[Evaluation of the left ventricle with three-dimensional echocardiography: comparison with cardiac magnetic resonance].
Three-dimensional echocardiography (3DE) is becoming increasingly common in clinical environments. However, the quality of the images depends on the acoustic window, and it can be difficult to identify the endocardial borders. The objective of this study was to evaluate the performance of 3DE in determining the volumes and left ventricular ejection fraction in unselected patients against the gold standard, cardiac magnetic resonance (CMR). In 47 unselected patients who underwent CMR, we performed 3DE using a real-time acquisition technique and semiautomatic border detection. We excluded 4 patients (8.5%) because they had an extremely deficient acoustic window. In the remaining 43 patients, including those with a suboptimal acoustic window, we obtained the following correlations between 3DE and CMR: end-diastolic volume, 0.71; end-systolic volume, 0.77; ejection fraction, 0.74. Although the end-diastolic volume was systematically underestimated, no significant differences were observed in the ejection fraction. When the 11 patients with suboptimal acoustic windows were excluded, we observed a systematic underestimation of the end-diastolic and end-systolic volumes, which paradoxically gave rise to improved correlation coefficients (0.79, 0.92, and 0.84, respectively) and a more accurate ejection fraction. Compared to CMR, 3DE systematically underestimates the ventricular volumes but enables adequate determination of the left ventricular ejection fraction regardless of the quality of the acoustic window.


DNA synthesis inhibitors block protein synthesis in the human lymphocyte.
We examined the requirement for early DNA synthetic events in the protein synthetic response of PHA-stimulated human lymphocytes using specific DNA synthesis inhibitors. The incorporation of H3-thymidine into DNA and H3-leucine into protein was assessed in PHA-stimulated lymphocytes cultured with cytosine arabinoside (8.5 X 10(-6)M), hydroxyurea (1.0 X 10(-2)M) or mitomycin-C (1.5 X 10(-2)M), each of which reduced DNA synthesis to the level of unstimulated lymphocytes. Under those conditions, protein synthesis was suppressed to 2, 14 and 1% of uninhibited cells at 48 h, respectively. Delaying addition of these inhibitors to 6, 12 and 24 h after initiation of PHA stimulation resulted in a parallel loss of inhibition of both RNA and protein synthesis. However, during the first 24 h of uninhibited mitogen stimulation, there is no DNA synthesis as measured by either H3-thymidine uptake or by flow cytometry. In contrast to the inhibition of protein synthesis when measured after 48 h, PHA-stimulated H3-leucine incorporation during the first 24 h was not affected by DNA synthesis inhibition. These results suggest that early events related to DNA synthesis are required for optimum mitogen-induced protein and RNA synthesis, but that new DNA synthesis does not occur until after 24 h of mitogen stimulation.


White Matter Correlates of Suicidality in Adults With Bipolar Disorder Who Have Been Prospectively Characterized Since Childhood.
Prevention of suicide in individuals with early-onset bipolar disorder (BD) remains a challenge. Diffusion magnetic resonance imaging studies in BD have identified neural correlates of emotional dysregulation implicated in BD and suicide. Using diffusion magnetic resonance imaging, we sought to identify neural signatures of suicide attempts in adults with childhood-onset BD who have been clinically followed for up to 19 years as part of the COBY (Course and Outcome of Bipolar Youth) study. Diffusion magnetic resonance imaging data were collected in 68 adults with BD: 20 in the suicide attempter (SA+) group and 48 in the non-suicide attempter (SA-) group. Multivariate analysis of covariance was used to identify the effect of group (SA+, SA-) on mean fractional anisotropy (indirect index of fiber collinearity) in key white matter tracts of emotional regulation. The effect of suicidal ideation and other clinical factors was further explored. False discovery rate was used to account for multiple comparison. Forty healthy control subjects were included. Analyses revealed a main effect of group on fractional anisotropy (F5,59 = 3.0, p = .017). Specifically, the SA+ group showed lower fractional anisotropy than the SA- and healthy control groups in the middle portion of the forceps minor (FMIN) (F1,63 = 8.5, p = .010) and in the anterior (F1,63 = 7.8, p = .010) and posterior (F1,63 = 8.7, p = .006) portion of the right cingulum bundle (CB). Abnormalities in the FMIN, but not CB, were also associated with suicidal ideation (F1,64 = 10.6, p = .002) and levels of emotional distress at scan. FMIN and CB abnormalities have been associated with emotional dysregulation in BD. Our findings suggest that the FMIN may represent a generic marker of suicidal ideation and, more broadly, emotional distress, while CB may represent a specific marker of attempted suicide.


Cardiac troponin T and N-terminal-pro-B type natriuretic peptide reflect myocardial function in preterm infants.
Cardiovascular compromise is increasingly recognized in preterm infants. Currently, echocardiography is the best tool to assess myocardial contractility and guide management. Elevated levels of cardiac troponin T (cTnT) and N-terminal-pro-B type natriuretic peptide (NTpBNP) are associated with poor myocardial contractility and low cardiac output in adults. To examine the range of cTnT and NTpBNP in preterm infants, to correlate NTpBNP and cTnT with echocardiographic markers of cardiac function and to assess the influence of antenatal and postnatal factors on these biochemical markers. Plasma concentrations of cTnT and NTpBNP were measured in infants <1500 g at 12 h of age. These were correlated with simultaneous echocardiographic measures of myocardial function and output. Antenatal data, infant demographics and postnatal characteristics were prospectively recorded. A total of 80 infant had samples taken and echocardiography performed. Their median (interquartile range) cTnT and NTpBNP values were 0.20 microg l(-1) (0.11 to 0.40) and 1273 pmol l(-1) (664 to 2798), respectively. There was a significant inverse correlation between cTnT and echocardiographic markers of myocardial function and stroke volume. NTpBNP significantly correlated with left atrial to aortic root ratio (LA:Ao). There was a weaker but significant negative correlation between NTpBNP and left ventricular (LV) function. The assays were not influenced by gestation, birth weight, gender or mode of delivery. cTnT and NTpBNP are correlated with echocardiographic measures of cardiac performance in preterm infants. Measurement of levels in the first hours of life may provide useful information regarding myocardial function and volume loading.


Update on imaging for functional endoscopic sinus surgery.
This article details the imaging modalities available for patients being considered for functional endoscopic sinus surgery. The pertinent radiologic anatomy is reviewed with an emphasis on normal variations. Imaging appearances of inflammatory sinus disease as well as postoperative appearances, including complications, are presented.


Developmental changes in neuronal sensitivity to excitatory amino acids in area CA1 of the rat hippocampus.
The laminar distribution of decreases in extracellular free calcium and concomitant field potentials induced by repetitive orthodromic stimulation, ionophoretic application of N-methyl-D-aspartate and quisqualate, was studied in the CA1 field of rat hippocampal slices, at two different stages during postnatal development. While stimulation-elicited and quisqualate-induced signals remain maximal in stratum pyramidale during the first postnatal month, the laminar profiles of responses to N-methyl-D-aspartate (NMDA) depend on age: the responses to this agonist are maximal in stratum pyramidale in 5-9-day-old rats and in stratum radiatum in 12-30-day-old rats. Our findings suggest that, during the second postnatal week, the apical dendrites of pyramidal neurons in area CAl become more sensitive to NMDA, which is expressed by big influxes of calcium at this level.


Hybrid Single-incision Laparoscopic Restorative Proctocolectomy with Ileal Pouch Anal Anastomosis for Ulcerative Colitis.
Single-incision laparoscopic surgery is a rapidly evolving field as a bridge between traditional laparoscopic surgery and natural orifice transluminal endoscopic surgery. We report one of the initial clinical experiences from India for Laparoscopic Restorative Proctocolectomy and Ileal Pouch Anal Anastomosis (RPC IPAA) with this new technique. A SILSTM port was used through the curved intra-umbilical 25-mm incision. A 12-mm port was placed in the right iliac fossa at the ileostomy site. Another 5 mm port was placed in the left iliac fossa at the drain site. 10 mm 0 degree lens was used through the SILS port. Two 5 mm port were placed from the SILS port. Right iliac fossa port was the surgeon's right hand port and left hand port was 5 mm SILS port. Left iliac fossa port and 5 mm SILS port were used by the assistant surgeon for retraction. The specimen was delivered through the umbilical incision by extending the incision for 1.5 cm on either side. Ileal J Pouch was created extracorporeally and then anastomosed to the anal canal with the circular stapler laparoscopically. The diverting loop ileostomy was brought out through the right iliac fossa 12 mm port. The pelvic drain was brought out through the left iliac fossa port. The procedure was completed without any perioperative complications. Operative time was 256 minutes. Postoperative follow-up did not reveal any umbilical wound complication. Till date we have performed 26 Laparoscopic RPC with IPAA and this was the first Single Incision Laparoscopic RPC with IPAA. For experienced laparoscopic colorectal surgeons, single incision laparoscopic colectomy (SILC) is feasible. Single-incision laparoscopic colectomy is a promising alternative method as minimally invasive abdominal surgery for the treatment of patients requiring colectomy.


Computer processing of x-ray films. Preliminary report on arteriograms.
An X-ray processing system by computer is described. The scanning device and display are illustrated. The main processing methods are analyzed, in particular the linear and non linear ones. An example of image processing which is the base for future work is shown.


Structure of the Yersinia pestis FabV enoyl-ACP reductase and its interaction with two 2-pyridone inhibitors.
The recently discovered FabV enoyl-ACP reductase, which catalyzes the last step of the bacterial fatty acid biosynthesis (FAS-II) pathway, is a promising but unexploited drug target against the reemerging pathogen Yersinia pestis. The structure of Y. pestis FabV in complex with its cofactor reveals that the enzyme features the common architecture of the short-chain dehydrogenase reductase superfamily, but contains additional structural elements that are mostly folded around the usually flexible substrate-binding loop, thereby stabilizing it in a very tight conformation that seals the active site. The structures of FabV in complex with NADH and two newly developed 2-pyridone inhibitors provide insights for the development of new lead compounds, and suggest a mechanism by which the substrate-binding loop opens to admit the inhibitor, a motion that could also be coupled to the interaction of FabV with the acyl-carrier protein substrate.


Purification and characterization of the Escherichia coli exoribonuclease RNase R. Comparison with RNase II.
Escherichia coli RNase R, a 3' --> 5' exoribonuclease homologous to RNase II, was overexpressed and purified to near homogeneity in its native untagged form by a rapid procedure. The purified enzyme was free of nucleic acid. It migrated upon gel filtration chromatography as a monomer with an apparent molecular mass of approximately 95 kDa, in close agreement with its expected size based on the sequence of the rnr gene. RNase R was most active at pH 7.5-9.5 in the presence of 0.1-0.5 mm Mg(2+) and 50-500 mm KCl. The enzyme shares many catalytic properties with RNase II. Both enzymes are nonspecific processive ribonucleases that release 5'-nucleotide monophosphates and leave a short undigested oligonucleotide core. However, whereas RNase R shortens RNA processively to di- and trinucleotides, RNase II becomes more distributive when the length of the substrate reaches approximately 10 nucleotides, and it leaves an undigested core of 3-5 nucleotides. Both enzymes work on substrates with a 3'-phosphate group. RNase R and RNase II are most active on synthetic homopolymers such as poly(A), but their substrate specificities differ. RNase II is more active on poly(A), whereas RNase R is much more active on rRNAs. Neither RNase R nor RNase II can degrade a complete RNA-RNA or DNA-RNA hybrid or one with a 4-nucleotide 3'-RNA overhang. RNase R differs from RNase II in that it cannot digest DNA oligomers and is not inhibited by such molecules, suggesting that it does not bind DNA. Although the in vivo function of RNase R is not known, its ability to digest certain natural RNAs may explain why it is maintained in E. coli together with RNase II.


Chemical characterization and bioactive potential of Thymus×citriodorus (Pers.) Schreb. preparations for anti-acne applications: Antimicrobial, anti-biofilm, anti-inflammatory and safety profiles.
Thymus × citriodorus (Pers.) Schreb. is an interspecific hybrid between Thymus pulegioides and Thymus vulgaris, known for its pharmacological activities as diaphoretic, deodorant, antiseptic and disinfectant, the last mostly related with its antimicrobial activity. The folk use of other extracts, as hydrolates, have also been disseminated, as regulators of oily skin with anti-acne effect. We aimed to evaluate the anti-acne potential of two Thymus x citriodorus (TC) preparations, the essential oil (EO) and the hydrolate, to be used as active ingredients for skin applications. Specifically, we intend to validate their anti-acne potential by describing their activity on acne related bacteria, bacterial virulence, anti-oxidant and anti-inflammatory potential, and biocompatibility on inflammatory cells. Additionally, we aimed to report their ecotoxicity under the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), thus focusing not only on the consumer, but also on environmental safety assessment. Minimum inhibitory concentration (MIC) against C. acnes, S. aureus and S. epidermidis was evaluated. Minimum lethal concentration (MLC) was also determined. The effect on C. acnes biofilm formation and disruption was evaluated with crystal violet staining. Anti-inflammatory activity was investigated on LPS-stimulated mouse macrophages (RAW 264.7), by studying nitric oxide (NO) production (Griess reagent) and cellular biocompatibility through MTT assay. In-vitro NO and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging potential were also evaluated. The ecotoxicity was evaluated using Daphnia magna acute toxicity assays. EO presented direct antimicrobial activity, with visual MICs ranging from 0.06% for S. epidermidis and C. acnes to 0.125% for S. aureus. MLCs were higher than the obtained MICs. Hydrolate revealed visual MIC only for C. acnes. TC essential oil was effective in preventing biofilm formation and disrupting preformed biofilms even at sub-inhibitory concentrations. Hydrolate showed a more modest anti-biofilm effect. Regarding anti-inflammatory activity, TC hydrolate has a higher cellular biocompatibility. Still, both plant preparations were able to inhibit at least 50% of NO production at non-cytotoxic concentrations. Both EO and hydrolate have poor anti-oxidant activities. Regarding the ecotoxicity, TC essential oil was classified under acute 3 category, while the hydrolate has proved to be nontoxic, in accordance to the GHS. These results support the anti-acne value of different TC preparations for different applications. TC hydrolate by presenting higher biocompatibility, anti-inflammatory potential and the ability to modulate C. acnes virulence, can be advantageous in a product for everyday application. On the other hand, EO by presenting a marked antimicrobial, anti-biofilm and anti-inflammatory activities, still with some cytotoxicity, may be better suited for application in acute flare-ups, for short treatment periods.


Isolation of porcine monocyte population: a simple and efficient method.
Monocytes are important mediators of inflammatory processes and are in the focus of immunological studies. While the preparation of human monocytes is widely established, little is published on the isolation of porcine monocytes for experimental studies. The aim of this study is to establish a cost efficient method of preparing and culturing porcine monocytes of considerable purity and reasonable yield. In our method, we combined and modified different protocols of human monocyte preparation. The blood of a single pig is harvested and treated with EDTA to prevent coagulation. Peripheral blood mononuclear cells are obtained by a density gradient centrifugation using a Bicoll gradient and monocytes are harvested by culturing on serum-treated culture flasks, rinsing and tapping. A high yield is obtained by constant cooling of flasks and tubes. The purity of the culture is evaluated by the expression of CD14, using flow cytometry. Using this method, we reached a purity of 92.6 % (± 3.06 %). With this procedure, we established a reliable method to prepare and cultivate porcine monocytes which can be performed cost effectively and does not require special equipment.


Protective effect of a novel antioxidative peptide purified from a marine Chlorella ellipsoidea protein against free radical-induced oxidative stress.
Protein derived the marine Chlorella ellipsoidea was hydrolyzed using different proteases (papain, trypsin, pepsin and α-chymotrypsin) for production of antioxidative peptide, and the antioxidant activities of their hydrolysates were investigated using free radical scavenging assay by electron spin resonance spin-trapping technique. Among the hydrolysates, the peptic hydrolysate exhibited the highest antioxidant activity compared to other hydrolysates. To identify antioxidant peptide, the peptic hydrolysate was purified using consecutive chromatographic methods, and the antioxidant peptide was identified to be Leu-Asn-Gly-Asp-Val-Trp (702.2 Da) by Q-TOF ESI mass spectroscopy. The antioxidant peptide scavenged peroxyl, DPPH and hydroxyl radicals at the IC(50) values of 0.02, 0.92 and 1.42 mM, respectively. The purified peptide enhanced cell viability against AAPH-induced cytotoxicity on normal cells. Furthermore, the purified peptide reduced the proportion of apoptotic and necrotic cells induced by AAPH, as demonstrated by decreased sub-G(1) hypodiploid cells and decreased apoptotic body formation by flow cytometry.


Draft Genome Sequence of a Pasteurella multocida Strain Isolated from a Spotted Deer (Axis axis) in India.
Here, we report the genome sequence of a Pasteurella multocida strain isolated from the heart blood of a spotted deer (Bareilly, India). The 2.44-Mbp genome has 2,227 coding sequences, with a G+C content of 40.7%.


A pan-cancer assessment of alterations of the kinase domain of ULK1, an upstream regulator of autophagy.
Autophagy is a key clearance process to recycle damaged cellular components. One important upstream regulator of autophagy is ULK1 kinase. Several three-dimensional structures of the ULK1 catalytic domain are available, but a comprehensive study, including molecular dynamics, is missing. Also, an exhaustive description of ULK1 alterations found in cancer samples is presently lacking. We here applied a framework which links -omics data to structural protein ensembles to study ULK1 alterations from genomics data available for more than 30 cancer types. We predicted the effects of mutations on ULK1 function and structural stability, accounting for protein dynamics, and the different layers of changes that a mutation can induce in a protein at the functional and structural level. ULK1 is down-regulated in gynecological tumors. In other cancer types, ULK2 could compensate for ULK1 downregulation and, in the majority of the cases, no marked changes in expression have been found. 36 missense mutations of ULK1, not limited to the catalytic domain, are co-occurring with mutations in a large number of ULK1 interactors or substrates, suggesting a pronounced effect of the upstream steps of autophagy in many cancer types. Moreover, our results pinpoint that more than 50% of the mutations in the kinase domain of ULK1, here investigated, are predicted to affect protein stability. Three mutations (S184F, D102N, and A28V) are predicted with only impact on kinase activity, either modifying the functional dynamics or the capability to exert effects from distal sites to the functional and catalytic regions. The framework here applied could be extended to other protein targets to aid the classification of missense mutations from cancer genomics studies, as well as to prioritize variants for experimental validation, or to select the appropriate biological readouts for experiments.


Effectiveness of the custom-mold room temperature vulcanizing silicone toe separator on hallux valgus: A prospective, randomized single-blinded controlled trial.
Silicone toe separator is considered as a conservative treatment for hallux valgus. The prefabricated toe separator does not fit all. However, effectiveness in prescription of the custom-mold toe separator is still unknown. To investigate the effect of using a custom-mold room temperature vulcanizing silicone toe separator to decrease hallux valgus angle and hallux pain. The compliances, complications, and satisfactions of toe separator were also explored. A prospective, randomized single-blinded controlled trial. A total of 90 patients with a moderate degree of hallux valgus were enrolled in a study at the Foot Clinic, Siriraj Hospital, Thailand. Patients were randomized into two groups; the study group was prescribed a custom-mold room temperature vulcanizing silicone toe separator for 6 h per night for 12 months. Patients in both groups received proper foot care and shoes and were permitted to continue drug treatment. In total, 40 patients in the study group and 39 patients in the control group completed the study. The hallux valgus angle was obtained through radiographic measurement. At month 12, both groups had significant differences in mean hallux valgus angle with a decrease of 3.3° ± 2.4° for the study group and increase of 1.9° ± 1.9° for the control group. There were statistically significant differences of hallux valgus angle between the two groups ( p < 0.05) at the end of the study. Hallux pain was decreased in the study group. A custom-mold room temperature vulcanizing silicone toe separator can decrease hallux valgus angle and pain with no serious complications. Clinical relevance The custom-mold room temperature vulcanizing silicone toe separator for treatment of hallux valgus reduces deformity and hallux pain.


Influence of amino acid size at the P3 position of N-Cbz-tripeptide Michael acceptors targeting falcipain-2 and rhodesain for the treatment of malaria and human african trypanosomiasis.
In recent decades, several structure-activity relationship (SAR) studies provided potent inhibitors of the cysteine proteases falcipain-2 (FP-2) and rhodesain (RD) from Plasmodium falciparum and Trypanosoma brucei rhodesiense, respectively. Whilst the roles of the warhead and residues targeting the P1 and P2 pockets of the proteases were extensively investigated, the roles of the amino acids occupying the S3 pocket were not widely assessed. Herein we report the synthesis and biological evaluation of a set of novel Michael acceptors bearing amino acids of increasing size at the P3 site (1a-g/2a-g, SPR20-SPR33) against FP-2, RD, P. falciparum, and T. brucei. Overall, the Michael acceptors bearing small amino acids at the P3 site exhibited the most potent inhibitory properties towards FP-2. In contrast, analogues with bulky residues at the P3 position were very potent rhodesain inhibitors. In cell based assays, single-digit micromolar EC50 values against the two protozoa were observed. These findings can be a starting point for the development of peptide-based FP-2 and RD inhibitors.


Binding kinetics redefine the antagonist pharmacology of the corticotropin-releasing factor type 1 receptor.
Corticotropin-releasing factor (CRF) receptor antagonists are under preclinical and clinical investigation for stress-related disorders. In this study the impact of receptor-ligand binding kinetics on CRF₁ receptor antagonist pharmacology was investigated by measuring the association rate constant (k₁), dissociation rate constant (k₋₁), and kinetically derived affinity at 37°C. Three aspects of antagonist pharmacology were reevaluated: comparative binding activity of advanced compounds, in vivo efficacy, and structure-activity relationships. Twelve lead compounds, with little previously noted difference of affinity, varied substantially in their kinetic binding activity with a 510-fold range of kinetically derived affinity (k₋₁/k₁), 170-fold range of k₋₁, and 13-fold range of k₁. The k₋₁ values indicated previous affinity measurements were not close to equilibrium, resulting in compression of the measured affinity range. Dissociation was exceptionally slow for three ligands (k₋₁ t(1/2) of 1.6-7.2 h at 37°C). Differences of binding behavior were consistent with in vivo pharmacodynamics (suppression of adrenocorticotropin in adrenalectomized rats). Ligand concentration-effect relationships correlated with their kinetically derived affinity. Two ligands that dissociated slowly (53 and 130 min) produced prolonged suppression, whereas only transient suppression was observed with a more rapidly dissociating ligand (16 min). Investigating the structure-activity relationship indicated exceptionally low values of k₁, approaching 100,000-fold less than the diffusion-limited rate. Retrospective interpretation of medicinal chemistry indicates optimizing specific elements of chemical structure overcame kinetic barriers in the association pathway, for example, constraint of the pendant aromatic orthogonal to the ligand core. Collectively, these findings demonstrate receptor binding kinetics provide new dimensions for understanding and potentially advancing the pharmacology of CRF₁ receptor antagonists.


Nasal valve repair (NVR) utilization and economic impact in the U.S. medicare population: 18-year trends.
Nasal valve repair (NVR) is an otolaryngological procedure indicated for the surgical correction of airway obstruction or collapse. Despite its growing popularity, the deployment and financial impact for NVR have not been well-described. Here, we evaluate trends in NVR utilization in the U.S. Medicare population on the state and national levels from 2001 to 2018. Historical utilization and reimbursement databases compiled by the U.S. Centers for Medicare & Medicaid Services (CMS) were queried for current procedural terminology (CPT) code 30465. Analyses were performed using Microsoft Excel v16. Nationally, we observed a 989.60% increase in the total number of NVRs performed annually (611.07% adjusted to growing enrollment). Concomitantly, total reimbursement increased by 2025.52% (878.29% adjusted), though the average cost per procedure only rose moderately (37.58%). From 2013 to 2018, the majority of providers were male (74.79%), with an M.D. (71.37%), practicing as individuals (76.5%), operating in a facility setting (93.59%), and classified as otolaryngologists (63.25%). In 2018, Indiana had the highest utilization rate, whereas Oregon received the largest reimbursement. Connecticut had the lowest values in both categories. The utilization and financial impact of NVR have increased substantially among the U.S. Medicare population over the last two decades.


High-frequency water quality time series in precipitation and streamflow: from fragmentary signals to scientific challenge.
Eighteen months of 7-hourly analyses of rainfall and stream water chemistry are presented, spanning a wide range of chemical determinands and building on over 20 years of weekly records for the moorland headwaters of the river Severn. The high-frequency time series data show that hydrochemical responses to major hydrological and biological drivers of short-term variability in rainfall and rivers are not captured by conventional low-frequency monitoring programmes. A wealth of flow related, flow independent, diurnal, seasonal and annual fluctuations indicate a cacophony of interactions within the catchment and stream. The complexity of the chemical dynamics is visually obvious, although there appears to be no clear way of translating this complexity into a simple algorithm. The work provides a proof of concept for the complex structure of catchment functioning revealed by extensive high-frequency measurements coupled with high analytical sensitivity and reproducibility. It provides new insights into hydrogeochemical functioning and a novel resource for catchment modelling.


Enantiomeric specificity at the deacylation process of tryptic catalysis.
Trypsin-specific substrate analogs, 'inverse substrates', carrying chiral acyl group were synthesized. Kinetic analysis of the trypsin-catalyzed hydrolysis of these substrates revealed that the deacylation process is also appropriate for discrimination between enantiomers. The enantiomeric preference during the deacylation process was analyzed by comparing the hydrolytic rates corresponding to eight enantiomeric pairs of the substrates. The spatial requirement of the enzyme active site for catalytic efficiency is discussed, based on the steric characteristics of the optically active acyl residues.


Definitive concurrent chemoradiotherapy with paclitaxel plus carboplatin is superior to cisplatin plus 5-fluorouracil in patients with inoperable esophageal squamous cell carcinoma using retrospective, real-world evidence.
The optimal definitive chemotherapy regimen during concurrent chemoradiotherapy (CRT) for patients with advanced esophageal squamous cell carcinoma (ESCC) remains unclear because of conflicting evidence. This study aimed to compare the effectiveness of taxane-based chemotherapy with that of conventional cisplatin plus 5-fluorouracil (PF) as the chemotherapy regimen in definitive CRT for ESCC. This retrospective study included patients with ESCC who received paclitaxel plus carboplatin (PC) or PF during definitive CRT between May 2012 and February 2015 in a medical center in Taiwan. Survival outcomes were compared after adjustment for risk factors. Overall, 229 patients were evaluated. Patients in the PC group had an objective response rate of 71.1% compared with the 51.4% of the PF group (p = 0.016). The PC group showed a significantly longer progression-free survival (PFS, p = 0.002) and overall survival (OS, p = 0.019) than the PF group. Salvage surgery also helped prolong both the PFS and OS (p < 0001). Sex (male vs. female, HR, 1.831; 95% CI, 1.016-3.303), clinical stage (HR, 1.282; 95% CI, 1.069-1.537), accumulative radiation dose (≥41.4 Gy vs. <41.4 Gy; HR, 0.640; 95% CI, 0.413-0.993), salvage surgery (yes vs. no, HR: 0.412, 95% CI: 0.298-0.570), and regimen (PF vs. PC; HR, 1.514; 95% CI, 1.109-2.067) were independent prognostic factors for cancer mortality. Compared with the PF regimen, the PC regimen for definitive CRT yielded significantly increased response rates and longer survival times; therefore, the PC regimen may be preferable for chemotherapy for definitive CRT in patients with advanced ESCC.


Equity and extramarital sexuality.
Equity theory has recently been found to be a useful framework for understanding the effects of imbalances in intimate "contractual" relationships such as marriage. Equitable couples seem to be happier, more satisfied with their relationship, and more confident that it will last than are their more mismatched, i.e., inequitable, counterparts. Furthermore, inequitable couples predictably act to "set things right" in their marriage. They either restore actual equity to the relationship or psychologically set their relationship in balance. If neither works, they may "leave the field." Extramarital sex may be viewed as an equity restoration mechanism in that (1) it may be used by the deprived partner to achieve actual equity, (2) it may indicate a partner's readiness to leave the relationship because he feels he can "do better," or (3) it may represent a desire to achieve equity in an alternative relationship(s) when inequity pervades the primary one. The hypothesis that the inequitable/underbenefited group should be more likely than the equitable group or the inequitable/overbenefited group to have engaged in extramarital sex was tested using data from a large-scale Psychology Today questionnaire. The results indicated that men and women in inequitable/underbenefited relationships had more extramarital affairs and began their extramarital activities earlier than did men and women in equitable and inequitable/overbenefited relationships. Alternative explanations of this finding, sex-role demands and length of the relationship, are explored and discarded as untenable.


Selective removal of cobalt and copper from Fe (III)-enriched high-pressure acid leach residue using the hybrid bioleaching technique.
Removal of metals from high pressure acid leaching (HPAL) residue was essential to alleviate potential environmental threat and avoid valuable metals loss. However, cost-effective metals extraction from HPAL residue remains a difficulty. In this study, a hybrid bioleaching process was developed for Co and Cu extraction from HPAL residue of Cu-Co sulfide ores. Results for microbial community structure optimization showed that moderate thermophilum consortium with coexistence of iron oxidizer and sulfur oxidizer was more efficient on metal extraction compared with mesophiles. Further addition of citric acid, Fe (II) and S0 significantly enhanced the release of metals through improving the total biomass, attached cells and community diversity. As a result, 87.91% of cobalt and 58.52% of copper were extracted at initial pH 1.4 and pulp density of 50 g/L by hybrid bioleaching. The hazardous potential assessments revealed that the bioleached residue could be disposed safely. These findings demonstrated that organic acids assisting bioleaching with community adjusting was a promising strategy for metals removal from HPAL residue.


Provision of onsite HIV Services in Substance Use Disorder Treatment Programs: A Longitudinal Analysis.
The provision of HIV education and testing in substance use disorder (SUD) treatment programs is an important public health strategy for reducing HIV incidence. For many at-risk individuals, SUD treatment represents the primary point of access for testing and receiving HIV-related services. This study uses two waves of nationally representative data of 265 privately-funded SUD treatment programs in the U.S. to examine organizational and patient characteristics associated with offering a dedicated HIV/AIDS treatment track, onsite HIV/AIDS support groups, and onsite HIV testing. Our longitudinal analysis indicated that the majority of treatment programs reported providing education and prevention services, but there was a small, yet significant, decline in the number of programs providing these services. Programs placed more of an emphasis on providing information on the transmission of HIV rather than on acquiring risk-reduction skills. There was a notable and significant increase (from 26.0% to 31.7%) in programs that offered onsite HIV testing, including rapid HIV testing, and an increase in the percentage of patients who received testing in the programs. Larger programs were more likely to offer a dedicated HIV/AIDS treatment track and to offer onsite HIV/AIDS support groups, while accredited programs and programs with a medical infrastructure were more likely to provide HIV testing. The percentage of injection drug users was positively linked to the availability of specialized HIV/AIDS tracks and HIV/AIDS support groups, and the percentage of female clients was associated with the availability of onsite support groups. The odds of offering HIV/AIDS support groups were also greater in programs that had a dedicated LGBT track. The findings suggest that access to hospitals and medical care services is an effective way to facilitate adoption of HIV services and that programs are providing a needed service among a group of patients who have a heightened risk of HIV transmission. Nonetheless, the fact that fewer than one third of programs offered onsite testing, and, of the ones that did, fewer than one third of their patients received testing, raises concern in light of federal guidelines.


Routine clinical examination is not sufficient for diagnosing and locating deeply infiltrating endometriosis.
To determine whether routine clinical examination is sufficient for the diagnosis and establishing the location of deeply infiltrating endometriosis (DIE). Retrospective analysis (Canadian Task Force classification II-2). University-affiliated hospital. Patients. One hundred sixty women with histologically proved deeply infiltrating endometriosis. Speculum examination allowed endometriotic lesions to be viewed in only 14.4% (23) of patients, and a classic, painful, spheric nodule was palpated in only 43.1% (69). Results of routine clinical examination varied significantly with location of DIE. Whereas a nodule was found in 80.0% (24) of patients with vaginal endometriosis, this rate dropped to only 35.3% (6) and 33.3% (34) in those with DIE of the digestive tract and uterosacral ligaments, respectively (p <0.0001). High locations of DIE lesions at the level of uterosacral ligaments, bottom of the pouch of Douglas, and upper one-third of the posterior vaginal wall explain why results of routine clinical examination are so poor. The term "deep endometriosis infiltrating the rectovaginal septum" is generally incorrect in the true anatomic sense.


Wearable systems for shoulder kinematics assessment: a systematic review.
Wearable sensors are acquiring more and more influence in diagnostic and rehabilitation field to assess motor abilities of people with neurological or musculoskeletal impairments. The aim of this systematic literature review is to analyze the wearable systems for monitoring shoulder kinematics and their applicability in clinical settings and rehabilitation. A comprehensive search of PubMed, Medline, Google Scholar and IEEE Xplore was performed and results were included up to July 2019. All studies concerning wearable sensors to assess shoulder kinematics were retrieved. Seventy-three studies were included because they have fulfilled the inclusion criteria. The results showed that magneto and/or inertial sensors are the most used. Wearable sensors measuring upper limb and/or shoulder kinematics have been proposed to be applied in patients with different pathological conditions such as stroke, multiple sclerosis, osteoarthritis, rotator cuff tear. Sensors placement and method of attachment were broadly heterogeneous among the examined studies. Wearable systems are a promising solution to provide quantitative and meaningful clinical information about progress in a rehabilitation pathway and to extrapolate meaningful parameters in the diagnosis of shoulder pathologies. There is a strong need for development of this novel technologies which undeniably serves in shoulder evaluation and therapy.


Automatic detection and classification of peri-prosthetic femur fracture.
Object classification and localization is a key task of computer-aided diagnosis (CAD) tool. Although there have been numerous generic deep learning (DL) models developed for CAD, there is no work in the literature to evaluate their effectiveness when utilized in diagnosing fractures in proximity of joint implants. In this work, we aim to assess the performance of existing classification systems on binary and multi-class problems (fracture types) using plain radiographs. In addition, we evaluated the performance of object detection systems using the one- and two-stage DL architectures. A data set of 1272 X-ray images of Peri-prosthetic Femur Fracture PFF was collected. The fractures were annotated with bounding boxes and classified according to the Vancouver Classification System (type A, B, C) by two clinical specialists. Four classification models such as Densenet161, Resnet50, Inception, VGG and two object detection models such as Faster RCNN and RetinaNet were evaluated, and their performance compared. Six confusion matrix-based measures were reported to evaluate fracture classification. For localization of the fracture, Average Precision and localization accuracy were reported. The Resnet50 showed the best performance with [Formula: see text] accuracy and [Formula: see text] F1-score in the binary classification: fracture/normal. In addition, the Resnet50 showed [Formula: see text] accuracy in multi-classification (normal, Vancouver type A, B and C). A large data set of PFF images and the annotations of fracture features by two independent assessments were created to implement a DL-based approach for detecting, classifying and localizing PFFs. It was shown that this approach could be a promising diagnostic tool of fractures in proximity of joint implants.


The association between renal stones and fasting: A systematic review.
Fasting is a common cultural practice worldwide for both religious and dietary reasons. However, there is concern that fasting may be a risk factor for the development of renal stones. To date, there has not been a systematic assessment of the literature regarding the association between renal stones and fasting. We conducted a systematic review following PRISMA guidelines of three databases: Medline-OVID, EMBASE, and CINAHL. All screening and extraction was completed in parallel with two independent reviewers. Of the 1501 database citations, a total of 10 observational studies with a total of 9906 participants were included. Nine of the studies were conducted in the context of Islamic fasting during Ramadan, with the majority (7/9) finding that renal colic incidence was unaffected by the month of fasting. In contrast, two studies noted an increased incidence among fasting populations. Two other studies noted that urine metabolites and density were altered with fasting but did not translate into clinical outcomes. Based on the available evidence, it is unlikely that fasting significantly increases the risk of renal stones. Physicians should counsel higher-risk patients on safe fasting practices.


Serotonin increases population coding of behaviorally relevant stimuli by enhancing responses of ON but not OFF-type sensory neurons.
How neural populations encode sensory input to generate behavioral responses remains a central problem in systems neuroscience. Here we investigated how neuromodulation influences population coding of behaviorally relevant stimuli to give rise to behavior in the electrosensory system of the weakly electric fish Apteronotus leptorhynchus. We performed multi-unit recordings from ON and OFF sensory pyramidal cells in response to stimuli whose amplitude (i.e., envelope) varied in time, before and after electrical stimulation of the raphe nuclei. Overall, raphe stimulation increased population coding by ON- but not by OFF-type cells, despite both cell types showing similar sensitivities to the stimulus at the single neuron level. Surprisingly, only changes in population coding by ON-type cells were correlated with changes in behavioral responses. Taken together, our results show that neuromodulation differentially affects ON vs. OFF-type cells in order to enhance perception of behaviorally relevant sensory input.


Optoelectronic plethysmography demonstrates abrogation of regional chest wall motion dysfunction in patients with pectus excavatum after Nuss repair.
We previously demonstrated that patients with pectus excavatum (PE) have significantly decreased chest wall motion at the pectus defect compared with the rest of the chest vs unaffected individuals and use abdominal respiratory contributions to compensate for decreased upper chest wall motion. We hypothesize that PE repair will reverse chest wall motion dysfunction. A prospective, institutional review board-approved study compared patients with PE before and after Nuss repair. Informed consent was obtained before motion analysis. Sixty-four patients with uncorrected PE ages 10 to 21 years underwent optoelectronic plethysmography analysis. Repeat analysis was performed in 42 patients 6 months postoperative (PO). Volume of the chest wall and its subdivisions were calculated. Total chest wall volume at rest was significantly increased after repair and in each thoracic compartment. PO patients developed increased midline marker excursion at the pectus defect and significantly decreased excursion at the level of the umbilicus. Optoelectronic plethysmography kinematic analysis demonstrates that chest wall remodeling during Nuss repair results in increased thoracic volume. Chest wall motion dysfunction at the pectus defect is reversed after Nuss repair. Abdominal respiratory contributions are also markedly decreased. These findings may help to explain why patients with PE report an improvement in endurance after the Nuss procedure.


Primary squamous cell carcinoma of the colorectum: case report and literature review of a rare entity.
A case of primary squamous cell carcinoma of the rectum is presented. Although it is a rare condition, the diagnosis, treatment, and natural history of the disease are similar to that of adenocarcinoma of the colorectum. The patient in this report has done well to date with an abdominal perineal resection and early post-operative radiation. A review of the literature reveals that the precise etiology of this entity remains unknown.


Lesions of the anterior thalamic nuclei and intralaminar thalamic nuclei: place and visual discrimination learning in the water maze.
Medial thalamic damage produces memory deficits in humans (e.g., Korsakoff's syndrome) and experimental animals. Both the anterior thalamic nuclei (ATN) and rostral intralaminar plus adjacent lateral thalamic nuclei (ILN/LT) have been implicated. Based on the differences in their main connections with other neural structures, we tested the prediction that ATN lesions would selectively impair acquisition of spatial location discrimination, reflecting a hippocampal system deficit, whereas ILN/LT lesions would impair acquisition of visual pattern discrimination, reflecting a striatal system deficit. Half the rats were first trained in a spatial task in a water maze before switching to a visual task in the same maze, while the remainder were tested with the reverse order of tasks. Compared with sham-operated controls, (1) rats with ATN lesions showed impaired place learning, but normal visual discrimination learning, (2) rats with ILN/LT lesions showed no deficit on either task. Rats with ATN lesions were also hyperactive when their home cage was placed in a novel room and remained more active than ILN/LT or SHAM rats for the subsequent 21 h, especially during the nocturnal phase. These findings confirmed the influence of ATN lesions on spatial learning, but failed to support the view that ILN/LT lesions disrupt striatal-dependent memory.


The on-line charge breeding program at TRIUMF's Ion Trap For Atomic and Nuclear Science for precision mass measurements.
TRIUMF's Ion Trap for Atomic and Nuclear science (TITAN) constitutes the only high precision mass measurement setup coupled to a rare isotope facility capable of increasing the charge state of short-lived nuclides prior to the actual mass determination in a Penning trap. Recent developments around TITAN's charge breeder, the electron beam ion trap, form the basis for several successful experiments on radioactive isotopes with half-lives as low as 65 ms and in charge states as high as 22+.


Optimization of conditions for high-performance size-exclusion chromatography of different soil humic acids.
A method of high-performance size-exclusion chromatography (HPSEC) for a wide variety of soil humic acids (HAs) was developed. Two types of soil HAs (Cambisol and Andosol HAs), which have substantially different chemical properties, showed different effects of salt and organic solvent concentrations in the eluent on chromatograms. A Shodex OHpak SB-805 HQ column with 10 mM sodium phosphate buffer (pH 7.0) containing 25% of acetonitrile (v/v) was found to be applicable for different HAs, and showed high reproducibility and recovery (87.0 - 94.5%). The Cambisol HA was fractionated into five fractions using an ultrafiltration with different molecular-weight cut-offs. The order of the molecular weights of the five fractions calculated from the HPSEC analysis corresponded to that defined by ultrafiltration. This supported the reliability of the method.


The genetic and pharmacogenomic landscape of snoRNAs in human cancer.
Emerging evidence has revealed significant roles for small nucleolar RNAs (snoRNAs) in tumorigenesis. However, the genetic and pharmacogenomic landscape of snoRNAs has not been characterized. Using the genotype and snoRNA expression data from The Cancer Genome Atlas, we characterized the effects of genetic variants on snoRNAs across 29 cancer types and further linked related alleles with patient survival as well as genome-wide association study risk loci. Furthermore, we characterized the impact of snoRNA expression on drug response in patients to facilitate the clinical utility of snoRNAs in cancer. We also developed a user-friendly data resource, GPSno (http://hanlab.uth.edu/GPSno), with multiple modules for researchers to visualize, browse, and download multi-dimensional data. Our study provides a comprehensive genetic and pharmacogenomic landscape of snoRNAs, which will shed light on future clinical considerations for the development of snoRNA-based targeted therapies.


Insulin-like growth factor I enhances gonadotropin-releasing hormone-stimulated luteinizing hormone release from bovine anterior pituitary cells.
The role of insulin-like growth factor I (IGF-I) in the release of luteinizing hormone (LH) is unclear in ruminants. In the present study, the effects of IGF-I on the release of LH stimulated by gonadotropin-releasing hormone (GnRH) were examined in primary cultures of bovine anterior pituitary (AP) cells, and the interaction between estradiol-17beta (E(2)) and IGF-I was characterized. GnRH(100nM)-stimulated LH release from the cultured cells was increased (P<0.05) 12, 24 and 36h after addition of IGF-I (250ng/ml), with a maximum at 12h (48.4ng/ml media versus 35.4ng/ml media in controls). IGF-I at concentrations of 25, 250 and 500ng/ml increased the release by 18.7, 24.2 and 28.9%, respectively (P<0.05), when compared with controls (37.2ng/ml media). E(2) (10nM), IGF-I (250ng/ml) and combined treatment of E(2) plus IGF-I also induced significant increases in LH release (P<0.05). The amounts of LH release after treatment with E(2) alone was 37.3% greater than with IGF-I alone (39.0ng/ml media versus 28.4ng/ml media) (P<0.05). When E(2) and IGF-I were added together (45.6ng/ml media), the release of LH was significantly greater than with either E(2) alone or IGF-I alone (P<0.05). E(2) (10nM) significantly (P<0.05) increased the amount of GnRH bound to the cells by 51.6% when compared with controls, however, IGF-I (250ng/ml) failed to increase GnRH binding. These results show that IGF-I enhances GnRH-stimulated LH release without changing the number of GnRH receptors in cattle, and IGF-I interacts with E(2) to increase the response to GnRH.


[A chromatographic method of analysis of mixtures of methylethyl ketone, n-butyl alcohol, xylene, ethylene glycol, ethylene glycol acetate, cyclohexanol, cyclohexanone and butyl glycol vapors in the air].
A gas chromatographic method for the determination of the mixture of organic solvents in air has been developed. The optimum conditions of the separation of the mixture were obtained in the column packed with 10% UCON HB 2000 coated on Chromosorb W AW DMCS 80-100 mesh. The components of the mixture are collected on activated charcoal and desorbed with CS2. A quantitative analysis is made using methyl isobutyl ketone as an internal standard. The lowest detectable limit under proposed air sampling and analysis conditions is 0.1 TLV (threshold limit value) for each component of the mixture.


Characterisation of influenza viruses isolated from turkeys in Great Britain during 1963--1977.
Seven influenza viruses isolated from turkeys in Great Britain since 1963 were typed by haemagglutination inhibition and neuraminidase inhibition tests as: A/turkey/England/63 (Hav 1 Nav 3), A/turkey/England/66 (Hav 6 N2), A/turkey/England/69 (Hav 7 N2), A/turkey/Scotland/70 (Hav ? Neq 1), A/turkey/England/N28/73 (Hav 5 N2), A/turkey/England/110/77 (Hav 6 N2), A/turkey/England/647/77 /Hav 1 Neq 1). A/turkey/Scotland/70 failed to show a haemagglutinin relationship with any of the representative strains and may possess a hitherto unreported haemagglutinin subtype. Intravenous pathogenicity tests in six-week-old birds showed only A/turkey/England/63 to have high virulence for turkeys and chickens. A/turkey/England/69 produced some signs of disease in chickens and, to a lesser extent, turkeys but all other isolates were avirulent.


Congenital Segmental Absence of Tracheal Rings in a Kitten.
Congenital anomalies of the trachea are rare in cats. This article reports segmental absence of tracheal cartilage rings in a kitten. An 8-month-old female kitten was presented with a history of weight loss and respiratory distress for 2 months. Radiographs of the thorax demonstrated a large air-filled sac suggestive of pneumomediastinum. No cartilaginous structures were evident radiographically over the caudal portion of the trachea. At necropsy examination, approximately 2 cm from the carina, a 3 cm segment of the trachea lacked cartilaginous rings. The clinical and morphological features of this lesion were similar to those described in human and canine cases of congenital segmental absence of tracheal rings.


Kinetics of HB S gelation. Effect of alkylureas, ionic strength and other hemoglobins.
Using a light scattering (turbidity) method to estimate the delay time of gelation of deoxy hemoglobin S hemolysates, we have examined the effects of various alkylureas, variations in ionic strength by addition of NaCl, and admixture with other hemoglobins on gelation kinetics. Each of these factors substantially prolonged the delay times to different extents, but the dependence of the delay times on a high power of the hemoglobin concentration varied only slightly. These findings suggest that the events preceding gelation, most likely the formation of nuclei, are affected by these factors, but the critical nuclear size for gelling is fairly constant. Parallel changes indicated good qualitative correlation between gelation, delay times, minimum gelling concentrations of solutions of mixed hemoglobins and kinetics of sickling of red cells containing these mixtures, with the exception of hemoglobin Charlem trait cells the sickling kinetics of which were slower than predicted by the solution properties.


Muscle mechanosensitive reflex is suppressed in the conscious condition: effect of anesthesia.
To test the hypothesis that a muscle mechanosensitive reflex is suppressed in the conscious condition, we examined the effect of anesthesia on the cardiovascular responses to passive mechanical stretch of the hindlimb triceps surae muscle in six conscious cats. The triceps surae muscle was manually stretched for 30 s by extending the hip and knee joints and subsequently by dorsiflexing the ankle joint; the lateral gastrocnemius muscle was lengthened by 19 +/- 2.6 mm. Heart rate (HR) and mean arterial blood pressure (MAP) did not change significantly during passive stretch of the muscle in the conscious condition. At 10-40 min after intravenously administering pentobarbital sodium (20-25 mg/kg), the identical passive stretch of the triceps surae muscle was able to induce the cardiovascular responses; HR and MAP were increased by 14 +/- 1.3 beats/min and 14 +/- 1.4 mmHg, respectively, and the cardiovascular responses were sustained throughout the passive stretch. In contrast, stretching skin on the triceps surae muscle evoked no significant changes in HR and MAP in the anesthetized condition. When anesthesia became light 40-90 min after injection of pentobarbital and the animals started to show spontaneous body movement, the cardiovascular response to passive muscle stretch tended to be blunted again. It is therefore concluded that passive mechanical stretch of skeletal muscle is capable of evoking the reflex cardiovascular response, which is suppressed in the conscious condition but exaggerated by anesthesia.


Immunocytochemical localization of myosin, tropomyosin and actin in vestibular hair cells of human fetuses and cats.
Semithin sections (1 micron) of human fetuses and young cat vestibular epithelium embedded in Epon were reacted with primary antibodies raised against myosin, tropomyosin, and actin. The results were very similar in the two species. Myosin and tropomyosin were colocalized and strictly limited to an apical superficial corona arranged in a punctiform pattern. The stereocilia and cuticular plate were unreactive to myosin and tropomyosin antibodies. Actin antibodies stained the stereocilia, cuticular plate, and a marginal ring surrounding and underlying the cuticular plate. At this level, myosin and tropomyosin were not detected. This result suggests that the circumferential actin ring has a structural role. Colocalization of myosin, tropomyosin, and actin in a superficial area around the stereocilia bundle and along the apical surface of the hair cell imply that active processes could exist at the apex of certain sensory vestibular hair cells. The specificity of myosin antibodies and their cross-reactivity with different types of myosin are discussed.


Pharmacokinetic scale-up: accurate prediction of human pharmacokinetic profiles from animal data.
Ceftizoxime pharmacokinetic parameters from mice, rats, monkeys, and dogs were scaled allometrically and used to predict the value of each parameter in a 70-kg human. Three methods of interspecies pharmacokinetic scale-up provided accurate simulations of the human biexponential serum concentration-time profiles for a 1-g iv bolus and a 4-g, 30-min intravenous infusion. Successful scale-up of animal pharmacokinetic data can have tremendous impact during the preclinical assessment of new pharmaceutical compounds by providing reasonable estimates of pharmacokinetic parameters in humans.


An unusual electrocardiographic presentation of acute obstruction of the left anterior descending coronary artery.
Acute obstruction of the left anterior descending coronary artery is generally presented electrocardiographically as isolated anterior or combined anterior and inferior ST-elevation myocardial infarction. We described an isolated inferolateral ST-elevation myocardial infarction due to acute occlusion of the distal left anterior descending coronary artery.


Sentinel lymph node mapping alone compared to more extensive lymphadenectomy in patients with uterine serous carcinoma.
The objective of our study was to assess survival among patients with uterine serous carcinoma (USC) undergoing sentinel lymph node (SLN) mapping alone versus patients undergoing systematic lymphadenectomy (LND). We retrospectively reviewed patients undergoing primary surgical treatment for newly diagnosed USC at our institution from 1/1/1996-12/31/2017. Patients were assigned to either SLN mapping alone (SLN cohort) or systematic LND without SLN mapping (LND cohort). Progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier method, compared using Logrank test. 245 patients were available for analysis: 79 (32.2%) underwent SLN, 166 (67.7%) LND. 132 (79.5%) in the LND cohort had paraaortic LND (PALND) versus none in the SLN cohort. Median age: 66 and 68 years in the SLN and LND cohorts, respectively (p>0.05). Proportion of stage I/II disease: 67.1% (n = 53) and 64.5% (n = 107) in the SLN and LND cohorts, respectively (p>0.05). Median follow-up: 23 (range, 1-96) and 66 months (range, 4-265) in the SLN and LND cohorts, respectively (p < 0.001). Two-year OS in stage I/II disease (n = 160, 60.1%): 96.6% (SE ± 3.4) and 89.6% (SE ± 2.2) in the SLN and LND cohorts, respectively (p = 0.8). Two-year OS in stage III disease (n = 77): 73.6% (SE ± 10.2) and 77.3% (SE ± 5.8) in the SLN and LND cohorts, respectively (p = 0.8). SLN mapping alone and systematic LND yielded similar survival outcomes in stage I-III USC. In our practice, the SLN algorithm has replaced systematic LND as the primary staging modality in this setting.


Cardiac Stim1 Silencing Impairs Adaptive Hypertrophy and Promotes Heart Failure Through Inactivation of mTORC2/Akt Signaling.
Stromal interaction molecule 1 (STIM1) is a dynamic calcium signal transducer implicated in hypertrophic growth of cardiomyocytes. STIM1 is thought to act as an initiator of cardiac hypertrophic response at the level of the sarcolemma, but the pathways underpinning this effect have not been examined. To determine the mechanistic role of STIM1 in cardiac hypertrophy and during the transition to heart failure, we manipulated STIM1 expression in mice cardiomyocytes by using in vivo gene delivery of specific short hairpin RNAs. In 3 different models, we found that Stim1 silencing prevents the development of pressure overload-induced hypertrophy but also reverses preestablished cardiac hypertrophy. Reduction in STIM1 expression promoted a rapid transition to heart failure. We further showed that Stim1 silencing resulted in enhanced activity of the antihypertrophic and proapoptotic GSK-3β molecule. Pharmacological inhibition of glycogen synthase kinase-3 was sufficient to reverse the cardiac phenotype observed after Stim1 silencing. At the level of ventricular myocytes, Stim1 silencing or inhibition abrogated the capacity for phosphorylation of Akt(S473), a hydrophobic motif of Akt that is directly phosphorylated by mTOR complex 2. We found that Stim1 silencing directly impaired mTOR complex 2 kinase activity, which was supported by a direct interaction between STIM1 and Rictor, a specific component of mTOR complex 2. These data support a model whereby STIM1 is critical to deactivate a key negative regulator of cardiac hypertrophy. In cardiomyocytes, STIM1 acts by tuning Akt kinase activity through activation of mTOR complex 2, which further results in repression of GSK-3β activity.


Testicular femininization with intraperitoneal disseminated mesothelial cysts.
A case report is given of a patient suffering from testicular femininization, a 13.5 l mesothelial-lined cyst associated with the right gonad, and several small intraperitoneal mesothelial cysts. No malignant changes were found, and no remnats of the Mullerian duct system were detected.


Urine D-arabinitol/L-arabinitol ratio in diagnosing Candida infection in patients with haematological malignancy and HIV infection.
Adult patients with hematologic malignancies along with HIV infected patients were prospectively studied to determine the performance of urine D-arabinitol/L-arabinitol (DA/LA) ratio in diagnosing invasive candidiasis. Ten evaluable febrile neutropenic patients had proven invasive candidiasis and elevated DA/LA ratios were found in 5. Invasive candidiasis with normal DA/LA ratios was most frequently due to Candida krusei infection. This Candida species is a non-producer of arabinitol. Only 4 of 81 febrile neutropenic patients given either antifungal prophylaxis or empiric antifungal treatment had elevated DA/LA ratios. Only 1 of 15 HIV positive patients with either oropharyngeal or esophageal candidiasis had elevated DA/LA ratios. Widespread use of fluconazole prophylaxis in bone marrow transplantation patients at the study hospital has led to an increased prevalence of C. krusei infection. This is the likely reason for the low sensitivity of the test in proven and suspected invasive Candida infections reported here.


Feasibility of nitric oxide administration by oxygen hood in neonatal pulmonary hypertension.
To test the hemodynamic efficacy and feasibility of nitric oxide (NO) administration by oxygen hood in neonatal pulmonary hypertension. A double-hood apparatus was used in which a combination of NO, O(2), and N(2) was introduced into the inner hood and suctioned from the outer hood. Chronically instrumented non-intubated piglets were exposed to 10% O(2) (hypoxia; n=8) or group B streptococci infusion (GBS; n=5) to produce pulmonary hypertension and were then exposed to 20 ppm NO. NO decreased (>50%) pulmonary artery pressure and vascular resistance in both hypoxia- and GBS-induced pulmonary hypertension, with minimal effects on systemic arterial pressure and cardiac output. NO administration could be performed without detectable environmental leakage. Hood NO administration is feasible and shows hemodynamic efficacy in neonatal piglets with pulmonary hypertension.


Noma (cancrum oris).
Noma is an opportunistic infection promoted by extreme poverty. It evolves rapidly from a gingival inflammation to grotesque orofacial gangrene. It occurs worldwide, but is most common in sub-Saharan Africa. The peak incidence of acute noma is at ages 1-4 years, coinciding with the period of linear growth retardation in deprived children. Noma is a scourge in communities with poor environmental sanitation. It results from complex interactions between malnutrition, infections, and compromised immunity. Diseases that commonly precede noma include measles, malaria, severe diarrhoea, and necrotising ulcerative gingivitis. The acute stage responds readily to antibiotic treatment. The sequelae after healing include variable functional and aesthetic impairments, which require reconstructive surgery. Noma can be prevented through promotion of national awareness of the disease, poverty reduction, improved nutrition, promotion of exclusive breastfeeding in the first 3-6 months of life, optimum prenatal care, and timely immunisations against the common childhood diseases.


[A case or Leber hereditary optic neuropathy (LHON): differential diagnosis with post inflammatory atrophy of nerve II using the mtDNA analysis].
The Leber hereditary optic neuropathy (LHON) is a disease due to a mtDNA mutation. The disorder results from enzymatic perturbations in the mitochondrial respiratory chain. Clinically the LHON may present as a progressive axonal atrophy of the optic nerves with or without other neurological symptoms. The process of reaching the diagnosis of the LHON by means of the molecular analysis of mtDNA is discussed.


Histochemical demonstration of type IV collagen in the renal glomerulus.
Disulfide-groups are demonstrated in the basement membranes of glomerular capillaries, proximal convoluted tubules, and collecting ducts by means of a thiosulfathion/Alcian Blue +0.8 Mol MgCl2-staining sequence. It is suggested that the reaction shows type IV collagen of basal lamina material, which is characterized by a relatively high cystine content (8 half-cystine residues/1000).


Synthesis and antifungal activity of benzofuran-5-ols.
Benzofuran-5-ol derivatives were synthesized and tested for in vitro antifungal activity against Candida, Aspergillus species, and Cryptococcus neoformans. Among them tested, many benzofuran-5-ols showed good antifungal activity. The results suggest that benzofuran-5-ols would be promising antifungal agents.


Test-retest and inter-rater reliability for the Comprehensive Developmental Inventory for Infants and Toddlers diagnostic and screening tests.
Reliability information for the Comprehensive Developmental Inventory for Infants and Toddlers diagnostic (CDIITDT) and screening tests (CDIITST) is inadequate. To assess the test-retest and inter-rater reliability of the CDIITDT and CDIITST. A repeated measures design was selected. Non-disabled term (n=15; mean age 8.4+/-1.6 months) and preterm infants (n=16; mean age 9.3+/-2.9 months), and children with developmental disabilities (n=15; mean age 24.7+/-11.8 months) were recruited. A single rater assessed the children twice in 3 days to examine the test-retest reliability; and a second rater observed and scored performance while the same rater conducted the first assessment for the inter-rater reliability analysis. The raw score, developmental age (DA) and developmental quotient (DQ)/Z score for the six subtests, two motor subdomains and the whole test were used as outcome measures for the CDIITDT and CDIITST. The test-retest reliabilities for the CDIITDT were rated good for the three pediatric groups (ICC 0.76-1.00), with the exception of moderate ratings for the self-help subtest for the term infants and for the social, self-help and fine-motor DQs for the preterm group. The CDIITDT inter-rater reliabilities were good for the three groups (ICC 0.76-1.00), with the exception of only moderate reliability for the cognitive DQs for the preterm infants. The reliabilities for the whole CDIITST for the three groups were high (ICC 0.93-1.00). The reliabilities for the whole CDIITDT and its various subtests and the whole CDIITST are acceptable for clinical use.


Size effect of fluorescent thiol-organosilica particles on their distribution in the mouse spleen.
We investigated the distribution of intravenously administered thiol-organosilica particle (thiol-OS) in the spleen to evaluate their size effect in mice. A single administration of particles of thiol-OS containing rhodamine B (Rh) (90, 280, 340, 450, 630, 1110, 1670, and 3030 nm in diameter) was performed. After 24 h, we conducted a combination analysis using histological studies by fluorescent microscopy and quantitative inductively coupled plasma optical emission spectrometry (ICP-OES), which revealed no clear correlation between the particle size and spleen uptake of particle weight and number per tissue weight, and the injection dose. Moreover, Rh with 450 nm diameter (Rh450) showed the highest uptake, and Rh with 340 nm diameter (Rh340) showed the lowest uptake. Histologically, large fluorescent areas in the marginal zone (MZ) and red pulp (RP) of the spleen were observed for all particle sizes, but less in the follicle of white pulp. Using combination analysis using the particle weights of ICP-OES and the fluorescent area, we compared the distributions of each particle in each region. Rh450 had the largest accumulated weight in the MZ and RP. Particles larger than Rh450 showed negative correlations between their sizes and accumulated weight in the MZ and RP. Simultaneous dual administration of particles using Rhs and thiol-OS containing fluorescein (90 nm in diameter) showed the size-dependent difference in cellular distribution and intracellular localization. Immunohistochemical staining against macrophage markers, CD169, and F4/80 showed various colocalization patterns with macrophages that uptook particles, indicating differences in particle uptake in each macrophage may have novel significance.


Carvedilol for the treatment of benign prostatic hypertrophy in patients with heart failure?
Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that commonly coexist in men 60 years and older. Carvedilol is the only β-adrenergic blocker approved for HF that also has additional α1-adrenergic blockade. As α1-adrenergic blockers are used in the treatment of BPH, it is intuitive that carvediolol could improve BPH symptoms. We present a case where carvedilol was replaced with bisoprolol resulting in acute urinary retention. When carvediolol was reinstituted, the patient's symptoms of BPH resolved. Benign prostatic hypertrophy was later diagnosed by digital rectal exam. Six month after reinstituting the carvediolol, the patient remains free of his BPH symptoms. This case suggests that carvedilol may be considered for the management of HF with systolic dysfunction in patients with concomitant BPH thus eliminating the need for an α1-adrenergic blockers.


Recent advances in the development of treatments for alcohol and cocaine dependence: focus on topiramate and other modulators of GABA or glutamate function.
Neuroscientific developments have promulgated interest in developing efficacious medications for the treatment of substance dependence. Previous pharmacological strategies that involve the use of relatively specific medications to alter corticomesolimbic dopaminergic neuronal activity--the critical pathway for expression of the reinforcing effects of abused drugs--have yielded modest efficacy in the treatment of alcohol dependence, and no medication has been established as a treatment for cocaine dependence. Since corticomesolimbic dopaminergic neurons interact with other neurotransmitters that modulate the effects of dopamine in the nucleus accumbens, would it not be possible to control these dopaminergic effects more reliably with a medication that acts contemporaneously on more than one neuromodulator of dopaminergic function? Further, since the long-term use of either alcohol or cocaine results in neuronal adaptations as a result of sensitisation, would the chances of effective therapy not be bolstered by administering a medication that was also able to mitigate these chronic effects? Thus, a new conceptual approach is needed. My proposal is that a medication--in this case topiramate--that principally potentiates inhibitory GABA(A) receptor-mediated input and antagonises excitatory glutamatergic afferents to the corticomesolimbic dopaminergic system should have therapeutic potential in treating either alcohol or cocaine dependence or perhaps both. This is because the principal neurochemical effects of topiramate would not only serve to decrease the acute reinforcing effects of alcohol or cocaine, but might also facilitate cessation of their use following a period of long-term use by decreasing neuronal sensitisation. This overview highlights the scientific concepts and clinical evidence for the development of topiramate in the treatment of alcohol dependence and introduces preliminary evidence to indicate that it might also have utility in treating cocaine dependence. Finally, to place the material on topiramate in context, information has been included on the utility and development of other medications that modulate GABA- or glutamate-mediated neuronal systems for the treatment of alcohol or cocaine dependence.


The local and systemic accumulation of ethylene determines the rapid defence responses induced by flg22 in tomato (Solanum lycopersicum L.).
Plant defence responses induced by the bacterial elicitor flg22 are highly dependent on phytohormones, including gaseous ethylene (ET). While the regulatory role of ET in local defence responses to flg22 exposure has been demonstrated, its contribution to the induction of systemic responses is not clearly understood. For this consideration, we examined the effects of different ET modulators on the flg22-induced local and systemic defence progression. In our experiments, ET biosynthesis inhibitor aminoethoxyvinyl glycine (AVG) or ET receptor blocker silver thiosulphate (STS) were applied 1 h before flg22 treatments and 1 h later the rapid local and systemic responses were detected in the leaves of intact tomato plants (Solanum lycopersicum L.). Based on our results, AVG not only diminished the flg22-induced ET accumulation locally, but also in the younger leaves confirming the role of ET in the whole-plant expanding defence progression. This increase in ET emission was accompanied by increased local expression of SlACO1, which was reduced by AVG and STS. Local ET biosynthesis upon flg22 treatment was shown to positively regulate local and systemic superoxide (O2.-) and hydrogen peroxide (H2O2) production, which in turn could contribute to ET accumulation in younger leaves. Confirming the role of ET in flg22-induced rapid defence responses, application of AVG reduced local and systemic ET, O2.- and H2O2 production, whereas STS reduced it primarily in the younger leaves. Interestingly, in addition to flg22, AVG and STS induced stomatal closure alone at whole-plant level, however in the case of combined treatments together with flg22 both ET modulators reduced the rate of stomatal closure in the older- and younger leaves as well. These results demonstrate that both local and systemic ET production in sufficient amounts and active ET signalling are essential for the development of flg22-induced rapid local and systemic defence responses.


The complexity analysis of cerebral oxygen saturation during pneumoperitoneum and Trendelenburg position: a retrospective cohort study.
The human brain is a highly complex and nonlinear system, nonlinear complexity measures such as approximate entropy (ApEn) and sample entropy (SampEn) can better reveal characteristics of brain dynamics. However, no studies report complexity of perioperative physiological signals to reveal how brain complexity associates with age, varies along with the development of surgery and postoperative neurological complications. This study examined the complexity of intraoperative regional cerebral oxygen saturation (rSO2), aiming to reveal brain dynamics during surgery. This retrospective cohort study enrolled patients who scheduled for robot-assisted urological surgery. Intraoperative rSO2 was continuously monitored throughout the surgery. Postoperative delirium (POD) was diagnosed by the Confusion Assessment Method. ApEn and SampEn were used to characterize the complexity of rSO2. Pearson correlation coefficients were used to measure the correlation between complexity of rSO2 and age. The association between complexity of rSO2 and POD was examined using T tests. A total of 68 patients (mean [SD] age, 63.0 (12.0) years; 47 (69.1%) males) were include in this analysis. There was a significant reverse relationship between the complexity of rSO2 and age (The correlation coefficients range between - 0.32 and - 0.28, all p < 0.05). Patients ≥ 75 years showed significantly lower complexity of rSO2 than the other two groups. Older age remained an independent factor influencing complexity of rSO2 after adjusting for a number of covariates. Six patients (8.8%) developed POD, and POD patients had lower complexity of rSO2 compared with non-POD patients. The complexity of rSO2 may serve as a new candidate marker of aging and POD prediction.


Long-Term Continuous Assessment of Internal Limiting Membrane Filling Induced Super-Large Macular Hole Healing.
To assess the long-term continuous anatomical and functional healing process of a super-large full-thickness macular hole (FTMH) after internal limiting membrane (ILM) filling and air tamponade. Prospective, interventional case series. Pars plana vitrectomy with ILM filling and air tamponade was performed in eyes with idiopathic super-large FTMH (> 900 µm). Patients were divided into 3 groups according to the macular hole (MH) diameter: group A, < 1000 µm; group B, 1000 to 1100 µm; and group C, > 1100 µm. The MH closure pattern was analyzed using optical coherence tomography. The preoperative and postoperative macular hole sensitivity, parafoveal sensitivity, and fixation status were assessed using a Microperimeter-3. The preoperative and postoperative best corrected visual acuity were measured. A monthly follow-up was conducted for 15 months postoperatively. Ninety-seven eyes from 96 consecutive patients with super-large FTMH were included in the study. Primary closure was seen in 93 of 97 eyes (95.88%), in which 88 of 97 eyes (90.72%) had a closed MH 1 week after surgery. The MH closure pattern continuously improved and significantly differed in the 3 groups (P < .05). Significant improvements in best corrected visual acuity (P < .01), parafoveal sensitivity (P < .05), and fixation stability (P < .01) were observed in all groups. Super-large FTMH (> 900 µm) closed promptly within 1 week postoperatively after ILM filling and air tamponade. The morphological and functional improvement lasted over an extended period postoperatively. No central scotoma enlargement was found regardless of the closure patterns, and there was significant retinal sensitivity and fixation status improvement.


Post-operative infection and prophylactic antibiotic administration after radical cystectomy with orthotopic neobladder urinary diversion.
The purpose of this study was to investigate the association between prophylactic antibiotic administration (PAA) and post-operative infection in radical cystectomy with orthotopic neobladder urinary diversion carried out for patients with bladder cancer. Fifty-seven consecutive cases were analyzed retrospectively. Post-operative infections were categorized as urinary tract, wound, and remote infections. We used the antibiotics tazobactam/piperacillin (TAZ/PIPC), sulbactam/ampicillin (SBT/ABPC), flomoxef (FMOX), cefazolin (CEZ), cefotiam (CTM), and cefmetazole (CMZ). Twenty-five (43.9%) patients had post-operative infections. Five of these (8.77%) patients had wound infections, 22 (38.6%) patients had urinary tract infections, and 2 (3.51%) had remote infections. Our statistical analysis demonstrated that the patients with TAZ/PIPC used for PAA (5/18: 27.8%) had a significantly lower post-operative infection rate than patients with other antibiotics (24/39: 61.5%) (p = 0.0442). In addition, the patients with a shorter-duration PAA (within 72 h after the operation (48-72 h)) had a significantly lower rate of post-operative infections (12/33: 36.4%) than those with longer-duration PAA (longer than 72-96 h after the operation) (16/24: 66.7%) (p = 0.0239). Taken together, these results suggest that TAZ/PIPC with shorter PAA duration (within 72 h) might lead to a lower rate of post-operative infections. In conclusion, our data showed that PAA with TAZ/PIPC with a shorter duration PAA (within 72 h) might be recommended for radical cystectomy with orthotopic neobladder reconstruction. A prospective study based on our data is desirable to establish or revise guidelines for prophylactic medication for preventing post-operative infection after radical cystectomy with orthotopic neobladder urinary diversion.


Lipid-membranes interaction, structural assessment, and sustainable production of polyhydroxyalkanoate by Priestia filamentosa AZU-A6 from sugarcane molasses.
This study presented for the first time the PHA-lipid interactions by circular dichroism (CD) spectroscopy, besides a sustainable PHA production strategy using a cost-effective microbial isolate. About 48 bacterial isolates were selected from multifarious Egyptian sites and screened for PHAs production. The Fe(AZU-A6) was the most potent isolate, and identified genetically as Priestia filamentosa AZU-A6, while the intracellular PHA granules were visualized by TEM. Sugarcane molasses (SCM) was used an inexpensive carbon source and the production conditions were optimized through a Factor-By-Factor strategy and a Plackett-Burman statistical model. The highest production (6.84 g L-1) was achieved at 8.0 % SCM, pH 8.0, 35 °C, 250 rpm, and 0.5 g L-1 ammonium chloride after 72 h. The complementary physicochemical techniques (e.g., FTIR, NMR, GC-MS, DSC, and TGA) have ascertained the structural identity as poly-3-hydroxybutyrate (P3HB) with a characteristic melting temperature of 174.5 °C. The circular dichroism analysis investigated the existence of interactions between the PHB and the different lipids, particularly 1,2-dimyristoyl-sn-glycero-3-phosphocholine. The ATR technique for the lipid-PHB films suggested that both the hydrophobic and electrostatic forces control the lipid-PHB interactions that might induce changes in the structuration of PHB.


Frege on intuition and objecthood in projective geometry.
In recent years, several scholars have been investigating Frege's mathematical background, especially in geometry, in order to put his general views on mathematics and logic into proper perspective. In this article I want to continue this line of research and study Frege's views on geometry in their own right by focussing on his views on a field which occupied center stage in nineteenth century geometry, namely, projective geometry.


Purification and immunocytochemical detection of a protein that reveals layer V pyramidal cells in the rat cortex.
Protein 36 is a soluble protein isolated and purified from a high-speed supernatant fraction from homogenates of rat brain. To identify this protein in the brain, two-dimensional gel electrophoretograms of soluble proteins were prepared. The protein was separated by ion exchange and gel filtration chromatography. The chromatographic fractions were analyzed by two-dimensional electrophoresis. Protein 36 is a homodimer with a molecular weight of 64,000 Da and monomeric weight of 37,000 Da with an isoelectric point of 6.5. A rabbit antibody was raised to this protein. Immunocytochemical studies indicate that protein 36 is localized in large pyramidal cells, dendrites and axons of layer V of the cerebral cortex. The hippocampus contained cells in the stratum radiata and processes in the stratum pyramidalis. A variety of cell types were also observed in the globus pallidus, thalamus and hypothalamus.


A role of Na+, K+ -ATPase in spatial memory deficits and inflammatory/oxidative stress after recurrent concussion in adolescent rats.
Sports-related concussions are particularly common during adolescence, and there is insufficient knowledge about how recurrent concussions in this phase of life alter the metabolism of essential structures for memory in adulthood. In this sense, our experimental data revealed that seven recurrent concussions (RC) in 35-day-old rats decreased short-term and long-term memory in the object recognition test (ORT) 30 days after injury. The RC protocol did not alter motor and anxious behavior and the immunoreactivity of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Recurrent concussions induced the inflammatory/oxidative stress characterized here by increased glial fibrillary acidic protein (GFAP), interleukin 1β (IL 1β), 4-hydroxynonenal (4 HNE), protein carbonyl immunoreactivity, and 2',7'-dichlorofluorescein diacetate oxidation (DCFH) levels and lower total antioxidant capacity (TAC). Inhibited Na+,K+-ATPase activity (specifically isoform α2/3) followed by Km (Michaelis-Menten constant) for increased ATP levels and decreased immunodetection of alpha subunit of this enzyme, suggesting that cognitive impairment after RC is caused by the inability of surviving neurons to maintain ionic gradients in selected targets to inflammatory/oxidative damage, such as Na,K-ATPase activity.


3-O-Methyl-D-glucose mutarotation and proton exchange rates assessed by 13C, 1H NMR and by chemical exchange saturation transfer and spin lock measurements.
3-O-Methyl-D-glucose (3OMG) was recently suggested as an agent to image tumors using chemical exchange saturation transfer (CEST) MRI. To characterize the properties of 3OMG in solution, the anomeric equilibrium and the mutarotation rates of 3OMG were studied by 1H and 13C NMR. This information is essential in designing the in vivo CEST experiments. At room temperature, the ratio of α and β 3OMG anomers at equilibrium was 1:1.4, and the time to reach 95% equilibrium was 6 h. The chemical exchange rates between the hydroxyl protons of 3OMG and water, measured by CEST and spin lock at pH 6.14 and a temperature of 4 °C, were in the range of 360-670 s-1.


Cell motility: an interplay between local and non-local measurement.
The bending motions of an ATP-activated actin filament and a flagellar axoneme of starfish spermatozoon exhibit a one-to-many correspondence between the displacement of the medium and the force actualized in the medium, demonstrating sharp contrast to the one-to-one correspondence in classical mechanics. Uniqueness of the actualized forces is lacking. Cell motility suggests the absence of a completely specifiable boundary condition that would unambiguously control the dynamics of generating mechanical forces in motile cells. The one-to-many relationship between the displacement of the medium and the force actualized in the medium necessitates a materialistic capacity for making choices on the part of molecules and cells in transforming future possibilities into actualized reality, the latter of which again serves as the source of the further future possibilities.


Measurement of cardiac output using improved chromatographic analysis of sulfur hexafluoride (SF6).
A constant current variable frequency pulsed electron capture detector has been incorporated into the gas chromatographic analysis of trace amounts of sulfur hexafluoride (SF6) in water and blood. The resulting system offers a broader effective operating range than more conventional electron capture units and has been utilized for measurements of cardiac output employing constant-rate infusion of dissolved SF6. The SF6 technique has been validated against direct volumetric measurements of cardiac output in a canine right-heart bypass preparation and used subsequently for rapidly repeated measurements in conscious animals and man.


Effect of heat application on adhesion of epoxy resin sealer.
Sealers are subjected to high temperatures during the warm condensation of gutta-percha; however, there are few reports on the impact of this temperature rise on the physical properties of a sealer. The purpose of this study was to compare the bond strength of AH26 to human dentin substrates, with or without heat application, by measuring the shear bond strength with a single plane shear test assembly. The results showed that there was no statistically significant difference between the shear bond strength of AH26 with or without heat application, indicating that the use of this sealer with all warm compaction techniques might be considered safe from this perspective.


The Laborist trend: its implications.
To offer obstetrical practitioners a current perspective about an important contemporary practice model which has implications that may not have been adequately recognized. A description of individual past professional experience. A resultant perspective from decades of professional obstetric practice. A description of potential clinical impact on patients and practitioners alike.


"I felt like I had no options": Navigating an ultrasound prediction of a large baby in pregnancy.
Pregnancy ultrasound is deeply embedded in maternity care worldwide, undertaken routinely and in response to clinical indicators. Though ultrasound fetal size predictions can be inaccurate, they heavily influence clinical decision-making. As a result, women with a scan prediction of a 'large' baby may be more likely to have unnecessary interventions. This study aimed to explore the implications of an ultrasound prediction of a 'large' baby on birthing women's experiences of their pregnancies and births. The study was underpinned by feminist poststructural theory. Semi-structured interviews were undertaken with women who had an ultrasound prediction of a 'large' baby. Transcripts were analysed using reflexive thematic analysis, with particular attention to discourse. Dominant medicalising discourses prioritised surveillance and risk-centric care, and problematised large babies. Engagement with these produced oppressive effects on women including loss of control as they were directed towards high intervention care, and the experience of fear and guilt. A 'large' baby prediction has a negative impact on women's experiences. Women take up dominant discourses that frame predicted large babies as a medical problem to be managed, with little tangible improvement in outcomes. They struggle with fear and guilt as they experience their pregnancies as sites of risk and are constituted as failed mothers who are responsible for their large babies. The prediction of a 'large' baby in pregnancy has undeniably negative impacts on women. We encourage midwives to scrutinise the dominant discourses of authoritative scans and problematic large babies, becoming vectors for critical thinking and resistance.


Laparoscopic 5-mm trocar site herniation and literature review.
To evaluate the evidence for fascial closure of 5-mm laparoscopic trocar sites. We conducted electronic database searches of PubMed and the Cochrane Library for articles published between November 2008 and December 2010. We used the keywords trocar hernia, trocar-site hernia, laparoscopic hernia, trocar port-site hernia, laparoscopic port-site hernia. Prospective and retrospective case series, randomized trials, literature reviews, and randomized animal studies of trocar hernias on abdominal wall defects from gynecologic, urologic, and general surgery literature were reviewed. The Cochrane Database was reviewed for pertinent studies. Metaanalysis was not possible due to the significant heterogeneity between studies and lack of randomized trials large enough to assess the incidence of this rare complication. Trocar-site hernias are a rare but known complication of laparoscopic surgery. Trocar size ≥10mm is associated with an increased rate of hernia development. Currently, the accepted gynecologic surgical practice is closure of fascial incisions ≥10mm, while incisions <10mm do not require closure. However, large prospective and retrospective case series reports from general surgery and urology literature support nonclosure of blunt or radially dilating trocars in paramedian sites. Expert opinion and small case reports suggest that in cases of prolonged manipulation of 5-mm trocar sites the surgeon should consider fascial closure, because extension of the initial incision may have occurred. There is no evidence to recommend routine closure of 5-mm trocar incisions; the choice should continue to be left to the discretion of the individual surgeon.


How Do Women React to the COVID-19 Pandemic Period? Relationship Between Ego-Resiliency, Anxiety, Alcohol Consumption and Aggression Among Polish Women.
There are many reports in the literature on the impact of the COVID-19 pandemic on mental health, including the condition of women. Most of these studies refer to a single time point, while there is a lack of studies controlling for selected parameters during different periods of the pandemic. This work aimed to determine the role of ego-resiliency in women's adaptation to the COVID-19 pandemic. The survey was conducted in two stages - all via online forms. A total of 762 Polish women took part in the overall project. The scales used in the study were the Ego-resiliency scale (ER89-R12), Generalized Anxiety Disorder 7 Scale (GAD-7), Alcohol Use Disorders Identification Test (AUDIT), and Buss-Perry Aggression Questionnaire (BPAQ). Statistical analysis was performed using Statistica 13.3. Women participating in the second study had significantly lower scores on ego-resilience and its components compared to the first study. In the first research, ego-resiliency and optimal regulation were statistically significantly correlated with anxiety, alcohol consumption, generalised aggression, verbal aggression and hostility, while openness to life experiences was correlated with alcohol consumption and hostility. The second part of the project highlighted new significant correlations between ego-resiliency and optimal regulation and physical aggression and anger, but a non-significant correlation of these variables with alcohol consumption. The effect of openness to life experiences on alcohol consumption and anxiety, evident in the first study, was no longer present in the second part of the study. The lack of a significant effect of openness to life experience on alcohol consumption, lower ego-resiliency and optimal regulation scores are observed in the second part of the research, which might be an expression of adaptation to the COVID-19 pandemic. Ego-resiliency is a protective factor against aggression, while optimal regulation against anxiety among Polish women.


Isolation of Exosomes or Extracellular Vesicles from West Nile Virus-Infected N2a Cells, Primary Cortical Neurons, and Brain Tissues.
Several flaviviruses compromise the blood-brain barrier integrity, infect the central nervous system, and elicit neuroinvasion to successfully cause neuropathogenesis in the vertebrate host. Therefore, understanding the pathway(s) and mechanism(s) to block the transmission and/or dissemination of flaviviruses and perhaps other neuroinvasive viruses is considered as an important area of research. Moreover, studies that address mechanism(s) of neuroinvasion by flaviviruses are limited. In this chapter, we discuss detailed methods to isolate exosomes or extracellular vesicles (EVs) from mouse and human N2a cells, primary cultures of murine cortical neurons, and mouse brain tissue. Two different methods including differential ultracentrifugation and density gradient exosome (DG-Exo) isolation are described for the preparation of exosomes/EVs from N2a cells and cortical neurons. In addition, we discuss the detailed DG-Exo method for the isolation of exosomes from murine brain tissue. Studies on neuronal exosomes will perhaps enhance our understanding of the mechanism of neuroinvasion by these deadly viruses.


Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC.
The antioxidant properties of aqueous and ethanolic extracts of the Uncaria tomentosa bark were evaluated. The analysis included trolox equivalent antioxidant capacity (TEAC), peroxyl radical-trapping capacity (PRTC), superoxide radical scavenging activity (SOD) and quantitation of total tannins (TT) and total phenolic compounds (TPC). The obtained results indicate high antioxidant capacity of the studied materials in comparison to the other extracts of fruits, vegetables, cereals and medicinal plants. Higher antioxidant activity and total phenolic compounds of the alcoholic preparations -- TEAC=0.57 mmol of Trolox/g, PRTC=0.52 mmol of Trolox/g and SOD=0.39 U/mg than of the aqueous preparation -- TEAC=0.34 mmol of Trolox/g, PRTC=0.19 mmol of Trolox/g and SOD=0.10 U/mg were observed. These results might suggest higher medical suitability of alcoholic extracts. However, the highly elevated level of tannins in alcoholic extracts may cause undesirable gastric effects.