Temporal effect of carbofuran on estrous cycle compensatory ovarian hypertrophy and follicles in hemiovariectomized albino mice.
Carbofuran, a systemic N-methyl carbamate pesticide was administered orally with an effective dose of 1.3mg/kg per day to hemiovariectomized (HOVX) mice for 5, 10, and 15 days. Sham-operated and HOVX control mice were administered a similar quantity of olive oil. The vaginal smear and body weight of the mice were recorded daily and mice were sacrificed on day 16. The results of the present study indicate that there is a significant decrease in the duration of the estrus with a concomitant significant increase in the duration of the diestrus with carbofuran treatment for 10 days. In the HOVX mice treated with carbofuran for 15 days there was a significant decrease in the length of the estrous cycle and the duration of the estrus and metestrus with a concomitant significant increase in the diestrus. There was a significant increase in the ovarian weight in HOVX control mice when compared to that of the sham operated control mice. HOVX mice treated with carbofuran for 10 and 15 days showed a significant decrease in the relative ovarian weight with a concomitant inhibition of compensatory ovarian hypertrophy in HOVX mice. There was also a significant decrease in the ovarian growth rate in relation to the contralateral ovary of the same animal. There was a significant decrease in the number of small and total number of healthy follicles with a concomitant significant increase in the number of medium, large and total number of atretic follicles in HOVX mice treated with carbofuran for 10 days. There was a significant decrease in the number of small, medium, large, and total number of healthy follicles with a concomitant significant increase in the number of medium, large, and total number of atretic follicles in HOVX mice treated with carbofuran for 15 days. The administration of carbofuran in the present study showed that there is no significant change in the body and organs weight such as uterus, kidney, adrenals, liver, spleen, thymus and thyroid in all the carbofuran-treated mice. The above findings such as disruption in the estrous cycle, inhibition of compensatory ovarian hypertrophy, and follicular toxicity may be due to a direct effect on the ovary or through the hypothalamo-hypophysial-ovarian axis.


Results and complications of conventional repair of bullous retinal detachment using posterior segment air injection.
The aims of this retrospective study were to determine the outcome of retinal detachment repair using the drainage, air injection, cryotherapy and explant surgical sequence ('D-ACE' technique) for bullous retinal detachments and also to identify the complications attributable to the injection of the gas. The D-ACE technique was used to repair 206 detachments over a ten year period of which 138 (67%) were successfully re-attached with a single operation. The sub-group of these patients (n = 66) with bullous retinal detachments who would be considered suitable for repair using the technique of pneumoretinopexy (PR) showed a single operation success rate of 85% after D-ACE. Complications attributable to the gas injection occurred in 18 eyes (8.5%). In only four of these (1.9%) did retinal surgery ultimately fail as a result of complications caused by injection of the gas, which represents 10% of all the failures. The results of this series show that the serious complication rate from injecting air into the vitreous cavity is low and that the success rate for treating relatively uncomplicated bullous retinal detachments using the D-ACE technique compares favourably with the results of other published series using either the D-ACE procedure or pneumoretinopexy.


Marginal microleakage and modified microtensile bond strength of Activa Bioactive, in comparison with conventional restorative materials.
This study aimed to assess the enamel and dentin marginal microleakage and dentin microtensile bond strength (μTBS) of ACTIVA BioACTIVE Restorative with and without a bonding agent compared with conventional restorative materials. For enamel and dentin microleakage, Class II boxes were prepared in the mesial (1 mm under the cementoenamel junction) and distal (1 mm above the cementoenamel junction) surfaces of 90 extracted human third molars. The teeth were randomly divided into five groups (n = 18): Group Z (G-Premio Bond + Filtek Z250 XT), Group X (G-Premio Bond + X-tra fil bulk-fill), Group AA (G-Premio Bond + Activa Bioactive restorative), Group A (Activa Bioactive restorative), and Group G (dentin conditioner + Fuji II LC Improve). The teeth were thermocycled, and their microleakage was quantified using the dye penetration test under a stereomicroscope. For dentin μTBS measurement, 12 specimens were fabricated in metal molds (1 × 1 × 12 mm³) for each group mentioned above, and a universal testing machine measured their μTBS. Data were analyzed using one-way analysis of variance (ANOVA), the Kruskal-Wallis test, and multiple comparisons tests. Significant differences were noted among the groups in marginal microleakage and μTBS (p < .001). The highest mean microleakage scores at the enamel and dentin margins were noted in Group A, which had significant differences with other groups (p < .001). The highest μTBS was found in Group X, with significant differences with Group G and Group A (p < .05). The lowest µTBS was noted in Group A, with significant differences with Groups X, Group AA, and Group Z (p < .001). Activa Bioactive without a bonding agent showed significantly lower µTBS to dentin, and higher microleakage at the enamel and dentin margins. Application of adhesive resin with Activa Bioactive provided a dentine bond strength and marginal seal comparable to other restorative materials.


Induction of oxidative stress in rat epididymal sperm after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The ability of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) to induce oxidative stress in various tissues of animals has been reported. The nature and mechanism of action of TCDD on the antioxidant system of sperm has not been studied. In the present study we have sought to investigate whether TCDD induces oxidative stress in the epididymal sperm of rats. Subchronic doses of TCDD (1, 10, and 100 ng/kg body weight per day) were administered orally to male Wistar strain rats for 45 days. After 24 h of the last treatment the rats were killed using diethyl ether. The epididymides were removed and cleared from the adhering tissues. Epididymal sperm were collected by cutting the epididymides into small pieces in Ham's F12 medium, and counted using a hemocytometer. The epididymal sperm counts in the TCDD-treated groups decreased in a dose-dependent manner from the control value of 8.2+/-0.14 x 10(8) to 5.31+/-0.15 x 10(8). Since a positive correlation (r=0.95; n=24) was observed between sperm count and DNA content of the epididymal sperm, DNA content was routinely used as an indicator of sperm count, and the results were expressed in terms of both protein and DNA. There was a significant decline in the activities of superoxide dismutase (40+/-2.17 to 27.1+/-0.76/mg protein and 32.41 to 18.07+/-0.76/mg DNA), catalase (2.49+/-0.13 to 2.03+/-0.05/mg protein and 2.01+/-0.05 to 1.35+/-0.05/mg DNA), glutathione reductase (71.2+/-3.87 to 48+/-1.79/mg protein and 57.58+/-1.52 to 31.94/mg DNA) and glutathione peroxidase (22.4+/-1.43 to 16.9+/-1.57/mg protein and 18.08+/-0.61 to 11.38+/-1.22/mg DNA) while there were increases in the levels of hydrogen peroxide (20.8+/-1.96 to 55.3+/-0.88/ mg protein and 16.18+/-1.88 to 36.87+/-0.88/ mg DNA) and lipid peroxidation (2.17+/-0.2 to 6.08/mg protein and 1.75+/-0.12 to 4.05+/-0.12/mg DNA) in the epididymal sperm. The results suggest that graded doses of TCDD elicit depletion of antioxidant defense system in sperm, indicating TCDD-induced oxidative stress in the epididymal sperm. In conclusion, the adverse effect on male reproduction in TCDD-treated rats may be due to the induction of oxidative stress in sperm.


Normal equine ocular anatomy and eye examination.
When compared with small domestic animals, the horse has unique ocular characteristics (complete bony orbit, well-developed eyelid muscles, a nasal and temporal gray limbal line, granulae iridica, paurangiotic fundus). Knowledge of normal equine ocular anatomy is essential for ocular lesion interpretation. It is important to obtain a full history and general examination before sedation, nerve blocks, or other diagnostic ophthalmic tests are performed. All ocular examinations should include a systematic evaluation of both the anterior and posterior segments. Selection of other diagnostic tests depends on information obtained from the history, general inspection, and ophthalmic examination. The appropriate order of performing various special diagnostic tests must be considered before beginning the examination. If a diagnosis is elusive, referral to an ophthalmologist for further diagnostics should be considered.


Racial disparities in organ donation and why.
High prevalence of comorbidities such as diabetes, hypertension, obesity, hepatitis B and C, in minority groups, results in racial minorities being disproportionally represented on transplant waiting lists. Organ transplantation positively impacts patient survival but greater access is limited by a severe donor shortage. Unfortunately, minority groups also suffer from disparities in deceased and living donation. African-Americans comprise 12.9% of the population and 34% of the kidney transplant waiting list but only 13.8% of deceased donors. Barriers to minority deceased donation include: decreased awareness of transplantation, religious or cultural distrust of the medical community, fear of medical abandonment and fear of racism. Furthermore, African-Americans comprise only 11.8% of living donors. Barriers to minority living donation include: unwillingness to donate, medical comorbid conditions, trust or fear of medical community, loss to follow-up, poor coping mechanisms, financial concerns, reluctance to ask family members and friends, fear of surgery, and lack of awareness about living donor kidney transplantation. Transplant center-based education classes significantly and positively impact African-American concerns and beliefs surrounding living donation. Community and national strategies utilizing culturally sensitive communication and interventions can ameliorate disparities and improve access to transplantation.


Extracellular matrix protein anosmin-1 overexpression alters dopaminergic phenotype in the CNS and the PNS with no pathogenic consequences in a MPTP model of Parkinson's disease.
The development and survival of dopaminergic neurons are influenced by the fibroblast growth factor (FGF) pathway. Anosmin-1 (A1) is an extracellular matrix protein that acts as a major regulator of this signaling pathway, controlling FGF diffusion, and receptor interaction and shuttling. In particular, previous work showed that A1 overexpression results in more dopaminergic neurons in the olfactory bulb. Prompted by those intriguing results, in this study, we investigated the effects of A1 overexpression on different populations of catecholaminergic neurons in the central (CNS) and the peripheral nervous systems (PNS). We found that A1 overexpression increases the number of dopaminergic substantia nigra pars compacta (SNpc) neurons and alters the striosome/matrix organization of the striatum. Interestingly, these numerical and morphological changes in the nigrostriatal pathway of A1-mice did not confer an altered susceptibility to experimental MPTP-parkinsonism with respect to wild-type controls. Moreover, the study of the effects of A1 overexpression was extended to different dopaminergic tissues associated with the PNS, detecting a significant reduction in the number of dopaminergic chemosensitive carotid body glomus cells in A1-mice. Overall, our work shows that A1 regulates the development and survival of dopaminergic neurons in different nuclei of the mammalian nervous system.


Longitudinal monitoring of angiogenesis in a murine window chamber model in vivo.
Angiogenesis induced by administered growth factors, which can augment the blood supply in regenerative applications, has drawn wide attention in medical research. Longitudinal intravital monitoring of vasculature structure is important for understanding and evaluating the dynamics of involved biological processes. In this work, a dual-modality imaging system consisting of photoacoustic microscopy (PAM) and optical coherence tomography (OCT) was applied for non-invasive in vivo imaging of angiogenesis in a murine model. Fibrin scaffolds, with and without basic fibroblast growth factor (bFGF), were implanted in a flexible intravital imaging window and longitudinally observed over 9 days. Imaging was conducted 3, 5, 7, and 9 days after implantation to monitor vascularization in and around the scaffold. The following morphometric parameters were derived from the PAM images: vessel area density (VAD), total vessel length (TVL), and vessel mean diameter (VMD). On days 7 and 9, mice receiving bFGF-laden fibrin gels exhibited significantly greater VAD and TVL compared to mice with fibrin-only gels. Additionally, VMD significantly decreased in +bFGF mice versus fibrin-only mice on days 7 and 9. Blood vessel density, evaluated using immunohistochemical staining of explanted gels and underlying tissue on day 9, corroborated the findings from the PAM images. Overall, the experimental results highlight the utility of a dual-modality imaging system in longitudinally monitoring angiogenesis, thereby providing an effective tool to visualize the vasculature in vivo with high resolution and sensitivity.


CT-guided versus laparoscopic radiofrequency ablation in recurrent small hepatocellular carcinoma against the diaphragmatic dome.
Computed tomography-guided radiofrequency ablation (CT-RFA) and laparoscopic RFA (L-RFA) have been used to treat intrahepatic recurrent small hepatocellular carcinoma (HCC) against the diaphragmatic dome. However, the therapeutic safety, efficacy, and hospital fee have never been compared between the two techniques due to scarcity of cases. In this retrospective study, 116 patients were divided into two groups with a total of 151 local recurrent HCC lesions abutting the diaphragm. We compared overall survival (OS), local tumor progression (LTP), postoperative complications, and hospital stay and fee between the two groups. Our findings revealed no significant differences in 5-year OS (36.7% vs. 44.6%, p = 0.4289) or 5-year LTP (73.3% vs. 67.9%, p = 0.8897) between CT-RFA and L-RFA. The overall hospital stay (2.8 days vs. 4.1 days, p < 0.0001) and cost (¥ 19217.6 vs. ¥ 25553.6, p < 0.0001) were significantly lower in the CT-RFA in comparison to that of L-RFA. In addition, we elaborated on the choice of percutaneous puncture paths depending on the locations of the HCC nodules and 11-year experience with CT-RFA. In conclusion, CT-RFA is a relatively easy and economic technique for recurrent small HCC abutting the diaphragm, and both CT-RFA and L-RFA are effective techniques.


Effect of simulated intraoperative heating and shaping on mechanical properties of a bioabsorbable fracture plate material.
Heating bioabsorbable fracture fixation plates to above their glass transition temperature renders them temporarily malleable, thus facilitating their adaptation to the underlying bone geometry, although the consequence of heating is not well understood. Poly (L-lactide-co-glycolide) copolymer specimens were heated under various conditions, and the effects on specimen mechanics were assessed. Heating temporarily increased toughness while slight reducing flexural modulus. No lasting effects on in vitro material degradation were seen.


Association Analysis of Chromosome X to Identify Genetic Modifiers of Huntington's Disease.
Huntington's disease (HD) is caused by an expanded (>35) CAG trinucleotide repeat in huntingtin (HTT). Age-at-onset of motor symptoms is inversely correlated with the size of the inherited CAG repeat, which expands further in brain regions due to somatic repeat instability. Our recent genetic investigation focusing on autosomal SNPs revealed that age-at-onset is also influenced by genetic variation at many loci, the majority of which encode genes involved in DNA maintenance/repair processes and repeat instability. We performed a complementary association analysis to determine whether variants in the X chromosome modify HD. We imputed SNPs on chromosome X for ∼9,000 HD subjects of European ancestry and performed an X chromosome-wide association study (XWAS) to test for association with age-at-onset corrected for inherited CAG repeat length. In a mixed effects model XWAS analysis of all subjects (males and females), assuming random X-inactivation in females, no genome-wide significant onset modification signal was found. However, suggestive significant association signals were detected at Xq12 (top SNP, rs59098970; p-value, 1.4E-6), near moesin (MSN), in a region devoid of DNA maintenance genes. Additional suggestive signals not involving DNA repair genes were observed in male- and female-only analyses at other locations. Although not genome-wide significant, potentially due to small effect size compared to the power of the current study, our data leave open the possibility of modification of HD by a non-DNA repair process. Our XWAS results are publicly available at the updated GEM EURO 9K website hosted at https://www.hdinhd.org/ for browsing, pathway analysis, and data download.


Comparison of specimen extraction site and another site for protective loop ileostomy in laparoscopic low anterior rectal resection: a retrospective comparative study.
Protective loop ileostomy is commonly performed in laparoscopic low anterior rectal resection to prevent the serious complications of anastomotic fistula. It is usually created at the right lower quadrant of the abdomen and another wound is required for stoma. The study aimed to evaluate the outcomes of ileostomy at the specimen extraction site (SES) and another site (AS) beside the auxiliary incision. A retrospective analysis was conducted on 101 eligible patients with pathologically diagnosed adenocarcinoma of the rectum from January 2020 to December 2021 in the study center. According to whether the ileostomy was at the specimen extraction site, patients were divided into SES group (40 patients) and AS group (61 patients). Clinicopathological characteristics, the intraoperative details, and postoperative outcomes of the two groups were measured. Univariate analysis showed that the operative time was significantly shorter and the blood loss was significantly less in the SES group than in the AS group during laparoscopic low anterior rectal resection, the time to first flatus was significantly shorter, and the pain was significantly less in the SES group than in the AS group during ileostomy closure. The postoperative complications were similar in both groups. Multivariable analysis showed that ileostomy at the specimen extraction site was a significant factor influencing the operative time and blood loss of rectal resection, and influencing the pain and the time to first flatus during ileostomy closure. Compared to ileostomy at AS, protective loop ileostomy at SES was time-saving and less bleeding during laparoscopic low anterior rectal resection, and more quick to first flatus and less pain during stoma closure, and did not lead to more postoperative complications. The median incision of the lower abdomen and the left lower abdominal incision were both good sites for ileostomy.


Decursin alleviates the aggravation of osteoarthritis via inhibiting PI3K-Akt and NF-kB signal pathway.
Osteoarthritis (OA) is a common joint disease that takes joint degeneration or aging as its pathological basis, and joint swelling, pain or dysfunction as its main clinical manifestations. Decursin (DE), the major active component isolated from Angelica gigas Nakai, has been demonstrated to possess anti-inflammatory effect in many diseases. But, the specific physiological mechanism of DE on OA is not clear yet. Therefore, the object of this study was to assess the therapeutic effect of DE on OA, and to explore its potential anti-inflammatory mechanisms. In vitro cell experiments, the inflammatory response in chondrocytes is mediated via interleukin-1β (IL-1β), which led to abnormal secretion of pro-inflammatory factors, such as prostaglandin E2 (PGE2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), nitric oxide (NO) and inducible nitric oxide synthase (iNOS). These cytokines were all decreased by the preconditioning of DE in a dose-dependent form of 1, 5, and 10 µM. Moreover, DE could restrain IL-1β-mediated inflammatory reaction and the collapse of extracellular matrix (ECM) via reducing the secretion of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) and MMPs (matrix metalloproteinases). In short, DE restrained IL-1β-mediated abnormal excitation of PI3K/AKT/NF-κB axis. Furthermore, molecular docking analysis showed that DE has a strong binding affinity with the inhibitory targets of PI3K. In vivo animal studies, DE treatment could helped to improve destruction of articular cartilage and decreased the serum inflammatory factor levels in an operationally induced mouse OA model. To sum up, these data obtained from the experiment indicate that DE has good prospects for the treatment of osteoarthritis.


The link between myocardial contraction and relaxation: the effects of calcium antagonists.
In isolated rat hearts perfused at constant coronary flow and heart rate the amount of shortening in their major axis (L), the developed tension (T) and their time derivatives (L and T) were measured after different interventions. Relative changes of maximal velocities of contraction (+L, +T) and relaxation (-L, -T) were assessed by the ratio between both velocities (+L/-L, +T/-T). After the interventions, cAMP intracellular levels and cAMP dependent protein kinase activity were measured. The negative inotropic effect of verapamil (10(-7) M) and nifedipine (5 X 10(-7) M) was accompanied by a relatively greater decrease in maximal velocity of relaxation. Consequently the ratio +L/-L increased. Verapamil increased +L/-L from 1.27 +/- 0.07 to 1.57 +/- 0.08 (P less than 0.001). Nifedipine increased +L/-L from 1.25 +/- 0.05 to 1.77 +/- 0.12 (P less than 0.001). Whereas nifedipine increased intracellular cAMP levels from 0.403 +/- 0.036 pmol/mg wet weight to 0.534 +/- 0.047 (P less than 0.05), verapamil did not alter them. Neither verapamil nor nifedipine affected cAMP protein kinase activity. Increasing Ca2+ in the perfusate did not change the ratio +L/-L. A decrease in extracellular Ca2+, on the other hand, produced a greater decrease in -L than in +L, so that the ratio +L/-L increased from 1.27 +/- 0.05 to 1.49 +/- 0.10 (P less than 0.05). No changes were detected in cAMP levels or its protein kinase activity. Similar results were obtained when +T/-T was analyzed. To offset the negative inotropic effect caused by calcium antagonists, either increased extracellular Ca2+ or isoproterenol can be used.(ABSTRACT TRUNCATED AT 250 WORDS)


Tips and tricks to facilitate ultrasound-guided placement of peripheral nerve catheters in children.
To describe an approach to facilitate ultrasound (US)-guided placement of peripheral nerve catheters in children. Continuous peripheral nerve blocks (CPNB) provide excellent surgical anesthesia and postoperative analgesia. However, catheters can be difficult to place, especially in children. Ten US-guided peripheral nerve catheters were placed and placement difficulties encountered were recorded. Four series of 15 consecutive US-guided CPNB were then performed, adding in each series one possible solution to each of the troubles previously encountered. Finally, all maneuvers were employed in the placement of 15 US-guided CPNB in children 3-10 years old and then followed clinically. Initial difficulties encountered were as follows: (i) introducing the catheter, (ii) catheter tip visualization, (iii) length of catheter to be introduced, and (iv) catheter fixation and appropriate long-lasting dressing. The proposed facilitating procedure that addresses each of these difficulties is as follows: (i) three-hand technique: an assistant's hand holds the US transducer, the proceduralist anesthetist slightly withdraws and rotates the needle tip with one hand and advances the catheter with the other, (ii) needle visualization in long axis (LAX) whenever possible with catheter placed inside the needle and US guidance of spread of local anesthetic (LA) through the catheter, (iii) catheter advanced until resistance is found or up to a maximum of 5 cm, and (iv) subcutaneous tunneling of the catheter, Dermabond glue, and careful transparent dressing. All catheters in the last series were 100% effective during surgery and provided complete analgesia for ≥3 days without complications. Continuous peripheral nerve blocks in children should be placed under US guidance in LAX whenever possible, with a three-hand technique and slightly withdrawing or rotating the needle tip to introduce the catheter, administering LA through the catheter, and performing subcutaneous tunneling and careful dressing.


Collagen proportionate area correlates with histological stage and predicts clinical events in primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease in need of accurate biomarkers for stratification and as surrogates for clinical endpoints in trials. Quantitative liver fibrosis assessment by collagen proportionate area (CPA) measurement has been demonstrated to correlate with clinical outcomes in chronic hepatitis C, alcohol-related and non-alcoholic fatty liver disease. We aimed to investigate the ability of CPA to quantify liver fibrosis and predict clinical events in PSC. Biopsies from 101 PSC patients from two European centres were retrospectively assessed by two expert pathologists in tandem, using grading (Ishak and Nakanuma) and staging (Ishak, Nakanuma, Ludwig) systems recently validated to predict clinical events in PSC. CPA was determined by image analysis of picro-Sirius red-stained sections following a standard protocol. We assessed the correlations between CPA, staging and grading and their associations with three outcomes: (1) time to PSC-related death, liver transplant or primary liver cancer; (2) liver transplant-free survival; (3) occurrence of cirrhosis-related clinical manifestations. CPA correlated strongly with histological stage determined by each scoring system (P < .001) and was significantly associated with the three endpoints. Median time to endpoint-1, endpoint-2 and endpoint-3 was shorter in patients with higher CPA, on Kaplan-Meier analyses (P = .011, P = .034 and P = .001, respectively). Quantitative fibrosis assessment by CPA has utility in PSC. It correlates with established histological staging systems and predicts clinical events. CPA may be a useful tool for staging fibrosis and for risk stratification in PSC and should be evaluated further within prospective clinical trials.


Phosphorus-31 NMR analysis of dynamic energy metabolism in intact crystalline lens treated with ouabain: phosphorylated metabolites.
Changes in phosphatic metabolites and intralenticular pH of the intact crystalline rabbit lens induced by ouabain (10(-3), 10(-4), 10(-5) M) were measured during time-course incubations using phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) in order to study the metabolic manifestations of this steroid on lens glycolytic activity. Significant alterations in the glycolytic intermediates of the crystalline lens only occurred with ouabain at the concentration of 10(-3) M. A significant time-dependent increase in alpha-glycerophosphate, an unidentified pentose phosphate, the nucleoside diphosphosugars (uridine diphosphoglucose and uridine diphosphomannose), inorganic orthophosphate, and inosine monophosphate, and decline in glucose 6-phosphate and ATP were detected in 10(-3) M ouabain-treated lenses. The uridine diphosphosugars exhibited a maximum at approximately the time when the lens ATP content was 50% of control levels (12.5 h). A progressive decrease in intralenticular pH indicative of hydrogen-ion-pump damage was detected concomitant with the changes in lens metabolite levels. Lenses maintained transparency throughout the time-course. Since metabolite manifestations effecting the intermediates of glycolysis occur in lens tissue with its high glycolytic and low oxidative activity, we hypothesize the effects of 10(-3) M ouabain may represent metabolic actions of ouabain which are independent of its effects on tissue oxygen consumption as is presumed from studies involving tissues more dependent on oxidative metabolism.


Factors associated with a high or low implantation of self-expanding devices in TAVR.
Optimizing valve implantation depth (ID) plays a crucial role in minimizing conduction disturbances and achieving optimal functional integrity. Until now, the impact of intraprocedural fast (FP) or rapid ventricular pacing (RP) on the implantation depth has not been investigated. Therefore, we aimed to (1) evaluate the impact of different pacing maneuvers on ID, and (2) identify the independent predictors of deep ID. 473 TAVR patients with newer-generation self-expanding devices were retrospectively enrolled and one-to-one propensity-score-matching was performed, resulting in a matching of 189 FP and RP patients in each cohort. The final ID was analyzed, and the underlying functional, anatomical, and procedural conditions were evaluated by univariate and multivariate analysis. The highest ID was reached under RP in severe aortic valve calcification and valve size 26 mm. Multivariate analysis identified left ventricular outflow (LVOT) calcification [OR 0.50 (0.31-0.81) p = 0.005*], a "flare" aortic root [OR 0.42 (0.25-0.71), p = 0.001*], and RP (OR 0.49 [0.30-0.79], p = 0.004*) as independent highly preventable predictors of a deep ID. In a model of protective factors, ID was significantly reduced with the number of protective criteria (0-2 criteria: - 5.7 mm ± 2.6 vs. 3-4 criteria - 4.3 mm ± 2.0; p < 0.0001*). Data from this retrospective analysis indicate that RP is an independent predictor to reach a higher implantation depth using self-expanding devices. Randomized studies should prove for validation compared to fast and non-pacing maneuvers during valve delivery and their impact on implantation depth. Clinical Trial registration: NCT01805739. Evaluation of the impact of different pacing maneuvers (fast ventricular pacing-FP vs. rapid ventricular pacing-RP) on implantation depth (ID). After one-to-one-propensity-score-matching, independent protective and risk factors for a very deep ID beneath 6 mm toward the LVOT (< - 6 mm) were identified. Stent frame pictures as a courtesy by Medtronic®. AVC aortic valve calcification.


Integrative annotation and knowledge discovery of kinase post-translational modifications and cancer-associated mutations through federated protein ontologies and resources.
Many bioinformatics resources with unique perspectives on the protein landscape are currently available. However, generating new knowledge from these resources requires interoperable workflows that support cross-resource queries. In this study, we employ federated queries linking information from the Protein Kinase Ontology, iPTMnet, Protein Ontology, neXtProt, and the Mouse Genome Informatics to identify key knowledge gaps in the functional coverage of the human kinome and prioritize understudied kinases, cancer variants and post-translational modifications (PTMs) for functional studies. We identify 32 functional domains enriched in cancer variants and PTMs and generate mechanistic hypotheses on overlapping variant and PTM sites by aggregating information at the residue, protein, pathway and species level from these resources. We experimentally test the hypothesis that S768 phosphorylation in the C-helix of EGFR is inhibitory by showing that oncogenic variants altering S768 phosphorylation increase basal EGFR activity. In contrast, oncogenic variants altering conserved phosphorylation sites in the 'hydrophobic motif' of PKCβII (S660F and S660C) are loss-of-function in that they reduce kinase activity and enhance membrane translocation. Our studies provide a framework for integrative, consistent, and reproducible annotation of the cancer kinomes.


Increased production of cytotoxic macrophage progenitors by Lactobacillus casei in mice.
Heat-killed Lactobacillus casei YIT9018 (LC9018), when administered intravenously to normal mice, induced increase in Mac-1+ cells and Mac-2+ cells but not in Mac-3+ cells in spleen. The number of both populations changed in the same time course and was maximal 14 d after the administration. To know the effect of LC9018 on hematopoietic progenitor level, we examined the number of macrophage colony-forming cells (M-CFC), granulocyte-macrophage CFC (GM-CFC), and colony-forming units in spleen (CFU-S) in bone marrow 3 d after the administration. LC9018 stimulated the proliferation of M-CFC but not that of GM-CFC and CFU-S. LC9018-induced M-CFC were similar to normal M-CFC in dependence on macrophage colony-stimulating factor (M-CSF) and buoyant density. M-CFC-derived macrophages cultured in the presence of M-CSF expressed Mac-1 and Mac-2 but not Mac-3. They showed cytotoxic activity against syngenic tumor cells, Meth A, via direct contact, when assayed by using an in vitro colony inhibition assay or an in vivo Winn test. These results indicate that LC9018 stimulates the proliferation of cytotoxic macrophage progenitors in bone marrow and induces their differentiation in spleen. These effects may be one of the ways in which LC9018 suppresses tumor growth.


Local recurrence after curative anterior resection for carcinoma of the rectum.
From 1972 to 1985, 60 patients with rectal carcinoma underwent curative anterior resections. There was a local recurrence in three (5 per cent). Pelvic recurrence was seen in two patients and there was a suture line recurrence in one. The length of the distal margin of the normal bowel or lymph node involvement did not appear to be a significant determining factor of the local recurrence. As for the factor responsible for the recurrence, tumor implantation into the pelvic cavity or into the suture line was suspected. Care should be taken to avoid implantation of tumor cells during operative procedures. There were no local recurrences in patients with lower rectal carcinoma. This finding might be related to the selection of patients with carcinoma of stage I and II.


Vascular time-activity variation in patients undergoing ¹²³I-MIBG myocardial scintigraphy: implications for quantification of cardiac and mediastinal uptake.
For the quantification of cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, the mediastinum is commonly used as a reference region reflecting nonspecific background activity. However, variations in the quantity of vascular structures in the mediastinum and the rate of renal clearance of (123)I-MIBG from the blood pool may contribute to increased interindividual variation in uptake. This study examined the relationship between changes in heart (H) and mediastinal (M) counts and the change in vascular (123)I-MIBG activity, including the effect of renal function. Fifty-one subjects with ischemic heart disease underwent early (15 min) and late (4 h) anterior planar images of the chest following injection of (123)I-MIBG. Vascular (123)I-MIBG activity was determined from venous blood samples obtained at 2 min, 15 min, 35 min, and 4 h post-injection. From the vascular clearance curve of each subject, the mean blood counts/min per ml at the time of each acquisition and the slope of the clearance curve were determined. Renal function was expressed as the estimated creatinine clearance (e-CC) and the estimated glomerular filtration rate (e-GFR). Relations between H and M region of interest (ROI) counts/pixel, vascular activity, and renal function were then examined using linear regression. Changes in ROI activity ratios between early and late planar images could not be explained by blood activity, the slope of the vascular clearance curves, or estimates of renal function. At most 3% of the variation in image counts could be explained by changes in vascular activity (p = 0.104). The e-CC and e-GFR could at best explain approximately 1.5% of the variation in the slopes of the vascular clearance curve (p = 0.194). The change in measured H and M counts between early and late planar (123)I-MIBG images is unrelated to intravascular levels of the radiopharmaceutical. This suggests that changes in M counts are primarily due to decrease in soft tissue activity and scatter from the adjacent lungs.


Fate of antibiotic resistance genes in farmland soil applied with three different fertilizers during the growth cycle of pakchoi and after harvesting.
The increasing prevalence of antibiotic resistance genes (ARGs) in the soil environment poses a serious threat to crop safety and even public health. In this study, the fate of ARGs in the soil was investigated during the growth period of pakchoi and after harvesting with the application of different kinds of fertilizers. The result showed that increasing rate of soil ARGs during the growth period of pakchoi followed the order of composted manure > commercial fertilizer > mineral fertilizer. After harvesting, soil ARGs abundance treated with mineral fertilizer, commercial fertilizer or composted manure significantly increased by 0.63, 3.19 and 8.65 times (p < 0.05), respectively, compared with the non-fertilized soil. The ARGs abundance in the pakchoi treated with composted manure was significantly higher than that of treatments with mineral fertilizer and commercial organic fertilizer. These findings indicated the application of composted pig manure would significantly increase the pollution load of ARGs in farmland soil and plant, and also promote the proliferation of farmland ARGs. Principal component analysis suggested that bacterial communities might have a significant influence on ARGs changes during the growth period of pakchoi. Network analysis further indicated ARGs changes may be mainly related to their host bacteria (including Gammaproteobacteria, Flavobacteriia and Bacilli). The results provided a proper method and useful information on reducing transmission risk of ARGs and control the propagation of ARGs in agricultural activities.


Evolution of the ancestral mammalian karyotype and syntenic regions.
Decrypting the rearrangements that drive mammalian chromosome evolution is critical to understanding the molecular bases of speciation, adaptation, and disease susceptibility. Using 8 scaffolded and 26 chromosome-scale genome assemblies representing 23/26 mammal orders, we computationally reconstructed ancestral karyotypes and syntenic relationships at 16 nodes along the mammalian phylogeny. Three different reference genomes (human, sloth, and cattle) representing phylogenetically distinct mammalian superorders were used to assess reference bias in the reconstructed ancestral karyotypes and to expand the number of clades with reconstructed genomes. The mammalian ancestor likely had 19 pairs of autosomes, with nine of the smallest chromosomes shared with the common ancestor of all amniotes (three still conserved in extant mammals), demonstrating a striking conservation of synteny for ∼320 My of vertebrate evolution. The numbers and types of chromosome rearrangements were classified for transitions between the ancestral mammalian karyotype, descendent ancestors, and extant species. For example, 94 inversions, 16 fissions, and 14 fusions that occurred over 53 My differentiated the therian from the descendent eutherian ancestor. The highest breakpoint rate was observed between the mammalian and therian ancestors (3.9 breakpoints/My). Reconstructed mammalian ancestor chromosomes were found to have distinct evolutionary histories reflected in their rates and types of rearrangements. The distributions of genes, repetitive elements, topologically associating domains, and actively transcribed regions in multispecies homologous synteny blocks and evolutionary breakpoint regions indicate that purifying selection acted over millions of years of vertebrate evolution to maintain syntenic relationships of developmentally important genes and regulatory landscapes of gene-dense chromosomes.


Enhanced Photocatalytic Activity of Two-Dimensional Polar Monolayer SiTe for Water-Splitting via Strain Engineering.
A two-dimensional (2D) polar monolayer with a polarization electric field can be used as a potential photocatalyst. In this work, first principle calculations were used to investigate the stability and photocatalytic properties of 2D polar monolayer SiTe as a potential promising catalyst in water-splitting. Our results show that the 2D polar monolayer SiTe possesses an indirect band gap of 2.41 eV, a polarization electric field from the (001) surface to the (001¯) surface, a wide absorption region, and a suitable band alignment for photocatalytic water-splitting. We also discovered that the photocatalytic activity of 2D polar monolayer SiTe could be effectively tuned through strain engineering. Additionally, strain engineering, particularly compressive strain in the range from -1% to -3%, can enhance the photocatalytic activity of 2D polar monolayer SiTe. Overall, our findings suggest that 2D polar monolayer SiTe has the potential to be a promising catalyst for photocatalytic water-splitting using visible light.


Cost-consciousness among Swiss doctors: a cross-sectional survey.
Knowing what influences physicians attitudes toward health care costs is an important matter, because most health care expenditures are the results of doctors' decisions. Many decisions regarding medical tests and treatments are influenced by factors other than the expected benefit to the patient, including the doctor's demographic characteristics and concerns about cost and income. Doctors (n = 1184) in Geneva, Switzerland, answered questions about their cost-consciousness, practice patterns (medical specialty, public.vs. private sector, number of patients per week, time spent with a new patient), work satisfaction, and stress from uncertainty. General linear models were used to identify independent risk factors of higher cost-consciousness. Most doctors agreed that trying to contain costs was their responsibility ("agree" or "totally agree": 90%) and that they should take a more prominent role in limiting the use of unnecessary tests (92%); most disagreed that doctors are too busy to worry about costs (69%) and that the cost of health care is only important if the patient has to pay for it out-of-pocket (88%). In multivariate analyses, cost-consciousness was higher among doctors in the public sector, those who saw fewer patients per week, who were most tolerant of uncertainty, and who were most satisfied with their work. Thus even in a setting with very high health care expenditures, doctors' stated cost-consciousness appeared to be generally high, even though it was not uniformly distributed among them.


Green synthesis and biological evaluation of some novel azoles as antimicrobial agents.
A series of novel fluorine-containing triazoles 3, thiadiazoles 4, and oxadiazoles 5 were synthesized from thiosemicarbazides 2. These reactions were carried out by green technique such as ultrasonication and microwave. All products have been characterized by IR, (1)H NMR, and Mass spectral study and screened for their antimicrobial activity.


Extracorporeal shock wave lithotripsy with a transportable electrohydraulic lithotripter: experience with >300 patients.
To review a multicentre experience of using a transportable lithotripter (STS-T, Medstone, Inc, Aliso Viejo, CA. USA) for treating patients with urolithiasis in all parts of the urinary tract. In all, 326 patients with a total of 370 stones were treated as outpatients with the STS-T lithotripter. All patients received a single shock wave lithotripsy treatment and were followed after 4-6 weeks in the outpatient clinic, the primary endpoint being to determine the efficacy (as defined by the stone-free rate). Secondary objectives included establishing a database of patient demographic information, stone characteristics, stone location, procedural endpoints, and complication rates. In all there were 370 procedures, with a mean of 2394 shocks administered at an energy level of 24 kV. The mean treatment time was 51 min, excluding anaesthesia-induction time. The mean stone aggregate size was 8.2 mm; 62% of the stones were in the kidney while 38% were in various locations in the ureter. Of the treated stones, 90% had definite or probable evidence of fragmentation. The overall stone-free rate after one treatment with the STS-T was 52.8%. Of patients with residual fragments, most (61%) had fragments of <4 mm in aggregate diameter. The overall complication rate was 3.8%, the most common complication being postoperative pain. The Medstone STS-T lithotripter was an effective device for treating urolithiasis in all parts of the urinary tract. This system had a high margin of safety, as shown by the low complication rate. With no apparent sacrifice of efficacy compared to first-generation or fixed (not transportable) second-generation devices, the Medstone STS-T represents an important advance in the development of a truly transportable lithotripter.


Effect of Danshen on TLR2-triggered inflammation in macrophages.
Danshen (Salvia Miltiorrhiza Radix et Rhizoma) is a valued herbal plant widely used to treat cardiovascular diseases in Asian countries. In modern medicine, innate immunity-induced inflammation is considered a risk factor for cardiovascular diseases. However, little is known about the anti-inflammatory effects and molecular mechanism of Danshen. To evaluate the molecular mechanisms of Danshen on Toll-like receptor (TLR) 2-triggered inflammation in macrophages and identify its bioactive components. Pam3CSK4-stimulated bone marrow-derived macrophages (BMMs) were treated with Danshen water extract (DSE), and the levels of proinflammatory cytokines (interleukin (IL)-6, IL-12 and tumor necrosis factor (TNF)-α) were measured by both real-time quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). RNA sequencing (RNA-seq)-based bioinformatics analyses were applied to reveal the novel molecular mechanisms of DSE, followed by western blotting for verification. Additionally, HPLC-UV analysis along with bioassays was performed to identify the bioactive ingredients of DSE. The results of RT-qPCR and ELISA showed that DSE significantly inhibited proinflammatory cytokine expression in a dose-dependent manner. Transcriptome analyses revealed that a wider panel of inflammatory cytokines responded to the regulatory effect of DSE, and that the TNF signaling pathway might have played a vital role. Western blotting data confirmed the involvement of extracellular signal-regulated protein kinases (ERK) and Jun N-terminal Kinase (JNK) related singling pathway. Among the seven components identified in DSE, Danshensu (DSS) and protocatechuic aldehyde (PA) were confirmed as bioactive ones with anti-inflammatory effects. DSE showed a promising effect against TLR2-triggered inflammation associated with the inhibition of the TNF cascade down-streamed mitogen-activated protein kinase (MAPK) signaling pathway, in which IL-6 acts as the key effective molecule, and ERK and JNK phosphorylation was inhibited. Notably, DSS and PA were considered bioactive components with anti-inflammatory bioactivity.


The utility of contrast-enhanced MRI in diagnosis of muscle injuries occult to conventional MRI.
Our goal was to define the utility of contrast-enhanced MRI in the diagnosis of occult muscle injuries on T2 and STIR sequences. We retrospectively reviewed the pre- and postcontrast MR studies of four professional athletes with a clinical diagnosis of suspected muscle injuries. The four cases demonstrated muscle strain injuries not visualized on the conventional T2 and STIR sequences but visualized on the postcontrast MR studies as areas of localized enhancement. We recommend the intravenous administration of gadolinium in the setting of clinically suspected muscle injuries not visualized on T2 and STIR sequences.


Induction of mitochondria-mediated apoptosis by methanol fraction of Ulmus davidiana Planch (Ulmaceae) in U87 glioblastoma cells.
Mitochondria play a pivotal role in apoptosis of mammalian cells by releasing apoptogenic proteins such as cytochrome c into the cytoplasm. Mitochondrial membrane permeability during apoptosis is regulated directly by the Bcl-2 family of proteins. In glioma cells, there are no specific features of apoptosis compared with apoptosis in other cell types. Ulmus davidiana Planch (Ulmaceae) is a deciduous tree, which is widely distributed in Korea. The barks of the stem and the root of the plant have been used in oriental traditional medicine for the treatment of oedema, mastitis, gastric cancer, and inflammation. Our results demonstrate that the methanol fraction of the stem bark extracts of Ulmus davidiana Planch induce mitochondria-mediated apoptosis in U87 glioblastoma cells. The methanol fraction exhibited a comparatively higher cytotoxic activity (IC(50)=7.5±0.7μg/ml) in a dose-dependent manner than chloroform, and hexane fractions. The results show the typical ladder profile of oligonucleosomal fragments characteristics of apoptosis and the secreted cytosolic cytochrome c level was increased by treatment of methanol fraction of UD. Moreover, the expressional changes of the Bcl-2 family protein occurred within 30min after treatment with methanol fraction. All results indicate that the methanol fraction of U. davidiana Planch (the barks of the stem) is capable of inducing apoptosis in U87 glioblastoma cells.


Activation of polyphosphoinositide phospholipase C by fluoride in WRK1 cell membranes.
Partially purified plasma membranes prepared from myo-[3H]inositol-prelabeled WRK1 cells exhibit a phosphatidylinositol 4,5-biphosphate (PIP2) phospholipase C activity sensitive to NaF. NaF increased the production of IP2 and IP3 in a time- and concentration-dependent manner. The maximal increase in IP2 and IP3 production rates represented 400 +/- 18 and 360 +/- 40% of the basal production rate, respectively. Half-maximum stimulation was reached with 2-4 mM NaF. The observed effect was specific for F-. Aluminium potentiated fluoride-induced IP3 and IP2 accumulation in a concentration-dependent manner. The effect of fluoride on the PIP2 phospholipase C from WRK1 cell membranes appears to be similar to the well-documented effect of F- on the well-characterized Ns. Ni and transducin GTP-binding proteins. This observation constitutes an additional argument to suggest that a GTP-binding protein is involved in the process of receptor-mediated activation of PIP2 phospholipase C.


Evaluation of optimally designed planar-concave collimators in single-photon emission tomography.
The imaging properties of optimally designed planar-concave (PC) collimators were evaluated by means of Monte Carlo simulations. The evaluation was done with respect to total system spatial resolution and the overall image noise distribution in single-photon emission tomography. The results showed that the non-isotropy with PC collimators, assessed by the ratio of the full-width at half-maximum in the radial and tangential directions, was reduced by about 60% as compared with a conventional parallel-hole collimator for sources located 200 mm away from the centre of rotation. Furthermore, the image noise distribution along the object radius became more uniform when the curved collimator was used. The maximum increase in noise due to use of the curved collimator was about 45% close to the edge of the phantom, where the hole length was about 3 times longer. We also showed with Monte Carlo simulations that the spatial resolution of the lateral cortex when using the curved collimator was significantly improved due to improved radial resolution.


Enhanced effect of water vapor on complete oxidation of formaldehyde in air with ozone over MnOx catalysts at room temperature.
At room temperature, the enhanced effect of water vapor on ozone catalytic oxidation (OZCO) of formaldehyde to CO2 over MnOx catalysts and the reaction stability was reported. In a dry air stream, only below 20% of formaldehyde could be oxidized into CO2 by O3. In humid air streams (RH≥55%), ∼100% of formaldehyde were oxidized into CO2 by O3 and the reaction stability was significantly enhanced. Meanwhile, in situ Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectra of OZCO of HCHO demonstrate that the amount of both monodentate and bidentate carbonate species on MnOx, in the dry stream, increased gradually with time on stream (TOS). However, in the humid stream, almost no accumulation of carbonate species on the catalysts was observed. To clarify the enhanced mechanism, formaldehyde surface reactions and CO2 adsorption/desorption on the fresh, O3 and O3+H2O treated MnOx catalysts were examined comparatively.


Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy.
The clinical responses observed following treatment with immune checkpoint inhibitors (ICIs) support immunotherapy as a potential anticancer treatment. However, a large proportion of patients cannot benefit from it due to resistance or relapse, which is most likely attributable to the multiple immunosuppressive cells in the tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSCs), a heterogeneous array of pathologically activated immature cells, are a chief component of immunosuppressive networks. These cells potently suppress T-cell activity and thus contribute to the immune escape of malignant tumors. New findings indicate that targeting MDSCs might be an alternative and promising target for immunotherapy, reshaping the immunosuppressive microenvironment and enhancing the efficacy of cancer immunotherapy. In this review, we focus primarily on the classification and inhibitory function of MDSCs and the crosstalk between MDSCs and other myeloid cells. We also briefly summarize the latest approaches to therapies targeting MDSCs.


Advanced Practice Nurses' Organization Commitment: Impact of Job Environment, Job Satisfaction, and Person-Organization Fit.
The demand for advanced practice nurses (APNs) has increased globally due to a shortage of physicians and an increased demand for high-quality healthcare. Research is needed on the enhancement of advanced practice nurses' organization commitment. Organization commitment (OC) directly impacts the retention of APNs. This study aims to identify the key factors affecting the OC of advanced practice nurses. A cross-sectional survey was conducted at the largest hospital in South Korea. A total of 189 APNs answered survey questions. A partial least squares-structural equation modeling method was employed to analyze the survey responses. A pay scale of APNs is positively associated with person-organization fit (POF). However, the effect of job location and computer self-efficacy on POF is not significant. Job satisfaction plays a salient direct role in supervision and POF. Job satisfaction is also a significant moderator in the relationship between supervision and POF. POF is significantly associated with both OC and supervision. Supervision has a positive effect on organization commitment. Pay scale, job satisfaction, supervision, and POF are significant factors affecting organization commitment. Establishing an intra-organization entity, such as APN steering committee, to ensure mutual consensus and transparent communication between administrators and APNs would enhance POF, the rating of supervision, and organization commitment.


Exercise during pregnancy: a review of patterns and determinants.
The mental and physical health benefits of exercise during pregnancy highlight the importance of understanding the determinants of pregnant women's physical activity. This paper presents a review of the existing research on pregnancy and physical activity, in order to (a) summarize the existing body of literature since 1986 examining changes in physical activity during pregnancy, (b) summarize correlates and predictors of physical activity during pregnancy, and (c) present directions for future research. A literature search yielded 25 articles published from 1986 to 2009 in English peer-reviewed journals. The major findings were categorized into the following: (a) exercise patterns, (b) demographic correlates/predictors, (c) the influence of pre-pregnancy exercise on pregnancy exercise, (d) theory-based predictors and (f) other correlates of exercise (e.g. general health and safety concerns). Results indicated that pregnant women are less active than non-pregnant women and that pregnancy leads to a decrease in physical activity. Consistent demographic predictors of higher exercise participation during pregnancy include higher education and income, not having other children in the home, being white, and being more active prior to becoming pregnancy. Only a few studies used theoretical models to understand physical activity during pregnancy with varied results. The review outlines demographic and theory-based correlates/predictors that should be taken into consideration when developing interventions to increase physical activity among pregnant women.


Management of renal masses in patients medically unsuitable for nephrectomy--natural history, complications, and outcome.
To examine a group of elderly patients with much larger tumors who were deemed unlikely to survive surgery or who would require dialysis postoperatively to establish the natural history of larger renal tumors if left untreated. Little is known of the growth rate and natural history of renal cancer progression because the tumor is usually removed in those patients who can tolerate surgery. The only published data have been in relation to unfit patients with small, homogeneous, well-circumscribed tumors less than 4 cm. We identified 36 patients whose tumor had not been removed, without evidence of metastasis at diagnosis, from a database of 421 patients with renal cancer. The data were examined retrospectively for symptoms, survival, and size change. The mean age of the patients treated conservatively was 76.1 years (range 56 to 91), with median tumor size of 6.0 cm (range 3.5 to 20.0) at diagnosis. The median follow-up period was 24 months (range 3 to 136). Of the 36 patients, 13 had died at follow-up, 8 of an unrelated illness and 5 of an unknown cause with no radiologic evidence of progression but severe comorbidity. The median time to death was 9 months (range 3 to 24) after diagnosis. One patient developed metastasis at 132 months and was still alive at 136 months of follow-up. Significant hematuria occurred in 11% of the patients and was successfully managed either conservatively or by embolization. The tumor size was unchanged in most patients during the follow-up period. In elderly patients, or those with severe comorbidity, conservative management of larger renal masses is a reasonable and safe option.


Tissue-specific modulation of insulin receptor mRNA levels in adrenaline-treated rats.
Insulin receptor (IR) gene expression at the mRNA level was investigated in liver, hindlimb skeletal muscle, and epididymal adipose tissue of rats exposed to prolonged in vivo administration of adrenaline in relation to control rats. In the liver of adrenaline-treated rats, there were no differences in relation to controls when DNA and protein content were measured. In skeletal muscle, only a slight decrease in protein concentration was detected. By contrast, a clear increase in both protein and DNA content was observed in the adipose tissue of treated animals. Northern blot assays revealed two IR mRNA species of approximately 9.5 and 7.5 Kb in the three tissues from controls. Adrenaline treatment induced an increase of approximately 60% in the levels of both RNAs in adipose tissue but not in liver or skeletal muscle. These results provide evidence for an in vivo tissue-specific regulation of IR gene expression at the mRNA level in rats under an experimental condition of excess of catecholamines.


Chronic oxytocin-driven alternative splicing of Crfr2α induces anxiety.
The neuropeptide oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including anxiety and autism spectrum disorders. However, the behavioral and molecular consequences associated with chronic OXT treatment and chronic receptor (OXTR) activation have scarcely been studied, despite the potential therapeutic long-term use of intranasal OXT. Here, we reveal that chronic OXT treatment over two weeks increased anxiety-like behavior in rats, with higher sensitivity in females, contrasting the well-known anxiolytic effect of acute OXT. The increase in anxiety was transient and waned 5 days after the infusion has ended. The behavioral effects of chronic OXT were paralleled by activation of an intracellular signaling pathway, which ultimately led to alternative splicing of hypothalamic corticotropin-releasing factor receptor 2α (Crfr2α), an important modulator of anxiety. In detail, chronic OXT shifted the splicing ratio from the anxiolytic membrane-bound (mCRFR2α) form of CRFR2α towards the soluble CRFR2α (sCRFR2α) form. Experimental induction of alternative splicing mimicked the anxiogenic effects of chronic OXT, while sCRFR2α-knock down reduced anxiety-related behavior of male rats. Furthermore, chronic OXT treatment triggered the release of sCRFR2α into the cerebrospinal fluid with sCRFR2α levels positively correlating with anxiety-like behavior. In summary, we revealed that the shifted splicing ratio towards expression of the anxiogenic sCRFR2α underlies the adverse effects of chronic OXT treatment on anxiety.


Spermatogenesis of a marine snail, Littorina sitkana.
The fine structure of the spermatogonium, spermatocyte and spermatid of a marine snail, Littorina sitkana is described. The ring centriole (annulus) is formed from the distal centriole and it migrates to the base of the mitochondrial region where it lies in a joint-like structure which is formed by an area of invaginated plasma membrane. The distal and proximal centrioles are at first perpendicular to each other but the proximal centriole rotates to a position coaxial with the distal centriole and fuses with it. The peripheral doublet fibers are continuous between the two centrioles but the central fibers originate only in the distal centriole. The acrosome differentiates from the proacrosomal granule which is derived from a Golgi body. Microtubules, present at this stage, may assist acrosomal formation. Chromatin condensation begins with the formation of fibrous strands, then to lamellar plates which become folded and later twisted around the flagellar shaft. In the final stages the lamellae appear in cross section as concentric rings which eventually fuse to form a homogeneously dense nuclear tube.


Ventricular vortex loss analysis due to various tricuspid valve repair techniques: an ex vivo study.
The deteriorating nature of severe functional tricuspid regurgitation (FTR) has led to the heightened interest in this pathology. However, therapies are heterogeneous and an ideal technique is uncertain. The hemodynamic impact on the cardiac chamber following therapeutic repairs has not been well studied, while its analysis could be used to predict the treatment success. In this study, the hemodynamics of the right ventricle (RV) after 1) clover edge-to-edge tricuspid repair, and 2) double orifice tricuspid repair was evaluated in three right heart models using an ex vivo pulsatile platform emulating severe FTR with the aid of stereoscopic particle image velocimetry. Although all repairs substantially reduced tricuspid regurgitant area, they resulted in a more than 50% reduction in diastolic tricuspid valve (TV) opening area. Splitting the TV orifice into multiple smaller orifices by both repairs eliminated the ring-shaped vortical structure inside the RV observed in FTR cases. Postrepair RV domain was mostly occupied with irregular vortical features and isolated vortex residuals. Moreover, vortical features varied among repair samples, indicating enhanced sensitivity of RV flow to postrepair TV morphology. Compared with clover repair, double orifice subjected the RV to enhanced swirling motions and exposed more regions to vortical motions, potentially indicating better rinsing and lower risk of mural thrombus formation. Double orifice repair increased the levels of RV mean kinetic energy and viscous energy loss than those observed in clover repair, although the impact of these on the cardiac efficiency remains unclear. These preliminary insights could be used to improve future treatment design and planning.NEW & NOTEWORTHY While clover and double orifice tricuspid repairs markedly improved leaflet coaptation, they substantially reduced diastolic tricuspid opening area. Postrepair right ventricle (RV) exhibited specific hemodynamic traits, including the loss of ring-shaped vortical structure and the enhanced sensitivity of RV flow to postrepair tricuspid valve morphology. Compared with clover technique, double orifice repair led to higher swirling motions in the RV domain, which could indicate lower risk of mural thrombus formation.


Meta-analysis of associations between polymorphisms in the promoter regions of matrix metalloproteinases and the risk of colorectal cancer.
Matrix metalloproteinases (MMPs) play important roles in pathogenesis and development of cancer. Recently, lots of studies showed that there were associations between polymorphisms in the promoter regions of MMPs and risk of colorectal cancer; however, the results remained inconclusive. To clarify these associations, we conducted a meta-analysis. We conducted a computerized literature search in the database of PubMed, Embase, ISI Web of Knowledge, and Medline (from January 2000 to July 2010). Overall and subgroup analysis based on the ethnicity of study population was carried out. Odds ratio (OR) and 95% confidence interval (95%CI) were used to evaluate these associations. Statistical analysis was performed with software Review Manager (version 5.0). There were 12 studies involving five polymorphic sites in four MMP genes. For MMP1 (-1607), 2G polymorphism increased the risk of colorectal cancer under dominant and recessive models (dominant, OR = 1.23, 95%CI 1.01-1.49; recessive, OR = 1.52, 95%CI 1.30-1.77). For MMP3 (-1612), 6A/6A genotype increased this risk under the recessive model (OR = 1.33, 95%CI 1.04-1.70); however, this association was lost under the dominant model. For MMP2 -1306 C>T, MMP3 -1171 5A>6A, and MMP9 -1562 C>T, there was no association between these polymorphisms and the risk of colorectal cancer under the dominant and recessive models. Polymorphisms of MMP1 (-1607) and MMP3 (-1612) increased the risk of colorectal cancer; these two polymorphic sites could be used as markers for early diagnosis of colorectal cancer. However, for MMP2 (-1306), MMP3 (-1171), and MMP9 (-1562), further studies with large sample size should be carried out.


An overview of recent progress in multiple dual-mode counter-current chromatography.
Counter-current chromatography is a chromatographic separation and purification technique being developed. The development of different elution modes has significantly contributed to this field. Multiple dual-mode elution is a method developed based on dual-mode elution, which consists of a series of changing cycles of the phase role and the direction by switching between normal and reverse elution modes of counter-current chromatography. This dual-mode elution method takes full advantage of the liquid nature of stationary and mobile phases of counter-current chromatography and effectively improves the separation efficiency. So, this unique elution mode has gained extensive attention for separating complex samples. This review mainly describes and summarizes in detail its development, applications, and characteristics in recent years. Meanwhile, its advantages, limitations, and future outlook also have been discussed in this paper.


Alzheimer-type of pathological changes in Chinese.
There has been no previous description of the pathological features of Alzheimer's disease and little description of Alzheimer-type changes in Chinese brains. In this study, we examined the brains of 17 cases of Alzheimer's disease and concurrently 95 consecutive autopsy cases of non-demented patients aged above 60. Six standard regions of the brains were stained for beta-amyloid immunostaining, Bielschowsky and Bodian. Neuritic plaques, neurofibrillary tangles and diffuse plaques were quantified as per mm2. The Alzheimer's disease brains exhibited a marked increase of neurodegenerative changes over the non-demented brains. Plaque counts were similar to those proposed by Khachaturian (1985; Arch. Neurol. 42: 1097-1105) and CERAD, although the distribution of tangles was more variable with some regions of the neocortex containing few or no tangles. For the non-demented brains, overall neuritic plaques were seen in 31% and neurofibrillary tangles were seen in 42% of cases, with the overall plaque score being 1.8 per mm2 and tangle score being 0.7 per mm2. No age-dependent variation of plaque count and tangle count could be demonstrated in this group of elderly brains. Comparison with similar studies of Caucasians suggests that neuritic plaques and neurofibrillary tangles were less frequently encountered in aging Chinese brains than among the western populations.


Tuning efficiency of the 4-exo-trig cyclization by the electronic effect: ring closure of 3,3-difluoro-4-pentenyl carbon radicals and synthesis of a gem-difluorocyclobutane nucleoside.
4-exo-trig Cyclization reaction of a 4-pentenyl carbon radical containing the gem-difluoromethylene moiety adjacent to a radical accepting α,β-unsaturated ester was found to proceed efficiently to furnish a novel gem-difluorocyclobutane derivative. The cyclized product could be transformed into a gem-difluoromethylene analogue of oxetanocin T.


Brief Report: Leg Length Inequality and Hip Osteoarthritis in the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative.
Studies suggest that persons with a leg length inequality (LLI) of ≥2 cm have an increased risk of developing knee osteoarthritis (OA) in that limb. The present study was undertaken to examine whether LLI also confers an increased risk of hip OA. Using long limb radiographs from subjects in the Multicenter Arthritis Study (MOST) and the Osteoarthritis Initiative (OAI), we measured LLI and scored hip radiographs that were obtained at baseline and 3-5-year follow-up. The associations of LLI of ≥1 cm and LLI of ≥2 cm with radiographic hip OA were examined cross-sectionally and longitudinally, assessing risk in shorter limbs and longer limbs compared to limbs from subjects with no LLI. We carried out logistic regression analyses with generalized estimating equations and adjusted for age, sex, body mass index, height, and cohort of origin. There were 1,966 subjects from the MOST and 2,627 subjects from the OAI. Twelve percent had LLI of ≥1 cm and 1% had LLI of ≥2 cm. For LLI ≥1 cm, the adjusted odds ratio for prevalent hip OA in the shorter leg was 1.47 (95% confidence interval [95% CI] 1.07-2.02) and for LLI ≥2 cm, it was 2.15 (95% CI 0.87-5.34). For LLI ≥1 cm, the odds of incident hip OA in the shorter leg were 1.39 (95% CI 0.81-2.39) while for LLI ≥2 cm, they were 4.20 (95% CI 1.26-14.03). We found no increased risk of hip OA in longer limbs. Our findings suggest that, as with knee OA, legs that are at least 2 cm shorter than the contralateral leg are at increased risk of hip OA.


Association of IFNA16 and TNFRSF19 Polymorphisms with Intramuscular Fat Content and Fatty Acid Composition in Pigs.
Interferon-alpha-16 (IFNA16) and tumor necrosis factor receptor superfamily member 19 (TNFRSF19) are cytokines that may play a role in adipogenesis and fatness. Single nucleotide polymorphisms (SNPs) of the porcine IFNA16 and TNFRSF19 genes were verified and their association with intramuscular fat (IMF) content and fatty acid (FA) composition were evaluated in commercial crossbred pigs. Two non-synonymous SNPs of the porcine IFNA16 c.413G > A and TNFRSF19 c.860G > C loci were detected in commercial crossbred pigs. The porcine IFNA16 c.413G >A polymorphism was significantly associated with stearic acid, total saturated FAs (SFAs), and the ratio of monounsaturated FAs (MUFAs) to SFAs (p < 0.05). Furthermore, the porcine TNFRSF19 c.860G > C polymorphism was found to be significantly associated with IMF content and arachidic acid levels (p < 0.05). The results revealed that porcine IFNA16 and TNFRSF19 polymorphisms are related to IMF content and/or FA composition and affirmed the importance of these cytokine genes as potential candidate genes for lipid deposition and FA composition in the muscle tissue of pigs.


Association between Cataract and Keratinocytic Skin Cancers or Melanoma: Speculating on the Common Role of Sun and Ultraviolet Radiation Exposures.
Cataract and sun-related skin conditions are proxies to lifetime UV exposure. We examined the association between them using real-world data from an unselected Israeli population. Computerized data was obtained from an Israeli health maintenance organization regarding cases of sun-related skin pathologies and cataract diagnosed between 2006 and 2011 in 686,260 members aged 40 or above. Sun-related skin disorders were found in 9.3% of the study population, more commonly among the elderly, and those who reside in areas of higher socioeconomic status. Cataract was diagnosed in 13.1% of the study population, with highest prevalence (47%) among squamous cell carcinoma patients, who were the oldest group. Multivariable analysis adjusting for age, sex, residential district, birth region, smoking, and chronic comorbidities showed no statistically significant association between melanoma and cataract (OR = 1.06; 95% CI: 0.91-1.22). Basal cell carcinoma, squamous cell carcinomas, and actinic keratosis were associated with increased likelihood of prevalent cataract with adjusted odds ratios (95% CI) of 1.14 (1.08-1.20), 1.11 (1.01-1.19), and 1.16 (1.13-1.19), respectively. When stratified by gender, the association between actinic keratosis and cataract was stronger in women than in men, particularly in patients under 65 years. The association between the prevalence of skin cancers and the prevalence of cataract enhances the conclusion that cataract is related to UVR exposure.


Y-29794--a non-peptide prolyl endopeptidase inhibitor that can penetrate into the brain.
A novel non-peptide prolyl endopeptidase (PPCE) inhibitor, Y-29794, has been identified. Y-29794 selectively and competitively inhibited rat brain PPCE (Ki = 0.95 nM) in a reversible manner. Ex vivo study demonstrated that Y-29794 could penetrate into brain to exhibit dose-dependent and long-lasting inhibition. Furthermore, Y-29794 was found to potentiate the effect of TRH on the release of ACh in the rat hippocampus. These results indicate that Y-29794 is an orally active, potent and specific PPCE inhibitor and should be of value in studies on the physiological role of the enzyme in neuropeptide metabolism especially in memory process.


High-throughput immunoassays for SARS-CoV-2 - considerable differences in performance when comparing three methods.
The recently launched high-throughput assays for detecting antibodies against SARS-CoV-2 has contributed to the managing strategies for the COVID-19 pandemic. This study aimed to investigate the performance of three high-throughput assays and one rapid lateral flow test relative to regulatory authorities' recommended criteria. A total of 315 samples, including 150 pre-pandemic samples, 152 samples from SARS-CoV-2 RT-PCR positive individuals and 13 potentially cross-reactive samples were analysed with SARS-CoV-2 IgG (Abbott, Abbott Park, IL), Elecsys Anti-SARS-CoV-2 (Roche, Solna, Sweden), LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin, Saluggia, Italy) and 2019-nCOV IgG/IgM Rapid Test (Dynamiker Biotechnology Co., Tianjin, China). All assays performed with a high level of specificity ranging from 96.7% to 99.3%. Sensitivity differed more between the assays, Roche exhibiting the highest sensitivity of 98.7%. The corresponding figures for Abbott, DiaSorin and Dynamiker Biotechnology were 80.9%, 89.0% and 72.4%, respectively. The results of the evaluated SARS-CoV-2 assays vary considerably, as well as their ability to fulfil the performance criteria proposed by regulatory authorities. Introduction into clinical use in low-prevalent settings, should, therefore, be made with caution.


Baicalein, an active component of Scutellaria baicalensis Georgi, improves cardiac contractile function in endotoxaemic rats via induction of heme oxygenase-1 and suppression of inflammatory responses.
To evaluate the protective effect of baicalein on myocardial dysfunction caused by endotoxaemia in rats and to explore the possible mechanisms. Baicalein (10mg/kg, intravenous) was administered to conscious Wistar rats 30min after lipopolysaccharide (LPS; 10mg/kg, intravenous) challenge. Six hours after LPS administration, the contractile function of the isolated heart was examined using the Langendorff technique. Cardiac protein expression related to inflammatory responses, superoxide anion production and caspase-3 activity were measured. Post-treatment with baicalein significantly attenuated the LPS-induced hypotension with accompanying tachycardia. The contractile function of isolated heart was significantly preserved 6h after LPS administration, following treatment with baicalein. Furthermore, baicalein induced the expression of heme oxygenase-1 protein and reduced superoxide anion formation in the myocardium of LPS-treated rats. Cardiac levels of inducible nitric oxide synthase, monocyte chemoattractant protein-1, phospho-IκBα and phospho-p65 protein and caspase-3 activity significantly increased 6h after LPS challenge but baicalein significantly attenuated these LPS-induced changes. Baicalein improves myocardial contractility in LPS-induced sepsis, which may be related to reductions in oxidative stress, myocardial inflammatory responses and apoptosis.


Chemotherapy or endocrine therapy, first-line treatment for patients with hormone receptor-positive HER2-negative metastatic breast cancer in China: a real-world study.
Although endocrine therapy (ET) is the preferred option for hormone receptor-positive HER2-negative metastatic breast cancer (HR+/HER2- MBC), chemotherapy (CT) is still commonly used. The objective of this real-world study was to present the actual choice of first-line treatment for patients with HR+/HER2- MBC and evaluate the consistency with guidelines in China. Patients with HR+/HER2- MBC between 1996 and September 2018 were identified from of the database of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC). The statistical description was conducted to present the first-line treatment. Factors influencing the prescription of ET or CT were obtained using univariate and multivariate analysis. The consistency of the actual treatment with the guideline of Chinese Society of Clinical Oncology Breast Cancer (CSCO BC guideline) was evaluated. Of 1,877 patients, 662 (35.3%) received ET, and 1,215 (64.7%) received CT. ET proportion was only 25.4% in 1996-2005 and gradually increased to 44.6% in 2016-2018. Aromatase inhibitors (69% of ET) and taxane-based regimens (66% of CT) were the most commonly used ET and CT, respectively. Univariate and multivariate analysis showed that patients with age ≥60, distant relapse-free interval (DRFI) ≥24 months, ER+/PR+, bone metastasis only, or progression on (neo)adjuvant ET were preferably chosen for ET as first-line treatment. Factors associated with preferring CT were de novo stage IV, liver or lung metastasis. 17.2% of patients (322 cases) who had neither visceral metastasis nor progression on (neo)adjuvant ET wrongly received CT instead of ET, which is inconsistent with CSCO BC guideline. More than half of patients receiving CT discontinued their initial treatment due to adverse events and other non-disease progression reasons. Although high proportion of HR+/HER2- MBC patients received CT as first-line treatment in China, it is gratifying to see that the proportion of patients receiving ET has gradually increased. Our study revealed that 17.2% of patients were over-treated according to CSCO BC guideline, which may provide data to promote guideline adherence. The clinical application for ET should be appropriately expanded in first-line treatment, especially for patients without visceral disease and proof of endocrine resistance.


Diseases of the Synaptic Vesicle: A Potential New Group of Neurometabolic Disorders Affecting Neurotransmission.
The general concept of inborn error of metabolism is currently evolving into the interface between classical biochemistry and cellular biology. Basic neuroscience is providing increasing knowledge about the mechanisms of neurotransmission and novel related disorders are being described. There is a necessity of updating the classic concept of "inborn error of neurotransmitters (NT)" that considers mainly defects of synthesis and catabolism and transport of low weight NT molecules. Monogenic defects of the synaptic vesicle (SV), and especially those affecting the SV cycle are a potential new group of NT disorders since they end up in abnormal NT turnover and release. The most common clinical manifestations include epilepsy, intellectual disability, autism and movement disorders, and are in the continuum symptoms of synaptopathies. Interestingly, brain malformations and neurodegenerative conditions are also present within SV diseases. Metabolomics, proteomics, and other -omic techniques probably will provide biomarkers and contribute to therapeutic targets in the future.


Organization, replication and modification of the human genome: temporal order of synthesis and methylation of two classes of HeLa nDNA separated in Ag+--Cs2-SO4 gradients.
During the HeLa S-phase, DNA was methylated, at 1-hr intervals in isolated nuclei and fractionated in Ag+-Cs2SO4 gradients providing a heavy GC-rich peak and a main light AT-rich peak. Both size and specific methylation of these peaks changed during the nDNA duplicative phase. Replication of the heavy GC-rich nDNA fraction, which contains genes for ribosomal RNA, occurred in early S; in contrast, replication of the main AT-rich nDNA fraction was maximal in late S. Concomitantly, specific methylation of the GC-rich nDNA was maximal in the first part of S, while that of the AT-rich nDNA was maximal in the second part of S. This suggested that genes are replicated and methylated with order during the S-phase.


Sustained MRD negative remission in del17p and TP53 mutated B cell prolymphocytic leukemia with ibrutinib and venetoclax.
B cell prolymphocytic leukemia is a rare and aggressive disorder often with high risk features including TP53 mutation, deletion 17p and complex karyotype. There is scarcity of data regarding treatment and existing therapies induce short lived remissions. Ibrutinib, a Bruton tyrosine kinase inhibitor, has had success in some patients with high risk features. Venetoclax, a BCL-2 inhibitor, has primarily been used in the relapsed setting. We present a case of B PLL with deletion 17p and mutated TP53 treated with ibrutinib and venetoclax in the frontline setting which resulted in measurable/minimal residual disease negative remission for approximately three years.


Elucidation of the Transport Mechanism of Puerarin and Gastrodin and Their Interaction on the Absorption in a Caco-2 Cell Monolayer Model.
Puerarin (PUR) and gastrodin (GAS) are often used in combined way for treating diseases caused by microcirculation disorders. The current study aimed to investigate the absorption and transportation mechanism of PUR and GAS and their interaction via Caco-2 monolayer cell model. In this work, the concentration in Caco-2 cell of PUR and GAS was determined by HPLC method. The bidirectional transport of PUR and GAS and the inhibition of drug efflux including verapamil and cyclosporine on the transport of these two components were studied. The mutual influence between PUR and GAS, especially the effect of the latter on the former of the bidirectional transport were also investigated. The transport of 50 μg·mL-1 PUR in Caco-2 cells has no obvious directionality. While the transport of 100 and 200 μg·mL-1 PUR presents a strong directionality, and this directionality can be inhibited by verapamil and cyclosporine. When PUR and GAS were used in combination, GAS could increase the absorption of PUR while PUR had no obvious influence on GAS. Therefore, the compatibility of PUR and GAS is reasonable, and GAS can promote the transmembrane transport of PUR, the effect of which is similar to that of verapamil.


Potentiation of N-methyl-D-aspartate-receptor-mediated currents detected using the excised patch technique in the hippocampal dentate gyrus.
The excised patch mode of the patch-clamp technique has been used to record isolated patch N-methyl-D-aspartate-receptor-mediated currents (patch NMDA-receptor-currents) evoked by electrical stimulation in the dentate gyrus of the hippocampal slice. The patch NMDA-receptor-currents were recorded by placing a patch of membrane isolated from the cell body in the inner molecular layer of the dentate gyrus and applying stimulation to the proximal commissural/associational pathway. The patch NMDA-receptor-currents, recorded at +40 mV in the presence of AMPA-receptor and GABAA-receptor antagonists, consisted of two to six summated unitary openings of NMDA-receptor channels, lasting several hundred milliseconds. Tetanic pathway stimulation evoked a rapid increase in the amplitude of the patch NMDA-receptor-currents which lasted for a period of at least 20 min following the tetanus. The study suggests that the potentiation of the patch NMDA-receptor-currents is due to either an increase in transmitter release, or alternatively, to the release of an extracellular messenger which directly enhances NMDA-receptor responsiveness.


Utility of 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin)-ester-lipase for monitoring dogs with chronic pancreatitis.
The utility of 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin)-ester-(DGGR)-lipase activity (DLA) in monitoring clinical progression of chronic pancreatitis (CP) in dogs is unknown. To examine the association of DLA with clinical signs of CP, as assessed by a CP clinical severity score (CPCSS). Twenty-four dogs. This is a retrospective study. Chronic pancreatitis was diagnosed based on clinical signs and DLA > 250 U/L and monitored using CPCSS and DLA. The study included 134 visits (median, 10 visits/dog; range, 2-11). Mild-moderate (CPCSS, 0-3) and severe (CPCSS, ≥4) disease were documented in 94 (70%) and 40 (30%) visits, respectively. In emergency visits (n = 44; 33%) CPCSS (median, 5; range, 0-15) and DLA (median, 534 U/L; range, 63-7133) were higher (P < .001 and P = .003, respectively) than in scheduled ones (n = 90; 67%; median, 1; range, 0-6 and median, 384 U/L; range, 49-3747, respectively). DGGR-lipase activity was associated (P = .009) with the CPCSS, with a lower activity documented in mild-moderate CPCSS (median 391 U/L; range, 49-3747), compared to severe score (median, 558 U/L; range, 63-7133). DGGR-lipase activity was significantly, but weakly, correlated with CPSS (r = 0.233, P = .007). DGGR-lipase activity inefficiently discriminated mild-moderate vs severe CP (area under the receiver operator characteristics curve, 0.64; 95% confidence interval, 0.53-0.75; P = .012), with DLA cutoff of 428 U/L corresponding to sensitivity of 65% and specificity of 63%. Increased DLA is associated with emergency revisits in dogs with CP, possibly reflecting acute flare-ups. DGGR-lipase activity was associated with the CPCSS over the follow-ups but could not differentiate disease severity.


Evaluation of Apoptotic Marker Bcl2, CD4+, Human Hepatocyte Growth Factor and Metalloproteinase-9 as Tumor Markers for Patients with Hepatocellular Carcinoma.
To examine the possible involvement of human B cell leukemia/lymphoma 2 (Bcl-2), CD4+ cells, hepatocyte growth factor (HGF), and metalloproteinase-9 (MMP-9), as biomarkers in early diagnosis of hepatocellular carcinoma (HCC), activities of these biomarkers in serum were demonstrated by the method of Enzyme Linked Immunosorbant Assay. Two groups of subjects (60 for each), were examined in this study; healthy controls and patients with HCC. The present results declare that, significant decrease in Bcl-2 (p ≤ 0.0001), and CD 4+ (p ≤ 0.001), while significant increase in HGF and MMP-9 (p ≤ 0.05). These findings imply an influence of these biomarkers by the existence of hepatic carcinoma that might reflect the progression of disease and a distinction between the pathological mechanisms involved in hepatic carcinoma. Since, the serum MMP-9 activity was significantly varied between each stage of HCC. An individual profile of the present investigated parameters was detected that might serve as an easy accessing serum marker to monitor the progression of hepatic cell disorders.


Reflexes and preflexes: on the role of sensory feedback on rhythmic patterns in insect locomotion.
Neuromuscular systems are stabilized and controlled by both feedforward and feedback signals. Feedforward pathways driven by central pattern generators (CPGs), in conjunction with preflexive mechanical reaction forces and nonlinear muscle properties, can produce stable stereotypical gaits. Feedback is nonetheless present in both slow and rapid running, and preflexive mechanisms can join with neural reflexes originating in proprioceptive sensors to yield robust behavior in uncertain environments. Here, we develop a single degree-of-freedom neuromechanical model representing a joint actuated by an agonist/antagonist muscle pair driven by motoneurons and a CPG in a periodic rhythm characteristic of locomotion. We consider two characteristic feedback modes: phasic and tonic. The former encodes states such as position in the timing of individual spikes, while the latter can transmit graded measures of force and other continuous variables as spike rates. We use results from phase reduction and averaging theory to predict phase relationships between CPG and motoneurons in the presence of feedback and compare them with simulations of the neuromechanical model, showing that both phasic and tonic feedback can shift motoneuronal timing and thereby affect joint motions. We find that phase changes in neural activation can cooperate with preflexive displacement and velocity effects on muscle force to compensate for externally applied forces, and that these effects qualitatively match experimental observations in the cockroach.


Tachykinins and tachykinin receptors in human uterus.
(1) Studies were undertaken to determine the nature of the receptors mediating contractile effects of tachykinins in the uteri of nonpregnant women, and to analyse the expression of preprotachykinins (PPT), tachykinin receptors and the cell-surface peptidase, neprilysin (NEP), in the myometrium from pregnant and nonpregnant women. (2) The neurokinin B (NKB) precursor PPT-B was expressed in higher levels in the myometrium from nonpregnant than from pregnant women. Faint expression of PPT-A mRNA was detectable in the myometrium from nonpregnant but not pregnant women. PPT-C, the gene encoding the novel tachykinin peptide hemokinin-1 (HK-1), was present in trace amounts in the uteri from both pregnant and nonpregnant women. (3) Tachykinin NK(2) receptors were more strongly expressed in tissues from nonpregnant than from pregnant women. NK(1) receptor mRNA was present in low levels in tissues from both pregnant and nonpregnant women. A low abundance transcript corresponding to the NK(3) receptor was present only in tissues from nonpregnant women. (4) The mRNA expression of the tachykinin-degrading enzyme NEP was lower in tissues from nonpregnant than from pregnant women. (5) Substance P (SP), neurokinin A (NKA) and NKB, in the presence of the peptidase inhibitors thiorphan, captopril and bestatin, produced contractions of myometrium from nonpregnant women. The order of potency was NKA>>SP>/=NKB. The potency of NKA was unchanged in the absence of peptidase inhibitors. (6) The tachykinin NK(2) receptor-selective agonist [Lys(5)MeLeu(9)Nle(10)]NKA(4-l0) was approximately equipotent with NKA, but the tachykinin NK(1) and NK(3) receptor-selective agonists [Sar(9)Met(O(2))(11)]SP and [MePhe(7)]NKB were ineffective in the myometrium from nonpregnant women. (7) The uterotonic effects of [Lys(5)MeLeu(9)Nle(10)]NKA(4-10) were antagonized by the tachykinin NK(2) receptor-selective antagonist SR48968. Neither atropine, nor phentolamine nor tetrodotoxin affected responses to [Lys(5)MeLeu(9)Nle(10)]NKA(4-10). (8) These data are consistent with a role of tachykinins in the regulation of human uterine function, and reinforce the importance of NK(2) receptors in the regulation of myometrial contraction.


l-Alanine methyl ester hydro-chloride monohydrate.
The enanti-opure title compound, C(4)H(10)NO(2) (+)·Cl(-)·H(2)O, forms a two-dimensional network by inter-molecular hydrogen bonding parallel to (010). Non-merohedral twinning with a twofold rotation about the reciprocal c* axis as twin operation was taken into account during intensity integration and structure refinement. This twinning leads to alternative orientations of the stacked hydrogen-bonded layers.


A longitudinal study of women's representations and experiences of pregnancy and childbirth.
To explore women's representations of pregnancy and childbirth and how these representations are constructed and have changed. In the 1980s, many women in Quebec demanded that the birthing process be both demedicalised and humanised, resulting in the legalisation of the midwife profession while expanding their choices over birthing locations within the public health system (e.g., birthing centres, the home, or hospitals). Birth-related technologies were also improving at that time. Nearly 40 years later, we wanted to learn about their perceptions. This qualitative and contextualised phenomenological study surveyed 25 first-time mothers who had received care from midwives, general practitioners, or obstetricians. Each participant met with the researcher twice during her pregnancy and once after giving birth to engage in narrative conversations, which were analysed from an interdisciplinary viewpoint (socio-anthropology). Participant perceptions of pregnancy varied. Some saw it as a state that distorted the body, while others saw it as a long period of struggle with a compulsory step that was also fascinating and/or even happy. Women undergo an incremental process of change before contemplating childbirth, and typically undergo a transitional period when nearing the event itself. They may think of childbirth as joyful and/or painful. Representations are built intersubjectively through influences involving family, the media, and care providers. Stories from their mothers, therefore, created undeniable impressions. In a context heavily influenced by technology, easy pregnancies and/or childbirth events are typically deemed "lucky." This negatively reinforces both the cultural and intergenerational values transmitted regarding these events.


The Evolution of the Treatment of Clubfoot from Posterior Medial Release to the Ponseti Technique: My 42-Year Journey at the Permanente Medical Group.
Traditionally, the Kite manipulation and casting were utilized for the treatment of the congenital clubfoot. This was followed by an extensive posterior medial soft tissue surgical release followed by more casting. Often, the results were less than optimal with scarred, painful feet that needed further corrective surgery. Dr. Ponseti developed a different technique of manipulation, casting, and an Achilles tenotomy that fully corrected these clubfeet without the need for the extensive surgery. This was followed by the mandatory use of night braces with special shoes for a period of 4 years. The Ponseti method is now universally utilized around the world and is the standard of care for the management of clubfoot. I was fortunate to have been personally trained by Dr. Ponseti, and I have exclusively practiced this technique for the past 25 years.


Methods of forward feature selection based on the aggregation of classifiers generated by single attribute.
Compared to backward feature selection (BFS) method in gene expression data analysis, forward feature selection (FFS) method can obtain an expected feature subset with less iteration. However, the number of FFS method is considerably less than that of BFS method. More efficient FFS methods need to be developed. In this paper, two FFS methods based on the pruning of the classifier ensembles generated by single attribute are proposed for gene selection. The main contributions are as follows: (1) a new loss function, p-insensitive loss function, is proposed to overcome the disadvantage of the margin Euclidean distance loss function in the pruning of classifier ensembles; (2) two FFS methods based on the margin Euclidean distance loss function and the p-insensitive loss function, named as FFS-ACSA1 and FFS-ACSA2 respectively, are proposed; (3) the comparison experiments on four gene expression datasets show that FFS-ACSA2 obtains the best results among three FFS methods (i.e. signal-to-noise ratio (SNR), FFS-ACSA1 and FFS-ACSA2), and is competitive to the famous support vector machine-based recursive feature elimination (SVM-RFE), while FFS-ACSA1 is unstable.