Impact of platelet reactivity to adenosine diphosphate before implantation of drug-eluting stents on subsequent adverse cardiac events in patients with stable angina.
Diverse pharmacological effects of anti-platelet thienopyridines due to individual differences in metabolism have been reported. However, an association between on-treatment platelet reactivity and adverse ischemic events after drug-eluting stent (DES) implantation in Japanese patients has not been fully elucidated. A total of 450 consecutive patients on dual anti-platelet therapy (aspirin and ticlopidine) with stable angina who underwent DES implantation were enrolled. Adenosine diphosphate (ADP)-induced platelet aggregation was measured before DES implantation using the screen filtration pressure method. The ADP concentration necessary for 50% aggregation was designated as the platelet aggregation threshold index (PATI). A composite primary endpoint of cardiac death, myocardial infarction, target lesion revascularization (TLR), and stent thrombosis occurring within 1 year after stenting, was evaluated. A PATI value <4.8 µmol/L was defined as high on-treatment reactivity to ADP. The composite primary endpoint occurred in 55 patients (12.2%) in the 1-year-period after DES implantation, and the prevalence was 19.0% and 5.1% in groups with high and low on-treatment reactivity to ADP, respectively, showing a significantly higher prevalence in the high reactivity group (P<0.001). The main event was TLR (18.1% vs. 5.1%, P<0.001). These data suggested that high on-treatment platelet reactivity to ADP and subsequent occurrence of adverse ischemic events (particularly TLR) were correlated in patients with stable angina who underwent DES implantation.


Temporal relationship between A1 adenosine receptor upregulation and alterations in bicuculline seizure susceptibility in rats.
The temporal requirements for theophylline-induced upregulation of A1 adenosine receptors and elevation of seizure threshold were examined. Chronic theophylline exposure (75 mg/kg twice daily) elicited a significant upregulation of [3H]cyclohexyladenosine ([3H]CHA) binding sites following 7 and 14 days of treatment. Alterations in seizure threshold followed a similar temporal pattern of development. The reversibility of theophylline-induced upregulation of high affinity [3H]CHA binding sites was complete at 10 days following cessation of theophylline administration, while the alteration of seizure threshold required 21 days to return to control values.


Modulation of c-myc and c-fos gene expression in regenerating rat liver by 2-mercaptopropionylglycine.
Expression of the two proto-oncogenes, c- myc and c- fos, in proliferating liver, and the modulation of their expression by 2-mercaptopropionylglycine (MPG) has been investigated. A significant increase in the expression of both c-myc and c-fos was observed, attaining a peak at 30 min, followed by a gradual decline for 8h after partial hepatectomy. Treatment of partially hepatectomized animals with MPG resulted in a significant decrease in the expression of both genes, the decrease being more marked in c- myc mRNA levels. At later time points, there was a very small rise in the mRNA levels of these genes in MPG-treated animals but they still remained much lower than the peak levels observed in both genes 30 min after surgery. A decline in the recovery of liver weight in MPG-treated animals was also observed.


Characteristics and outcomes of patients admitted to Spanish ICU: A prospective observational study from the ENVIN-HELICS registry (2006-2011).
To describe the case-mix of patients admitted to intensive care units (ICUs) in Spain during the period 2006-2011 and to assess changes in ICU mortality according to severity level. Secondary analysis of data obtained from the ENVN-HELICS registry. Observational prospective study. Spanish ICU. Patients admitted for over 24h. None. Data for each of the participating hospitals and ICUs were recorded, as well as data that allowed to knowing the case-mix and the individual outcome of each patient. The study period was divided into two intervals, from 2006 to 2008 (period 1) and from 2009 to 2011 (period 2). Multilevel and multivariate models were used for the analysis of mortality and were performed in each stratum of severity level. The study population included 142,859 patients admitted to 188 adult ICUs. There was an increase in the mean age of the patients and in the percentage of patients >79 years (11.2% vs. 12.7%, P<0.001). Also, the mean APACHE II score increased from 14.35±8.29 to 14.72±8.43 (P<0.001). The crude overall intra-UCI mortality remained unchanged (11.4%) but adjusted mortality rate in patients with APACHE II score between 11 and 25 decreased modestly in recent years (12.3% vs. 11.6%, odds ratio=0.931, 95% CI 0.883-0.982; P=0.008). This study provides observational longitudinal data on case-mix of patients admitted to Spanish ICUs. A slight reduction in ICU mortality rate was observed among patients with intermediate severity level.


The role of surface ECG and transthoracic echocardiography for predicting postoperative atrial fibrillation after coronary artery bypass surgery.
To evaluate the roles of surface electrocardiogram (ECG) and transthoracic echocardiography (ECHO) for prediction of atrial fibrillation (AF) after coronary artery bypass grafting (CABG). This study was conducted from 2002-2004 at the Cardiovascular Department of Hacettepe University, Ankara, Turkey. Seventy consecutive patients were enrolled in this study that underwent elective CABG. A 12-lead ECG was recorded one day before cardiac surgery and was repeated during the 5 days after CABG. P-wave dispersion (PWD) was defined as the difference between maximum and minimum P-wave duration. Differences in P-wave duration were compared between the pre- and postoperative 12-lead ECG measurements. Postoperative AF developed in 17 (24%) cases of 70 patients. The PWD was found to be significantly higher in patients with AF preoperatively (60+/-19 versus 47+/-13, p=0.003), postoperative first day (56+/-12 versus 44+/-11, p<0.002) and fifth day (51+/-29 versus 41+/-11, p<0.001). Patients with AF were significantly older, the mean age of the AF group was (68+/-7) years and of the sinus rhythm (SR) group was (59+/-10 years) (p<0.001). The AF group had left ventricular systolic dysfunction (56+/-13% versus 56+/-8%, p=0.042, preoperatively; 49+/-8% versus 60+/-10%, p=0.001, postoperatively) and a larger left atrium (46+/-5 versus 39+/-5 mm, p<0.001, preoperatively and 44+/-7 versus 39+/-5 mm, p=0.046, postoperatively) than the SR group. This prospective study demonstrated that PWD on surface ECG and additional echocardiographic parameters are simple and reliable indexes to predict the development of AF after CABG.


Currarino syndrome as an etiology of a neonatal Escherichia coli meningitis.
We report the case of a 29-day-old baby girl in whom Escherichia coli meningitis led to the diagnosis of Currarino syndrome (CS) (OMIM 176450), an autosomal-dominant genetic disorder associated with sacral agenesis, anorectal malformation, presacral masses and spinal cord malformations. Her condition improved with antibiotics and early surgical treatment. A familial study identified other genetically related individuals with similar symptoms.


Vegetarian Diet Was Associated With a Lower Risk of Chronic Kidney Disease in Diabetic Patients.
Diabetes mellitus (DM) is a pathological hyperglycemic state related to the dysregulation of insulin. Chronic kidney disease (CKD) is a common chronic complication in diabetic patients. A vegetarian diet could be one of the preventive strategies for the occurrence of CKD in patients with diabetes mellitus. However, it is still unknown whether a vegetarian diet lowers the occurrence of CKD in DM patients. This retrospective study was conducted at Taipei Tzu Chi Hospital from 5 September 2005 to 31 December 2016. Subjects with an HbA1c level > 6.5% or previous history of diabetes mellitus elder than 40 years were grouped based on self-reported dietary habits (vegetarians, lacto-ovo vegetarians and omnivores) in the structured questionnaire. Structural equation modeling (SEM) was applied to estimate the direct and indirect effects of variables on the occurrence of chronic kidney disease. Among these 2,797 subjects, the participants were grouped into dietary habits as vegans (n = 207), lacto-ovo vegetarians (n = 941) and omnivores (n = 1,649). The incidence of overall CKD was higher in the omnivore group [36.6% vs 30.4% (vegans) and 28.5% (lacto-ovo vegetarian), p < 0.001]. In the SEM model, after adjusting for age and sex, the lacto-ovo vegetarian [OR: 0.68, 95% confidence interval (CI): 0.57-0.82] and vegan groups (OR 0.68, 95% CI: 0.49-0.94) were both associated with a lower risk of CKD occurrence than the omnivore group. The vegan diet and lacto-ovo diet lowered the risk related to a high BMI (OR: 0.45, p < 0.001, OR: 0.58, p < 0.001) and hyperuricemia (OR: 0.53, p < 0.001; OR: 0.55, p < 0.001) for the occurrence of CKD. Vegetarian dietary habits were associated with a lower occurrence of CKD in DM patients.


The pathology of tumours at the limbus.
The histopathology of tumours originating at the corneoscleral limbus is reviewed with special reference to some 636 specimens examined over a 40 year period at the Institute of Ophthalmology, London. Over half the lesions involved melanocytes (351 cases) derived from the limbal conjunctiva and of these two-thirds were benign naevi. Conversely, benign squamous cell tumours were rare, only five unequivocal papillomas having been seen compared with 137 premalignant lesions and 73 carcinomas. Solid dermoids accounted for approximately 10 per cent of all tumours involving the limbus.


Hydrophobic forces as a key factor in crystalline biofilm formation on ureteral stents.
Current discussions about biofilm formation focus on the solid/liquid interface between a medical device and body fluids. Yet it has been shown that gas bubbles (GB) can stably form on ureteral stents in artificial urine and that their fate depends on the stent's surface properties. The liquid/gas interface constitutes an adhesion site for precipitating salts as well as hydrophobic organic molecules. The surface wettability of polyurethane stents is varied by coating with amorphous hydrogenated carbon (a-C:H). GB and crystalline biofilm formation on the stents are investigated in a novel encrustation device which avoids gravitation- or sample-position-related influences on the results. Bigger and more stable GB form on hydrophobic stents than on hydrophilic, coated stents. Appearance and amount of crystalline deposits differ significantly between the surfaces. With decreasing wettability the number of hollow crystalline spheres and the mass of precipitate increase. On hydrophobic surfaces, stable GB increase precipitation of salts and become incorporated in the growing encrustation layer in vitro. In contrast, GB quickly lift off from hydrophilic surfaces taking part of the precipitate with them. This self-cleaning mechanism slows down the encrustation process. A similar effect may explain the prolonged complication-free indwelling time of amorphous-carbon coated stents in vivo.


Platelet dysfunction in thrombosis patients treated with vitamin K antagonists and recurrent bleeding.
Recurrent bleeding can complicate the treatment of thrombosis patients with vitamin K antagonists (VKA), even at a well-regulated level of anticoagulation. In this proof-of-principle study, we investigated whether alterations in platelet function or von Willebrand factor (vWf) contribute to a bleeding phenotype in these patients. In this case-control study 33 well-regulated patients without bleeding events (controls) and 33 patients with recurrent bleeding (cases) were retrospectively included. Thrombin generation and vWf were determined in plasma. Platelet function was assessed by light transmission aggregometry and flow cytometry using a validated panel of agonists. Thrombin generation was similarly reduced in controls and cases, in comparison to normal plasma. Plasma vWf level was above the normal range in 85% of controls and 67% of the cases. vWf activity was similarly increased in all patients in comparison to healthy volunteers. Platelet aggregation was in the normal range for almost all patients irrespective of the type of agonist. However, in response to a low collagen dose, platelets from 21% of controls and 27% of cases showed diminished responses. Agonist-induced secretion of alpha- and dense-granules or integrin αIIbβ3 activation were affected in platelets from neither controls nor cases. Recurrent bleeding in well-controlled patients on VKA therapy is not explained by anti-hemostatic changes in platelet or vWf function.


China Act on the Energy Efficiency of Civil Buildings (2008): A decade review.
China has launched the energy efficiency project (EEP) for its civil building sector beginning in the mid-1980s; however, its implementation has not been effective. To better promote the EEP for the Chinese civil building sector, the Chinese government issued the China Act on the Energy Efficiency of Civil Buildings in 2008. This is the first paper to present a review of this act's implementation over the past decade. Based on China Database of Building Energy Consumption and Carbon Emissions and official documents, the achievements of this act are assessed by examining a variety of indicators. The success of the act can be attributed to the following factors: 1) a strong and sustained government commitment to top policies of building energy efficiency (BEE); 2) extensive efforts to apply the BEE standards to newly built civil buildings; 3) various incentive schemes involving energy efficiency retrofitting for existing civil buildings; 4) the increasing adoption of renewable energy to the civil building sector and of systems and platforms of energy efficiency supervision to commercial buildings; and 5) the rapid development of green buildings. Nevertheless, the revised act must address several challenges in the upcoming phase. These challenges mainly include the following: 1) the "double-control" strategy for the civil building sector; 2) the substantial development of the EEP in rural China; 3) the further development of green buildings for the low-carbon civil buildings; 4) the improvement of official statistical data systems on energy consumption and carbon emissions for civil buildings; and 5) building industrialization and informatization. It's expected that our efforts as constituting significant guidance for evaluating the EEP in the Chinese civil building sector, and the efforts will also be treated as an example for other developing countries to evaluate and revise their BEE acts.


Catastrophic healthcare expenditure and coping strategies among patients attending cancer treatment services in Addis Ababa, Ethiopia.
With the rapid increase in magnitude and mortality of cancer, which is costly disease to manage, several patients particularly in developing countries are facing a huge financial burden. The study aimed to examine the incidence of catastrophic health expenditure (CHE), identify associated factors and coping strategies among patients attending cancer treatment services in Addis Ababa, Ethiopia. A hospital-based cross-sectional survey of patients with cancer was conducted in public and private hospitals between January and March 2018. Data was collected using a structured questionnaire. All direct medical and nonmedical expenditures were measured and reported as expenditure (US$) per patient (1US$ equivalent to 23.41 Ethiopian Birr). The CHE was estimated using a threshold of 10% of annual household income. A total of 352 (response rate of 87.1%) participants were interviewed. Majority (73.3%) of the respondents were females; most (94%) from public hospitals and their mean (±SD) age was 48 ± 13.2 years. Vast majority (74.4%) of patients experienced CHE with mean overall expenditure of $2366 per patient (median: $1708). Medical expenditure shared the highest overall expenditure (83.6%) with mean medical and nonmedical costs of $1978 (median: $1394) and $388 (median: $222), respectively. Patients who took greater than six cycles of chemotherapy (AOR: 3.64; 95% CI: 1.11-11.92), and age (AOR: 1.03; 95% CI: 1.01-1.06) were significantly associated with CHE. Household saving (85.5%) followed by financial support received (43.0%) was the main coping strategy. A substantial number of patients with cancer were exposed to CHE with a considerable medical expenditure. Hence, in addition to the popularization of the already introduced health insurance scheme, other better prepayment or insurance mechanisms should also be considered to ensure financial risk protection and realize universal health coverage for patients with cancer.


Less-invasive chromosome screening of embryos and embryo assessment by genetic studies of DNA in embryo culture medium.
To perform a preliminary exploration of a new embryo rank in clinical practice by combining the embryo chromosome copy number and mitochondrial copy number analysis of DNA extracted from embryo culture medium and blastocoel fluid. Eighty-three ICSI embryos from day 2 or day 3 were cultured to day 5 or day 6. Thirty-two blastocysts of 3 cc or above were obtained. Culture medium and blastocoel fluid were collected at 24 h before blastocyst formation. The genomic DNA and mitochondrial DNA (mtDNA) from the culture medium combined with blastocoel fluid and the whole blastocyst were amplified and sequenced by MALBAC-NGS. We compared the chromosomal information generated by the new protocol from the culture medium and the information employed by the whole embryo method. A multivariable linear regression was performed to study the impact of the blastocyst morphological score, chromosomal abnormality, embryo mtDNA copy number, and female age on the culture medium mtDNA copy number. (1) The DNA from 31 blastocysts was successfully amplified, and the successful amplification rate was 96.9% (31/32). The success rate of the amplification of genomic DNA extracted from the culture medium was 87.5% (28/32). (2) There were 18 blastocysts in which the less invasive method and the whole embryo method revealed the same results. The consistency rate was 66.7% (18/27). (3) The culture medium mitochondrial DNA copy number (MCN) had a significantly positive correlation with the blastocyst mitochondrial DNA copy number (P = 0.001), female age (P = 0.012), and blastocyst score (P = 0.014), but there was no obvious correlation with blastocyst chromosome (P = 0.138). The preliminary exploration result of the less invasive approach for having an embryo rank was not satisfying, which still awaits further long-term evaluation.


Neonatal Reserpine Administration Produces Widespread Neuronal Losses and ⍺-Synuclein Inclusions in a Rat Model.
Historically, reserpine was widely used as an antihypertensive drug. However, severe motor and non-motor symptoms such as dyskinesia and depression led to the discontinuation of reserpine as a first-line treatment for hypertension. Reserpine functions by inhibiting vesicular monoamine transporter 2 (VMAT2), reducing sequestration of monoamines into synaptic vesicles. The consequent reduction in monoamines, most notably dopamine, serotonin and norepinephrine, in the central nervous system, causes well-defined symptoms such as catalepsy, hypoactivity and sedation in animals, and these motor and non-motor symptoms are well defined for reserpine treatment. However, no gross neuropathological changes in response to reserpine treatment have been reported previously in any animal model. In contrast, reducing VMAT2 expression in genetically modified VMAT2 LO mice leads to the production of ⍺-synuclein-positive aggregates and progressive nigrostriatal neuronal loss. These VMAT2 LO mice have reduced VMAT2 functionality during critical brain developmental stages and this could be the key to producing a reserpine model with matching histopathologies. The aim of this study was therefore to investigate the effect of neonatal reserpine administration on brain histology. We report here that a single dose of 5 mg kg-1 reserpine administered subcutaneously to neonatal rats on postnatal day 3 leads to widespread neuronal loss in various brain regions including the substantia nigra pars compacta, ventral tegmental area, striatum, hippocampus, locus coeruleus, amygdala and cerebral cortex, and the presence of ⍺-synuclein-positive inclusions in the substantia nigra pars compacta and the dorsal striatum within 30 days of administration.


The Fanconi anemia ortholog FANCM ensures ordered homologous recombination in both somatic and meiotic cells in Arabidopsis.
The human hereditary disease Fanconi anemia leads to severe symptoms, including developmental defects and breakdown of the hematopoietic system. It is caused by single mutations in the FANC genes, one of which encodes the DNA translocase FANCM (for Fanconi anemia complementation group M), which is required for the repair of DNA interstrand cross-links to ensure replication progression. We identified a homolog of FANCM in Arabidopsis thaliana that is not directly involved in the repair of DNA lesions but suppresses spontaneous somatic homologous recombination via a RecQ helicase (At-RECQ4A)-independent pathway. In addition, it is required for double-strand break-induced homologous recombination. The fertility of At-fancm mutant plants is compromised. Evidence suggests that during meiosis At-FANCM acts as antirecombinase to suppress ectopic recombination-dependent chromosome interactions, but this activity is antagonized by the ZMM pathway to enable the formation of interference-sensitive crossovers and chromosome synapsis. Surprisingly, mutation of At-FANCM overcomes the sterility phenotype of an At-MutS homolog4 mutant by apparently rescuing a proportion of crossover-designated recombination intermediates via a route that is likely At-MMS and UV sensitive81 dependent. However, this is insufficient to ensure the formation of an obligate crossover. Thus, At-FANCM is not only a safeguard for genome stability in somatic cells but is an important factor in the control of meiotic crossover formation.


Genomic imprinting at the mammalian Dlk1-Dio3 domain.
Genomic imprinting causes genes to be expressed or repressed depending on their parental origin. The majority of imprinted genes identified to date map in clusters and much of our knowledge of the mechanisms, function and evolution of imprinting have emerged from their analysis. The cluster of imprinted genes delineated by the delta-like homolog 1 gene and the type III iodothyronine deiodinase gene (Dlk1-Dio3) is located on distal mouse chromosome 12 and human chromosome 14. Its developmental importance is exemplified by severe phenotypes associated with altered dosage of these genes in mice and humans. The domain contains three imprinted protein-coding genes, Dlk1, Rtl1 and Dio3, expressed from the paternally inherited chromosome and several imprinted large and small noncoding RNA genes expressed from the maternally inherited homolog. Here, we discuss the function and regulation of imprinting at this domain.


An open study of antibiotics for the treatment of pre-pouch ileitis following restorative proctocolectomy with ileal pouch-anal anastomosis.
Pre-pouch ileitis is a recently described condition which may occur following restorative proctocolectomy. Its aetiology remains unknown and only one study has reported the effect of treatment. We report a series of fourteen patients treated and followed up with repeat pouchoscopy. To study the effectiveness of antibiotics for the treatment of pre-pouch ileitis following restorative proctocolectomy with ileal pouch-anal anastomosis. Fourteen consecutive patients with symptomatic pre-pouch ileitis were treated with ciprofloxacin 500 mg b.d. and metronidazole 400 mg b.d. for 28 days. All had concurrent pouchitis. Symptomatic, endoscopic and histological assessment was performed before and following treatment using the pouchitis disease activity index (PDAI). Symptomatic remission was defined as a score of 0 in the clinical component of the PDAI. Twelve (86%) patients experienced symptomatic remission. Stool frequency fell from a median of 12 (range 8-20) to 6 (4-17) (P = 0.002). There was a significant reduction in the anatomical length of pre-pouch ileitis with nine (64%) patients having either a resolution or a reduction in length of pre-pouch ileitis from a median of 10 cm (range 3-20 cm) to a median of 1 cm (range 0-10 cm) (P = 0.007). Combination antibiotic therapy in this uncontrolled study appears effective in reducing the length of pre-pouch ileitis and in inducing symptomatic remission in most patients whether or not its extent is reduced.


SKL2001 suppresses colon cancer spheroid growth through regulation of the E-cadherin/β-Catenin complex.
Aberrant activation of Wnt signaling plays a pivotal role in the development of human cancers including colon cancer. Small compounds that regulate Wnt signaling are attractive candidate for the colon cancer therapy. Here, we showed that SKL2001, which has been identified as an activator for Wnt signaling by disrupting the Axin/β-Catenin complex, negatively regulates growth of colon cancer spheroids cultured in the 3D condition that simulates tumor microenvironment in vivo. SKL2001 inhibited proliferation of colon cancer cells cultured in 3D spheroid and induced them accumulation in the G0/G1 phase of the cell cycle with a reduced c-myc level. To examine the potential of arrested cells to recover, colon cancer spheroids that were treated with SKL2001 were then cultured in the SKL2001-free medium. We found that SKL2001-treated cells were resumed cell cycle progression and proliferated in the SKL2001-free medium. Notably, SKL2001 facilitated round-shape spheroid formation. This was associated with upregulated expressions of E-cadherin and β-Catenin. These findings suggest that SKL2001 can suppress colon cancer spheroid growth through regulating cell cycle progression and cadherin/catenin mediated cell-cell contact.


Comparison of two procedures for determination of cholinesterase in livestock.
Our data indicate that the serum or plasma Bio-Dynamics/bmc automated procedure may be substituted satisfactorily for, or used as an alternative method to the Radeleff procedure for determining cholinesterase activity in cattle, swine, and sheep. The automated procedure is capable of 77 determinations/hr, and the Radeleff procedures about 20/hr. Either serum or plasma may be used, but the sample must be hemolyzed.


Drug and alcohol intoxication in major trauma: Associations, trends and outcomes over a decade.
Drug and alcohol intoxication is common among injured patients altering trauma presentation and characteristics. However, uncertainty exists regarding the effect of intoxication on injury severity, as well as outcomes. The present study aims to provide an update on substance-use patterns and their association with traumatic presentation and outcome within a contemporary Australian context. All major trauma patients captured in our centre's Trauma Registry between July 2010 and June 2020 were included. Demographic, injury characteristic, outcome and substance-use data were collected. Differences in injury severity and characteristics were explored using χ2 tests, while outcomes were modelled using adjusted binomial logistic regression. Among 9700 patients, 9% were drug-intoxicated prior to injury, while 9.4% were alcohol-intoxicated. Drug use almost tripled between 2010 (4.8%) and 2020 (13.3%), while alcohol intoxication fell, from 11.7% to 7.3%, over the same period. Although there were significant differences in trauma mechanism among intoxicated patients, group comparison found no difference in Injury Severity Score for any group. Regarding outcomes, all intoxication resulted in significantly greater odds (odds ratio 1.62-2.41) of ICU admission. No difference in mortality was found among individual substance-use groups; however, polysubstance-intoxicated patients had 3.52 times greater odds of dying (95% confidence interval 1.21-10.23) compared to non-intoxicated patients. Within this contemporary Australian population, we demonstrate escalating rates of drug intoxication and declining rates of alcohol intoxication prior to trauma. Intoxication was associated with more frequent violent and non-accidental injury, and despite no difference in severity, it was associated with worse outcomes.


Intracellular lumen extension requires ERM-1-dependent apical membrane expansion and AQP-8-mediated flux.
Many unicellular tubes such as capillaries form lumens intracellularly, a process that is not well understood. Here we show that the cortical membrane organizer ERM-1 is required to expand the intracellular apical/lumenal membrane and its actin undercoat during single-cell Caenorhabditis elegans excretory canal morphogenesis. We characterize AQP-8, identified in an ERM-1-overexpression (ERM-1[++]) suppressor screen, as a canalicular aquaporin that interacts with ERM-1 in lumen extension in a mercury-sensitive manner, implicating water-channel activity. AQP-8 is transiently recruited to the lumen by ERM-1, co-localizing in peri-lumenal cuffs interspaced along expanding canals. An ERM-1[++]-mediated increase in the number of lumen-associated canaliculi is reversed by AQP-8 depletion. We propose that the ERM-1/AQP-8 interaction propels lumen extension by translumenal flux, suggesting a direct morphogenetic effect of water-channel-regulated fluid pressure.


Management of treatment with direct-acting antiviral (DAA) in clinical practice.
The triple therapy has brought about a genuine revolution in the care of patients with chronic hepatitis C virus infection, although achieving a high cure rate requires adding disciplines beyond the attending physician when confronted by a motivated patient. The treatment is complex because of the many parameters involved (such as fibrosis score, patient's history of previous antiviral treatment and viral kinetics during treatment). A working knowledge of drug interactions and contraindications for drugs other than antiviral therapy is required, as well as meticulous follow-up.


Infection of the HTLV-I-harbouring T-lymphoblastoid line MT-2 by Epstein-Barr virus.
Epstein-Barr virus (EBV), a ubiquitous human B-lymphotropic virus, is associated with certain lymphoproliferative diseases of T-cell lineage. To understand the mechanism by which EBV infects T cells, we have tested the susceptibility of various human T-cell lines to the virus. We report here that the HTLV-I-harbouring T-lymphoblastoid line MT-2 carries a high level of CD21/EBV receptors on their surface, adsorbs fluorescein isothiocyanate-labeled EBV, and synthesizes virus latent antigens (EBNA-1 and LMP) following EBV infection. Pretreatment of MT-2 cells with anti-CD21 monoclonal antibody OKB7 inhibited the virus binding as well as the synthesis of virus latent antigen. These data suggest that human T-cells can be infected with EBV via functionally active virus receptors.


Lactoferrin binding to neutrophilic polymorphonuclear leucocytes.
Neutrophilic polymorphonuclear leukocytes (PMN) bind specifically lactoferrin. This binding was characterized by two types of binding sites: with higher affinity and low capacity and another site with lower affinity and higher capacity (respectively Kaff 1 = 2.2 X 10(9) M-1 and about 39,000 binding sites per cell and Kaff2 = 0.6 X 10(9) M-1 and 76,000 binding sites per cell). The lactoferrin binding to PMN leucocytes depends on the concentration of labelled lactoferrin, the number of cells and the time for incubation. The presence of lactoferrin receptors on the PMN leucocytes is connected most probably with its effect on the cell function of these cells.


Tribbles 2 pseudokinase confers enzalutamide resistance in prostate cancer by promoting lineage plasticity.
Enzalutamide, a second-generation antiandrogen, is commonly prescribed for the therapy of advanced prostate cancer, but enzalutamide-resistant, lethal, or incurable disease invariably develops. To understand the molecular mechanism(s) behind enzalutamide resistance, here, we comprehensively analyzed a range of prostate tumors and clinically relevant models by gene expression array, immunohistochemistry, and Western blot, which revealed that enzalutamide-resistant prostate cancer cells and tumors overexpress the pseudokinase, Tribbles 2 (TRIB2). Inhibition of TRIB2 decreases the viability of enzalutamide-resistant prostate cancer cells, suggesting a critical role of TRIB2 in these cells. Moreover, the overexpression of TRIB2 confers resistance in prostate cancer cells to clinically relevant doses of enzalutamide, and this resistance is lost upon inhibition of TRIB2. Interestingly, we found that TRIB2 downregulates the luminal markers androgen receptor and cytokeratin 8 in prostate cancer cells but upregulates the neuronal transcription factor BRN2 (Brain-2) and the stemness factor SOX2 (SRY-box 2) to induce neuroendocrine characteristics. Finally, we show that inhibition of either TRIB2 or its downstream targets, BRN2 or SOX2, resensitizes resistant prostate cancer cells to enzalutamide. Thus, TRIB2 emerges as a potential new regulator of transdifferentiation that confers enzalutamide resistance in prostate cancer cells via a mechanism involving increased cellular plasticity and lineage switching.


Cognitive impairment after neuroleptanalgesia in cataract surgery.
This study was undertaken to evaluate the mental recovery of patients following cataract operations under neuroleptanalgesia. Mental function was assessed by Mini-Mental State (MMS) preoperatively and at 6 and 24 hours postoperatively. Preoperatively, 18.7% of the elderly had cognitive impairment of mental function while none in the younger group had any impairment (P less than 0.02). At six hours postoperatively, 29.7% of the elderly had cognitive impairment compared with 4% of the younger group (P less than 0.01). At 24 hours postoperatively, the percentage of elderly and younger patients with cognitive impairment had returned to preoperative levels. Baseline score and age were found to be significant predictors (P less than 0.004) of the 6-hour score and 24-hour score. In conclusion, cognitive impairment of mental function occurred in patients undergoing cataract operation with retrobulbar block and intravenous sedation at 6 hours postoperatively; MMS has the potential for use as a screening preoperative test for outpatients to identify those at risk for developing cognitive impairment.


Absence of promotion potential for calcium L-ascorbate, L-ascorbic dipalmitate, L-ascorbic stearate and erythorbic acid on rat urinary bladder carcinogenesis.
The effects of treatment with calcium L-ascorbate, L-ascorbic dipalmitate, L-ascorbic stearate and erythorbic acid on two-stage urinary bladder carcinogenesis in F344 rats after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined. Carcinogen was administered at a dose of 0.05% in drinking water for 4 weeks and thereafter the test chemicals were given as a 5% supplement in the diet for the following 32 weeks. No increase in the induction of preneoplastic lesions, papillomas or carcinomas was apparent and it was concluded that none of the test chemicals possess promoting activity for urinary bladder carcinogenesis.


Gonadotrophin-releasing hormone-antagonist luteolysis during the preceding mid-luteal phase is a feasible protocol in ovarian hyperstimulation before in vitro fertilization.
The aims of this study were to investigate whether a high dose of gonadotrophin-releasing hormone antagonist during the preceding luteal phase yields satisfactory luteolysis and downregulation prior to ovarian hyperstimulation in an in vitro fertilization program. The treatment protocol was designed as a prospective pilot study in IVF units at two university hospitals. Fifty-one patients with documented poor or normal response to ovarian stimulation underwent 57 treatment cycles. Treatment consisted of 3 mg gonadotrophin-releasing hormone antagonist (cetrorelix) given during the preceding mid-luteal phase as gonadotrophin-releasing hormone-receptor inhibition before ovarian stimulation with follicle-stimulating hormone. All women experienced menstrual bleeding within 2-3 days after the injection of 3 mg cetrorelix. Follicle hormone stimulation could subsequently commence in all cycles. All but three patients developed growing follicles and underwent oocyte retrieval. Seventy-five percent of started cycles reached transfer of one or two good-quality embryos. A single high-dose gonadotrophin-releasing hormone antagonist given during the preceding luteal phase presents a new and feasible protocol to initiate controlled ovarian hyperstimulation in an in vitro fertilization program.


In vitro and in vivo targeting imaging of pancreatic cancer using a Fe3O4@SiO2 nanoprobe modified with anti-mesothelin antibody.
Pancreatic cancer is a highly malignant disease with a 5-year survival rate <5% mainly due to lack of early diagnosis and effective therapy. In an effort to improve the early diagnostic rate of pancreatic cancer, a nanoprobe Fe3O4@SiO2 modified with anti-mesothelin antibody (A-MFS) was prepared to target cells and tumor tissues highly expressing mesothelin in vitro (human pancreatic cancer cell line SW1990) and in vivo (subcutaneously transplanted tumors) studies. The A-MFS probe was successfully prepared and was spherical and uniform with a hydrodynamic diameter between 110 and 130 nm. Cell Counting Kit-8 testing indicated that A-MFS was nontoxic in vitro and in vivo studies. The in vitro study showed that the A-MFS probe specifically targeted SW1990 cells with high mesothelin expression. The in vivo study was conducted in Siemens 3.0 T magnetic resonance imaging. The average T2-weighted signal values of the xenografts were 966.533±31.56 before injecting A-MFS and 691.133±56.84 before injecting saline solution. After injection of 0.1 mL A-MFS via nude mouse caudal vein for 2.5 hours, the average T2-weighted signal of the xenograft decreased by 342.533±42.6. The signal value decreased by -61.233±33.9 and -58.7±19.4 after injection of the saline and Fe3O4@SiO2. The decrease of tumor signal by A-MFS was much more significant than that by saline and Fe3O4@SiO2 (P<0.05). The results demonstrated the high stability and nontoxicity of A-MFS, which effectively targeted pancreatic cancer in vitro and in vivo. A-MFS is a promising agent for diagnosis of pancreatic cancer.


Differentiation-arrested rat fetal lung in primary monolayer cell culture. I. Development of a differentiation-arrested and growth-supporting culture system using carbon-stripped bovine fetal calf serum.
In vitro observations of fetal lung maturation are complicated by continued epithelial cell maturation in culture. Removal of trace quantities of cortisol from the culture system has been reported elsewhere by Torday to prevent epithelial cell differentiation, but also prevent cell growth. In this report we have developed monolayer cell cultures from 18-, 19-, 20-, and 22-day-gestation fetal rat lung in a culture system stripped of steroid and thyroid hormones. These cultures demonstrate lamellar body development comparable to that seen in vivo at the gestational age at which cultures were developed; the gestation-dependent increase in precursor incorporation into saturated lecithin observed in these cultures is similar to that reported in in vivo studies, yet cell growth in culture has been preserved.


Room-temperature strategy for networked nonspherical gold nanostructures from Au(III)[G-2]CO2H dendrimer complex.
The present work describes a convenient approach to fabricate networked nonspherical gold nanostructures by using [G-2]CO2H dendrimer and toluene as capping and bridging agents in a CH2Cl2 and H2O biphasic system. A controlled linear assembly is achieved without the use of any catalyst at room temperature. UV-vis spectrum, transmission electron microscopy (TEM), selected area electron diffraction (SAED), and X-ray diffraction (XRD) analysis show that the product is well networked nanostructures with diameter of 4-10 nm and consists of coalesced face-centered cubic gold nanocrystals. Extended experiments reveal that both benzene and dimethylbenzene can also inhabit the gold ions to make them crosslinked, prolong the nucleation points and eventually facilitate the formation of the networks.


Phospholipase D activation is required for 1-aminocyclopropane 1-carboxylic acid signaling during sexual reproduction in the marine red alga Neopyropia yezoensis (Rhodophyta).
1-aminocyclopropane 1-carboxylic acid (ACC) is the immediate precursor of the plant hormone ethylene. However, recent studies have suggested that ACC also acts as a signaling molecule to regulate development and growth independently from ethylene biosynthesis. In red algae, ACC stimulates the switch from a vegetative to a sexual reproductive phase. However, despite evidence that ACC signaling in plants and algae is widespread, the mechanistic basis of the ACC signaling pathway remains unknown. We demonstrate that exogenous ACC increased the activity of phospholipase D (PLD) and induced the accumulation of PLD transcripts in the marine red alga Neopyropia yezoensis. The product of PLD, the lipid second messenger phosphatidic acid (PA), also increased in response to ACC. Furthermore, the pharmacological inhibition of PLD by 1-butanol blocked ACC-induced spermatangia and carpospore production, but the inactive isomer t-butanol did not. In addition, 1-butanol prevented ACC-induced growth inhibition and inhibited transcript accumulation of genes upregulated by ACC, including extracellular matrix (ECM)-related genes, and alleviated the transcriptional decrease of genes downregulated by ACC, including photosynthesis-related genes. These results indicate that PLD is a positive regulator of sexual cell differentiation and a negative regulator of growth. This study demonstrates that PLD and its product, PA, are components of ACC signaling during sexual reproduction in N. yezoensis.


Development and validation of a sensitive radioimmunoassay for progesterone estimation in unextracted mithun (Bos frontalis) plasma.
The objective of the study was to develop and validate a simple, reliable, and highly sensitive radioimmunoassay (RIA) for progesterone determination in mithun (Bos frontalis) plasma. The RIA was carried out in 20 microL unextracted mithun plasma. The progesterone standards ranging from 2 to 500pg/20 microL/tube were prepared in charcoal-treated hormone-free plasma. The sensitivity of the RIA procedure was 2 pg progesterone/20 microL/tube, which corresponds to 0.1 ng/mL; the 50 percent relative binding sensitivity was seen at 32pg/20 microL/tube. Plasma volumes for the RIA, viz. 10 and 20 microL, did not influence the shape of standard curve, even though a slight drop in the counts was seen with higher plasma volumes. For the biological validation of the assay, three cyclic, three in early pregnancy, and two in late pregnancy mithuns were used. Blood samples collected at weekly intervals for 42 days, from all animals, were assayed for plasma progesterone. The peak level of progesterone was registered at day 14 (day 21 of sampling) of the estrous cycle and the lowest at estrus; the progesterone concentrations increased and decreased gradually as sampling time advanced, in early and late pregnancy, respectively, which confirm the biological validation of the RIA. The RIA avoids the troublesome and laborious plasma extraction procedures. In conclusion, the RIA developed for progesterone determination in mithun blood plasma is sufficiently reliable, simple, and sensitive enough to estimate progesterone in all physiological variations in mithun.


Stabilization of beryllium-containing planar pentacoordinate carbon species through attaching hydrogen atoms.
The diagonal relationship between beryllium and aluminum and the isoelectronic relationship between BeH unit and Al atom were utilized to design nine new planar and quasi-planar pentacoordinate carbon (ppC) species CAl n Be m H x q (n + m = 5, q = 0, ±1, x = q + m - 1) (1a-9a) by attaching H atoms onto the Be atoms in CAl4Be, CAl3Be2 -, CAl2Be3 2-, and CAlBe4 3-. These ppC species are σ and π double aromatic. In comparison with their parents, these H-attached molecules are more stable electronically, as can be reflected by the more favourable alternative negative-positive-negative charge-arranging pattern and the less dispersed peripheral orbitals. Remarkably, seven of these nine molecules are global energy minima, in which four of them are kinetically stable, including CAl3Be2H (2a), CAl2Be3H- (4a), CAl2Be3H2 (5a), and CAlBe4H4 + (9a). They are the promising target for the experimental realization of species with a ppC.


Oligocene moisture variations as evidenced by an aeolian dust sequence in Inner Mongolia, China.
The aridification of Central Asia since the Eocene has widespread evidence, but climate-controlled environmental reorganizations during the Oligocene remain ambiguous. We employed environmental magnetic, mineralogical and geochemical methods on a latest Eocene to late Oligocene terrestrial sequence in Inner Mongolia, China, to examine how global climatic trends and regional factors influenced the evolution of moisture and weathering in the region. Highlighting the climatic influence, our weathering and rainfall proxy data document the drawdown of atmospheric CO2 and global cooling during the early Oligocene semi-arid phase, which culminated in the Early Oligocene Aridification Event at 31 Ma. Moreover, for the first time in the terrestrial eastern Central Asian setting, we provide geochemical and geophysical evidence for a second major Oligocene aridification event nearly synchronous to the mid-Oligocene Glacial Maximum at around 28 Ma. These aridification events were interrupted by periods of increased rainfall and weathering and can be associated with the terminations of glacial events seen in marine oxygen isotope records.


Attitudes of Italian gynaecologists towards prophylactic oophorectomy at hysterectomy for non-malignant conditions.
To compare the attitudes of Italian oncologic gynaecologists towards prophylactic oophorectomy at hysterectomy for a non-neoplastic reason. A four-item two-part questionnaire was submitted to 170 gynaecologists attending a national conference on gynaecologic oncology. About 92% of gynaecologists reported they would perform prophylactic oophorectomy in women over 50 years, but only 14% said they would in patients aged 45-50; a family history of cancer emerged as a major decision-making criterion for performing oophorectomy in the younger set of patients. Our brief survey confirms the wide variability in attitudes among gynaecologists towards performing prophylactic oophorectomy at hysterectomy for a non-neoplastic pathology in women aged 40-50.


The expression of the proximodistal axis patterning genes Distal-less and dachshund in the appendages of Glomeris marginata (Myriapoda: Diplopoda) suggests a special role of these genes in patterning the head appendages.
The genes Distal-less, dachshund, extradenticle, and homothorax have been shown in Drosophila to be among the earliest genes that define positional values along the proximal-distal (PD) axis of the developing legs. In order to study PD axis formation in the appendages of the pill millipede Glomeris marginata, we have isolated homologues of these four genes and have studied their expression patterns. In the trunk legs, there are several differences to Drosophila, but the patterns are nevertheless compatible with a conserved role in defining positional values along the PD axis. However, their role in the head appendages is apparently more complex. Distal-less in the mandible and maxilla is expressed in the forming sensory organs and, thus, does not seem to be involved in PD axis patterning. We could not identify in the mouthparts components that are homologous to the distal parts of the trunk legs and antennnae. Interestingly, there is also a transient premorphogenetic expression of Distal-less in the second antennal and second maxillary segment, although no appendages are eventually formed in these segments. The dachshund gene is apparently involved both in PD patterning as well as in sensory organ development in the antenna, maxilla, and mandible. Strong dachshund expression is specifically correlated with the tooth-like part of the mandible, a feature that is shared with other mandibulate arthropods. homothorax is expressed in the proximal and medial parts of the legs, while extradenticle RNA is only seen in the proximal region. This overlap of expression corresponds to the functional overlap between extradenticle and homothorax in Drosophila.


Increase in penguin populations during the Little Ice Age in the Ross Sea, Antarctica.
Penguins are an important seabird species in Antarctica and are sensitive to climate and environmental changes. Previous studies indicated that penguin populations increased when the climate became warmer and decreased when it became colder in the maritime Antarctic. Here we determined organic markers in a sediment profile collected at Cape Bird, Ross Island, high Antarctic, and reconstructed the history of Adélie penguin colonies at this location over the past 700 years. The region transformed from a seal to a penguin habitat when the Little Ice Age (LIA; 1500-1800 AD) began. Penguins then became the dominant species. Penguin populations were the highest during ca. 1490 to 1670 AD, a cold period, which is contrary to previous results in other regions much farther north. Different responses to climate change may occur at low latitudes and high latitudes in the Antarctic, even if for same species.


Revision of the South American genus Gaujonia Dognin (Noctuidae, Pantheinae) with descriptions of five new genera and twenty-one new species.
The endemic Neotropical genus Gaujonia Dognin is revised. Morphological characters and a phylogenetic analysis demonstrate paraphyletic relationships among the species. Four different groups are interpreted to represent four different genera. The G. arbosi group is the only remaining clade in the genus Gaujonia, and the other groups have been arranged into three new genera: Millerana gen. nov., Oculicattus gen. nov., and Cicadoforma gen. nov. Additionally, two other genera Cicadomorphus gen. nov., and Gaujoptera gen. nov. were found using morphological and molecular analyses based on some specimens that were misidentified as Gaujonia spp. A total of five new genera, three new combinations (Cicadoforma vau-nigrum Hampson, comb. nov., Oculicattus renifera Hampson, comb. nov., and Millerana arbosioides Dognin, comb. nov.) and 21 new species (Cicadoforma ocelotus sp. nov., Cicadomorphus chicharra sp. nov., Cicadomorphus chuya sp. nov., Cicadomorphus falkasiska sp. nov., Cicadomorphus lilianae sp. nov., Gaujonia bichu sp. nov., Gaujonia chiqyaq sp. nov., Gaujonia kanakusika sp. nov., Gaujonia sourakovi sp. nov., Gaujoptera amsa sp. nov., Millerana austini sp. nov., Millerana cajas sp. nov., Millerana cundinamarquensis sp. nov., Millerana matthewsae sp. nov., Millerana tigrina sp. nov., Oculicattus boliviana sp. nov., Oculicattus brehmi sp. nov., Oculicattus inca sp. nov., Oculicattus raizae sp. nov., Oculicattus schmidti sp. nov., and Oculicattus uturunku sp. nov.) are established.


Introduction to the special issue on evaluator education.
After years in preparation, we are pleased to introduce this special issue of Evaluation and Program Planning that focuses on evaluator education, a topic that we believe is of considerable importance to the field's future. Before describing the issue's content, let us ground the articles in two ways: by examining the larger context within which evaluator education finds itself, and by briefly explaining who we are and describing how the issue came into being.


Sparser macula microvasculature in neuromyelitis optica spectrum disorder occurs independently of optic neuritis.
To evaluate the macula microvascular perfusion in neuromyelitis optica spectrum disorder (NMOSD) patients and assess the correlation with their clinical features. 35 aquaporin-4 seropositive NMOSD patients (38 NMOSD eyes without optic neuritis, NMOSD-NON, and 32 NMOSD eyes with optic neuritis) and 35 healthy controls (HC) were included in our study. Swept-source optical coherence tomography angiography (SS-OCTA) was used to image and segment the macula microvasculature into the inner macula vascular complex (IVC), superficial vascular plexus (SVC), and deep vascular plexus (DVC). An inbuilt software within the OCTA tool was used to measure the microvascular perfusion in these two plexuses. NMOSD eyes without optic neuritis showed sparser (P < 0.05) IVC and SVC compared with healthy controls; NMOSD eyes with optic neuritis showed significantly sparser (P < 0.001) IVC, SVC, and DVC when compared with healthy controls respectively. NMOSD eyes with optic neuritis showed significantly sparser IVC (P = 0.002), SVC (P = 0.001) and DVC (P = = 0.040) when compared with eyes without optic neuritis. Microvascular impairment in NMOSD patients occurs independently of ON. Microvascular impairment is associated with reduced visual acuity and frequency of ON.


Neuropathic pain in patients with chronic leg ulcers.
Leg ulcers are a frequent and often painful disorder. This pain is not always correctly evaluated and relieved. The aim of this prospective study is to assess the contribution of neuropathic pain in leg ulcers. A visual analog scale and the DN4 questionnaire were fulfilled by 81 patients with leg ulcers. Of the patients with leg ulcers, 58% (n = 47) had a positive DN4 score. No predictive factor leading to neuropathic pain was found. The aetiology of the ulcers did not influence the DN4 score. This high prevalence of neuropathic pain in leg ulcers might be explained by an impairment of peripheral nerves due to ischaemia. This study also highlights the difficulty to relieve pain in chronic wounds; 16 patients had an analogous visual scale above 7. These results should encourage practitioners to regularly screen for neuropathic pain and to initiate appropriate treatment if necessary.


Evaluation and optimization of anammox baffled reactor (AnBR) by artificial neural network modeling and economic analysis.
Anammox baffled reactor (AnBR) had a moderate start-up period of 53 days. Interestingly, tangled relationships between key parameters affecting anammox performance were observed, i.e., polynomial function for nitrogen loading rate (NLR) with extracellular polymeric substances (EPS), linear relationships between EPS with granules diameter, granules diameter with settling velocity, and settling velocity with biomass concentration. The correlation coefficients (R2) were 0.97, 0.84, 0.86, and 0.88, respectively. Furthermore, a multi-layered feed forward artificial neural network (ANN) was utilized for simulating and predicting the performance of AnBR. An ANN structure of two hidden layers with four neurons at 1st layer and eight neurons at 2nd layer achieved the best goodness of fit with the minimum mean squared error (MSE) and maximum R2 of 0.002 and 0.99, respectively. Additionally, economic assessment stated that using AnBR at NLR of 4.04 ± 0.10 kg-N/m3/day achieved the maximum net present value of $48100.9.


Proton pump inhibitors omeprazole, lansoprazole and pantoprazole induce relaxation in the rat lower oesophageal sphincter.
We aimed to investigate effects of the proton pump inhibitors (PPIs) omeprazole, lansoprazole and pantoprazole, which are currently used for the treatment of hyperacidity and gastro-oesophageal reflux, on the reactivity of the isolated rat lower oesophageal sphincter. Omeprazole, lansoprazole and pantoprazole (all 10(-9) -10(-3) m, cumulatively) were tested on carbachol-induced (10(-6) m) contraction. In addition, the effects of PPI preincubation (all 10(-3) m) on the contractions induced by cumulative carbachol (10(-9) -10(-5) m), angiotensin-2 (10(-9) -10(-5) m) or electrical field stimulation (EFS; 40 V, 32 Hz, 1 ms, 10 s) were assessed. Finally, the effects of PPI on the spontaneous contractile activity of the tissue were also evaluated. PPI relaxed precontracted lower oesophageal sphincter in a concentration-dependent manner and suppressed carbachol-, angiotensin- and EFS-induced contractions. Furthermore, PPI attenuated spontaneous contractile activity of the tissue. Omeprazole, lansoprazole and pantoprazole had a suppressor effect on lower oesophageal sphincter contractions.


A computer-assisted study of quantitative morphological features of C type horizontal cells in retina.
Biphasic C type horizontal cells of the retina of crucian carp were intracellularly stained with horseradish peroxidase (HRP) and quantitatively studied with computer-aided three-dimensional reconstruction techniques. Several parameters characterizing their morphology were determined and compared among different subtypes of horizontal cells. The results show that both cell body area and horizontal extension are proper parameters by which different subtypes of biphasic horizontal cells can be clearly classified.


Effect of infrastructure design on commons dilemmas in social-ecological system dynamics.
The use of shared infrastructure to direct natural processes for the benefit of humans has been a central feature of human social organization for millennia. Today, more than ever, people interact with one another and the environment through shared human-made infrastructure (the Internet, transportation, the energy grid, etc.). However, there has been relatively little work on how the design characteristics of shared infrastructure affect the dynamics of social-ecological systems (SESs) and the capacity of groups to solve social dilemmas associated with its provision. Developing such understanding is especially important in the context of global change where design criteria must consider how specific aspects of infrastructure affect the capacity of SESs to maintain vital functions in the face of shocks. Using small-scale irrigated agriculture (the most ancient and ubiquitous example of public infrastructure systems) as a model system, we show that two design features related to scale and the structure of benefit flows can induce fundamental changes in qualitative behavior, i.e., regime shifts. By relating the required maintenance threshold (a design feature related to infrastructure scale) to the incentives facing users under different regimes, our work also provides some general guidance on determinants of robustness of SESs under globalization-related stresses.


Chronic ethanol exposure and protracted abstinence alter NMDA receptors in central amygdala.
We recently reported that chronic ethanol treatment (CET) and early withdrawal (2-8 h) altered glutamatergic transmission at both pre- and postsynaptic sites in central nucleus of the amygdala (CeA). Acute ethanol (44 mM) inhibited the NMDA receptor (NMDAR)-mediated EPSCs (NMDA-EPSCs) more in CeA neurons from CET rats than from naïve rats and also decreased paired-pulse facilitation (PPF) of NMDA-EPSCs only in CET rats. To determine whether these CET effects persisted after prolonged withdrawal, we recorded intracellularly in rat CeA slices and measured mRNA and protein expression of CeA NMDAR subunits from CET rats and those withdrawn from ethanol for 1 or 2 weeks. At 1 week withdrawal, acute ethanol decreased evoked NMDA-EPSC amplitudes and NMDA currents induced by exogenous NMDA ( approximately 20%) equally to that in naïve rats, indicating that CET effects on postsynaptic mechanisms reversed 1 week after CET cessation. However, acute ethanol still decreased PPF of NMDA-EPSCs, indicating that the acute ethanol-induced increase in glutamate release in CeA seen in CET rats was still present at this time. CET also significantly increased mRNA levels of NR1 and NR2B NMDAR subunits compared to control rats. At 1 week withdrawal, mRNA levels for NR1 and NR2B subunits were significantly decreased. These changes reversed at 2 weeks withdrawal. In Western blots, a significant increase in protein for all three subunits occurred in CeA from CET rats, but not after 1 and 2 weeks of withdrawal. These data indicate that CET induces reversible neuroadaptations in synaptic function, gene expression, and protein composition of NMDAR at CeA synapses.


Endoscopic endonasal transclival removal of tumors of the clivus and anterior region of the posterior cranial fossa (results of surgical treatment of 140 patients).
Until recently, tumors of the clivus and the anterior region of the posterior cranial fossa were considered extremely difficult to access and often inoperable using standard transcranial approaches. With the introduction into the neurosurgical practice of minimally invasive methods utilizing endoscopic techniques, it became possible to effectively remove hard-to-reach tumors, including central tumors of the anterior region of the posterior cranial fossa. From 2008 to the present time, the inpatient institution has operated on 140 patients with various tumors of the base of the skull, localized to the clivus and anterior region of the posterior cranial fossa (65 men and 75 women). The age of patients ranged from 3 to 74 years. Tumor distribution according to the histopathological features was as follows: chordomas, 103 (73.57%); meningiomas, 12 (8.57%); pituitary adenomas, 9 (6.43%); fibrous dysplasia, 4 (2.86%); cholesteatoma, 3 (2.14%); craniopharyngiomas, 2 (1.43%); plasmacytomas, 2 (1.43%); and other tumors (giant cell tumor, neurohypophyseal glioma, osteoma, carcinoid, chondroma), 5 (3.57%). The tumors had the following size distribution: giant (more than 60 mm), 35 (25%); large (35-59 mm), 83 (59.3%); medium (21-35 mm), 21 (15%); and small (less than 20 mm), 1 (0.7%). In 11 cases, intraoperative monitoring of the cranial nerves was performed (21 cranial nerves were identified). Upper, middle, and lower transclival approaches provide access to the anterior surface of the upper, middle, and lower neurovascular complexes of the posterior cranial fossa. The chordoma cases were distributed as follows according to extent of removal: total removal, 68 (66.02%); subtotal removal, 25 (24.27%); and partial removal, 10 (9.71%). The adenomas of the pituitary gland were removed totally in 6 cases, subtotally in 1 case and partially in 2 cases. The meningiomas were removed totally in 1 case, subtotally in 5 cases, and partially in 5 cases, with less than 50% of the tumor removed in 1 case. Other tumors (cholesteatoma, craniopharyngioma, fibrous dysplasia, giant cell tumor, glioma of the neurohypophysis, osteoma, plasmacytoma, carcinoid, and chondroma) were removed totally in 9 cases and subtotally in 7 cases. Postoperative CSF leaks occurred in 9 cases (6.43%) and meningitis in 13 cases (9.29%). Oculomotor disorders developed in 19 patients (13.57%), 12 of which regressed during the period from 4 to 38 days after surgery, and 7 of which were permanent. In 2 cases, surgical treatment had a lethal outcome (1.43%). The endoscopic endonasal transclival approach can be used to obtain access to the centrally located tumors of the posterior cranial fossa. It is an alternative to transcranial approaches in the surgical treatment of tumors of the clivus. The results of using this approach are comparable with the results of transcranial and transfacial approaches and, in some cases, surpass them in effectiveness. The extended endoscopic endonasal posterior (transclival) approach, considering its minimally invasive nature, allows fora radical and low-risk (in terms of postoperative complications and lethality) removal of various skull base tumors of central localization with the involvement and without the involvement of the clivus, which, until recently, were considered to be almost inoperable.


Electrodiagnosis-based management of patients with radiculopathy: The concept and application involving a patient with a large lumbosacral disc herniation.
The evaluation of patients with lower back pain (LBP) is based mainly on clinical examinations and imaging procedures that are subjective or anatomic in nature. The treatments, either physical therapy or osteopathy, lack evidence-based protocol and may be disruptive to the spine. Therefore, a neurophysiologic-based approach to managing such patients is necessary. A 40-year-old female complained of LBP and radiculopathy for more than 12 years, a condition that was accompanied by numbness, tingling and weakness in the left leg. This study examined the effectiveness of using an innovative concept and method on a patient with a 19-mm disc herniation. An electro diagnosis-based evaluation and treatment approach testing tool, Soleus H-reflexes, was applied during unloading (with the patient lying down), loading (with the patient standing or sitting), and various trunk position protocols. A structured treatment was based on the results of H-reflex, including direction-sensitive exercises and manipulation, progressing from unloading to full loading. A custom-based home program was developed for sleeping and sitting positions, with all being directed at non-invasively decompressing the compromised nerve root. Data was analyzed using descriptive statistics. Stepwise application of the developed procedures resulted in complete resolution of the radicular and spinal symptoms, with a reduction in the size of the herniated disc from 19 mm to 4 mm and recovery of the H-amplitude by the end of the treatment. Functional recovery was also complete by the end of the program. A follow-up after 12 months showed maintained results. The discussed concept and method exhibited their effectiveness in this case study, and the results obtained are due to the consistency and maintenance of the neural decompression using a direction sensitive therapy protocol. Direction sensitive exercise therapy based on H-reflex testing is effective in treating large herniated lumbar discs.


Effects of hypertonic saline (7.5%) on extracellular fluid volumes in healthy volunteers.
This study evaluated the effects of 7.5% saline on plasma and other extracellular fluid volumes. After baseline measurements, eight healthy postmenopausal female volunteers received 4 ml.kg-1 of hypertonic saline over 30 min. After the fluid infusion, the volunteers were studied for 60 min. Plasma volume was measured using a dilution of 125-iodine-labelled human albumin. Extracellular water and cardiac output were measured by whole body impedence cardiography. The infused volume was 4 ml.kg-1 (average 260 ml). Plasma volume increased rapidly during the infusion (mean +/- standard deviation, 442 +/- 167 ml). At the end of the 1-h follow-up period, plasma volume had increased by on average 465 ml (SD 83). The increase of extracellular water at the end of infusion and at the end of study was 650 ml (SD 93) and 637 ml (SD 192), respectively. The highest serum sodium recorded in the volunteers was 158 mmol.l-1. The effect of 7.5% saline on plasma volume was rapid and lasted for at least 1 h. Plasma volume remained elevated by more than the infused volume at the end of the study. The increase in plasma and extracellular fluid volumes was partly achieved by mobilizing intracellular water to extracellular compartment.


Structural investigation and photoluminescent properties of gadolinium(III), europium(III) and terbium(III) 3-mercaptopropionate complexes.
This work reports on the synthesis, crystallographic determination and spectroscopic characterization of gadolinium(III), terbium(III) and europium(III) 3-mercaptopropionate complexes, aqua-tris(3-mercaptopropionate)lanthanide(III)--[Ln(mpa)3(H2O)]. The Judd-Ofelt intensity parameters were experimentally determined from emission spectrum of the [Eu(mpa)3(H2O)]complex and they were also calculated from crystallographic data. The complexes are coordination polymers, where the units of each complex are linked together by carboxylate groups leading to an unidimensional and parallel chains that by chemical interactions form a tridimensional framework. The emission spectrum profile of the [Eu(mpa)3(H2O)] complex is discussed based on point symmetry of the europium(III) ion, that explains the bands splitting observed in its emission spectrum. Photoluminescent analysis of the [Gd(mpa)3(H2O)] complex show no efficient ligand excitation but an intense charge transfer band. The excitation spectra of the [Eu(mpa)3(H2O)] and [Tb(mpa)3(H2O)] complexes do not show evidence of energy transfer from the ligand to the excited levels of these trivalent ions. Therefore the emission bands are originated only by direct f-f intraconfigurational excitation of the lantanide(III) ions.


An incidental finding of mitral valve network.
A 63-year-old male presented with a 6-month history of worsening exertional dyspnea and was found to have three-vessel coronary artery disease. Transesophageal echocardiography revealed a filamentous structure attached to the anterior mitral valve leaflet, which was confirmed during surgery as filamentous network. To our knowledge, this is the first report to describe such a network attached to the mitral valve.


Ligand blotting with 125I-fluoresceinamine-heparin.
A highly sensitive method for ligand blotting with heparin has been developed. This ligand-blotting method is successful largely due to the ability to prepare heparin derivatives of high radiospecific activity. Heparin was modified with fluoresceinamine according to the method of C.G. Glabe, P.K. Harty, and S.D. Rosen [1983) Anal. Biochem. 130, 287-294), and this fluoresceinamine-derivatized heparin can be radioiodinated to a specific activity of 100,000 cmp/ng of uronic acid. This is a 500-fold increase in specific activity over Bolton-Hunter-modified heparin, as prepared by A.D. Cardin, K.R. Witt, and R.L. Jackson [1984) Anal. Biochem. 137, 368-373). 125I-Fluoresceinamine-derivatized heparin retains its ability to interact specifically with heparin-binding proteins such as human protease nexin-I and antithrombin III. 125I-Fluoresceinamine-derivatized heparin can be used to visualize and quantify heparin binding proteins on nitrocellulose. Protease nexin-I can be visualized at the nanogram level. In addition, ligand blotting with 125I-fluoresceinamine heparin can be combined with Cleveland digestion (D.W. Cleveland, S. Fisher, M.W. Kirschner, and U.K. Laemmli (1977) J. Biol. Chem. 252, 1102-1106) in order to identify heparin binding fragments of proteins with heparin binding domains.


Bone mass, nutrition, and other lifestyle factors.
Since the proceedings of the last Consensus Conference on Osteoporosis were published as a supplement to The American Journal of Medicine in November 1991, there has been a plethora of well-documented studies reported in the literature. This article will address some of the issues concerning the relation between bone mass and nutrition raised in those studies.


Plastome phylogenomic analysis reveals evolutionary divergences of Polypodiales suborder Dennstaedtiineae.
Polypodiales suborder Dennstaedtiineae contain a single family Dennstaedtiaceae, eleven genera, and about 270 species, and include some groups that were previously placed in Dennstaedtiaceae, Hypolepidaceae, Monachosoraceae, and Pteridaceae. The classification and phylogenetic relationships among these eleven genera have been poorly understood. To explore the deep relationships within suborder Dennstaedtiineae and estimate the early diversification of this morphologically heterogeneous group, we analyzed complete plastomes of 57 samples representing all eleven genera of suborder Dennstaedtiineae using maximum likelihood and Bayesian inference. The phylogenetic relationships of all the lineages in the bracken fern family Dennstaedtiaceae were well resolved with strong support values. All six genera of Hypolepidoideae were recovered as forming a monophyletic group with full support, and Pteridium was fully supported as sister to all the other genera in Hypolepidoideae. Dennstaedtioideae (Dennstaedtia s.l.) fell into four clades with full support: the Microlepia clade, the northern Dennstaedtia clade, the Dennstaedtia globulifera clade, and the Dennstaedtia s.s. clade. Monachosorum was strongly resolved as sister to all the remaining genera of suborder Dennstaedtiineae. Based on the well resolved relationships among genera, the divergence between Monachosorum and other groups of suborder Dennstaedtiineae was estimated to have occurred in the Early Cretaceous, and all extant genera (and clades) in Dennstaedtiineae, were inferred to have diversified since the Late Oligocene. This study supports reinstating a previously published family Monachosoraceae as a segregate from Dennstaedtiaceae, based on unique morphological evidence, the shady habitat, and the deep evolutionary divergence from its closest relatives.


Identification of non-lipid LPA3 antagonists by virtual screening.
In the present study, we utilized virtual screening to identify LPA(3) antagonists. We have developed a three-point structure-based pharmacophore model based on known LPA(3) antagonists. This model was used to mine the NCI database. Docking, pharmacophore development, and database mining produced new, non-lipid leads. Experimental testing of seven computationally selected pharmacophore hits produced one potentiator and three antagonists, one of which displays both LPA(3) selectivity and nanomolar potency. Similarity searching in the ChemBridge database using the most promising lead as the search target produced four additional LPA(3) antagonists and a potent dual LPA(1&2) antagonist.


The induction of apoptosis by a combined 1,25(OH)2D3 analog, EB1089 and TGF-beta1 in NCI-H929 multiple myeloma cells.
Previously, we reported that EB1089 inhibited the growth of NCI-H929 myeloma cells via cell cycle arrest and apoptosis. In the present study, we investigated whether a combined EB1089 and TGF-beta1 synergistically inhibited the cell proliferation of myeloma cell lines. While TGF-beta1 alone could not inhibit the proliferation of any of the tested myeloma cells, synergistic effect between EB1089 (1 x 10(-8) M) and TGF-beta1 (1 ng/ml) was observed in NCI-H929 cells. TGF-beta1 intensified the decreased expression of CDK2, CDK4, CDK6 and cyclin D1 in EB1089-treated NCI-H929 cells. However, these effects did not intensify to decrease CDK2 activity of EB1089-treated NCI-H929 cells, resulting in no difference in the extent of G1 arrest between EB1089- and both agents-treated cells. Remarkably, both agents synergistically induce apoptosis of NCI-H929 cells, which was accompanied with up-regulation of Bax, degradation of PARP and Rb proteins, and loss of mitochondrial transmembrane potential (deltapsim). EB1089 caused the induction of SMAD4, a mediator of TGF-beta1 signaling. In addition, a combined EB1089 and TGF-beta1 increased p21 and JNK/SAPK activity whereas neither EB1089 nor TGF-beta1 affected p21 and JNK/SAPK activity. Taken together, these results suggest that treatment with both EB1089 and TGF-beta1 synergistically inhibits the proliferation of NCI-H929 cells through apoptosis.


Amplification and molecular cloning of murine adenosine deaminase gene sequences.
A previously isolated mouse Cl-1D derived cell line (B-1/25) overproduces adenosine deaminase (EC 18.104.22.168) by 3200-fold. The present studies were undertaken to determine the molecular basis of this phenomenon. Rabbit reticulocyte lysate and Xenopus oocyte translation studies indicated that the B-1/25 cells also overproduced adenosine deaminase mRNA. Total poly(A+) RNA derived from B-1/25 was used to construct a cDNA library. After prehybridization with excess parental Cl-1D RNA to selectively prehybridize nonamplified sequences, 32P-labeled cDNA probe synthesized from B-1/25 total poly(A+) RNA was used to identify recombinant colonies containing amplified mRNA sequences. Positive clones containing adenosine deaminase gene sequences were identified by blot hybridization analysis and hybridization-selected translation in both rabbit reticulocyte lysate and Xenopus oocyte translation systems. Adenosine deaminase cDNA clones hybridized with three poly(A+) RNA species of 1.5, 1.7, and 5.2 kilobases in length, all of which were overproduced in the B-1/25 cell line. Dot blot hybridization analysis using an adenosine deaminase cDNA clone showed that the elevated adenosine deaminase level in the B-1/25 cells was fully accounted for by an increase in adenosine deaminase gene copy number. The adenosine deaminase cDNA probes and the cell lines with amplified adenosine deaminase genes should prove extremely useful in studying the structure and regulation of the adenosine deaminase gene.


Trial of transcutaneous electrical acupoint stimulation in laryngopharyngeal reflux disease: study protocol for a randomized controlled trial.
Patients with persistent globus sensation, throat clearing, chronic cough, hoarseness, and other throat symptoms account for a large proportion of patients in ears, nose, and throat clinics. Laryngopharyngeal reflux disease (LPRD) is increasingly valued by otolaryngologists. Transcutaneous electrical acupoint stimulation (TEAS) is possibly a new method for the treatment of LPRD. This trial aims to determine whether TEAS combined with proton pump inhibitor (PPI) is better than PPI alone in the treatment of LPRD. This prospective randomized controlled trial will be implemented in a tertiary hospital in China. Seventy patients diagnosed with LPRD will be randomly assigned to the TEAS + PPI group (intervention group) or PPI group (control group), at a ratio of 1:1. In addition to using PPI, the intervention group will receive TEAS at four groups of acupoints, and each group will be treated for 15 min, once for 60 min, five times a week, for 12 weeks, 60 times. The main outcome will be changes in the Reflux Symptom Index scores at 4, 12, and 24 weeks after treatment. The secondary outcomes will include changes in the reflux finding score, Laryngopharyngeal Reflux-Health-related Quality of Life score, and throat pain visual analog scale score. This trial will explore the feasibility of TEAS combined with PPI for the treatment of LPRD and provide potential evidence for its effectiveness and safety. The results of this study will be published in a peer-reviewed journal. Chinese Clinical Trial Registry ChiCTR2100046755 . Registered on May 28, 2021.


A stable genetic polymorphism underpinning microbial syntrophy.
Syntrophies are metabolic cooperations, whereby two organisms co-metabolize a substrate in an interdependent manner. Many of the observed natural syntrophic interactions are mandatory in the absence of strong electron acceptors, such that one species in the syntrophy has to assume the role of electron sink for the other. While this presents an ecological setting for syntrophy to be beneficial, the potential genetic drivers of syntrophy remain unknown to date. Here, we show that the syntrophic sulfate-reducing species Desulfovibrio vulgaris displays a stable genetic polymorphism, where only a specific genotype is able to engage in syntrophy with the hydrogenotrophic methanogen Methanococcus maripaludis. This 'syntrophic' genotype is characterized by two genetic alterations, one of which is an in-frame deletion in the gene encoding for the ion-translocating subunit cooK of the membrane-bound COO hydrogenase. We show that this genotype presents a specific physiology, in which reshaping of energy conservation in the lactate oxidation pathway enables it to produce sufficient intermediate hydrogen for sustained M. maripaludis growth and thus, syntrophy. To our knowledge, these findings provide for the first time a genetic basis for syntrophy in nature and bring us closer to the rational engineering of syntrophy in synthetic microbial communities.


Depression, anxiety and their associated factors among patients with cancer receiving treatment at oncology units in Amhara Region, Ethiopia: a cross-sectional study.
To assess the prevalence of anxiety and depression symptoms, and their associated factors among patients with cancer receiving cancer treatment in Amhara region oncology centres in Northwest, Ethiopia. Institution-based cross-sectional study was conducted. Three oncology units at comprehensive hospitals in the Amhara region, Ethiopia. Adult patients who had a pathologically confirmed cancer diagnosis and received cancer therapy were our study participants. The Hospital Anxiety and Depression Scale was used to assess anxiety and depression symptoms. A total of 392 patients with cancer participated in this study, of which 57.1% (95% CI 52.1% to 62.1%) and 60.2% (95% CI 55.2% to 65.1%) had anxiety and depression, respectively.Poor social support (adjusted OR, AOR=4.43, 95% CI (1.70 to 11.50)), poor performance status (AOR=1.97, 95% CI (1.02 to 3.79)) and increased pain severity (AOR=1.30, 95% CI (1.14 to 1.48)) were factors associated with anxiety. Furthermore, poor performance status (AOR=2.77, 95% CI: (1.42, 5.39)) and pain severity (AOR=1.25, 95% CI: (1.11 to 1.42)) were significantly associated with depression. Anxiety and depression were common among patients with cancer. Social support, performance status and pain were determinant factors of anxiety in patients with cancer. Moreover, performance status and pain were associated with depressive symptoms. Therefore, patients with low social support, poor performance status and severe pain should get special emphasis.


Physiome-model-based state-space framework for cardiac deformation recovery.
To more reliably recover cardiac information from noise-corrupted, patient-specific measurements, it is essential to employ meaningful constraining models and adopt appropriate optimization criteria to couple the models with the measurements. Although biomechanical models have been extensively used for myocardial motion recovery with encouraging results, the passive nature of such constraints limits their ability to fully count for the deformation caused by active forces of the myocytes. To overcome such limitations, we propose to adopt a cardiac physiome model as the prior constraint for cardiac motion analysis. The cardiac physiome model comprises an electric wave propagation model, an electromechanical coupling model, and a biomechanical model, which are connected through a cardiac system dynamics for a more complete description of the macroscopic cardiac physiology. Embedded within a multiframe state-space framework, the uncertainties of the model and the patient's measurements are systematically dealt with to arrive at optimal cardiac kinematic estimates and possibly beyond. Experiments have been conducted to compare our proposed cardiac-physiome-model-based framework with the solely biomechanical model-based framework. The results show that our proposed framework recovers more accurate cardiac deformation from synthetic data and obtains more sensible estimates from real magnetic resonance image sequences. With the active components introduced by the cardiac physiome model, cardiac deformations recovered from patient's medical images are more physiologically plausible.


Cooperative activation of the T-type CaV3.2 channel: interaction between Domains II and III.
T-type CaV3 channels are important mediators of Ca(2+) entry near the resting membrane potential. Little is known about the molecular mechanisms responsible for channel activation. Homology models based upon the high-resolution structure of bacterial NaV channels predict interaction between the S4-S5 helix of Domain II (IIS4-S5) and the distal S6 pore region of Domain II (IIS6) and Domain III (IIIS6). Functional intra- and inter-domain interactions were investigated with a double mutant cycle analysis. Activation gating and channel kinetics were measured for 47 single mutants and 20 pairs of mutants. Significant coupling energies (ΔΔG(interact) ≥ 1.5 kcal mol(-1)) were measured for 4 specific pairs of mutants introduced between IIS4-S5 and IIS6 and between IIS4-S5 and IIIS6. In agreement with the computer based models, Thr-911 in IIS4-S5 was functionally coupled with Ile-1013 in IIS6 during channel activation. The interaction energy was, however, found to be stronger between Val-907 in IIS4-S5 and Ile-1013 in IIS6. In addition Val-907 was significantly coupled with Asn-1548 in IIIS6 but not with Asn-1853 in IVS6. Altogether, our results demonstrate that the S4-S5 and S6 helices from adjacent domains are energetically coupled during the activation of a low voltage-gated T-type CaV3 channel.


Repair of sternoclavicular joint ligament: a novel approach.
Posterior sternoclavicular dislocations are common in younger patients and are frequently due to high energy sporting incidents. We aim to demonstrate a novel technique that is safe and aims to provide good functional post-operative outcomes for patients with this injury. This was a single-surgeon case series of four young patients from October 2017 to July 2019. The operative technique involved relocating the joint and holding it in situ with nylon suture tape. The tape was anchored in holes drilled in the sternum and passed through tunnels drilled into the medial clavicle. All of the patients were contacted retrospectively and a Nottingham Clavicle Score (NCS) was performed for each patient on a post-operative basis. No intra-operative or post-operative complications were noted. All of the patients demonstrated a significant improvement in their functional outcomes after the operation. The average NCS for the four patients was 82/100. There are a variety of techniques described in the literature to repair this ligament using either plates or tendon grafts. All of these techniques describe the drilling of anteroposterior holes in the manubrium and clavicle which run the intra-operative risk of perforating a major vessel. This paper is the first one to describe a technique which uses superior inferior holes which minimizes the risks, making the procedure safer for the patient. We believe this novel technique is safer than the existing described techniques, and it does not compromise on functional outcomes.


Posterior capsular plaque in bilateral congenital cataracts.
Many cases of unilateral congenital cataract have an associated posterior capsular plaque. Observations such as this have led to the hypothesis that posterior capsular plaque is caused by persistent fetal vasculature, generally a unilateral condition, even if no obvious hyaloid remnant is visible. We investigated the incidence of posterior capsular plaque associated with bilateral congenital cataracts. Children with bilateral congenital cataracts were identified from three surgical practices. Children were included if lensectomies were performed prior to age 7 months. Surgical videos were evaluated for cataract morphology. Fourteen children with bilateral cataracts were identified. Surgical videos were available for 24 eyes. Five eyes (21%) had evidence of persistent hyaloid remnants. Of the remaining 19 eyes, cataracts were categorized as nuclear in 10 cases, nuclear with cortical extension in 6 cases, and posterior cortical in 3 cases. Evidence of posterior capsular plaque was seen in seven cases (37%) on video review. Video review revealed a much lower incidence of posterior capsular plaque in eyes with bilateral congenital cataracts compared to unilateral congenital cataracts, lending presumptive evidence to the hypothesis that most unilateral lens opacities arise from persistent fetal vasculature.


A novel tetra-PEG based hydrogel for prevention of esophageal stricture after ESD in a porcine model.
Endoscopic submucosal dissection (ESD) is an accepted treatment for early esophageal cancer and precancerous lesions, but resection of a large mucosal area often leads to postoperative esophageal stricture. Biomaterials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a well-defined ammonolysis-based tetra-armed poly (ethylene glycol) (Tetra-PEG) hydrogel and investigated its efficacy and related mechanisms for preventing esophageal ESD-induced stricture in a porcine model. In terms of material properties, Tetra-PEG hydrogel present great biocompatibility,great capability to retain moisture, strong tissue adhesion and high mechanical strength. Then, six domestic female pigs were randomly divided into PEG (n = 3) and control groups (n = 3). A 3/4 of the esophageal circumference ESD was performed in all pigs. In PEG group, Tetra-PEG hydrogel was easily delivered via endoscopy and adhered to the ulcer bed tightly. Compared to control group, Tetra-PEG hydrogel accelerated esophageal ulcer healing at an early stage with enhanced epithelium regeneration, milder inflammation and lesser fibrosis by regulating TGF-β/Smad2 signaling. Taken together, our findings reveal Tetra-PEG hydrogel is a promising and attractive candidate for preventing the formation of fibrotic stricture in the process of esophageal ESD-induced ulcer repair.


Effect of proximal versus distal 50% enterectomy on nutritional parameters in rats preconditioned with a high-fat diet or regular chow.
Obesity may protect against the nutritional consequences of short bowel syndrome. We hypothesized that rats preconditioned with an obesogenic diet would have better outcomes after surgical induction of short bowel syndrome compared to rats on regular chow. Rats were fed a high-fat diet or regular rat chow for six months, and then underwent 50% proximal, 50% distal, or sham enterectomy. Food intake, weight, and body composition were monitored before and for 4 weeks after surgery. The high-fat diet consistently produced obesity (>25% body fat). All procedures induced weight loss, but there was no discernable difference between resection vs. sham resection. Rats on the high-fat diet had a greater post-resection loss of body fat compared to rats on chow (36 vs. 26 g, respectively). There was a nonsignificant trend of less lean mass loss in the former compared to the latter rats (16 vs. 33 g, respectively). Enterectomy moderated serum ghrelin, GIP, PPY, insulin, and leptin. Intestinal adaptation was not different between obese vs. non-obese rats. Rats preconditioned with the high-fat diet may have had better retention of lean body mass after a surgical procedure compared to rats on chow. The effect of 50% enterectomy was less than expected.


The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastasis, and prognosis.
Lung cancer is the most common cause of cancer deaths in the western world. Progress in treatment results has been limited, and the prognosis is poor with a 5-year survival less than 15%. Based on new developments in molecular biology, our knowledge about lung carcinogenesis and mechanisms for invasion and metastasis has expanded and may in the future lead to more specific targeted therapies and better prognosis. The E-cadherin-catenin complex is critical for intercellular adhesiveness and maintenance of normal and malignant tissue architecture. Reduced expression of this complex in malignant disease is associated with tumour invasion, metastasis, and unfavorable prognosis. This review is based on search in the Medline database from 1991 to 2001. We have reviewed the relevance of the E-cadherin-catenin adhesion complex in malignancy in general and lung cancer in particular. Furthermore, its role as target for specific therapy is discussed. Available data indicate that alterations of proteins involved in the E-cadherin-catenin complex are early incidents in cancer development. Reduced or altered expression of one or more of the components in this complex is associated with extended invasive and progressive behavior of cancer cells. Consistently, the E-cadherin-catenin complex appears to be increasingly delicate with regard to cancer prognosis. beta-Catenin, one of the components of the adhesion complex, also plays a significant role in cell signal transduction, gene activation, apoptosis inhibition, and increased cellular proliferation and migration. Inactivation of the E-cadherin-catenin adhesion complex, induced by genetic and epigenetic events, plays a significant role in multistage carcinogenesis, and seems to be associated with dedifferentiation, local invasion, regional metastasis, and reduced survival in lung cancer.


A new approach to exponential stability analysis of neural networks with time-varying delays.
This paper considers the problem of exponential stability analysis of neural networks with time-varying delays. The activation functions are assumed to be globally Lipschitz continuous. A linear matrix inequality (LMI) approach is developed to derive sufficient conditions ensuring the delayed neural network to have a unique equilibrium point, which is globally exponentially stable. The proposed LMI conditions can be checked easily by recently developed algorithms solving LMIs. Examples are provided to demonstrate the reduced conservativeness of the proposed results.


Candidate genes for grape white rot resistance based on SMRT and Illumina sequencing.
White rot is one of the most dangerous fungal diseases and can considerably affect grape berry production and quality. However, few studies have focused on this disease, and thus, finding candidate white rot resistance genes is of great importance for breeding resistant grapevine cultivars. Based on field observations and indoor experiments, the cultivars "Victoria" and "Zhuosexiang" showed significant differences in white rot resistance. For understanding the molecular mechanisms behind it, different phenotypes of grapevine leaves were used for RNA sequencing via Illumina and single-molecule real-time (SMRT) sequencing technology. A transcript library containing 53,906 reads, including known and novel transcripts, was constructed following the full-length transcriptome sequencing of the two grapevine cultivars. Genes involved in salicylic acid (SA) and jasmonic acid (JA) synthesis pathways showed different expression levels. Furthermore, four key transcription factors (TFs), NPR1, TGA4, Pti6, and MYC2, all involved in the SA and JA signal pathways were identified, and the expression profile revealed the different regulation of the pathogenesis related protein1 (PR1) resistance gene, as mediated by the four TFs. Full-length transcript sequencing can substantially improve the accuracy and integrity of gene prediction and gene function research in grapevine. Our results contribute to identify candidate resistance genes and improve our understanding of the genes and regulatory mechanisms involved in grapevine resistance to white rot.


Mixed culture of plants improved nutrient removal in constructed wetlands: response of microbes and root exudates.
Root exudates are determined by plant species configuration and affect microbial community, which in turn affect purification efficiency of constructed wetlands (CWs). However, it is not well understood how plant configuration affects CW purification efficiency through specific root exudates. Herein, four mixed culture CWs were constructed; CW-G3 with Iris pseudacorus, Iris sibirica, Juncus effusus, and Hydrocotyle vulgaris showed the optimal diversity nutrients removal efficiency (TN: 94.2%, TP: 82.9%, COD: 74.7%). Highly increased antioxidant enzymes (peroxidase and catalase) reduced photosynthesis-negative enzyme (malondialdehyde) activity of plants in CW-G3, which ensured oxygen (O2) and organic carbon (OC) production and successfully released to rhizosphere by well-developed root aeration tissues. Further, CW-G3 enriched higher abundance of genus Saccharimonadales and Flavobacterium, which benefited nitrogen removal. Moreover, as OC, higher contents of maltose in CW-G3 (6.6 ~ 11.1-fold of that in other three CWs), as well as lauramide, choline, triethylamine and urocanic acid contributed to microbial denitrifying. Differently, higher contents of unsaturated fatty acids (linoleic acid and oleic acid) in other three CWs inhibited microbial nitrifying as inhibitors, which also proved by co-occurrent network. Thereby, plant configuration in CW-G3 provided higher O2 and OC contents for bacteria and reduced nitrifying inhibitors, which contributed to higher purifying efficiency. The study promoted the understanding about root exudates' effects on bacteria through plant configurations and improved the purification efficiency of CWs.


Predictability of intraocular lens power calculation in eyes after phototherapeutic keratectomy.
To compare the predictability of intraocular lens (IOL) power calculation using several corneal power measurements in eyes that underwent phototherapeutic keratectomy (PTK). Retrospective case series. We reviewed the clinical charts of 42 eyes of 25 consecutive patients who underwent cataract surgery after PTK for granular corneal dystrophy or band keratopathy. IOL power calculations were performed using the SRK/T formula with four corneal power measurements [automated keratometry (AK) measured with a partial coherence interferometer, simulated keratometry (Sim K), true net power (TNP), and total corneal refractive power (TCRP) measured with a rotating Scheimpflug camera]; we determined the prediction error, absolute error, and percentage within ± 1.0 D of the targeted refraction, 1 month postoperatively. The prediction error in the TCRP group was significantly better than those in the AK, Sim K, and TNP groups. The absolute error was also significantly better than those in the AK and Sim K groups, but not significantly different from that in the TNP group. The percentages of within ± 0.5 and 1.0 D in the TCRP group were significantly higher than those in the AK and Sim K groups, but not significantly different from that in the TNP group. The TCRP provides the highest predictability of IOL power calculation in post-PTK eyes. This result suggests that the use of the TCRP, rather than of conventional anterior keratometry, may be clinically helpful for improving the refractive accuracy of post-PTK eyes.