Conceptual fluency increases recollection: behavioral and electrophysiological evidence.
It is widely established that fluency can contribute to recognition memory. Previous studies have found that enhanced fluency increases familiarity, but not recollection. The present study was motivated by a previous finding that conceptual priming affected recollection. We used event-related potentials to investigate the electrophysiological correlates of these effects with conceptually related two-character Chinese words. We found that previous conceptual priming effects on conceptual fluency only increased the incidence of recollection responses. We also found that enhanced conceptual fluency was associated with N400 attenuation, which was also correlated with the behavioral indicator of recollection. These results suggest that the N400 effect might be related to the impact of conceptual fluency on recollection recognition. These study findings provide further evidence for the relationship between fluency and recollection.


The effects of irradiation at different times of the day on rat intestinal goblet cells.
Quantitative changes in jejunal goblet cells were studied in control and whole body irradiated rats using PAS-Alcian blue staining of crypt sections. A circadian dependence was observed when control animals were killed at different times during the light/dark cycle. Irradiation with 3 Gy produced a 2-3-fold increase within 36 h in goblet cells relative to controls, followed by a reduction to very low levels. There was a return to pre-treatment levels later than was observed for the columnar cells. The present results on the pattern of response of goblet cells and those of brush border enzyme activity are consistent with the hypothesis that ionizing radiation can influence differentiation. In fact during the first hours after irradiation an early induction of differentiation is evident while during the early repopulation phase columnar cells prevailed relative to the goblet cells. Only at later times were normal differentiation patterns seen. Groups of animals exposed to the same dose of radiation at different times of the day showed similar general patterns of behaviour even if the group irradiated at midnight showed a more marked and longer lasting injury.


The effect of adrenomedullin and proadrenomedullin N-terminal 20 peptide on angiotensin II induced vascular smooth muscle cell proliferation.
The study aimed to investigate the effects of adrenomedullin (ADM) and proadrenomedullin N- terminal 20 peptide (PAMP) on angiotensin (AngII)-stimulated proliferation in vascular smooth muscle cells (VSMCs). Thoracic aorta was obtained from Wistar rats and VSMCs were isolated from aorta tissues and then cultured. In vitro cultured VSMCs were stimulated with Ang II (10(-8) mol/l) followed by various doses of PAMP or ADM (10(-9), 10(-8), or 10(-7) mol/l). Cell proliferation as assessed by (3)H-TdR incorporation. Protein kinase C (PKC) activity was measured by counting γ-(32)P radioactivity with liquid scintillation. In a separate cohort, in vitro cultured rat aortic vessels were treated with different doses of Ang II or PAMP (10(-9), 10(-8), or 10(-7) mol/l). Cellular and secreted levels of PAMP, ADM and Ang II were measured using radioimmunoassay in the tissues and intubation mediums, respectively. Ang II (10(-8) mol/l) treatment significantly increased both (3)H-TdR incorporation and PKC activity in VSMCs (by 2.68 and 1.02-fold, respectively; both P<0.01 vs. the control). However, Ang II-induced elevation of (3)H-TdR incorporation, and PKC activity was significantly inhibited by various doses of ADM and PAMP (all P<0.01 vs. the Ang II group). In rat aortic vascular tissues or intubation media, Ang II treatments stimulated the expression and secretion of PAMP and ADM in a dose-dependent manner, while PAMP treatments had no significant effects on Ang II levels. ADM and PAMP inhibit Ang II-induced VSMCs proliferation. The interaction of Ang II, ADM and PAMP may regulate VSMCs and cardiovascular function.


Two-Dimensional Gel Electrophoresis to Study the Activity of Type IIA Topoisomerases on Plasmid Replication Intermediates.
DNA topoisomerases are the enzymes that regulate DNA topology in all living cells. Since the discovery and purification of ω (omega), when the first were topoisomerase identified, the function of many topoisomerases has been examined. However, their ability to relax supercoiling and unlink the pre-catenanes of partially replicated molecules has received little attention. Here, we used two-dimensional agarose gel electrophoresis to test the function of three type II DNA topoisomerases in vitro: the prokaryotic DNA gyrase, topoisomerase IV and the human topoisomerase 2α. We examined the proficiency of these topoisomerases on a partially replicated bacterial plasmid: pBR-TerE@AatII, with an unidirectional replicating fork, stalled when approximately half of the plasmid had been replicated in vivo. DNA was isolated from two strains of Escherichia coli: DH5αF' and parE10. These experiments allowed us to assess, for the first time, the efficiency of the topoisomerases examined to resolve supercoiling and pre-catenanes in partially replicated molecules and fully replicated catenanes formed in vivo. The results obtained revealed the preferential functions and also some redundancy in the abilities of these DNA topoisomerases in vitro.


Rational engineering of a fluorescein-binding anticalin for improved ligand affinity.
The anticalin FluA is an artificial lipocalin with novelspecificity for the fluorescein group, which was engineered from an insect bilin-binding protein by targeted random mutagenesis and selection. Based on the crystal structure of FluA, an attempt was made to improve the complementarity of its ligand pocket to fluorescein by rational protein design. Several side chains participating in sub-optimal interactions with the ligand were identified and replaced by residues that promised a better steric fit. As a result, the substitution of Ala45 by Ile and of Ser114 by Thr or Arg led to a tight affinity of ca. 1 nM, which is approximately 30-fold better than that of the parental anticalin. Similar to the original FluA, the improved version shows almost complete quenching of the bound ligand fluorescence. Interestingly, the quenching effect was significantly reduced when Trp129 was replaced by Tyr, thus supporting the previously postulated role of this residue, which closely packs against the bound ligand, for efficient electron transfer to the excited fluorescein. Circular dichroism spectra revealed that all variants investigated had retained the lipocalin fold. Corresponding thermal unfolding experiments confirmed similar folding stabilities, with melting temperatures ranging from 52.9 to 60.5 degrees C (i.e., for the high-affinity variant).


The reproductive value in distributed optimal control models.
We show that in a large class of distributed optimal control models (DOCM), where population is described by a McKendrick type equation with an endogenous number of newborns, the reproductive value of Fisher shows up as part of the shadow price of the population. Depending on the objective function, the reproductive value may be negative. Moreover, we show results of the reproductive value for changing vital rates. To motivate and demonstrate the general framework, we provide examples in health economics, epidemiology, and population biology.


Immune checkpoint inhibitors in neoadjuvant therapy of non-small cell lung cancer: a systematic review and meta-analysis.
Our objective was to explore the safety and feasibility of immune checkpoint inhibitors (ICIs) in the neoadjuvant treatment of non-small cell lung cancer (NSCLC). Embase, PubMed and Web of Science were systematically searched from 1st January 2018 to 1st August 2021 for studies with data on the treatment-related adverse reactions (TRAE), immune-related adverse events (irAE), perioperative information, major pathological response (MPR), pathologic complete remission (pCR) and objective response rate (ORR). The QUADAS-2 tool was used to assess the quality of the studies, then the data were transformed for meta-analysis. Review Manager 5.3 (Cochrane) was used for statistical analyses with a P value of <0.05 considered significant. Thirteen studies with 358 patients were included in this meta-analysis, of which, 218 patients received ICI and chemotherapy-containing regimens and 140 patients received neoadjuvant ICIs only. The 157 (72.0%) patients who received combined neoadjuvant therapy showed a higher incidence of TRAEs, while only 37 (26.4%) patients who received neoadjuvant ICIs experienced TRAEs. Grade 3 or higher irAEs were observed in 92 (25.7%) patients, of which, 81 patients belonged to the neoadjuvant immunochemotherapy subgroup. The surgical resection rate was between 38.5-100%, with only two patients experiencing a delay in surgery. Complication rates were between 3.6-100% in the 8 studies that reported postoperative complications, with more postoperative complications [35 (18.9%)] identified in the neoadjuvant immunochemotherapy subgroup. Of which 176 patients achieved MPR, 126 received ICI and chemotherapy combined neoadjuvant therapy. Seventy-one of 95 patients who had achieved pCR had undergone ICI and chemotherapy. Compared with the neoadjuvant immunotherapy group, patients undergoing ICI and chemotherapy achieved more radiological response [118 (54.1%)] than patients undergoing ICIs [25 (17.9%)] only. The odds ratio (OR) value of the MPR/pCR/ORR rate in the neoadjuvant immunochemotherapy group was higher [OR =0.55/0.32/0.39, 95% confidence interval (CI): 0.44-0.66/0.22-0.44/0.26-0.53, P=0.0004/0.14/<0.0001] after transformation. Neoadjuvant immunotherapy shows lower toxicity and fewer perioperative complications. ICI combined chemotherapy can achieve more pathological relief and clinical benefits in the neoadjuvant treatment of NSCLC but is associated with increased irAE and perioperative complications. However, the small sample size limits the reliability of the research.


Actinopolyspora alba sp. nov. and Actinopolyspora erythraea sp. nov., isolated from a salt field, and reclassification of Actinopolyspora iraqiensis Ruan et al. 1994 as a heterotypic synonym of Saccharomonospora halophila.
Three actinomycetal strains, designated YIM 90479, YIM 90480(T) and YIM 90600(T), were isolated from a salt field in Xinjiang province, North-west China and subjected to polyphasic taxonomic study. All three strains were moderately halophilic and were able to grow on agar at NaCl concentrations of up to 20-25 % (w/v). No growth was observed in the absence of NaCl. Good growth occurred at 37 °C and 15 % (w/v) NaCl. The cell walls of the three strains were of the type IV variety and their phospholipid patterns were type PIII. MK-9 (H(4)) and MK-10 (H(4)) or MK-9 (H(4)) and MK-9 (H(2)) were the predominant menaquinones. iso-C(16 : 0) and anteiso-C(17 : 0) or anteiso-C(15 : 0) and anteiso-C(17 : 0) were the major fatty acids. The G+C contents of the genomic DNA were 66.4-68.3 mol%. Based on differential phenotypic, chemotaxonomic and phylogenetic characteristics and the results of DNA-DNA hybridization tests, the three novel stains represent two novel species, for which the names Actinopolyspora alba sp. nov. and Actinopolyspora erythraea sp. nov. are proposed. The type strains of the species are YIM 90480(T) ( = DSM 45004(T) = KCTC 19119(T)) and YIM 90600(T) ( = CCTCC M 208247(T) = KCTC 19372(T)). In addition, we propose that Actinopolyspora iraqiensis (Ruan et al., 1994) be transferred to the genus Saccharomonospora as a heterotypic synonym of Saccharomonospora halophila based on present research results.


Inhibition of crystal nucleation and growth by water-soluble polymers and its impact on the supersaturation profiles of amorphous drugs.
The impact of water-soluble polymers on drug supersaturation behavior was investigated to elucidate the role of water-soluble polymers in enhancing the supersaturation levels of amorphous pharmaceuticals. Hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), and Eudragit L-100 (Eudragit) were used as representative polymers, and griseofulvin and danazol were used as model drugs. Supersaturation profiles of amorphous drugs were measured in biorelevant dissolution tests. Crystal growth rate was measured from the decrease in dissolved drug concentration in the presence of seed crystals. Nucleation kinetics was evaluated by measuring the induction time for nucleation. All experiments were performed in the presence and absence of polymers. The degree of supersaturation of the amorphous model drugs increased with an increase in the inhibitory efficiency of polymers against crystal nucleation and growth (HPMC > PVP > Eudragit). In the presence of HPMC, the addition of seed crystals diminished the supersaturation ratio dramatically for griseofulvin and moderately for danazol. The results demonstrated that the polymers contributed to drug supersaturation by inhibiting both nucleation and growth. The effect of the polymers was drug dependent. The detailed characterization of polymers would allow selection of appropriate crystallization inhibitors and a planned quality control strategy for the development of supersaturable formulations.


Massive perineal wound slough after treatment of complex pelvic and acetabular fractures using a traction table.
An operating table with the capacity for skeletal traction against a pudendal post is a helpful and commonly used piece of equipment for certain pelvic and acetabular fracture patterns. Perineal soft tissue trauma and urogenital injuries are associated with some pelvic and acetabular fractures. The perineal region is vulnerable to compromise after such injuries. There is little documentation available in the literature that addresses intraoperative complications of the perineum after the use of a traction table for pelvic fractures. We present here a case in which prolonged traction against a pudendal post during operative fixation of complex pelvic and acetabular fractures resulted in massive perineal wound slough. This case should heighten surgeons' awareness of the vulnerability of the perineum to injury with the use of a traction table and should prompt measures to prevent complications.


Radiomics Analysis on Multiphase Contrast-Enhanced CT: A Survival Prediction Tool in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.
Patients with HCC receiving TACE have various clinical outcomes. Several prognostic models have been proposed to predict clinical outcomes for patients with hepatocellular carcinomas (HCC) undergoing transarterial chemoembolization (TACE), but establishing an accurate prognostic model remains necessary. We aimed to develop a radiomics signature from pretreatment CT to establish a combined radiomics-clinic (CRC) model to predict survival for these patients. We compared this CRC model to the existing prognostic models in predicting patient survival. This retrospective study included multicenter data from 162 treatment-naïve patients with unresectable HCC undergoing TACE as an initial treatment from January 2007 and March 2017. We randomly allocated patients to a training cohort (n = 108) and a testing cohort (n = 54). Radiomics features were extracted from intra- and peritumoral regions on both the arterial phase and portal venous phase CT images. A radiomics signature (Rad-signature) for survival was constructed using the least absolute shrinkage and selection operator method in the training cohort. We used univariate and multivariate Cox regressions to identify associations between the Rad- signature and clinical factors of survival. From these, a CRC model was developed, validated, and further compared with previously published prognostic models including four-and-seven criteria, six-and-twelve score, hepatoma arterial-embolization prognostic scores, and albumin-bilirubin grade. The CRC model incorporated two variables: The Rad-signature (composed of features extracted from intra- and peritumoral regions on the arterial phase and portal venous phase) and tumor number. The CRC model performed better than the other seven well-recognized prognostic models, with concordance indices of 0.73 [95% confidence interval (CI) 0.68-0.79] and 0.70 [95% CI 0.62-0.82] in the training and testing cohorts, respectively. Among the seven models tested, the six-and-12 score and four-and-seven criteria performed better than the other models, with C-indices of 0.64 [95% CI 0.58-0.70] and 0.65 [95% CI 0.55-0.75] in the testing cohort, respectively. The CT radiomics signature represents an independent biomarker of survival in patients with HCC undergoing TACE, and the CRC model displayed improved predictive performance.


Anemia and heart failure: a cause of progression or only a consequence?
Anemia is one of the most frequent co-morbidities in the patients with heart failure. Its prevalence increases from 4-7% in the subjects with asymptomatic left ventricular dysfunction to >30% in the patients with severe heart failure. Renal insufficiency, activation of inflammatory mediators, and treatment with renin-angiotensin antagonists seem to be its main determinants. The results of many studies agree in showing that anemia is a powerful independent determinant of survival in patients with heart failure. However, the mechanisms of this relation are still incompletely understood. Moreover a favourable effect on prognosis of the correction of anemia has not been shown, yet, and also controlled studies assessing its effects on exercise tolerance have yielded controversial results.


The Biology and Ecology of Cat Fleas and Advancements in Their Pest Management: A Review.
The cat flea Ctenocephalides felis felis (Bouché) is the most important ectoparasite of domestic cats and dogs worldwide. It has been two decades since the last comprehensive review concerning the biology and ecology of C. f. felis and its management. Since then there have been major advances in our understanding of the diseases associated with C. f. felis and their implications for humans and their pets. Two rickettsial diseases, flea-borne spotted fever and murine typhus, have been identified in domestic animal populations and cat fleas. Cat fleas are the primary vector of Bartonella henselae (cat scratch fever) with the spread of the bacteria when flea feces are scratched in to bites or wounds. Flea allergic dermatitis (FAD) common in dogs and cats has been successfully treated and tapeworm infestations prevented with a number of new products being used to control fleas. There has been a continuous development of new products with novel chemistries that have focused on increased convenience and the control of fleas and other arthropod ectoparasites. The possibility of feral animals serving as potential reservoirs for flea infestations has taken on additional importance because of the lack of effective environmental controls in recent years. Physiological insecticide resistance in C. f. felis continues to be of concern, especially because pyrethroid resistance now appears to be more widespread. In spite of their broad use since 1994, there is little evidence that resistance has developed to many of the on-animal or oral treatments such as fipronil, imidacloprid or lufenuron. Reports of the perceived lack of performance of some of the new on-animal therapies have been attributed to compliance issues and their misuse. Consequentially, there is a continuing need for consumer awareness of products registered for cats and dogs and their safety.


Note: Demonstration of an external-cavity diode laser system immune to current and temperature fluctuations.
We demonstrate an external-cavity laser system using an anti-reflection coated laser diode as gain medium with about 60 nm fluorescence spectrum, and a Rb Faraday anomalous dispersion optical filter (FADOF) as frequency-selecting element with a transmission bandwidth of 1.3 GHz. With 6.4% optical feedback, a single stable longitudinal mode is obtained with a linewidth of 69 kHz. The wavelength of this laser is operating within the center of the highest transmission peak of FADOF over a diode current range from 55 mA to 142 mA and a diode temperature range from 15 °C to 35 °C, thus it is immune to the fluctuations of current and temperature.


Diptera--ovary structure and oogenesis in midges and flies.
Comparative study of ovary development and oogenesis in the dipterans revealed significant differences between the Nematocera (lower dipterans, midges) and the Brachycera (true flies). The occurrence of these differences emphasizes well the phylogenetic division of the Diptera into these major subgroups. Basic discrepancies were found in the course of ovary development and in the mode of follicular cell differentiation. In contrast to more advanced flies, in midges the initial stages of germ cell differentiation, i.e. divisions of gonial cells, germ cell cluster formation and diversification of cystocytes within clusters take place exclusively in the larval and early pupal stages. Moreover, the formation of cystocyte clusters precedes that of ovarioles. Differences in the behaviour of some follicular cells found between the ovarian follicles of midges and advanced flies suggest that both major dipteran subgroups may differ in the scenario and/or the mechanisms of terminal signalling leading to the determination of the anteriormost part of the body.


Discharge planning revisited: what do social workers actually do in discharge planning?
The professional literature reflects a lack of clarity regarding the activities performed in discharge planning. Does discharge planning primarily focus on the provision of concrete services, counseling, or both? Within a structured interview format, 80 social workers in 36 acute care hospitals were asked to estimate the amount of time they spent on and the importance of 73 discharge planning tasks. Respondents were also asked to locate themselves on an activity continuum. The survey results are discussed in terms of the prospective payment system's emphasis on expeditious discharge and the challenge to social workers in enabling patients and families to have some control over decision making in this climate.


Effects of high-intensity training on prostate cancer-induced cardiac atrophy.
Recent evidence suggests prostate cancer independent of treatment has atrophic effects on whole heart and left ventricular (LV) masses, associated with reduced endurance exercise capacity. In a pre-clinical model, we tested the hypothesis that high-intensity training could prevent cardiac atrophy with prostate cancer and alter cardiac protein degradation mechanisms. Dunning R-3327 AT-1 prostate cancer cells (1×105) were injected into the ventral prostate lobe of 5-6 mo immunocompetent Copenhagen rats (n=24). These animals were randomized into two groups, tumor-bearing exercise (TBEX, n=15) or tumor bearing sedentary (TBS, n=9). Five days after surgery, TBEX animals began exercise on a treadmill (25 m/min, 15° incline) for 45-60 min/day for 18±2 days. Pre-surgery (Pre), and post-exercise training (Post) echocardiographic evaluation (Vivid S6, GE Health Care), using the parasternal short axis view, was used to examine ventricle dimensions. Markers of protein degradation (muscle atrophy F-box, Cathepsin B, Cathepsin L) in the left ventricle were semi-quantified via Western Blot. There were no significant differences in tumor mass between groups (TBEX 3.4±0.7, TBS 2.8±0.6 g, P=0.3), or body mass (TBEX 317±5, TBS 333±7 g, P=0.2). Heart-to-body mass ratio was lower in TBS group compared to TBEX (2.3±0.1 vs. 2.5±0.1 mg/g, P<0.05). LV/body mass ratio was also lower in the TBS group (1.6±0.1 vs. 1.8±0.1 mg/g, P<0.05). From Pre-Post, TBEX had significant increases in SV (~20% P<0.05) whereas TBS had no significant change. There were no significant differences between groups for markers of protein degradation. This study suggests that high-intensity exercise can improve LV function and increase LV mass concurrent with prostate cancer development, versus sedentary counterparts. Given cardiac dysfunction often manifests with conventional anti-cancer treatments, a short-term high-intensity training program, prior to treatment, may improve cardiac function and fatigue resistance in cancer patients.


Evaluation of the pre-posterior distribution of optimized sampling times for the design of pharmacokinetic studies.
Information theoretic methods are often used to design studies that aim to learn about pharmacokinetic and linked pharmacokinetic-pharmacodynamic systems. These design techniques, such as D-optimality, provide the optimum experimental conditions. The performance of the optimum design will depend on the ability of the investigator to comply with the proposed study conditions. However, in clinical settings it is not possible to comply exactly with the optimum design and hence some degree of unplanned suboptimality occurs due to error in the execution of the study. In addition, due to the nonlinear relationship of the parameters of these models to the data, the designs are also locally dependent on an arbitrary choice of a nominal set of parameter values. A design that is robust to both study conditions and uncertainty in the nominal set of parameter values is likely to be of use clinically. We propose an adaptive design strategy to account for both execution error and uncertainty in the parameter values. In this study we investigate designs for a one-compartment first-order pharmacokinetic model. We do this in a Bayesian framework using Markov-chain Monte Carlo (MCMC) methods. We consider log-normal prior distributions on the parameters and investigate several prior distributions on the sampling times. An adaptive design was used to find the sampling window for the current sampling time conditional on the actual times of all previous samples.


[Exon-intron structure and organization of the 5'-terminal region of the human p53 gene].
S1 mapping and nucleotide sequencing were used for localization of exon-intron junctions of the human p53 gene. The 3'-end of the gene was localized 12 nucleotides downstream AATAAA sequence, though an mRNA, 94 nucleotides shorter, was observed in one tumor. No typical promoter sequences were found at the 5'-end of the gene. In cell-free HeLa extracts transcription of RNA initiates within the sequence of possible hairpin-loop structure. Organization of the promoter region of the human p53 gene is discussed.


Mini Review: Circular RNAs as Potential Clinical Biomarkers for Disorders in the Central Nervous System.
Circular RNAs (circRNAs) are a type of non-coding RNAs (ncRNAs), produced in eukaryotic cells during post-transcriptional processes. They are more stable than linear RNAs, and possess spatio-temporal properties. CircRNAs do not distribute equally in the neuronal compartments in the brain, but largely enriched in the synapses. These ncRNA species can be used as potential clinical biomarkers in complex disorders of the central nervous system (CNS), which is supported by recent findings. For example, ciRS-7 was found to be a natural microRNAs sponge for miRNA-7 and regulate Parkinson's disease/Alzheimer's disease-related genes; circPAIP2 is an intron-retaining circRNA which upregulates memory-related parental genes PAIP2 to affect memory development through PABP reactivation. The quantity of circRNAs carry important messages, either when they are inside the cells, or in circulation, or in exosomes released from synaptoneurosomes and endothelial. In addition, small molecules such as microRNAs and microvesicles can pass through the blood-brain barrier (BBB) and get into blood. For clinical applications, the study population needs to be phenotypically well-defined. CircRNAs may be combined with other biomarkers and imaging tools to improve the diagnostic power.


Critical pulmonary stenosis.
Critical pulmonary stenosis causes cyanosis and can be potentially lethal in the neonate. Initial treatment includes general resuscitation and infusion of prostaglandin E1 to dilate the ductus. The diagnosis is usually made echocardiographically, but a right ventriculogram in the outflow tract may be necessary in some patients with only a tiny valve opening. Preformed catheters may aid in the passage of an appropriate guidewire. Valvuloplasty should be performed with a balloon approximately 1.2 times the annulus diameter. Most patients remain mildly to moderately cyanotic immediately after the procedure. With right ventricular (RV) growth and improved RV compliance, the cyanosis eventually resolves. Some patients may require prolonged prostaglandin infusion, a surgical shunt, or other mechanical means of maintaining systemic-to-pulmonary artery flow. Intermediate--to long-term results are excellent. However, only 5%-10% of patients may require surgical relief of residual valve or subvalvular stenosis. Very long-term follow-up raises concern about the significance of induced pulmonary insufficiency. Up to 30% of patients may require repeat balloon valvuloplasty.


Evaluating the diagnosis and treatment of Chlamydia trachomatis and Neisseria gonorrhoeae in pregnant women to prevent adverse neonatal consequences in Gaborone, Botswana: protocol for the Maduo study.
Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are extremely common sexually transmitted infections (STIs) that are associated with adverse birth and neonatal outcomes, and the risk of vertical transmission of CT and NG during delivery is high. The majority of CT and NG infections are asymptomatic and missed by the standard of care in most countries (treatment based on symptoms). Thus, it is likely that missed maternal CT and NG infections contribute to preventable adverse health outcomes among women and children globally. This study aims to assess the effectiveness of CT and NG testing for asymptomatic pregnant women to prevent adverse neonatal outcomes, understand the inflammatory response linking CT and NG infections to adverse neonatal outcomes, and conduct an economic analysis of the CT and NG testing intervention. The Maduo ("results" in Setswana) is a prospective, cluster-controlled trial in Gaborone, Botswana to compare a near point-of-care CT and NG testing and treatment intervention implemented in "study clinics" with standard antenatal care (World Health Organization-endorsed "syndromic management" strategy based on signs and symptoms without laboratory confirmation) implemented in "standard of care clinics" among asymptomatic pregnant women. The primary outcome is vertical transmission of CT/NG infection. Secondary outcomes include preterm birth (delivery < 37 completed weeks of gestation) and/or low birth weight (< 2500 g). The trial will also evaluate immunological and inflammatory markers of adverse neonatal outcomes, as well as the costs and cost-effectiveness of the intervention compared with standard care. The Maduo study will improve our understanding of the effectiveness and cost-effectiveness of CT and NG testing among asymptomatic pregnant women. It will also increase knowledge about the CT/NG-related immune responses that might drive adverse neonatal outcomes. Further, results from this study could encourage expansion of STI testing during antenatal care in low resource settings and improve maternal and neonatal health globally. This trial is registered with ClinicalTrials.gov (Identifier NCT04955717, First posted: July 9, 2021)).


Effect of Salinity on DMSP Production in Gambierdiscus belizeanus (Dinophyceae).
Dimethylsulfoniopropionate (DMSP) is produced by many species of marine phytoplankton and has been reported to provide a variety of beneficial functions including osmoregulation. Dinoflagellates are recognized as major DMSP producers; however, accumulation has been shown to be highly variable in this group. We explored the effect of hyposaline transfer in Gambierdiscus belizeanus between ecologically relevant salinities (36 and 31) on DMSP accumulation, Chl a, cell growth, and cell volume, over 12 d. Our results showed that G. belizeanus maintained an intracellular DMSP content of 16.3 pmol cell-1 and concentration of 139 mM in both salinities. Although this intracellular concentration was near the median reported for other dinoflagellates, the cellular content achieved by G. belizeanus was the highest reported of any dinoflagellate thus far, owing mainly to its large size. DMSP levels were not significantly affected by salinity treatment but did change over time during the experiment. Salinity, however, did have a significant effect on the ratio of DMSP:Chl a, suggesting that salinity transfer of G. belizeanus induced a physiological response other than DMSP adjustment. A survey of DMSP content in a variety of Gambierdiscus species and strains revealed relatively high DMSP concentrations (1.0-16.4 pmol cell-1 ) as well as high intrageneric and intraspecific variation. We conclude that, although DMSP may not be involved in long-term (3-12 d) osmoregulation in this species, G. belizeanus and other Gambierdiscus species may be important contributors to DMSP production in tropical benthic microalgal communities due to their large size and high cellular content.


Zika Virus Outbreak - Should assisted reproduction patients avoid pregnancy?
To discuss the requirement from the National Health Surveillance Agency (ANVISA), for assisted reproduction treatment patients to undergo laboratory tests for ZIKV detection, and if the public health authorities and government leaders' recommendations to women simply avoid pregnancy is prudent. This study was performed in a university-affiliated in vitro fertilization center in Brazil. We present a critical discussion on the risk of microcephaly due to ZIKV infection and the prevalence of other harmful pathogens to vulnerable pregnant women and infants. We assessed, 954 patients undergoing intracytoplasmic sperm injection cycles (ICSI), between April and November of 2016, concerning the results of ZIKV test, according to different regions in Brazil. Patients undergoing ICSI cycles were split into groups, according to their region of origin: 28 (3.0%) were from the North, 27 (2.8%) were from the Northeast, 40 (4.2%) were from the Midwest, 830 (87.2%) were from the Southeast, and 29 (3.0%) were from the South. Concerning the diagnosis, 112 samples had a positive or inconclusive result for ZIKV, by chromatography immunoassay. These samples were re-analyzed by ELISA and no result was positive. All positive results were from the Southeast region and none from the Northeast or Midwest regions, which are considered endemic regions. ZIKV test before the onset of assisted reproduction treatments does not rule out the risk of the infection during pregnancy. In addition, although ZIKV infection risk is extremely high, the microcephaly risk due to ZIKV is not higher than the risk of miscarriage and birth defects due to other recognized pathogens.


Gramicidin-based fluorescence assay; for determining small molecules potential for modifying lipid bilayer properties.
Many drugs and other small molecules used to modulate biological function are amphiphiles that adsorb at the bilayer/solution interface and thereby alter lipid bilayer properties. This is important because membrane proteins are energetically coupled to their host bilayer by hydrophobic interactions. Changes in bilayer properties thus alter membrane protein function, which provides an indirect way for amphiphiles to modulate protein function and a possible mechanism for "off-target" drug effects. We have previously developed an electrophysiological assay for detecting changes in lipid bilayer properties using linear gramicidin channels as probes. Gramicidin channels are mini-proteins formed by the transbilayer dimerization of two non-conducting subunits. They are sensitive to changes in their membrane environment, which makes them powerful probes for monitoring changes in lipid bilayer properties as sensed by bilayer spanning proteins. We now demonstrate a fluorescence assay for detecting changes in bilayer properties using the same channels as probes. The assay is based on measuring the time-course of fluorescence quenching from fluorophore-loaded large unilamellar vesicles due to the entry of a quencher through the gramicidin channels. We use the fluorescence indicator/quencher pair 8-aminonaphthalene-1,3,6-trisulfonate (ANTS)/Tl(+) that has been successfully used in other fluorescence quenching assays. Tl(+) permeates the lipid bilayer slowly but passes readily through conducting gramicidin channels. The method is scalable and suitable for both mechanistic studies and high-throughput screening of small molecules for bilayer-perturbing, and potential "off-target", effects. We find that results using this method are in good agreement with previous electrophysiological results.


Cryo-EM analysis of PIP2 regulation in mammalian GIRK channels.
G-protein-gated inward rectifier potassium (GIRK) channels are regulated by G proteins and PIP2. Here, using cryo-EM single particle analysis we describe the equilibrium ensemble of structures of neuronal GIRK2 as a function of the C8-PIP2 concentration. We find that PIP2 shifts the equilibrium between two distinguishable structures of neuronal GIRK (GIRK2), extended and docked, towards the docked form. In the docked form the cytoplasmic domain, to which Gβγ binds, becomes accessible to the cytoplasmic membrane surface where Gβγ resides. Furthermore, PIP2 binding reshapes the Gβγ binding surface on the cytoplasmic domain, preparing it to receive Gβγ. We find that cardiac GIRK (GIRK1/4) can also exist in both extended and docked conformations. These findings lead us to conclude that PIP2 influences GIRK channels in a structurally similar manner to Kir2.2 channels. In Kir2.2 channels, the PIP2-induced conformational changes open the pore. In GIRK channels, they prepare the channel for activation by Gβγ.


The Role of HMGB1 in Rheumatic Diseases.
HMGB1, a highly conserved non-histone nuclear protein, is widely expressed in mammalian cells. HMGB1 in the nucleus binds to the deoxyribonucleic acid (DNA) to regulate the structure of chromosomes and maintain the transcription, replication, DNA repair, and nucleosome assembly. HMGB1 is actively or passively released into the extracellular region during cells activation or necrosis. Extracellular HMGB1 as an alarmin can initiate immune response alone or combined with other substances such as nucleic acid to participate in multiple biological processes. It has been reported that HMGB1 is involved in various inflammatory responses and autoimmunity. This review article summarizes the physiological function of HMGB1, the post-translational modification of HMGB1, its interaction with different receptors, and its recent advances in rheumatic diseases and strategies for targeted therapy.


Proton magnetic resonance spectroscopy: an in vivo method of estimating hippocampal neuronal depletion in schizophrenia.
Diffuse loss of cortical volume and ventricular enlargement have been demonstrated in schizophrenia using imaging. In addition, histological studies have provided evidence that the number of neurons in the medial temporal lobe structures is reduced and that the cytoarchitecture is abnormal. In an attempt to correlate these histological findings with in vivo estimates of neuronal integrity we have studied the concentration of the neuronal marker N-acetyl aspartate (NAA) in the hippocampi of schizophrenics using in vivo Magnetic Resonance Spectroscopy (MRS). Compared with a group of healthy volunteers schizophrenics showed a 22% loss of NAA in the left hippocampus. Two other metabolites, choline and creatine showed bilateral reduction in schizophrenics and these achieved significance in the left hippocampus. These results indicate a significant depletion of NAA in schizophrenia and are in close agreement with the reported neuronal loss in the hippocampus detected histologically. We propose that in vivo MRS is a valid measure of integrity of neuronal populations in schizophrenia.


A permanent transvenous lead system for an implantable pacemaker cardioverter-defibrillator. Nonthoracotomy approach to implantation.
A transvenous lead system for implantable defibrillators would obviate a surgical thoracotomy and reduce the morbidity and mortality associated with implantation. We evaluated the clinical performance of a new nonthoracotomy lead system that included a defibrillation lead in the coronary sinus. At the time of defibrillator implantation, transvenous defibrillation leads were inserted percutaneously through the left subclavian vein into the right ventricular apex (RVA), superior vena cava (SVC), and distal coronary sinus (CS) under fluoroscopic guidance. A subcutaneous patch electrode (SQ) was also available if required. The first single- or dual-pathway electrode configuration that successfully terminated three of four ventricular fibrillation episodes using 18 J or less was implanted. Eleven men and three women aged 39-77 years (60.0 +/- 10.1 years) with left ventricular ejection fraction ranging from 16% to 63% (33.4 +/- 13.1%) were evaluated. Nine presented with ventricular tachycardia, three had ventricular fibrillation, and two had both. A totally transvenous lead system (RVA/CS/SVC) was implanted in seven patients (50%) with a mean defibrillation threshold of 15.6 +/- 2.9 J (10-18 J). Four patients received a partial transvenous lead system (RVA/CS/SQ). An effective nonthoracotomy lead system was not found in three patients; they received epicardial electrodes. After cumulative follow-up of 73 patient-months, nine patients remain alive and free of problems related to the implanted nonthoracotomy leads. One patient died of respiratory failure 3 months after defibrillator implant, and the leads from another patient were removed at 9 months because of bacterial infection. A transvenous lead system that includes a defibrillation lead in the coronary sinus is a safe, reliable, and, at least in the short term, effective nonthoracotomy approach for automatic defibrillator implantation.


Microtopography of the eye surface of the crab Carcinus maenas: an atomic force microscope study suggesting a possible antifouling potential.
Marine biofouling causes problems for technologies based on the sea, including ships, power plants and marine sensors. Several antifouling techniques have been applied to marine sensors, but most of these methodologies are environmentally unfriendly or ineffective. Bioinspiration, seeking guidance from natural solutions, is a promising approach to antifouling. Here, the eye of the green crab Carcinus maenas was regarded as a marine sensor model and its surface characterized by means of atomic force microscopy. Engineered surface micro- and nanotopography is a new mechanism found to limit biofouling, promising an effective solution with much reduced environmental impact. Besides giving a new insight into the morphology of C. maenas eye and its characterization, our study indicates that the eye surface probably has antifouling/fouling-release potential. Furthermore, the topographical features of the surface may influence the wettability properties of the structure and its interaction with organic molecules. Results indicate that the eye surface micro- and nanotopography may lead to bioinspired solutions to antifouling protection.


Anomalies in dual energy X-ray absorptiometry measurements of total-body bone mineral during weight change using Lunar, Hologic and Norland instruments.
A previous study showed that measurements of total-body bone mineral changes made with a Hologic QDR 1000W were unreliable when the subjects underwent weight change. The study has been extended to dual energy X-ray absorptiometry (DXA) apparatus from other manufacturers. Re-analysis of published results during weight loss using a Lunar DPX showed that they varied with the software used. Using the Extended mode, there was a 1% loss of bone mineral areal density (BMD), but no significant change in bone mineral content (BMC) or bone area (BA) following a weight loss of 16 kg, whereas the use of the Standard mode led to a larger fall of BMC and BMD. Similar findings arose from the consideration of two studies using Norland XR 26 HS absorptiometers. On the other hand, separation of two groups with similar weight changes from the population studied with a Hologic QDR 1000W confirmed that BMC changed directly with weight, but there was an inverse relationship for BMD, owing to an inappropriate change of BA. The use of Hologic Enhanced and Standard software modes led to significant differences in initial readings and measured changes. With each instrument there was a strong correlation between changes in BA and changes in BMC. When 6 kg of lard was wrapped around the limbs of volunteers or a semi-anthropomorphic phantom to simulate weight change, there were spurious increases of measured BMC and BA by about 5% with each instrument. There were no changes of BMD with Lunar, variable results with Norland, but decreases with Hologic. The results observed in vivo could be explained by the effects of fat changes, without there being any real change of bone mineral. Changes of BMD in the skeleton of the phantom were underestimated with all three brands. The anomaly observed with the Hologic QDR 1000W is less apparent with a Lunar DPX or a Norland XR 26, but there are sufficient uncertainties for all total-body measurements during weight change to be treated with suspicion.


Deuterium REDOR: principles and applications for distance measurements
The application of short composite pulse schemes ( and ) to the rotational echo double-resonance (REDOR) spectroscopy of X-2H (X: spin 12, observed) systems with large deuterium quadrupolar interactions has been studied experimentally and theoretically and compared with simple 180 degrees pulse schemes. The basic properties of the composite pulses on the deuterium nuclei have been elucidated, using average Hamiltonian theory, and exact simulations of the experiments have been achieved by stepwise integration of the equation of motion of the density matrix. REDOR experiments were performed on 15N-2H in doubly labeled acetanilide and on 13C-2H in singly 2H-labeled acetanilide. The most efficient REDOR dephasing was observed when composite pulses were used. It is found that the dephasing due to simple 180 degrees deuterium pulses is about a factor of 2 less efficient than the dephasing due to the composite pulse sequences and thus the range of couplings observable by X-2H REDOR is enlarged toward weaker couplings, i.e., larger distances. From these experiments the 2H-15N dipolar coupling between the amino deuteron and the amino nitrogen and the 2H-13C dipolar couplings between the amino deuteron and the alpha and beta carbons have been elucidated and the corresponding distances have been determined. The distance data from REDOR are in good agreement with data from X-ray and neutron diffraction, showing the power of the method. Copyright 1999 Academic Press.


Bicycle helmet-wearing variation and associated factors in Ontario teenagers and adults.
The incidence of bicycle helmet use and the factors associated with helmet use in Ontario are presented in this study. The Ontario Health Survey (1996), a population-based survey of Ontario residents, was used as the data source. As the factors associated with helmet use were found to differ between adults and teens, a separate analysis was performed for each age grouping. A logistic regression model (with Bootstrap confidence intervals--95%) was used and adjusted odds ratios (OR) are reported. Of the 7,693 respondents, 41.1% reported wearing their helmets on a regular basis when riding a bicycle. Helmet use was greatest among 12-14 year olds (71.7%) and lowest among those 15-18 years old (33.3%). In teenagers, drinking alcohol (OR: 2.8) and smoking (OR: 4.4) were strongly associated with helmet non-use. In the adult group, female gender (OR: 1.26), higher income (OR: 1.43), higher education (OR: 1.68), nonsmoking status (OR: 2.0) and abstinence from alcohol (1.27) were associated with helmet use. Living in a rural area was also associated with helmet use in the multi-variable analysis. This study indicates that bicycle helmet non-use is a multifaceted problem and thus any strategy for increasing helmet-wearing rates requires multi-dimensional interventions. The results of this study are discussed within the context of other studies and related to their public health implications.


Health for all.
From April 1, public health will become the responsibility of local government. Here, experts explain how this shift--overseen by the new health and wellbeing boards--could ease bottlenecks in health services and change how nurses work.


Immunological analyses of U.S. Space Shuttle crewmembers.
We have previously reported changes in the immunoresponsiveness of "T" lymphocytes following space flight. Additional data collected before and after 11 Shuttle space flights show that absolute lymphocyte numbers, lymphocyte blastogenic capability, and eosinophil percent in the peripheral blood of crewmembers are generally depressed postflight. These responses resemble those associated with physical and emotional stress and may not be related to flight per se. Additional data from Space Shuttle flights 41B and 41D, involving 11 crewmembers, indicate a postflight decrease in cells reacting with "B" lymphocyte and monocyte monoclonal antibody tags. Further, the loss of "T" lymphocyte blast capability interacts with the decreased monocyte count (correlation coefficient = 0.697). This finding implies that the previously reported loss of blastogenic capability may be a function of decreased monocyte control, as noted in several non-spaceflight related studies.


Closure of Tracheoesophageal Puncture after Total Laryngectomy.
Tracheoesophageal puncture with voice prosthesis placement is used to restore vocal function after total laryngectomy. However, closure of the fistula is sometimes needed. At our department, a simple and effective technique for closure was developed. It does not require interposed tissues or materials. Moreover, our procedure allows for a short rehabilitation time for swallowing and a short hospitalization. We describe advantages, pitfalls, and errors to avoid. This technique should not be performed for patients who are irradiated and those with large fistulas.


Using adverse outcome pathways to contextualise (Q)SAR predictions for reproductive toxicity - A case study with aromatase inhibition.
The development and application of (quantitative) structure-activity relationship ((Q)SAR) models for reproductive toxicology remains challenging, given the complexity of the endpoint and the risks associated with subsequent decision making. Adverse outcome pathways (AOPs) organise knowledge and provide context of model outputs, aiding risk assessors' decision making. Using aromatase as an example, we demonstrate how AOPs can be used to contextualise a variety of (Q)SAR approaches. AOPs stemming from aromatase inhibition - leading to adverse outcomes of regulatory significance - were synthesised and annotated with relevant assays, assay data and (Q)SAR models. The resulting framework enabled the deployment of different types of (Q)SAR models that predict for key events along the pathway. The use of models for molecular initiating events enables relevant knowledge to span a wider area of chemical space - compared to using models trained solely on in vivo toxicity data. Utilising such methods, alongside additional assay data and exposure information, could lead to improved risk assessment strategies during compound prioritisation and labelling.


Blastocyst classification systems used in Latin America: is a consensus possible?
To identify different blastocyst classification systems used by embryologists in Latin American countries and evaluate the possibility of establishing a consensus among these countries. An E-mail survey was carried out through the Latin American Network of Assisted Reproduction (REDLARA) aimed at embryologists from assisted reproduction centers in Latin countries. Sixty surveys were collected from 12 Latin American countries, of which 66.7% had >10years of professional practice as embryologists. Seven different blastocyst classification systems were reported, of which 5 have previously been described in the literature. Although the group of embryologists surveyed use different blastocyst classification systems, most in this group consider that the embryo score system should be unified in their countries as well as in the region.


Human infection by Rhizopus azygosporus and the occurrence of azygospores in Zygomycetes.
Fungal isolates from the peritoneal cavity, kidney and liver, respectively, of three premature Australian babies are described as Rhizopus azygosporus. All three babies died. This is the first report as far as we know of the isolation of this fungus from human infections. It has previously been isolated only from Indonesian tempeh. The source of these infections was not determined. Rhizopus azygosporus is closely related to R. microsporus var. microsporus, var. rhizopodiformis and var. chinensis. The occurrence of azygospores in Zygomycetes and the taxonomic position of R. azygosporus are discussed.


Cellular uptake of apidaecin 1b and related analogs in Gram-negative bacteria reveals novel antibacterial mechanism for proline-rich antimicrobial peptides.
Proline-rich antimicrobial peptides (PrAMPs) freely penetrate through the outer membrane into the periplasm of Gram-negative bacteria, before they are actively translocated by a permease/transporter-mediated uptake into the cytoplasm where they are reported to inhibit chaperone DnaK. Here we have studied the PrAMP apidaecin 1b, which is produced in honey bees in response to bacterial infections, and optimized apidaecin analogs for their bacterial uptake. The peptides were labeled with 5(6)-carboxyfluorescein and their internalization in Escherichia coli and Klebsiella pneumoniae was visualized by fluorescence microscopy and quantified by flow cytometry for four different time points over an incubation period of 4 h. Apidaecin 1b entered only 40% to 50% of the cells at detectable quantities, whereas designer peptides Api88, Api134 and Api155 entered more than 95% of the bacteria within 30 min at around fourfold higher quantities than the native peptide. Interestingly, a shortened version designated as (1-17)Api88, bound DnaK as efficiently as the 18-residue long Api88 and entered the bacteria at similar kinetics as Api88, but was unable to inhibit the bacterial growth. Similar conflicts with currently proposed mechanisms of PrAMPs were also obtained for some Ala-substituted analogs and reverse apidaecin sequences. Although peptides with C-terminal amides enter the cells much more efficiently than homologous C-terminal acids, this improved cell penetration does not improve the antibacterial activities. These studies suggest that PrAMPs utilize additional modes of action to kill sensitive organisms.


Nontuberculous mycobacterial lung infections in patients with eating disorders: plausible mechanistic links in a case series.
Nontuberculous mycobacteria (NTM) are widely distributed in the environment and are almost always acquired into the lungs by bioaerosol inhalation or aspiration of NTM-contaminated water, biofilms, and soil. NTM are increasingly recognized as causes of lung diseases in immunocompetent hosts, a not insignificant number of whom have a life-long or nearly life-long slender body habitus as well as thoracic cage abnormalities such as scoliosis and pectus excavatum. While several hypotheses have been offered to explain the purported increase in susceptibility to NTM lung disease in such individuals, the precise explanation remains unknown. We described three patients with eating disorders associated with severe malnutrition and either purging behaviors or other risks for aspiration who were diagnosed with NTM lung infections-the largest number of such patients to date in a single report. We discuss the clinical and experimental evidence that low body weight and chronic vomiting with attendant jeopardy for aspiration, as seen in patients with eating disorders, may represent risk factors for NTM lung disease. We also speculate the possibility of occult and undiagnosed eating disorders in some of the slender NTM lung disease patients with no known risk factors for the opportunistic infection other than their low body weight.


Mutation in the gene coding for coagulation factor V and resistance to activated protein C: detection of the genetic mutation by oligonucleotide ligation assay using a semi-automated system.
Resistance of coagulation factor Va to inactivation by activated protein C (APCR) is associated with a point mutation in which adenine is substituted for guanine at nucleotide 1691 in the gene coding for factor V (FV Leiden). To date, this mutation of factor V is the most frequent genetic risk factor for venous thrombophilia. In this report, we describe the adaptation of an automatable oligonucleotide ligation assay (OLA) to detect the mutation in polymerase chain reaction-amplified DNA samples from 40 normal, 20 affected heterozygous, and 3 affected homozygous individuals. The genotypes determined by conventional allele-specific restriction enzyme site analysis were in complete concordance with the results obtained by ELISA-based oligonucleotide-ligation assay. The automated oligonucleotide ligation assay provides a rapid, reliable, nonisotopic method to detect the mutation responsible for APCR that can rapidly be applied to large population screening.


An Overview of the Allopathic Match.
The number of allopathic emergency medicine (EM) programs has been progressively increasing over the years. In 2018, allopathic EM postgraduate year-1 spots, compared with 2012, increased by around 60% to reach 2278 positions. EM is considered a competitive specialty and therefore, in this article we help guide students interested in EM through the allopathic match requirements, application process, interviews, and ranking EM programs. Additionally, we tackle the combined emergency medicine residency programs, namely the combined EM-Family Medicine (FM), EM-Anesthesiology, EM-Internal Medicine (IM), EM-IM-Critical Care Medicine, and EM-Pediatrics residency programs. Finally, we explain the increased likelihood of matching with the single graduate medical education accreditation system expected to happen in the year 2020.


Accuracy of Routine 2D Echocardiography to Estimate Patent Ductus Arteriosus Type and Dimension and Predict Device Selection for Successful PDA Occlusion.
Assessment of the shape and dimensions of PDA is usually done angiographically and in the majority of cases need arterial access. Our aim was to evaluate the value of routine 2 D echocardiography (ECHO) in predicting type, dimensions of PDA and to anticipate device size to be used during the intervention. The charts of all patients who underwent transcatheter closure of PDA between January 2015 and December 2020 were reviewed. Their pre-procedure ECHO and catheterization details at the time of device closure were analyzed. Total of 139 patients were reviewed and 8 were excluded because of lack of adequate echocardiographic or angiographic images. The mean age and weight of the study population were 2.6 ± 2.5 years (range 0.2-14 years) and 11.2 ± 7.8 kg (range: 1.5-57 kg), respectively. There was no statistically significant difference in PDA narrowest diameter (p = 0.99) and predicted device type (p = 0.54) between Echo and angiography. Echo slightly overestimated PDA length (p = 0.01) and aortic ampulla dimension (p = 0.047), while morphology of PDA was correctly identified in the majority of cases (82%). Pre-procedure echocardiography correlates well with angiographically obtained measurements and hence can be used to estimate PDA diameter, shape and guide device decide selection. Routine echocardiography can be used successfully to plan the intervention and in some cases to guide transcatheter closure.


Prognosticating outcome using magnetic resonance imaging in patients with moderate to severe traumatic brain injury: a machine learning approach.
Over the last decade advancements in computer processing have enabled the application of machine learning (ML) to complex medical problems. Convolutional neural networks (CNN), a type of ML, have been used to interrogate medical images for variety of purposes. In this study, we aimed to investigate the potential application of CNN in prognosticating patients with traumatic brain injury (TBI). Patients with moderate to severe TBI and evidence of diffuse axonal injury (DAI) were selected retrospectively. A CNN model was developed using a training subgroup and a holdout subgroup was used as a testing dataset. We reported the model characteristics including area under the receiver operating characteristic curve (AUC). We included a total of 38 patient, of which we generated 725 MRI sections. We developed a CNN model based on a modified AlexNet architecture that interpreted the brain stem injury to generate outcome predictions. The model was able to predict GOS outcomes with a specificity of 0.43 and a sensitivity of 0.997. It showed an AUC of 0.917. The utilization of machine learning MRI analysis for prognosticating patients with TBI is a valued method that require further investigation. This will require multicentre collaboration to generate large datasets.


Larvicidal activity of a neem tree extract (Neemarin) against mosquito larvae in the Islamic Republic of Iran.
An insecticide containing azadirachtin, a neem tree (Azadirachta indica) extract, was tested against mosquito larvae in the Islamic Republic of Iran under laboratory and field conditions. LC50 and LC90 values for Neemarin were 0.35 and 1.81 mg/L for Anopheles stephensi, the main local malaria vector, and 0.69 and 3.18 mg/L for Culex quinquefasciatus. The mortality in the pupal stage was significantly higher than the other stages. In field trials, using recommended dosages of 1 and 2 L/hectare, mortality of Anopheles spp. larvae was also higher than Culex spp. Prevention of adult emerged and pupal mortality was the main activity of this compounds. The maximum time of efficacy was 7 days at the highest concentration (2 L/hectare).


A small-dose naloxone infusion alleviates nausea and sedation without impacting analgesia via intravenous tramadol.
Early studies showed that naloxone infusion decreases the incidence of morphine-related side effects from intravenous patient-controlled analgesia. This study aimed to determine whether naloxone preserved analgesia while minimizing side effects caused by intravenous tramadol administration. Eighty patients undergoing general anesthesia for cervical vertebrae surgery were randomly divided into four groups. All patients received 1 mg/kg tramadol 30 minutes before the end of surgery, followed by a continuous infusion with 0.3 mg x kg(-1) x h(-1) tramadol with no naloxone (group I, n = 20), 0.05 microg x kg(-1) x h(-1) naloxone (group II, n = 20), 0.1 microg x kg(-1) x h(-1) naloxone (group III, n = 20) and 0.2 microg x kg(-1) x h(-1) naloxone (group IV, n = 20). Visual analog scales (VAS) for pain during rest and cough, nausea five-point scale (NFPS) for nausea and vomiting, and ramsay sedation score (RSS) for sedation were assessed at 2, 6, 12, 24 and 48 hours postoperatively. Analgesia and side effects were evaluated by blinded observers. Seventy-eight patients were included in this study. The intravenous tramadol administration provided the satisfied analgesia. There was no significant difference in either resting or coughing VAS scores among naloxone groups and control group. Compared with control group, sedation was less in groups II, III, and IV at 6, 12, and 24 hours (P < 0.05); nausea was less in groups II, III and IV than group I at 2, 6, 12, 24 and 48 hours postoperatively (P < 0.05). The incidence of vomiting in the control group was 35% vs. 10% for the highest dose naloxone group (group IV) (P < 0.01). A small-dose naloxone infusion could reduce tramadol induced side effects without reversing its analgesic effects.


The biology of thrombin in acute coronary syndromes.
Thrombin, a serine protease, is the keystone of the twin processes of hemostasis and thrombosis. Through procoagulant, anticoagulant, and antifibrinolytic mechanisms, thrombin helps maintain vascular integrity in the face of hemorrhage. These same mechanisms, however, allow for the pathologic formation of thrombi in response to endothelial damage, which accompanies the erosion or rupture of atherosclerotic plaques. Alone or incorporated into plaques, thrombi can cause vessel occlusion resulting in acute coronary syndromes (ACS). Inhibiting thrombin can improve clinical outcomes in ACS, as well as in procedures such as percutaneous coronary interventions, which are designed to open the occluded vessels that cause ACS. Such improvements in outcomes with thrombin inhibition reflect the central and multivariate role of thrombin in thrombus formation.


Recognizing and treating ADHD in adults.
Patients with attention deficit hyperactivity disorder (ADHD) commonly present in primary care settings. Because untreated adult ADHD can impair patients' quality of life, clinicians need to know how to recognize and treat this potentially lifelong disorder.


Alternative selective oxidation pathways for aldehyde oxidation and alkene epoxidation on a SiO2-supported Ru-monomer complex catalyst.
We have prepared a novel Ru-mononer complex supported on a SiO(2) surface by using a Ru-monomer complex precursor with a p-cymene ligand, which was found to be highly active for the selective oxidation of aldehydes and the epoxidation of alkenes using O(2). The structure of the supported Ru catalyst was characterized by means of FT-IR, solid-state NMR, diffuse-reflectance UV/vis, XPS, Ru K-edge EXAFS, and DFT calculations, which demonstrated the formation of isolatedly located, unsaturated Ru centers behind a p-cymene ligand of the Ru-complex precursor. The site-isolated Ru-monomer complex on SiO(2) achieved tremendous TONs (turnover numbers) for the selective oxidation of aldehydes and alkenes; e.g. TONs of 38,800,000 for selective isobutyraldehyde (IBA) oxidation and 2,100,000 for trans-stilbene epoxidation at ambient temperature, which are among the highest TONs in metal-complex catalyzes to our knowledge. We also found that the IBA sole oxidation with an activation energy of 48 kJ mol(-1) much more facile than the trans-stilbene epoxidation with an activation energy of 99 kJ mol(-1) was completely suppressed by the coexistence of trans-stilbene. The switchover of the selective oxidation pathways from the IBA oxidation to the trans-stilbene epoxidation was explained in terms of energy profiles for the alternative selective oxidation pathways, resulting in the preferential coordination of trans-stilbene to the Ru-complex at the surface. This aspect gives an insight into the origin of the efficient catalysis for selective epoxidation of alkenes with IBA/O(2).


Effects of ospemifene on breast tissue morphology and proliferation: a comparative study versus other selective estrogen receptor modulators in ovariectomized rats.
Ospemifene is a tissue-selective estrogen agonist/antagonist that was recently approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy, which occurs in up to approximately 50% of postmenopausal women. The current analyses were conducted to determine whether ospemifene exhibits estrogenic activity in the mammary glands of ovariectomized rats and to compare potential estrogenic activity with selective estrogen receptor modulators (tamoxifen, raloxifene, and toremifene). Three separate studies with differing durations (6, 9, and 28 days) were conducted using similar procedures in ovariectomized Sprague-Dawley rats. Estradiol treatment and sham-treated ovariectomized rats were used as positive and negative controls, respectively. Cell proliferation was examined using labeled 5-bromo-2-deoxyuridine; cytoplasmic prolactin was characterized with antibody staining. The morphology of the mammary gland was studied by histological staining of sections from the right fourth mammary glands, and the excised gland from the left side was used for counting the lobulus number. Neither ospemifene nor selective estrogen receptor modulators substantially induced 5-bromo-2-deoxyuridine staining, altered the morphology of the mammary glands, or changed prolactin immunostaining in ovariectomized rats compared with the ovariectomized controls. With the exception of toremifene, the selective estrogen receptor modulators did not cause a substantial induction in mammary gland lobuli. Estradiol had effects opposite to those of the selective estrogen receptor modulators in these studies. Ospemifene exhibited no substantial estrogenic activity in the mammary gland of ovariectomized rats. Activity in the mammary gland of ovariectomized rats with ospemifene was comparable to raloxifene and tamoxifen.


[Advantages and disadvantages of cervical esophageal anastomosis using a stapler].
The authors evaluate the advantages and shortcomings of cervical anastomosis of the oesophagus by means of stapler according to the following criteria: 1. difficulty of implementation, 2. immediate results--fistulae, 3. long-term results--stenoses, 4. costs. The authors operated, using a stapler, 26 patients who developed in four instances /15.4%/ a fistula. By comparison with a retrospective group of 21 patients with eight fistule /38%/ where the anastomosis was sutured manually, they found that by using a stapler the number of complications declined. A disadvantage is the high price of staplers.


A Skinfold Model to Predict Fat-Free Mass in Female Athletes.
OBJECTIVE: Despite widespread use of skinfolds to estimate body fatness, few prediction models have been validated on female athletes. Most skinfold models have been validated with hydrodensitometry, which does not account for the variability in bone density that may exist among female athletes. Our purpose was to develop a skinfold model that predicts fat-free mass (FFM) in female collegiate athletes. DESIGN AND SETTING: A skinfold model was developed using dual-energy x-ray absorptiometry (DEXA) as the criterion method. Four skinfold measures (abdominal, suprailiac, thigh, triceps), height, and weight were entered into a regression model. The best model was developed and validated by calculating the predicted error sum of squares statistic. SUBJECTS: Study participants included 101 National Collegiate Athletic Association Division I female athletes (age = 20.3 +/- 1.4 years, height = 166.7 +/- 7.8 cm, mass = 63.1 +/- 8.1 kg) from several sports. MEASUREMENTS: Each participant's FFM was measured via DEXA. Skinfold thicknesses were measured and entered into the regression model. RESULTS: The final regression model included mass and abdominal and thigh skinfolds: FFM = 8.51 + (0.809 x mass) - (0.178 x abdominal skinfold) - (0.225 x thigh skinfold). The model showed excellent predictive ability (R = 0.98, standard error of the estimate = 1.1 kg). Pairwise comparisons indicated that prediction error showed no overprediction or underprediction bias. CONCLUSIONS: In female collegiate athletes, FFM can be predicted accurately from body mass and abdominal and thigh skinfolds. This model is practical and can be used in most athletic settings.


Loss of chromosomal high mobility group proteins HMG1 and HMG2 when mouse neuroblastoma and Friend erythroleukemia cells become committed to differentiation.
Chromosomal high mobility group (HMG) proteins HMG1 and HMG2 from mouse neuroblastoma cells and Friend erythroleukemic cells were analyzed by acetic acid/urea/polyacrylamide gel electrophoresis. Compared to rapidly growing cells, levels of HMG1 and HMG2 were decreased in mouse neuroblastoma cells that had been induced to differentiate by serum deprivation. This comparison revealed a reciprocal relationship between these HMG proteins and H10, a histone known to be in higher concentrations in nondividing cells. When cell growth was inhibited by means of density inhibition, however, HMG1 and -2 levels were not affected in either HeLa or mouse neuroblastoma cells, even though H10 did not accumulate. This observation establishes that HMG1 and -2 contents are not correlated with mitotic rate per se. Treatment of mouse neuroblastoma by sodium butyrate, which stops cell division without commitment to differentiation, had no effect on the level of HMG1 and -2. However, the level was decreased by dibutyryl cyclic AMP and dimethyl sulfoxide treatments, which, like serum deprivation, induced irreversible morphological differentiation in the neuroblastoma cells. Moreover, induction of differentiation (hemoglobin synthesis) in Friend erythroleukemic cells by dimethyl sulfoxide showed a decrease in the contents of HMG1 and -2. These observations suggest that preferential loss of HMG1 and -2 in mouse neuroblastoma and Friend erythroleukemia cells may be related to commitment of these cells to differentiation.


The Use of Osseodensification for Ridge Expansion and Dental Implant Placement in Narrow Alveolar Ridges: A Prospective Observational Clinical Study.
The osseodensification (OD) drilling technique was suggested as an alveolar ridge expansion technique, so the aim of this prospective clinical study was to evaluate the amount of bone expansion obtained by the OD drilling technique and its effect on implant stability in patients with narrow alveolar ridges. The width of the alveolar ridge was measured at the crest before and after implant site preparation, whereas the implant stability was measured using Osstell Beacon implant stability quotient (ISQ). The ISQ values were recorded immediately postoperatively and after 16 weeks. Twenty-three patients were included; they received 40 implants. The mean (± standard deviation [SD]) amount of expansion was 1.29 (± 0.41) mm, and the difference between preexpansion and post-expansion bone width was statistically significant ( P < 0.001). The mean (± SD) primary stability was 73.73 (± 2.85) ISQ, whereas the mean (± SD) secondary stability was 74.83 (± 2.73) ISQ, and the difference was statistically significant ( P = 0.043). The implant survival rate was 100%. It can be concluded that using the OD technique in narrow alveolar ridges resulted in bone expansion without dehiscence or fenestration and allowed simultaneous implant placement with high primary and secondary implant stability.


Memorial Sloan-Kettering Cancer Center experience with paclitaxel in the treatment of breast cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is the most important new cytotoxic agent to be introduced for the management of breast cancer in many years. During this decade, investigators at Memorial Sloan-Kettering Cancer Center have conducted multiple clinical and laboratory investigations aimed at optimally integrating this agent into therapeutic strategies for breast cancer. These studies address both single-agent and combination regimens in the metastatic and adjuvant settings. This report will review previous results, but focus on active studies and future avenues of research.


[The study of the active site of cytochrome P-450 LM2 using the chemical modification of tyrosine residues by tetranitromethane].
Selective chemical modification of the hemoprotein by tetranitromethane was used in order to elucidate the functional role of tyrosine residues in the cytochrome P-450 LM2 molecule. It was shown that the degree of cytochrome P-450 LM2 modification can be determined, using the second derivative of the UV absorption spectra. Modification of one tyrosine residue resulted in the inactivation of cytochrome P-450 LM2. Nitration of the cytochrome was accompanied by changes in the spectral properties of the hemoprotein with the formation of spectra typical of hyperporphyrin structures, thus suggesting the involvement of tyrosine residues in the formation of the active center of cytochrome P-450 LM2.


Accurate and confident prediction of electron beam longitudinal properties using spectral virtual diagnostics.
Longitudinal phase space (LPS) provides a critical information about electron beam dynamics for various scientific applications. For example, it can give insight into the high-brightness X-ray radiation from a free electron laser. Existing diagnostics are invasive, and often times cannot operate at the required resolution. In this work we present a machine learning-based Virtual Diagnostic (VD) tool to accurately predict the LPS for every shot using spectral information collected non-destructively from the radiation of relativistic electron beam. We demonstrate the tool's accuracy for three different case studies with experimental or simulated data. For each case, we introduce a method to increase the confidence in the VD tool. We anticipate that spectral VD would improve the setup and understanding of experimental configurations at DOE's user facilities as well as data sorting and analysis. The spectral VD can provide confident knowledge of the longitudinal bunch properties at the next generation of high-repetition rate linear accelerators while reducing the load on data storage, readout and streaming requirements.


Efficacy of regorafenib in the second-and third-line setting for patients with advanced hepatocellular carcinoma: A real life data of multicenter study from Turkey.
After failure of the first-line sorafenib treatment in advanced or metastatic stage hepatocellular carcinoma (HCC), regorafenib is one of the newly-approved targeted agents. We aimed to evaluate the efficacy of regorafenib in patients with advanced HCC treated in the second- or third-line setting. In this retrospective and multicenter study, advanced HCC patients not eligible for local therapies, who received a second- or third-line regorafenib therapy after progression on the first-line sorafenib or sequential therapy with chemotherapy (CT) followed by sorafenib, were included. In the first-line setting, 28 (28.9%) patients received CT and 69 (71.1%) patients received sorafenib. There were 24 (24.7%) patients who were intolerant to sorafenib. Disease control rate (DCR) was 53.6% for all patients treated with regorafenib, 62.3% in patients who received regorafenib in the second-line, and 32.1% for those receiving regorafenib in the third-line (p=0.007). Median progression-free survival (PFS) and overall survival (OS) were 5.6 (range; 4.3-6.9) and 8.8 (range, 6.3-11.3) months for all patients treated with regorafenib vs. 7.1 months and 10.3 months for patients who received regorafenib in the second-line vs. 5.1 and 8.7 months for patients who received regorafenib in the third-line, respectively; however, there was no statistically significant difference (pPFS=0.22 and pOS=0.85). Although receiving CT as a first-line therapy in advanced HCC patients did not affect the survival rates of subsequent regorafenib therapy, it might diminish the DCR of regorafenib.


Virulence factors associated with Escherichia coli present in a commercially produced competitive exclusion product.
In this study, we assessed the pathogenic potential of Escherichia coli associated with a commercial competitive exclusion (CE) product by examining the phenotypic characteristics associated with E. coli virulent for humans and domestic animals. Most E. coli isolates were capable of proliferating in iron-deplete chicken sera. Interestingly, none of the E. coli isolates from the commercial CE product contained the bacterial adhesin Tsh characteristic of avian pathogenic E. coli associated with airsacculitis and colisepticemia. In terms of virulence potential for humans, most E. coli isolates (78%) were sensitive to killing by 12.5% human sera. Because of their sensitivity to human sera, the E. coli in the CE product are not likely to cause a serious systemic infection in humans and, therefore, do not present a risk of causing septicemia in humans. Because these isolates also lack the gene tsh, they are also less likely to cause systemic disease or airsacculitis in poultry than pathogenic strains commonly isolated from diseased birds.


Evidence standards in experimental and inferential INSDC Third Party Annotation data.
The Third Party Annotation (TPA) project collects and presents high-quality annotation of nucleotide sequence. Annotation is submitted by researchers who have not themselves generated novel nucleotide sequence. In its first few years, the resource has proven to be popular with submitters from a range of biological research areas. Central to the project is the requirement for high-quality data, resulting from experimental and inferred analysis discussed in peer-reviewed publications. The data are divided into two tiers: those with experimental evidence and those with inferential evidence. Standards for TPA are detailed and illustrated with the aid of case studies.


Double knockouts. Production of mutant cell lines in cardiovascular research.
Double knockouts by homologous recombination is a method for producing cell lines with an inactivating mutation in any desired gene. The biochemical analysis of genetically altered cell lines has been important in determining the function of specific proteins. Until recently, mutant cell lines have been produced by random mutagenesis and then selection for a particular phenotypic change. Recent technological advances in gene targeting by homologous recombination now enable the production of mutants in any desired gene. Diploid cells contain two copies or alleles of each gene encoded on an autosome (nonsex) chromosome. In most cases, both alleles must be inactivated to produce a phenotypic change in a mutant cell line, hence the term "double knockout." We and others have described the production of mutationally altered cell lines by inactivating both alleles by the production of two targeting vectors, two separate homologous recombination events, and selection. A simpler procedure, involving considerably less effort and time, has been used to inactivate several alpha-subunits of G proteins and other genes. This method facilitates the inactivation of more than one gene in a single cell line.


Classification of common conserved sequences in mammalian intergenic regions.
Comparisons between orthologous intergenic regions of related genomes reveal numerous hits, i.e. pairs of relatively short highly similar sequences that evolved slowly, perhaps due to selective constraint. We analyzed and classified 2638 hits found within 100 pairs of complete, orthologous intergenic regions of human and murine genomes. We identified all common fragments of hits that align well with many other hits and constructed their classification. Our analysis revealed 20 abundant classes each containing 10 or more fragments. Fragments of the same class may perform the same function, e.g. bind a particular protein. Ten of the abundant classes apparently correspond to known functional consensuses, whereas others may represent novel conserved sites. Thus, large-scale comparative analysis of slowly evolving intergenic sequences can provide valuable insights into their function.


Congenital brucellosis in a Chinese preterm neonate: A case report.
Although extremely rare, congenital brucellosis can occur via perinatal transmission. We report a case of an infant born prematurely at 34-36 weeks' gestation who had pyrexia, shortness of breath, hepatosplenomegaly and thrombocytopenia. Blood cultures were positive for Gram-negative coccobacilli and Brucella infection was suspected. While, serological tests were negative for Brucella antibodies, B. melitensis infection was confirmed by polymerase chain reaction (PCR). Serology of the parents' blood confirmed the presence of Brucella. The family did not live in an endemic area but had ridden a camel 12 months before the pregnancy. The bacteria may have been sexually transmitted from father to mother and then to foetus via an intrauterine infection. In endemic areas or where the family has been in close contact with infected animals, brucellosis should be suspected in a severely ill neonate with an unknown infection. Thorough medical histories from the family are essential as early diagnosis and prompt therapy will almost certainly improve neonatal outcome.


[Gyrate atrophy and craniopharyngioma: a case report].
We report the case of a 13-year-old girl who developed a craniopharyngioma and a gyrate atrophy. No genetic link between these two diseases has ever been reported. This case recalls the characteristic features of gyrate atrophy.


A novel ex vivo murine retina angiogenesis (EMRA) assay.
Pathological retinal angiogenesis results from the imbalance of pro-angiogenic and anti-angiogenic factors. In particular, vascular endothelial growth factor (VEGF) plays a pivotal role in retinal neovascularization and various therapeutic VEGF blockers have evolved over time. Nevertheless, new retinal angiogenesis models are crucial for investigating anti-angiogenic therapies and bringing them to patients. Here, we developed a novel ex vivo murine retina angiogenesis (EMRA) assay in which endothelial sprouts originate from mature and quiescent retinal vessels. In this model, retina fragments from adult mice are embedded in a three-dimensional fibrin gel in the presence of human recombinant VEGF. Starting from the 3rd-4th day of incubation, endothelial cell sprouts invading the fibrin gel can be observed under an inverted microscope and measured at different time points thereafter. The effect of VEGF is dose-dependent, maximal stimulation being observed at day 7 for retina fragments stimulated with 25-75 ng/ml of the growth factor. To assess whether the EMRA assay is suitable for testing the activity of anti-angiogenic compounds, retina fragments were incubated with VEGF in the presence of the neutralizing anti-VEGF antibodies bevacizumab and ranibizumab. The results demonstrate that both antibodies inhibit VEGF activity in a dose-dependent manner. In conclusion, the EMRA assay represents a new ex vivo model of retinal neovascularization suitable for the rapid screening of novel anti-angiogenic therapeutics.


Cell-specific regulation of PTX3 by glucocorticoid hormones in hematopoietic and nonhematopoietic cells.
PTX3 (prototypic long pentraxin 3) is a fluid phase pattern recognition receptor, which plays nonredundant roles in the resistance against diverse pathogens, in the assembly of a hyaluronic acid-rich extracellular matrix, and in female fertility. Inflammatory signals induce production of PTX3 in diverse cell types, including myeloid dendritic cells (DC), fibroblasts, and endothelial cells (EC). The present study was designed to explore the effect of glucocorticoid hormones (GC) on PTX3 production in different cellular contexts. In myeloid DC, GC inhibited the PTX3 production. In contrast, in fibroblasts and EC, GC alone induced and, under inflammatory conditions, enhanced and extended PTX3 production. In vivo administration of GC augmented the blood levels of PTX3 in mice and humans. Moreover, patients with Cushing syndrome had increased levels of circulating PTX3, whereas PTX3 levels were decreased in subjects affected by iatrogenic hypocortisolism. In nonhematopoietic cells, GC receptor (GR) functioned as a ligand-dependent transcription factor (dimerization-dependent) to induce PTX3 gene expression. In contrast, in hematopoietic cells, GR repressed PTX3 gene transcription by interfering (dimerization-independent) with the action of other signaling pathways, probably NFkappaB and AP-1. Thus, divergent effects of GC were found to be due to different GR mechanisms. The results presented here indicate that GC have divergent effects on PTX3 production in hematopoietic (DC and macrophages) and nonhematopoietic (fibroblasts and EC) cells. The divergent effects of GC on PTX3 production probably reflect the different functions of this multifunctional molecule in innate immunity and in the construction of the extracellular matrix.


The GoPA! Second Set of Country Cards Informing Decision Making for a Silent Pandemic.
In 2012, the Global Observatory for Physical Activity (GoPA!) was established to provide information that would enable countries to initiate or improve research capacity, surveillance systems, program development, and policymaking to increase physical activity levels. Findings from the first GoPA! Country Cards showed an unequal distribution of physical activity surveillance, research productivity, and policy development and implementation around the world. Regular global monitoring of these factors, especially in countries with the largest data gaps, was recommended to combat the global pandemic of physical inactivity. After 6 years and using standardized methods, GoPA! is launching the second set of Country Cards based on data up to 2019 from 217 countries. Overall results showed that periodic national surveillance of physical activity was less common in low-income countries, compared with middle- and high-income countries. Large inequities were seen with more than a 50-fold difference in publications between high- and low-income countries and 32% of the countries worldwide had no physical activity policy. GoPA! has a critical role in facilitating evidence-based physical activity promotion building on international guidelines and the World Health Organization Global Action Plan. GoPA! will continue to monitor progress as we battle the global pandemic of physical inactivity.


Sodium and chloride transport in soft water and hard water acclimated zebrafish (Danio rerio).
While the zebrafish is commonly used for studies of developmental biology and toxicology, very little is known about their osmoregulatory physiology. The present investigation of Na(+) and Cl(-) transport revealed that the zebrafish is able to tolerate extremely low ambient ion concentrations and that this is achieved at least in part by a greatly enhanced apparent uptake capacity and affinity for both ions. Zebrafish maintain plasma and whole body electrolyte concentrations similar to most other freshwater teleosts even in deionized water containing only 35 microM NaCl, i.e soft water. We recorded an extremely low transport affinity constant (K(m)) of 8+/-1 microM for the active uptake of Cl(-) in soft water acclimated fish, while other transport kinetic parameters were in agreement with reports for other freshwater organisms. While both Na(+) and Cl(-) uptake in soft water clearly depends on apical proton pump activity, changes in abundance and possibly localization of this protein did not appear to contribute to soft water acclimation. Active Cl(-) uptake was strongly dependent on branchial carbonic anhydrase (CA) activity regardless of water type, while the response of Na(+) transport to a CA inhibitor was more variable. Differential response of Na(+) uptake to amiloride depending on acclimation medium suggests that different Na(+) transport mechanisms are employed by zebrafish acclimated to soft and hard water.


A carcinoid tumor of the rectum removed by strip biopsy.
In a 29-year-old male complaining of constipation, total colonoscopy revealed a 5 mm yellowish submucosal tumor at a distance of 6 cm from the anal ring. The histologic diagnosis of specimens obtained by biopsy was rectal carcinoid tumor and transanal ultrasonography revealed the tumor localization within the submucosal layer in the rectum. A strip biopsy was performed. Histopathological examination confirmed the diagnosis and ascertained complete excision. Rectal carcinoid tumors should be removed completely and strip biopsy may be a suitable procedure for removal of rectal submucosal tumors less than 10 mm in diameter.


Omentectomy, peritoneal biopsy and appendectomy in patients with clinical stage I endometrial carcinoma.
The aim of this study was to evaluate whether omentectomy, appendectomy, and peritoneal biopsy should be a routine part of staging surgery in endometrial carcinoma. Data of 97 patients who had been diagnosed with clinical stage I endometrial carcinoma were reviewed. Associations in the data obtained, pelvic and para-aortic lymph node status, depth of myometrial invasion, grade, and histology were investigated. The chi-square (chi2) test was used for statistical analysis. Of 97 patients, six (6%) had omental metastases, which was microscopic in four. There was a statistically significant relationship between omental metastasis and tumor grade (P < 0.01). Deep myometrial invasion was significantly more common in patients with omental metastases. Tumor was found in one of 55 appendectomy specimens (2%). Omentectomy may be included in surgical staging in patients with deeply invasive or grade 3 endometrial cancer because of the possibility of omental metastasis in spite of what appears to be stage I disease in laparotomy. In other cases, omentectomy and appendectomy and biopsies from peritoneal sites should be performed in the presence of grossly suspicious disease.


[Biomarkers in the modern medical and biologic practice].
The lecture deals with biomarkers, a newly introduced direction in biomedical research. The following terms, definitions, and characteristics were proposed to describe biomarkers: diagnostic tools, clinical endpoints and surrogate endpoints. Examples of predictors for cardiovascular diseases, acute-phase of inflammation and malignant tumors are represented. The special attention is given to the characteristic of the widespread biomarkers: homocysteine, transthyretin and C-reactive protein. Modern methods of identification, qualitative and quantitative determination of biomarkers are considered: mass spectrometric methods, immunoassay. The relationships between the latest achievements in the field of genomics, proteomics, bioinformatics and biomarker's investigations are established. The perspectives of biomarkers are discussed.


[Non-cholinergic effects of organophosphates].
The author summarizes contemporary knowledge on the action of organophosphates with emphasis on non-cholinergic mechanisms. Intoxication with these substances is characterized by four basic processes: absorption, transport, metabolism and the toxic effect proper. The latter involves cholinesterase inhibition at the cholinergic synapses with subsequent accumulation of acetylcholine. However, non-cholinergic processes are also involved such as the effect on levels of cyclic nucleotides, the peptidergic system, receptors, liver metabolism and the stressogenic action. From the review ensues that knowledge of non-cholinergic, mechanisms of action could reveal new approaches to treatment of intoxications with these substances.


[Transitory carotid ischemic attacks: clinical and pathogenic aspects].
The aim of this study is to describe the clinical characteristics and the pathological mechanisms of carotid transient ischemic attacks (TIA) in 117 patients which were hospitalised for such symptoms. Our results show a male predominance, except for age group under 40 and over 79 years. The principal cardiovascular index and risk factors are: arterial hypertension, smoking, hyperlipidemia, vascular intermittent claudication and hematocrit greater than 46%. Amongst our patients, 17% with hemispherical and mixed TIAs had a cerebral infarction proved by CT-Scan, the recent aspect and localisation of which were compatible with symptoms. The atherosclerotic causes are more frequently associated with mixed and retinal TIAs than hemispheric TIAs. This fact may be attributed to a larger proportion of stenotic atherosclerotic lesions by mixed TIAs than hemispheric ones. The cardiac embolic pathogenic mechanism is responsible for 11% of TIAs if considered individually; of 5% if associated with carotid atherosclerosis.


An alternative medical approach for the neuroprotective therapy to slow the progression of Parkinson's disease.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the core symptoms such as bradykinesia, resting tremor, rigidity and postural instability. Currently, pharmacotherapy and surgical approaches for the treatments of PD can only improve the neurological symptoms. Therefore, to search neuroprotective therapies using pharmacological and nonpharmacological approaches could be important to delay the progression of pathogenesis in PD. Coenzyme Q10 (CoQ10) is a component of the electron transport chain as well as an important antioxidant in mitochondrial and lipid membranes. The central role of CoQ10 in two areas implicated in the pathogenesis of PD, mitochondrial dysfunction and oxidative damages, suggest that it may be useful for treatment to slow the progression of PD. The neuroprotective effect of CoQ10 has been reported in several in vivo and in vitro models of neurodegenerative disorders. Although CoQ10 attenuated the toxin-induced reduction of dopamine content and tyrosine hydroxylase-immunoreactive neurons in the striatum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model, it is still unknown how this nutrition affects the mitochondrial function. We demonstrated that oral administration of CoQ10 significantly attenuated the loss of dopaminergic nerve terminals induced by MPTP treatment. Furthermore, our experimental data indicate that an inhibition of mitochondrial cytochrome c release is one of the primary targets for CoQ10 and may lead to a potent neuroprotection.


A conceptual framework for interdisciplinary curriculum design: a case study in neuroscience.
Teaching of interdisciplinary fields of study poses a challenge to course organizers. Often interdisciplinary courses are taught by different departments, and hence, at best provide a multidisciplinary overview. Scientific progress in neuroscience, for instance, is thought to depend heavily on interdisciplinary investigations. If students are only taught to think in particular disciplines without integrating these into a coherent framework to study the nervous system, it is unlikely that they will truly develop interdisciplinary thinking. Yet, it is this interdisciplinary thinking that is at the heart of a holistic understanding of the brain. It is, therefore, important to develop a conceptual framework in which students can be taught interdisciplinary, rather than multidisciplinary, thinking. It is also important to recognize that not all teaching needs to be interdisciplinary, but that the type of curriculum design is dependent on the aims of the course, as well as on the background of the students. A rational curriculum design that aligns learning and teaching objectives is, therefore, advocated.