacement. Three patients suffered from anastomotic stenosis, which was corrected by balloon dilatation. Individualized RVOT reconstruction with autologous pulmonary tissue preserved in situ as the posterior wall is adequate for treating PA-VSD.


Ultrafast relaxation in quasi-one-dimensional organic molecular crystals.
We present a comprehensive study of ultrafast relaxation properties of optical excitations in thin films of quasi-1D stacked organic materials PTCDA (3,4,9,10-perylenetetracarboxylic dianhydride) and MePTCDI (N,N'-dimethylperylene-3,4,9,10-dicarboximide) over five decades of time. Pump-probe experiments reveal excitonic intraband relaxation time constants of 65 fs for MePTCDI and 100 fs for PTCDA. The initial time-resolved luminescence anisotropy is consistent with the exciton model of Davydov-split states. The subsequent decay of the anisotropy can be explained with a thermally activated exciton hopping process. A full understanding of the pump-probe experiments calls for an explanation beyond the models presently available.


Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells.
C3H10T1/2 cells are an established mesenchymal stem cell line which can differentiate into muscle, fat and cartilage cells when treated with azacytidine. Bone morphogenetic protein-2 (BMP-2) caused a dose dependent differentiation of these cells into fat, cartilage and bone cells-low concentrations favoring adipocytes and high concentrations chondrocytes and osteoblasts. The differentiated phenotypes were stable in the absence of BMP-2. Furthermore, the addition of other growth factors during the differentiation process altered the frequency of the differentiated colony formation. Transfection of the C3H10T1/2 cells with a BMP-2 cDNA also induced a phenotypic change from the parental fibroblast to adipocytes and osteoblasts. Our results in this model system indicate that a single protein factor can cause differentiation of a stem cell line to multiple phenotypes, that phenotypes induced can be regulated by factor concentration, and that other factors can also influence BMP-2 induced differentiation.


The advancement of pure local anesthesia for penile surgeries: can an outpatient basis be sustainable?
Although topical anesthetic blockage for penile surgeries has been substantially reported in the medical literature, its methodology, reliability, and reproducibility have not been consistent. We report on several methods of topical blocks for local anesthesia in patients with indications for penile surgeries. From March 1993 to March 2003, a total of 1131 men, ages 19 to 87, underwent penile surgeries in which 165, 203, 708, 45, and 10 patients received penile implantation, modified Nesbit procedure, venous surgery, venous patches, and arterial revascularization respectively, under pure local anesthesia on an outpatient basis. They were categorized into the implant, Nesbit, venous, patch, and arterial groups respectively. Proximal dorsal nerve blockage, peripenile infiltration, and topical injection, although challenging, were sufficient local anesthesia for patients in the last 4 patient groups. A new method of crural blockade, however, was also required for optimal anesthesia of the cavernous nerve for implantation purposes. The anesthetic effects and postoperative results were satisfactory. Common immediate side effects included puncture of the corpus spongiosum or the deep dorsal vein as well as the innominate vessel, subcutaneous ecchymosis, transient palpitations, and acceptable low level of pain. There were no significant late complications. In the implant group, however, 6.1% of patients (10/165) had experienced pain over the perineum for 1 to 2 weeks postoperatively. Overall there were statistical differences in scoring between the 5 groups in which the implant group stood out when a visual analog scale of 100 mm was used. Topical nerve blockades proved to be reliable, simple, and safe, with minimal complications. They offer the advantages of less morbidity, reduced effects of anesthesia, protection of privacy, and a rapid return to preoperative daily activity.


Effects of operational taxonomic unit inference methods on soil microeukaryote community analysis using long-read metabarcoding.
Long amplicon metabarcoding has opened the door for phylogenetic analysis of the largely unknown communities of microeukaryotes in soil. Here, we amplified and sequenced the ITS and LSU regions of the rDNA operon (around 1500 bp) from grassland soils using PacBio SMRT sequencing. We tested how three different methods for generation of operational taxonomic units (OTUs) effected estimated richness and identified taxa, and how well large-scale ecological patterns associated with shifting environmental conditions were recovered in data from the three methods. The field site at Kungsängen Nature Reserve has drawn frequent visitors since Linnaeus's time, and its species rich vegetation includes the largest population of Fritillaria meleagris in Sweden. To test the effect of different OTU generation methods, we sampled soils across an abrupt moisture transition that divides the meadow community into a Carex acuta dominated plant community with low species richness in the wetter part, which is visually distinct from the mesic-dry part that has a species rich grass-dominated plant community including a high frequency of F. meleagris. We used the moisture and plant community transition as a framework to investigate how detected belowground microeukaryotic community composition was influenced by OTU generation methods. Soil communities in both moisture regimes were dominated by protists, a large fraction of which were taxonomically assigned to Ciliophora (Alveolata) while 30%-40% of all reads were assigned to kingdom Fungi. Ecological patterns were consistently recovered irrespective of OTU generation method used. However, different methods strongly affect richness estimates and the taxonomic and phylogenetic resolution of the characterized community with implications for how well members of the microeukaryotic communities can be recognized in the data.


nfi-I affects behavior and life-span in C. elegans but is not essential for DNA replication or survival.
The Nuclear Factor I (one) (NFI) family of transcription/replication factors plays essential roles in mammalian gene expression and development and in adenovirus DNA replication. Because of its role in viral DNA replication NFI has long been suspected to function in host DNA synthesis. Determining the requirement for NFI proteins in mammalian DNA replication is complicated by the presence of 4 NFI genes in mice and humans. Loss of individual NFI genes in mice cause defects in brain, lung and tooth development, but the presence of 4 homologous NFI genes raises the issue of redundant roles for NFI genes in DNA replication. No NFI genes are present in bacteria, fungi or plants. However single NFI genes are present in several simple animals including Drosophila and C. elegans, making it possible to test for a requirement for NFI in multicellular eukaryotic DNA replication and development. Here we assess the functions of the single nfi-1 gene in C. elegans. C. elegans NFI protein (CeNFI) binds specifically to the same NFI-binding site recognized by vertebrate NFIs. nfi-1 encodes alternatively-spliced, maternally-inherited transcripts that are expressed at the single cell stage, during embryogenesis, and in adult muscles, neurons and gut cells. Worms lacking nfi-1 survive but have defects in movement, pharyngeal pumping and egg-laying and have a reduced life-span. Expression of the muscle gene Ce titin is decreased in nfi-1 mutant worms. NFI gene function is not needed for survival in C. elegans and thus NFI is likely not essential for DNA replication in multi-cellular eukaryotes. The multiple defects in motility, egg-laying, pharyngeal pumping, and reduced lifespan indicate that NFI is important for these processes. Reduction in Ce titin expression could affect muscle function in multiple tissues. The phenotype of nfi-1 null worms indicates that NFI functions in multiple developmental and behavioral systems in C. elegans, likely regulating genes that function in motility, egg-laying, pharyngeal pumping and lifespan maintenance.


Characterization of the murine alpha interferon gene family.
Mouse and human genomes carry more than a dozen genes coding for closely related alpha interferon (IFN-alpha) subtypes. IFN-alpha, as well as IFN-beta, IFN-kappa, IFN-epsilon, and limitin, are thought to bind the same receptor, raising the question of whether different IFN subtypes possess specific functions. As some confusion existed in the identity and characteristics of mouse IFN-alpha subtypes, the availability of data from the mouse genome sequence prompted us to characterize the murine IFN-alpha family. A total of 14 IFN-alpha genes were detected in the mouse genome, in addition to three IFN-alpha pseudogenes. Four IFN-alpha genes (IFN-alpha1, IFN-alpha7/10, IFN-alpha8/6, and IFN-alpha11) exhibited surprising allelic divergence between 129/Sv and C57BL/6 mice. All IFN-alpha subtypes were found to be stable at pH 2 and to exhibit antiviral activity. Interestingly, some IFN subtypes (IFN-alpha4, IFN-alpha11, IFN-alpha12, IFN-beta, and limitin) showed higher biological activity levels than others, whereas IFN-alpha7/10 exhibited lower activity. Most murine IFN-alpha turned out to be N-glycosylated. However, no correlation was found between N-glycosylation and activity. The various IFN-alpha subtypes displayed a good correlation between their antiviral and antiproliferative potencies, suggesting that IFN-alpha subtypes did not diverge primarily to acquire specific biological activities but probably evolved to acquire specific expression patterns. In L929 cells, IFN genes activated in response to poly(I*C) transfection or to viral infection were, however, similar.


Imaging ERK and PKA Activation in Single Dendritic Spines during Structural Plasticity.
Extracellular signal-regulated kinase (ERK) and protein kinase A (PKA) play important roles in LTP and spine structural plasticity. While fluorescence resonance energy transfer (FRET)-based sensors for these kinases had previously been developed, they did not provide sufficient sensitivity for imaging small neuronal compartments, such as single dendritic spines in brain slices. Here we improved the sensitivity of FRET-based kinase sensors for monitoring kinase activity under two-photon fluorescence lifetime imaging microscopy (2pFLIM). Using these improved sensors, we succeeded in imaging ERK and PKA activation in single dendritic spines during structural long-term potentiation (sLTP) in hippocampal CA1 pyramidal neurons, revealing that the activation of these kinases spreads widely with length constants of more than 10 μm. The strategy for improvement of sensors used here should be applicable for developing highly sensitive biosensors for various protein kinases. VIDEO ABSTRACT.


Is There an Optimum Duration of Fluid Bolus in Pediatric Septic Shock? A Critical Appraisal of "Fluid Bolus Over 15-20 Versus 5-10 Minutes Each in the First Hour of Resuscitation in Children With Septic Shock: A Randomized Controlled Trial" by Sankar et al (Pediatr Crit Care Med 2017; 18:e435-e445).
To review the findings and discuss the implications of a longer duration for fluid boluses in the resuscitation of children with septic shock. We performed a PubMed.gov search using the criteria "Fluid Bolus" and "Children" and "Septic Shock," which yielded 29 references. One trial compared different durations of fluid boluses in pediatric septic shock and was therefore selected for critical appraisal. (Sankar J, Ismail J, Sankar MJ, et al: Fluid Bolus Over 15-20 Versus 5-10 Minutes Each in the First Hour of Resuscitation in Children with Septic Shock: A Randomized Controlled Trial. Pediatr Crit Care Med 2017; 18:e435-e445.) DATA EXTRACTION:: This trial compared the effectiveness of 20 mL/kg fluid boluses, in children with septic shock, given over 15-20 versus 5-10 minutes in terms of need for invasive ventilation and/or increase in oxygenation index by 5 from baseline at 6 and 24 hours post initial fluid resuscitation. The relative risk of the primary outcome was 0.62 (p = 0.04; 95% CI, 0.39-0.99) at 6 hours and 0.63 (p = 0.02; 95% CI, 0.42-0.93) at 24 hours. Fragility Index calculations for the primary outcomes of this trial were 1 and 2. Therefore, only one and two children would have needed different outcomes to have given nonsignificant p values greater than 0.05. Analysis of the results did not support the early stopping of this trial at the interim period. The article reviewed does not support a change in practice to a longer duration of fluid bolus. The "push" technique for titration of fluid boluses in pediatric septic shock should continue to be the method of choice. Critical Care trials using binary outcomes as endpoints should publish Fragility Index results to aid interpretation and generate stronger conclusions.


Progressive hemifacial atrophy with characteristic ocular manifestations in a Chinese patient with a CRB1 mutation.
Progressive hemifacial atrophy (PHA) is mainly characterized by asymmetrical atrophy of craniofacial tissue; however, 10% to 30% of patients with PHA exhibit ocular manifestations. Here, we describe abnormal ocular findings in a Chinese patient with PHA. The patient was a 29-year-old Chinese man. Characteristic ocular findings in his affected eye included keratic precipitate, corneal endothelial degeneration, fundus tessellation, pupillary dilation, direct light reflex loss, and visual evoked potential alteration. Whole exosome sequencing revealed that the patient harbored a mutation in the CRB1 gene; this gene has been associated with various retinal dystrophies. During 10 years of follow-up, the patient's ocular status remained stable. To the best of our knowledge, this is the first report of ocular manifestations of PHA in a Chinese patient, and the first report of a CRB1 mutation in a patient with PHA; these findings may inform future research regarding PHA.


Engineering the Surface of Smart Nanocarriers Using a pH-/Thermal-/GSH-Responsive Polymer Zipper for Precise Tumor Targeting Therapy In Vivo.
Nanocarrier surface chemistry plays a vital role in mediating cell internalization and enhancing delivery efficiency during in vivo chemotherapy. Inspired by the ability of proteins to alter their conformation to mediate functions, a pH-/thermal-/glutathione-responsive polymer zipper consisting of cell-penetrating poly(disulfide)s and thermosensitive polymers bearing guanidinium/phosphate (Gu+ /pY- ) motifs to spatiotemporally tune the surface composition of nanocarriers for precise tumor targeting and efficient drug delivery is developed. Surface engineering allows the nanocarriers to remain undetected during blood circulation and favors passive accumulation at tumor sites, where the acidic microenvironment and photothermal heating break the pY- /Gu+ binding and rupture the zipper, thereby exposing the penetrating shell and causing enhanced cellular uptake via counterion-/thiol-/receptor-mediated endocytosis. The in vivo study demonstrates that by manipulating the surface states on command, the nanocarriers show longer blood circulation time, minimized uptake and drug leakage in normal organs, and enhanced accumulation and efficient drug release at tumor sites, greatly inhibiting tumor growth with only slight damage to normal tissues. If integrated with a photothermal dye approved by the U.S. Food and Drug Administration (FDA), polymer zipper would provide a versatile protocol for engineering nanomedicines with high selectivity and efficiency for clinical cancer treatment.


Nanocomposites of Highly Monodisperse Encapsulated Superparamagnetic Iron Oxide Nanocrystals Homogeneously Dispersed in a Poly(ethylene Oxide) Melt.
Nanocomposite materials based on highly stable encapsulated superparamagnetic iron oxide nanocrystals (SPIONs) were synthesized and characterized by scattering methods and transmission electron microscopy (TEM). The combination of advanced synthesis and encapsulation techniques using different diblock copolymers and the thiol-ene click reaction for cross-linking the polymeric shell results in uniform hybrid SPIONs homogeneously dispersed in a poly(ethylene oxide) matrix. Small-angle X-ray scattering and TEM investigations demonstrate the presence of mostly single particles and a negligible amount of dyads. Consequently, an efficient control over the encapsulation and synthetic conditions is of paramount importance to minimize the fraction of agglomerates and to obtain uniform hybrid nanomaterials.


Host circadian clock as a control point in tumor progression.
The circadian timing system controlled by the suprachiasmatic nuclei (SCN) of the hypothalamus regulates daily rhythms of motor activity and adrenocortical secretion. An alteration in these rhythms is associated with poor survival of patients with metastatic colorectal or breast cancer. We developed a mouse model to investigate the consequences of severe circadian dysfunction upon tumor growth. The SCN of mice were destroyed by bilateral electrolytic lesions, and body activity and body temperature were recorded with a radio transmitter implanted into the peritoneal cavity. Plasma corticosterone levels and circulating lymphocyte counts were measured (n = 75 with SCN lesions, n = 64 sham-operated). Complete SCN destruction was ascertained postmortem. Mice were inoculated with implants of Glasgow osteosarcoma (n = 16 with SCN lesions, n = 12 sham-operated) or pancreatic adenocarcinoma (n = 13 with SCN lesions, n = 13 sham-operated) tumors to determine the effects of altered circadian rhythms on tumor progression. Time series for body temperature and rest-activity patterns were analyzed by spectral analysis and cosinor analysis. Parametric data were compared by the use of analysis of variance (ANOVA) and survival curves with the log-rank test. All statistical tests were two-sided. The 24-hour rest-activity cycle was ablated and the daily rhythms of serum corticosterone level and lymphocyte count were markedly altered in 75 mice with complete SCN destruction as compared with 64 sham-operated mice (two-way ANOVA for corticosterone: sampling time effect P<.001, lesion effect P =.001, and time x lesion interaction P<.001; for lymphocytes P =.001,.002, and.002 respectively). Body temperature rhythm was suppressed in 60 of the 75 mice with SCN lesions (P<.001). Both types of tumors grew two to three times faster in mice with SCN lesions than in sham-operated mice (two-way ANOVA: P<.001 for lesion and for tumor effects; P =.21 for lesion x tumor effect interaction). Survival of mice with SCN lesions was statistically significantly shorter compared with that of sham-operated mice (log-rank P =.0062). Disruption of circadian rhythms in mice was associated with accelerated growth of malignant tumors of two types, suggesting that the host circadian clock may play an important role in endogenous control of tumor progression.


Quality of life of adolescent males with attention-deficit hyperactivity disorder.
Most psychosocial research on attention-deficit/hyperactivity disorder (ADHD) has focused on deficits in school, family, or behavioral functioning without incorporating perceived quality of life (QoL) or the adolescents' perspective. The Youth Quality of Life Instrument--Research Version (YQOL-R), was used to assess self-perceived QoL in a community sample of adolescents aged 11-18 years. Fifty-five adolescent males with a clinical diagnosis of ADHD were compared to a group of 107 adolescents with no chronic conditions (NCC) and a group of 52 adolescents with mobility impairments (MI). The adolescents with ADHD reported significantly lower perceived QoL scores, particularly in the Self and Relationship domains, than the NCC group. Their scores were similar to those from the group with MI, a group previously shown to have a substandard QoL. Interventions to improve self-esteem and social interactions might use QoL outcomes in evaluating effectiveness.


Root canal anatomy illustrated by microcomputed tomography and clinical cases.
This study was designed to illustrate root anatomy by using microcomputed tomography and radiographs. Fresh human extracted teeth were selected randomly and prepared for scanning by a microscopic scanner. Each tooth was scanned at intervals of 0.9 degrees until it had been rotated 180 degrees. Data collected were used to generate cross-sectional images and three-dimensional tooth anatomy. Radiographs of completed endodontic cases that showed significant root canal anatomy also were collected and evaluated. Microcomputed tomographic scans showed that the main root canals branched out to finer branches and ended in multiple portals of exit. Intercommunication existed between the main and accessory canals. Apical exits of delta configuration were not common. Similar findings were evident in radiographs of the clinical cases. Both microcomputed tomographic scans and radiographs of completed clinical cases depicted similar complex root canal anatomy. This indicates that with an understanding of the anatomy, complex root canal systems can be cleaned, shaped, and obturated.


Antilipolytic actions of vanadate and insulin in rat adipocytes mediated by distinctly different mechanisms.
Vanadate, which mimics the biological effects of insulin, also inhibits lipolysis in rat adipocytes. Here we demonstrate that the antilipolytic effect of vanadate differs from that of insulin at least by the five following criteria: 1) vanadate inhibits lipolysis mediated by high (supraphysiological) concentrations of catecholamines; 2) vanadate antagonizes (Bu)2cAMP-mediated lipolysis; 3) vanadate antagonizes isobutylmethylxanthine-dependent lipolysis, 4) vanadate inhibits lipolysis mediated by okadaic acid; and 5) wortmannin, which blocks the antilipolytic effect of insulin, fails to block vanadate-mediated antilipolysis. Vanadate does activate phosphoinositol 3-kinase, and wortmannin blocks this activation. Our working hypothesis assumes that all of the insulin-like effects of vanadate, including antilipolysis, are initiated by the inhibition of protein phosphotyrosine phosphatases (PTPases). Among documented PTPase inhibitors we found that VOSO4 (oxidation state +4), several organic vanadyl compounds (+4), zinc (Zn2+), tungstate (W), and molybdate (Mo) also had antilipolytic activity. The order of potency was vanadyl acetylacetonate > or = VOSO4 > or = NaVO3 > or = vanadyl-dipicolinate > Zn2+ >> W > Mo, and it correlated better with the inhibition of adipose membranal-PTPases in cell-free experiments. We have concluded that the antilipolytic effect of vanadate is 1) mechanistically distinct from that of insulin, 2) independent of phosphoinositol 3-kinase activation, and 3) independent of the lipolytic cascade. We also strongly suggest that the antilipolytic effect of vanadate emanates from inhibiting adipose membranal, rather than cytosolic PTPases, and present preliminary data showing distinct differences in catalysis between these two PTPase categories. Overall, the study indicates that antilipolysis can be manifested via alternative, insulin-independent, signal-transducing pathways.


Perineal lipomas associated with anorectal malformations.
Newborns with anorectal malformations may have associated perineal lipomas. These lesions are rare but may make the repair of the anorectal malformation more complex. Knowledge about the functional consequences of these lesions is scanty. The purpose of this study was to review the experience of anorectal malformations with perineal lipomas in two Scandinavian paediatric surgical centres. Six patients with perineal lipomas and anorectal malformation treated in the two centres from 1991 to 2005 were retrospectively reviewed. Bowel function was evaluated in patients more than 4 years old. Three girls and three boys (age 4 months to 14 years) with anorectal malformations and perineal lipoma were included in the study. The boys all had high anorectal malformations with rectourethral or rectovesical fistulas. Two girls had a rectovestibular fistula and one girl had a cloaca. All patients had perineal lipomas, in one associated with an anterior meningocele. The lipomas were excised at time of anorectal reconstruction. One of the patients still has a colostomy, and two colostomies were recently closed. The bowel function was evaluated in three patients. Two patients have an ACE stoma to control constipation and soiling and one is soiling despite regular washouts. In conclusion, perineal lipomas associated with anorectal malformations are rare but may distort sphincter anatomy. Excision is best performed at time of anorectal reconstruction. Although our experience is limited, bowel function seems to be compromised by these lesions.


Prohibitin promotes androgen receptor activation in ER-positive breast cancer.
Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells. We obtained the expression of PHB is significantly low in breast cancer samples, and low PHB expression positively correlated with poor prognosis of breast cancer. We detected that PHB could inhibit breast cancer cell proliferation, change cell cycle distribution and promote cell apoptosis in the ER-positive breast cancer cells. Moreover, we found PHB could significantly increase AR expression in both mRNA and protein levels in the ER-positive breast cancer cells. Additionally, a significant positive correlation between PHB and AR expression was identified in the 121 breast cancer tissues. PHB and AR expression are associated with prognosis in the ER-positive breast cancer patients. Our results indicate that PHB promotes AR activation in ER-positive breast cancer, making PHB and AR potential molecular targets for ER-positive breast cancer therapy.


Glutamine supplementation for young infants with severe gastrointestinal disease.
Endogenous glutamine biosynthesis may be insufficient to meet the needs of people with severe gastrointestinal disease. Results from studies using experimental animal models of gastrointestinal disease have suggested that glutamine supplementation improves clinical outcomes. This review examines evidence on the effect of glutamine supplementation in young infants with severe gastrointestinal disease. To assess the effect of supplemental glutamine on mortality and morbidity in young infants with severe gastrointestinal disease. We searcheed the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 8), MEDLINE, EMBASE, and CINAHL (from inception to September 2014), conference proceedings, and reference lists from previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in infants up to three months old (corrected for preterm birth if necessary) with severe gastrointestinal disease defined as a congenital or acquired gastrointestinal condition that is likely to necessitate providing parenteral nutrition for at least 24 hours. Two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. We analysed the treatment effects in the individual trials and reported the risk ratio (RR) and risk difference (RD) for dichotomous data and mean difference for continuous data, with 95% confidence intervals (CI). We used a fixed-effect model in meta-analyses and explored the potential causes of heterogeneity in sensitivity analyses. We found three trials in which a total of 274 infants participated. The trials were of good methodological quality but were too small to detect clinically important effects of glutamine supplementation. Meta-analyses did not reveal a statistically significant difference in the risk of death before hospital discharge (typical RR 0.79, 95% CI 0.19 to 3.20; typical RD -0.01, 95% CI -0.05 to 0.03) or in the rate of invasive infection (typical RR 1.37, 95% CI 0.89 to 2.11; typical RD 0.08, 95% CI -0.03 to 0.18]). The available data from randomised controlled trials do not suggest that glutamine supplementation has any important benefits for young infants with severe gastrointestinal disease.


Octahedral distortion caused by hydrogen bonding in tris(diethylammonium) hexachloridoantimonate(III).
The factors influencing the distortion of inorganic anions in the structures of chloridoantimonates(III) with organic cations, in spite of numerous structural studies on those compounds, have not been clearly described and separated. The title compound, [(C(2)H(5))(2)NH(2)](3)[SbCl(6)], consisting of isolated distorted [SbCl(6)](3-) octahedra that have C(3) symmetry and [(C(2)H(5))(2)NH(2)](+) cations, unequivocally shows the role played by hydrogen bonding in the geometry variations of inorganic anions. The organic cations, which are linked to the inorganic substructure through N-H...Cl hydrogen bonds, are clearly responsible for the distortion of the octahedral coordination of Sb(III) in terms of differences (Delta) in both Sb-Cl bond lengths [Delta = 0.4667 (6) A] and Cl-Sb-Cl angles [Delta = 9.651 (17) degrees].


Increase in hypothalamic AMPK phosphorylation induced by prolonged exposure to LPS involves ghrelin and CB1R signaling.
Acute administration of lipopolysaccharide (LPS) from Gram-negative bacteria induces hypophagia. However, the repeated administration of LPS leads to desensitization of hypophagia, which is associated with increased hypothalamic p-AMPK expression. Because ghrelin and endocannabinoids modulate AMPK activity in the hypothalamus, we hypothesized that these neuromodulators play a role in the reversal of tolerance to hypophagia in rats under long-term exposure to LPS. Male Wistar rats were treated with single (1 LPS, 100μg/kg body weight, ip) or repeated injections of LPS over 6days (6 LPS). Food intake was reduced in the 1 LPS, but not in the 6 LPS group. 6 LPS rats showed an increased serum concentration of acylated ghrelin and reduced ghrelin receptor mRNA expression in the hypothalamus. Ghrelin injection (40μg/kg body weight, ip) increased food intake, body weight gain, p-AMPK hypothalamic expression, neuropeptide Y (NPY) and Agouti related peptide (AgRP) mRNA expression in control animals (Saline). However, in 6 LPS rats, ghrelin did not alter these parameters. Central administration of a CB1R antagonist (AM251, 200ng/μl in 5μl/rat) induced hypophagia in 6 LPS animals, suggesting that the endocannabinoid system contributes to preserved food intake during LPS tolerance. In the presence of AM251, the ability of ghrelin to phosphorylate AMPK in the hypothalamus of 6 LPS group was restored, but not its orexigenic effect. Our data highlight that the orexigenic effects of ghrelin require CB1R signaling downstream of AMPK activation. Moreover, CB1R-mediated pathways contribute to the absence of hypophagia during repeated exposure to endotoxin.


The selective estrogen receptor modulator trioxifene (LY133314) inhibits metastasis and extends survival in the PAIII rat prostatic carcinoma model.
Trioxifene (LY133314) is a selective estrogen receptor modulator (SERM) with competitive binding activity against estradiol for estrogen receptor alpha (ERalpha) and antagonistic activity against ERalpha-mediated gene expression. The PAIII rat prostatic adenocarcinoma (PCa) is an androgen receptor-negative, ERalpha- and ERbeta-positive, spontaneously metastatic rodent tumor cell line. After s.c. implantation of 10(6) PAIII cells in the tail, s.c. administration of trioxifene (2.0, 4.0, 20.0, or 40.0 mg/kg-day) for 30 days produced significant (P < 0.05) inhibition of PAIII metastasis from the primary tumor in the tail to the gluteal and iliac lymph nodes (maximum nodal weight decreases, 86% and 88% from control values, respectively). PAIII metastasis to the lungs was significantly inhibited by trioxifene treatment. Numbers of pulmonary foci in PAIII-bearing rats were significantly (P < 0.05) reduced by trioxifene administration in a dose-related manner (maximal reduction, 98% from control values). Continual administration of the compound significantly (P < 0.05) extended survival of PAIII-bearing rats. Trioxifene inhibited the proliferation of PAIII cells at micromolar levels in vitro but did not slow growth of the primary tumor growth in the tail. Trioxifene administration also produced regression of male accessory sex organs. In PAIII-tumor-bearing animals, trioxifene administration produced a maximal regression of 76% for ventral prostate and 64% for seminal vesicle (P < 0.05 for both). SERMs may be preferable to estrogens given their efficacy in experimental PCa models and relative lack of side effects observed in clinical trials. Our data support the contention that trioxifene represents a SERM with potential antimetastatic efficacy for the treatment of androgen-independent, metastatic PCa.


Adjacent level fracture incidence in single fraction high dose spinal radiosurgery.
Vertebral body compression fracture (VCF) is a complication following spinal stereotactic radiosurgery (SRS). However, the incidence of VCF in vertebrae adjacent to the level of SRS is unknown. This study aimed to determine the incidence of adjacent level VCF (adjVCF) following spinal SRS. A retrospective review of 239 lesions treated with single-fraction SRS from 2011-2014 was performed. Clinical and pathologic factors were collected including evaluation of VCFs in adjacent levels to SRS site. In patients with adjVCFs, dose-volume histograms for adjacent-level endplates were calculated. Cox regression analysis was performed to determine any association among clinical factors and adjVCF occurrence. Median follow-up was 14.7 months. Twenty-six adjVCFs occurred (10.8%). Of the adjVCFs, 19 had metastases following SRS, and seven did not (2.9% of total treatments). Median time to fracture post-SRS was 13.5 months. In adjVCFs, median of the mean dose to adjacent level fractured endplate was 23.3 Gy, and median of the mean dose of sixteen non-fractured endplates immediately adjacent to the SRS site was 19.1 Gy. Age, gender, and histology were not associated with adjVCF. AdjVCF after spinal SRS occurs at a rate of 2.9%, when excluding metastatic sites of disease. Adjacent level endplates should be investigated as an organ at risk during SRS planning.


Standardizing Pathogenicity Assays for Fusarium Wilt Pathogens of Ornamental Palms.
Standardized protocols for determining pathogenicity of Fusarium oxysporum ff. spp. canariensis and palmarum, the cause of Fusarium wilt of ornamental palms, were developed using small palm plants with a minimum of three to four seedling leaves. For both protocols, a standard amount of inoculum (25 ml of 106 spores/ml) was pipetted onto and between the leaf bases of each plant, with excess material running down onto the roots and collecting in the container. After 3 days, the palm plants were transplanted into 450-ml containers filled with pine bark/sedge peat/sand potting mix. The protocol for F. oxysporum f. sp. canariensis differed from the protocol of F. oxysporum f. sp. palmarum by requiring that the lower 20% of roots be cut prior to inoculation and having the assay run for 6 months versus 3 months. These two assays were used to evaluate pathogenicity of multiple isolates of each pathogen. All 15 isolates of F. oxysporum f. sp. palmarum were pathogenic, whereas only 7 of 13 F. oxysporum f. sp. canariensis isolates were pathogenic. These assays were also used to determine susceptibility of other palm species to these pathogens. Washingtonia filifera, Butia odorata, Phoenix dactylifera, and P. reclinata appeared susceptible to F. oxysporum f. sp. palmarum, at least in the seedling stage. Other inoculation techniques are described that may be useful for evaluating Fusarium wilt disease management methods.


Evidences of antagonism between amiodarone and triiodothyronine on the K+ channel activities of cultured rat cardiomyocytes.
Effects of acute and chronic treatments with amiodarone, both in the presence and the absence of exogenous triiodothyronine (T3), on repolarizing outward K+ currents were investigated by patch-clamp technique in cultured newborn rat ventricular cells. Acute exposure to amiodarone dose-dependently inhibited the transient outward (Ito IC50 = 4.9 microM) and the steady-state outward (IK, IC50 = 6.3 microM) K4 currents. The dose-response curve of this acute inhibitory action was unaffected by the presence of T3. When amiodarone was applied chronically. 72-h exposure to a low dose of the drug (1 microM) significantly decreased the current densities of Ito and I kappa for the cells cultured in a serum-supplemented medium containing 0.12 nM T3. In a serum-free medium without T3o chronic amiodarone treatment revealed null effect on either Ito or IK. In addition, 72-h in-vitro treatment with Ti enhanced the current densities of both Ito (EC50 = 0.13 nM) and I kappa (EC50 = 0.33 nM). Concentration-response analysis indicated that amiodarone (1 microM) showed competitive inhibition towards the action of T3 on Ito but noncompetitive inhibition towards the action of T3 on IK. These results suggest that different ionic mechanisms are produced by acute and long-term treatments with amiodarone. The latter showed T3-dependent inhibition of cardiac Ito and IK. When chronically administered, amiodarone may antagonize T3 and thereby counteract its hormonal effect on K+ channels. This implies that, at the myocyte level, antagonism of the action of thyroid hormones in K+ channel activities may contribute to the cardiac effects of chronic amiodarone therapy.


B cells enhance early innate immune responses during bacterial sepsis.
Microbes activate pattern recognition receptors to initiate adaptive immunity. T cells affect early innate inflammatory responses to viral infection, but both activation and suppression have been demonstrated. We identify a novel role for B cells in the early innate immune response during bacterial sepsis. We demonstrate that Rag1(-/-) mice display deficient early inflammatory responses and reduced survival during sepsis. Interestingly, B cell-deficient or anti-CD20 B cell-depleted mice, but not α/β T cell-deficient mice, display decreased inflammatory cytokine and chemokine production and reduced survival after sepsis. Both treatment of B cell-deficient mice with serum from wild-type (WT) mice and repletion of Rag1(-/-) mice with B cells improves sepsis survival, suggesting antibody-independent and antibody-dependent roles for B cells in the outcome to sepsis. During sepsis, marginal zone and follicular B cells are activated through type I interferon (IFN-I) receptor (IFN-α/β receptor [IFNAR]), and repleting Rag1(-/-) mice with WT, but not IFNAR(-/-), B cells improves IFN-I-dependent and -independent early cytokine responses. Repleting B cell-deficient mice with the IFN-I-dependent chemokine, CXCL10 was also sufficient to improve sepsis survival. This study identifies a novel role for IFN-I-activated B cells in protective early innate immune responses during bacterial sepsis.


Effects of N-acyl-2-hydroxymethyl aziridines on in vitro proliferative responses of human lymphocytes stimulated by mitogens.
Aziridines have been shown to possess marked immunotropic activity. The aim of this work was to study the in vitro effects of different concentrations of three novel aziridines, 2-hydroxy-methyl-1-(N-phtaloylglycyl) aziridine (aziridine 1), 2-hydroxy-methyl-1-(N-phtaloylalanyl) aziridine (aziridine 2) and 2-hydroxy-methyl-1-(N-phtaloylphenylalanyl) aziridine (aziridine 3), on the proliferative responses of human lymphocytes stimulated by mitogens (concanavalin A (Con A) and lipopolysaccharide (LPS)), and interleukin-2 (IL-2), interleukin-6 (IL-6) secretion. The results showed that aziridines 1 and 3 significantly stimulated the resting and Con A or LPS lymphocyte proliferation at concentrations between 1 micromol/l and 1 mmol/l, in a dose-dependent manner, the action of aziridine 3 being the highest. They also increased IL-2 and IL-6 secretion. However, aziridine 2 had no effect on the resting lymphocyte proliferation in the absence of mitogens, at any concentration used, reduced Con A-stimulated T lymphocyte proliferation and LPS- stimulated B lymphocyte proliferation in a dose dependent manner and diminished IL-2 and IL-6 production. None of the three aziridines affected cell viability. In conclusion, the three aziridines used in this study displayed immunomodulatory properties. Aziridines 1 and 3 are potentially immunostimulant while aziridine 2 is immunosuppressive and could be used to provide nonspecific cell-mediated immune responses.


High water content hydrogel with super high refractive index.
Transparent, high water content (>65%), and cytocompatible hydrogels, which also possess super high refractive indices (RI > 1.5), are needed for ophthalmological applications. Most hydrogels can achieve either high RI or high water content but not both in the same system because water is a low RI material. Here, high water content/high RI hydrogels fabricated through elevated-temperature UV polymerization of an aqueous solution of acrylamide (AM) and methacrylamide (MAM) with tri(ethylene glycol) dimethacrylate (TEDA) crosslinker are reported. By varying the AM:MAM ratios (2:8 to 8:2) and crosslinker density (5 to 11 mol %), it is discovered that high water content (66%) AM:MAM copolymer hydrogels exhibiting anomalously high refractive indices (1.53); they are also colorless, transparent (99.4%), and cytocompatible with human keratinocytes.


[Giant cutaneous benign fibrous histiocytoma of the breast: successful surgical approach in a young female patient].
Morphologically, the benign fibrous histiocytoma is a proliferation of the dermal areas and fibroblasts where the last may have a heterogenic localization in the human body. A number of malignant and benign skin lesions may be interpreted as a possible differential diagnosis. We are presenting a female patient with a tumor formation located under the right breast which, after the performance of an elliptical excision, was verified to be a benign fibrous histiocytoma with a tendency toward xantomatization.


[Risk factors and prognosis of node-positive cervical carcinoma].
Pelvic lymph node metastasis is an important prognostic factor of cervical carcinoma, but few have been reported on both risk factors and prognostic factors of node-positive cervical carcinoma. This study was to evaluate risk factors, distribution pattern, and prognosis of node-positive cervical carcinoma, and explore the forecast of lymph node metastasis and appropriate treatment. Clinical data of 205 cervical cancer patients who had undergone radical hysterectomy and bilateral pelvic lymphadenectomy were analyzed retrospectively. The overall prevalence of lymph node metastasis was 24.4% (50/205). Univariate analysis showed that risk factors of node metastasis were serum level of squamous cell carcinoma antigen (SCC-Ag) before treatment, clinical stage, invasive depth of cervical canal or vaginal portion of the cervix, and uterine ligaments involvement. SCC values exceeding 4 microg/L increased the risk of nodal metastasis by 4.2 folds (P<0.001, OR=4.212). Multivariate analysis showed that clinical stage and invasive depth of cervical canal were the major risk factors. The obturator and obturator fossae lymph nodes were the most frequently involved, with a rate of 48.0%. Moreover, 60.0% node-positive patients had multiple sites lymph node metastases, and saltatory metastasis was found. Lymph node metastasis was closely related to deep muscularis involvement of the cervix and parametrial involvement; 72.0% nodal metastases were accompanied with deep muscularis involvement of the cervix, 90.9% uterine ligament invasions were accompanied with lymph node metastasis. The 5-year survival rate was significantly higher in the patients received postoperative radiation than in the patients didn't receive radiation (89.1% vs. 45.5%, P=0.012). Serum level of SCC-Ag before treatment exceeding 4 microg/L, deep muscularis involvement of vaginal portion of the cervix, uterine ligaments involvement, especially advanced stage and deep muscularis involvement of the cervical canal, are risk factors of pelvic lymph node metastasis of cervical cancer. The standard type III radical hysterectomy and bilateral pelvic lymphadenectomy should be performed to the patients with high risk of lymph node metastasis to ensure enough amplitude of parametrectomy and excision of positive nodes. When lymph node metastasis is confirmed after surgery, postoperative radiation can improve the prognosis.


Cu2+-controlled hybridization of peptide nucleic acids.
We have prepared cyclic peptide nucleic acids (PNAs). These compounds do not bind complementary nucleic acids. One carboxylic ester group was introduced in the backbone of the cyclic PNAs. This group is cleaved in the presence of Cu(2+) or coordinatively unsaturated Cu(2+) complexes. The cleavage products are linear PNAs. In contrast to the cyclic PNAs, they are efficient nucleic acid binders. The rate of formation of the linear PNAs is proportional to the concentration of the cleaving agents. Therefore, one may apply highly sensitive methods of detection of linear PNAs for determination of Cu(2+) concentration. In particular, we have demonstrated that both fluorescent spectroscopy in combination with molecular beacons and MALDI-TOF mass spectrometry are suitable for the detection of Cu(2+). A range of related divalent metal ions and Eu(3+), Ln(3+), Pr(3+), Ce(3+), and Zr(4+) do not interfere with Cu(2+) detection.


Environmental Tobacco Exposure and Urinary Cotinine Levels in Smoking and Nonsmoking Adolescents.
We aimed to evaluate the association between environmental tobacco smoke (ETS) exposure and urinary cotinine levels in current adolescent smokers and nonsmokers. The secondary objective was to explore the association between ETS exposure and nicotine dependence in adolescent smokers. Using the results from a validation study for the 2012 Global Youth Tobacco Survey in Mexico, we quantified urinary cotinine levels in adolescent smokers and nonsmokers. We fitted a multivariate regression model to assess the association between household exposure to ETS and cotinine levels in adolescent smokers and nonsmokers. In addition, using the questionnaire's answers for morning cravings, we fitted a multivariate Poisson regression model to explore the association between household ETS exposure and nicotine dependence in adolescent smokers. For each day of household ETS exposure, cotinine levels increase by 5% in adolescent smokers compared to a 2% increase in nonsmokers, adjusting for the number of cigarettes smoked per week, age and sex (exp(β) 1.05; 95% confidence interval [CI] [1.00, 1.10]; p = .041). Morning cravings increase 11% for each day of household ETS exposure adjusting for the number of cigarettes smoked per week, age and sex (prevalence ratio [PR] 1.11; 95% CI [0.99, 1.25]; p = .064). There is an association between ETS exposure and cotinine levels, and ETS may contribute to nicotine dependence in adolescent smokers. If confirmed, avoiding ETS exposure could prove helpful for addiction control and quitting in adolescents. Evidence suggests that ETS increases cotinine levels in nonsmokers and adult smokers. However, no study has explored the association between ETS exposure and cotinine levels and addiction in adolescent smokers. This paper provides evidence of an association between ETS exposure and cotinine levels in adolescent smokers: each day of environmental tobacco smoke exposure at home increased cotinine levels by 5% among smokers. In addition, morning cravings in adolescent smokers increased 11% for every day of ETS exposure. ETS exposure is a significant source of nicotine for adolescent smokers and could play an important role in addiction.


IoT-Based Reinforcement Learning Using Probabilistic Model for Determining Extensive Exploration through Computational Intelligence for Next-Generation Techniques.
Computing intelligence is built on several learning and optimization techniques. Incorporating cutting-edge learning techniques to balance the interaction between exploitation and exploration is therefore an inspiring field, especially when it is combined with IoT. The reinforcement learning techniques created in recent years have largely focused on incorporating deep learning technology to improve the generalization skills of the algorithm while ignoring the issue of detecting and taking full advantage of the dilemma. To increase the effectiveness of exploration, a deep reinforcement algorithm based on computational intelligence is proposed in this study, using intelligent sensors and the Bayesian approach. In addition, the technique for computing the posterior distribution of parameters in Bayesian linear regression is expanded to nonlinear models such as artificial neural networks. The Bayesian Bootstrap Deep Q-Network (BBDQN) algorithm is created by combining the bootstrapped DQN with the recommended computing technique. Finally, tests in two scenarios demonstrate that, when faced with severe exploration problems, BBDQN outperforms DQN and bootstrapped DQN in terms of exploration efficiency.


Reversible pacemaker dysfunction in a patient with transient cardiac apical ballooning syndrome: a case report.
Transient cardiac apical ballooning syndrome (TCABS) is diagnosed by transthoracic echocardiography demonstrating apical akinesis with left ventricular (LV) apical ballooning and preserved mid-to-basal LV systolic function, and left heart catheterization showing the absence of significant obstructive epicardial coronary artery disease. Presenting symptoms are suggestive of an acute coronary syndrome and electrocardiogram findings mimic acute myocardial injury. Right ventricular involvement has been reported. We describe a case of acute pacemaker dysfunction caused by the TCABS, which responded to conservative therapy.


Review of genus Conocephalus Thunberg, 1815 (Orthoptera: Tettigoniidae: Conocephalinae) with one new species from India.
The present paper includes description of one new species Conocephalus (Anisoptera) rentzi sp. nov. and some known species of genus Conocephalus Thunberg, 1815 from India. Brief diagnosis of genus and subgenus with a key to species of subgenus Anisoptera and morphometric ranges of all the species are provided. The distributional map and illustrations of all the described and reported species with SEM photography of stridulatory files of C. (Anisoptera) maculatus C. (Anisoptera) rentzi sp. nov. have also been included. All type specimens have been deposited for posterity in the Zoology Department, Aligarh Muslim University, India (ZDAMU).


Histopathological aspects of transitional cell carcinoma of the bladder: analysis of 20 years experience.
In this study we used histopathological examinations performed over a 20-year period to describe the characteristics of newly diagnosed transitional cell carcinoma (TCC) of the bladder in relation to patient age, and to verify changes in the TCC over different periods of observation or in relation to patient age. We reviewed all histopathological examinations performed from January 1979 to December 1998 in patients undergoing surgery who were newly diagnosed with TCC of the bladder. All examinations were performed by the same pathologist and reviewed by two pathologists. In each case analyzed, we evaluated T classification of the tumor, histological grade, size, localization, growth type, multiplicity and carcinoma in situ (CIS). The study population included 3113 men and 620 women. The mean patient age was 66.31 +/- 10.84 years. A high percentage of Ta (52.2%) and T1 (27.7%) tumors were found. The number of cases observed and, in particular, the percentage of Ta tumors increased significantly and progressively from the first (1979-1983 = 376 cases; Ta = 37.8%) to the last (1994-1998 = 1732 cases; Ta = 56.3%) period of observation (P < 0.001). A significant difference in the distribution of histological grade and T classification in the different age decades was apparent (P < 0.001); in particular, for G1 and Ta tumors there was a trend to decrease, whereas for G3, T1 and T2 tumors there was a tendency to increase with age decades. In our analysis, age of patient and the period of examination significantly influenced different pathological characteristics of newly diagnosed TCC of the bladder.


Hybrid marriages and phenotypic heterosis in offspring: Evidence from China.
In genetics, heterosis refers to the phenomenon that cross-breeding within species leads to offspring that are genetically fitter than their parents and exhibit improved phenotypic characteristics. Based on the theory of heterosis and existing genetic evidence, offspring of "hybrid" marriages (spouses originating from different states/provinces/countries/areas), though relatively rare due to physical boundaries, may exhibit greater genetic fitness in terms of intelligence, height, or physical attractiveness (the "distance-performance" hypothesis). This study explores whether heterosis is a contributing factor to offspring's educational attainment in China by applying a high-dimensional fixed effects (HDFE) modelling framework to the unique 0.1% micro-sample of the 2000 Chinese Population Census data. Concerning potential endogeneity of hybrid marriages, we conduct a series of robustness checks. Reassuringly, the estimated heterosis effect remains significantly positive across various measurements, after controlling for parental educational attainments/height, environmental influences, and over a thousand region and region-by-year fixed effects. The effects in male and higher-educated offspring are found to be stronger. Results are replicated when analyzing body height using data from the China Health and Nutrition Survey. Although endogeneity of "hybrid marriages" may not be completely ruled out, the current study sheds light on the potentially beneficial effects of interprovincial migration on population-level human capital accumulation, and we hope that this paper can intrigue future studies that further address endogeneity. The implied heterosis effect could, therefore, be profound for Homo sapiens as a species from an evolutionary point of view. An additional important implication is that the overall genetic influences of parents on offspring's performance may be further decomposed into a conventional heredity effect and a heterosis effect that has been neglected previously.


Epidemiology and clinical features of post-transplant bloodstream infection: an analysis of 222 consecutive liver transplant recipients.
Bloodstream infection (BSI) is a significant cause of morbidity and mortality in liver transplant (LT) recipients. This study aimed to investigate the epidemiology and clinical features of post-transplant BSI in LT recipients. The microbiology, frequency, and outcome of post-transplant BSI in the first year after LT were retrospectively analyzed in 222 consecutive patients who had received liver transplants at a single center between 2005 and 2011. The risk factors for post-transplant BSI and death were evaluated. During a 1-year period after LT, 112 episodes of BSI occurred in 64 of the 222 patients (28.8%). A total of 135 microorganisms were isolated from 112 BSI episodes including 18 polymicrobial episodes. The median time to BSI onset ranged from 8 days for Klebsiella pneumoniae to 101 days for enterococci, and the overall median for all microorganisms was 28 days. The most frequent pathogens were Enterobacteriaceae members (32.5%), enterococci (17.8%), yeasts (14.0%), Staphylococcus aureus (10.3%), and Acinetobacter baumannii (10.3%); most of them showed resistance to major antibiotics. The major sources of BSI were biliary tract (36.2%), abdominal and/or wound (28.1%), and intravascular catheter (18.5%) infections. The independent risk factors for post-transplant BSI were biliary complications (odds ratio [OR]: 2.91, 95% confidence interval [CI]: 1.29 to 6.59, P = 0.010) and longer hospitalization in the intensive care unit (OR: 1.04, 95% CI: 1.00 to 1.08, P < 0.001) after LT. BSI was an independent risk factor for death (hazard ratio [HR]: 3.92, 95% CI: 2.22 to 6.91, P < 0.001), with a poorer survival rate observed in patients with BSI than in those without BSI (1-year survival rate: 60.0% versus 89.5%, respectively, P < 0.001) after LT. The strongest predictors for death in patients with BSI were hepatocellular carcinoma (HR: 3.82, 95% CI: 1.57 to 9.32, P = 0.003), candidemia (HR: 3.71, 95% CI: 1.58 to 8.71, P = 0.003), polymicrobial bacteremia (HR: 3.18, 95% CI: 1.39 to 7.28, P = 0.006), and post-transplant hemodialysis (HR: 2.44, 95% CI: 1.02 to 5.84, P = 0.044). BSI was a frequent post-transplant complication, and most of the causative pathogens were multi-drug resistant. Biliary complications and BSIs resulting from biliary infection are major problems for LT recipients. The prevention of BSI and biliary complications is critical in improving prognosis in liver transplant recipients.


Diastolic dysfunction in persons with hypertensive heart failure.
Arterial hypertension is the commonest cause of heart failure in the Savannah region of Nigeria. The prevalence of diastolic dysfunction in patients with hypertensive heart failure in this region is unknown. This needs to be determined, since it may influence therapy. Left ventricular function of 95 patients with hypertensive heart failure and 92 age-/sex-matched, healthy normotensive control was determined by echocardiography using ALOKA SSD 1700 two-dimensional echocardiograph/ Doppler and color flow ultrasound machine. Compared to the controls, the hypertensive heart failure patients had increased left ventricular mass index (LVMI), p = 0.0001; cardiothoracic ratio (CTR), p = 0.0001; and electrocardiographic left ventricular hypertrophy (ECG-LVH), p = 0.0001. Isolated diastolic dysfunction, E/A ratio < 1.0, and EF > 50%, was seen in 12 patients (12.6%). Twenty-three patients (24.2%) had combined diastolic and systolic dysfunction (E/A ratio < 1.0 and EF < 50%). Six patients (6.3%) had pseudonormalization (E/A ratio 1.0-2.0 and deceleration time, DT, 150-200 msec), while restrictive pattern of diastolic dysfunction was seen in 25 patients (26.3%). This prevalence of 69.4% of diastolic dysfunction in Nigerians with hypertensive heart failure seen in this study emphasizes the need for Doppler echocardiographic evaluation and diagnosis where these facilities are available. This will aid the physician to prescribe appropriate treatment.


Rate of CD4 decline and neuropsychological performance in HIV infection.
This study examined the relationship between performance on a battery of neuropsychologic tasks and rate of CD4 lymphocyte decline in 47 gay or bisexual men infected with the human immunodeficiency virus type 1. Subjects were volunteers for a longitudinal study of the human immunodeficiency virus infection and were not selected because of neuropsychiatric symptoms. Subjects were at all stages of illness, although most were asymptomatic. Faster rates of decline in percent CD4 lymphocyte were related to poorer performance on measures of memory and reaction time. This relationship was independent of stage of illness and CD4 level at the time of neuropsychologic examination, and was not due to medication effects. The rate of percent CD4 lymphocyte cell loss is associated with and may represent a risk factor for the development of the human immunodeficiency virus-related neurobehavioral deficit.


Translocation t(1;10) (q21;q26) in a case of acute nonlymphocytic leukemia.
Chromosome banding studies carried out on bone marrow cells from a 16 year-old boy with an M1 acute nonlymphocytic leukemia (ANLL) revealed an unbalanced translocation involving chromosomes 1 and 10: der(10) t(1;10) (q21;q26) that results in a partial trisomy 1q between bands 1q21-1qter. Marker del(6)(q21) and trisomies of chromosomes 18, 21 and 22 were also observed. To our knowledge, this der(10) is the first to be reported in a patient with ANLL.


SARS-CoV-2 Vaccines: Where Are We Now?
The best and safest way to control the coronavirus disease 2019 (COVID-19) pandemic is by using vaccination to generate widespread immunity. The urgent need to develop safe and effective COVID-19 vaccines was met with unprecedented speed and action from the global community. There are now 289 vaccines in the development pipeline. More remarkably, there are 20 publicly available vaccines, and more than 3.3 billion doses of COVID-19 vaccines have been administered across 180 countries. This is just the beginning of our fight against the pandemic. Even at the current vaccination rate, it could take years to vaccinate the world's population; many high-income countries are focusing on their needs, whereas the poorer nations are waiting for vaccines. There is still much that we do not understand about immunity to this new disease, and we will have to contend with the emerging variants. In this commentary, we describe the current status of COVID-19 vaccine development and provide insights into how the development and approvals happened so quickly. We discuss the clinical trial data that led to rapid emergency use authorization and the many challenges of global rollout. We also comment on some of the key unanswered questions and future directions for COVID-19 vaccine development and deployment.


Reversible bilateral simultaneous papillitis with no light perception.
This 14-year-old patient with bilateral simultaneous papillitis experienced no light perception in either eye for 24 hours and had a complete recovery of central and peripheral vision 3 weeks later. Fluorescein angiography confirmed the diagnosis. Although her hospital work-up was negative except for a mildly elevated CSF protein, it seems most likely that this was a postviral syndrome based on the bilaterality, rapid recovery of vision, and the age group.


Food safety and amino acid balance in processed cassava "Cossettes".
Processed cassava (Manihot esculenta Crantz) roots provide more than 60% of the daily energy intake for the population of the Democratic Republic of Congo. Insufficiently processed cassava roots in a diet deficient in sulfur amino acid have been reported to cause the irreversible paralytic disease konzo, afflicting thousands of women and children in the remote rural areas of Bandundu Province. "Cossettes" (processed cassava roots) purchased in several markets of Kinshasa were analyzed for their content of cyanogens, free amino acids, and total protein amino acids. Residual cyanogen levels were below the safe limit recommended by the codex FAO/WHO for cassava flour (10 mg kg(-1)). The amino acid score was evaluated. Lysine and leucine were the limiting amino acids. Methionine content was very low and contributed about 13% of the total sulfur amino acids. Dietary requirements for sulfur amino acids need to be adjusted for the loss caused by cyanogen detoxification.