Associations, follow up data, and postnatal outcome of antenatally diagnosed Urinary Tract Dilatation - Five-year single tertiary center experience from South India.
Urinary tract dilatations (UTD) are frequently diagnosed during Mid-Trimester Anomaly Scan (MTAS), at which time, given their variable progression and heterogeneous classification systems, offering suitable counsel to the couple is challenging. Based on postnatal data, we aimed to guide parental counseling, and further evaluation of UTD diagnosed at MTAS. Specifically, the utility of multi-disciplinary UTD classification system was tested. A retrospective observational study of all UTDs included from five years (2015-2020) MTAS register. The multi-disciplinary UTD classification system was used for antenatal/postnatal UTD categorization. Follow-up data were obtained from case records until the current age of children (2-6 years). Out of 527 fetal abnormalities, 103 had UTD at MTAS. Based on the third-trimester ultrasound, 49 were low-risk UTD A1, and 44 were increased-risk UTD A2-3 (including the nineteen UTD A1 at MTAS worsened to A2-3 by third-trimester). On postnatal follow-up of UTD A1 and A2-3, respectively, neonatal UTD P2/P3 was seen in 2% and 40.9%; complete spontaneous resolution was seen in 79.5% and 43.18%; none and 22.7% underwent surgical intervention; persistent P2/P3 UTD were seen on follow-up in 2% and 4.5% (excluding those who needed surgery); impaired renal function was seen in none and 36.3%, and recurrent UTI in 8.1% and 34.09%. The subgroup with progressive UTD (from A1 to A2-3 by third-trimester ultrasound) formed 43% of the final UTD A2-3 category. Among these 19 cases, surgical intervention was performed in eight (42%); impaired renal function was seen in 7 cases (36.8%), and recurrent UTI was seen in eight (42%). Given the diverse classification systems for UTD, ours is the second Indian data proving the prognostic utility of multi-disciplinary UTD classification system, specifically at third trimester scan, based on postnatal outcome. In contrast to published guidelines, our data suggests follow-up for renal pelvis anteroposterior diameter (APD) of 4-7 mm at MTAS, as some may worsen. Similar progression has been noted in other Indian studies, but the classification systems are different. Contrary to the published literature, we could not suggest a renal APD cut-off as a single criterion to predict surgical intervention. Significant limitations are retrospective observational design and multiple sonographers. Our data helps guide parental counseling and further evaluation for UTD diagnosed at MTAS. The multi-disciplinary Consensus UTD Classification system, was helpful in prognostication.


Brachial plexus anatomy.
The brachial plexus may be visualized simply as beginning with five nerves and terminating in five nerves. It begins with the anterior rami of C5, C6, C7, C8, and the first thoracic nerve. It terminates with the formation of the musculocutaneous, median, ulnar, axillary, and radial nerves. The intermediate portions are displayed in sets of threes: three trunks are formed, followed by three divisions, then three cords. Each trunk gives rise to two divisions and each cord gives rise to two branches. The lateral cord divides into the musculocutaneous nerve and the lateral branch of the median nerve. The medial cord divides into the medial branch of the median nerve and the ulnar nerve. The posterior cord divides into the axillary and the radial nerves. The anatomy of the brachial plexus can be confusing, especially because of frequent variations in length and caliber of each of its components.


Resveratrol enhances neovascularization in the infarcted rat myocardium through the induction of thioredoxin-1, heme oxygenase-1 and vascular endothelial growth factor.
We have previously shown that resveratrol possesses cardioprotective effect, which may be attributed to its ability to (i) stimulate nitric oxide production and (ii) free radical scavenging activity. Since resveratrol is one of the major components of certain varieties of red grapes, these events may underlie the cardioprotective effects thought to be obtained from moderate red wine consumption. Here we report resveratrol enhanced myocardial angiogenesis both in vivo and in vitro by induction of vascular endothelial growth factor (VEGF), which was regulated by thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO-1). Human coronary arteriolar endothelial cells exposed to resveratrol or Trx-1 on Matrigel demonstrated significantly accelerated tubular morphogenesis with induction of HO-1 and VEGF expression. This angiogenic response was repressed by tin-protoporphyrin IX (SnPP), an HO-1 inhibitor, along with downregulation of VEGF expression. However Trx-1 expression was not affected by SnPP. Again, rat neonatal cardiomyocytes treated with resveratrol significantly expressed Trx-1, HO-1 as well as VEGF. Rats were orally administered with resveratrol (1 mg/kg per day) for 14 days and then underwent permanent left anterior descending coronary artery (LAD) occlusion to document similar pro-angiogenic effect. Our results demonstrated that pretreatment with resveratrol markedly reduced infarct size 24 h after myocardial infarction (MI) and increased capillary density in the peri-infarct myocardium along with better left ventricular function 4 days after MI compared with vehicle-treated control. Concomitantly, resveratrol-treated myocardium after MI significantly induced Trx-1, HO-1 and VEGF expression. This effect was blocked by SnPP. Our findings suggest that resveratrol mediates cardioprotection and neovascularization through Trx-1-HO-1-VEGF pathway in rat ischemic myocardium.


Application of an accelerometer in adjusting parameters and detecting characteristics in the pacemaker rate response.
Objective.To study the application of an accelerometer in adjusting the parameters, setting the sensor indicated rate (SIR) and detecting characteristics in the pacemaker (PM) rate response.Approach.Three-axis (GT9X Link-type) accelerometers were positioned on the waist and chest in 33 participants implanted with rate responsive PMs while wearing an ambulatory ECG recorder (Holter). During the walking test, by collecting vertical axis (Axis-1) activity intensity counts, Axis-1' metabolic equivalent of energy (METaxis-1) and its expected heart rate (HRmet-axis1) were calculated by the relevant equations, and on the basis of the HRmet-axis1as the target heart rate, the SIR was set by programming the rate response slope parameter. During the following daily walking activity, the physical activity parameters and Holter ECG was recorded continuously. After the end of the whole test the analysis on these data recorded was performed retrospectively.Main results.After completing the SIR setting, in 24 participants with complete ventricular pacing the comparison between HRmet-axis1(92.5 ± 7.8 BPM) and the HRvp-Holter(94.0 ± 10.5 BPM) showed no statistical difference (ΔHR: 1.25 ± 6.69 BPM,P: 0.568) during the last one walking test, and there was also no significant difference (ΔHR: 2.8 ± 7.1 BPM,P: 0.398) between the HRmet-axis1(90.7 ± 7.1 BPM) and HRvp-Holter(93.4 ± 10.3 BPM) during daily walking activity. In addition, in the data of 108 time intervals selected during the daily walking activities in the abovementioned 24 participants, METaxis-1and HRvp-Holtercorrelation analysis showed good correlation and the regression equation was HR = 12.4 × MET±43.1 (P<0.0001).Significance.An accelerometer can play an important role in adjusting parameters, setting the SIR and detecting characteristics in the PM rate response.


Allotypic and isotypic aspects of human immunoglobulin A.
The location of isotypic, isoallotypic and allotypic determinants is reviewed in the light of data obtained when specific antisera are tested with proteolytic fragments of IgA molecules or mutants of IgA obtained from patients with alpha-heavy chain disease. Isotypic determinants are distributed throughout the alpha chain constant regions although when intact IgA proteins are used as immunogens the CH3 domain is immunodominant. Alpha 1 subclass specific isotypic determinants are present in both Fab and Fc fragments. Amino acid sequence analysis suggest that alpha 1 subclass isotypic determinants depend on substitution in the CH1, hinge and/or CH2 domain. The isoallotypic determinants nA2m(2) appears to be located on the CH1 domain and appears to require disulphide-linked alpha chains for its expression. The allotypic determinant A2m(2) appears to be located in the CH3 domain involving residues 428, 458 and/or 467. The latter residues are present in both A2m(1) and A1 proteins which indicates that for A2m(1) to be the antithetical determinant of A2m(2), the determinant formed by residues 428, 458 and/or 467 in these proteins must be influenced by subclass differences which allows its expression in A2m(1) proteins and not in A1 proteins.


Additives to biological substances. IV--Lyophilization conditions in the preparation of international standards: an analysis by high-performance liquid chromatography of the effects of secondary desiccation.
Many International Standards, Reference Preparations and Reference Reagents are routinely prepared by lyophilization in the presence of 'inert' carriers followed by an extensive period of secondary desiccation. In this study we have used high-performance liquid chromatography (HPLC) to analyse the effects of lyophilization and secondary desiccation on initial degradation and subsequent stability of a model protein, insulin. Secondary desiccation was found to promote a reaction of the insulin with a carrier consisting of non-volatile buffer salts and a sugar. Secondary desiccation did not improve the stability of the insulin as determined by accelerated thermal degradation and analysis using the Arrhenius equation. We conclude that careful consideration needs to be given, on a case-by-case basis, to the selection of the procedures for the preparation of International Standards, particularly those ampouled in the absence of carrier proteins and intended for physicochemical analysis such as HPLC.


Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival.
To reveal the genes relevant for prediction of cervical cancer after radiotherapy, we previously carried out cDNA microarray experiments on primary cervical cancer comparing patients with a complete response (CR) and those with no change (NC). Some of these genes had already been associated with the radiation response, such as x-ray repair cross-complementing 5 (XRCC5), which was found more in radioresistant tumors than in radiosensitive ones. The aim of this study was to confirm the possible roles of XRCC5 mRNA levels by a real-time polymerase chain reaction method in 20 cervical cancers, and Ku80 protein, which is the gene product of XRCC5, using a histopathologic method of formalin-fixed sections of tumor biopsies in determining tumor response to radiotherapy and survival in 89 patients with cervical cancer. The levels of XRCC5 mRNA were 10(4.82) +/- 10(0.2) copies/microg total RNA in tumor tissues in the CR group (mean +/- standard deviation) and 10(4.95) +/- 10(0.32) copies/microg total RNA in those in the NC group. The levels of XRCC5 mRNA were not significantly different between the CR and NC groups. Histopathologic methods revealed 29.2% (26 of 89) of the patients to be Ku80-negative, with Ku80-positive findings in 70.8% (63 of 89). Of the Ku80-negative patients, 19 had CR, 3 had a partial response (PR), and 4 had NC. Of the Ku80-positive patients, 25 had CR, 22 had PR, and 16 had NC. Ku80-negative tumors showed significantly better responses than Ku80-positive ones, comparing CR and PR/NC responses (p = 0.01). In addition, overall survival was significantly better in the Ku80-negative patients as compared with those who were Ku80-positive (p = 0.04). The results of this study suggest that a low expression of Ku80 protein leads to radiosensitivity in cervical cancer and that Ku80 might play a role in treatment outcome.


Combination of mid- and near-infrared spectroscopy for the determination of the quality properties of beers.
The combination of infrared (MIR) and near-infrared (NIR) spectroscopy has been employed for the determination of important quality parameters of beers, such as original and real extract and alcohol content. A population of 43 samples obtained from the Spanish market and including different types of beer, was evaluated. For each technique, spectra were obtained in triplicate. In the case of NIR a 1mm pathlength quartz flow cell was used, whereas attenuated total reflectance measurements were used in MIR. Cluster hierarchical analysis was employed to select calibration and validation data sets. The calibration set was composed of 15 samples, thus leaving 28 for validation. A critical evaluation of the prediction capability of multivariate methods established from the combination of NIR and MIR spectra was made. Partial least squares (PLS) and artificial neural networks (ANN) were evaluated for the treatment of data obtained in each individual technique and the combination of both. Different parameters of each methodology were optimized. A slightly better predictive performance was obtained for NIR-MIR combined spectra, and in all the cases ANN performs better than PLS, which may be interpreted from the existence of some non-linearity in the data. The root-mean-sqare-error of prediction (RMSEP) values obtained for the combined NIR-MIR spectra for the determination of real extract, original extract and ethanol were 0.076% w/w, 0.14% w/w and 0.091% v/v.


Molecular mechanisms of phytochrome signal transduction in higher plants.
Phytochromes in higher plants play a great role in development, responses to environmental stresses and signal transduction, which are the fundamental principles for higher plants to be adapted to changing environment. Deep and systematic understanding of the phytochrome in higher plants is of crucial importance to molecular biology, purposeful improvement of environment in practice, especially molecular mechanism by which higher plants perceive UV-B stress. The last more than 10 years have seen rapid progress in this field with the aid of a combination of molecular, genetic and cell biological approaches. No doubt, what is the most important, is the application of Arabidopsis experimental system and the generation of various mutants regarding phytochromes (phy A-E). Increasing evidence demonstrates that phytochrome signaling transduction constitutes a highly ordered multidimensional network of events. Some phytochromes and signaling intermediates show light-dependent nuclear-cytoplasmic partitioning, which implies that early signaling events take place in the nucleus and that subcellular localization patterns most probably represent an important signaling control point. The main subcellular localization includes nucleus, cytosol and chloroplasts, respectively. Additionally, proteasome-mediated degradation of signaling intermediates most possibly function in concert with subcellular partitioning events as an integrated checkpoint. What higher plants do in this way is to execute accurate responses to the changes in the light environment on the basis of interconnected subcellular organelles. By integrating the available data, at the molecular level and from the angle of eco-environment, we should be able to construct a solid foundation for further dissection of phytochrome signaling transduction in higher plants.


Principles of genome activation in the early embryo.
A major hurdle in an embryo's life is the initiation of its own transcriptional program, a process termed Zygotic Genome Activation (ZGA). In many species, ZGA is intricately timed, with bulk transcription initiating at the end of a series of reductive cell divisions when cell cycle duration increases. At the same time, major changes in genome architecture give rise to chromatin states that are permissive to RNA polymerase II activity. Yet, we still do not understand the series of events that trigger gene expression at the right time and in the correct sequence. Here we discuss new discoveries that deepen our understanding of how zygotic genes are primed for transcription, and how these events are regulated by the cell cycle and nuclear import. Finally, we speculate on the evolutionary basis of ZGA timing as an exciting future direction for the field.


Study on reservoir optimal operation based on coupled adaptive ε constraint and multi strategy improved Pelican algorithm.
The optimal operation of reservoir groups is a strongly constrained, multi-stage, and high-dimensional optimization problem. In response to this issue, this article couples the standard Pelican optimization algorithm with adaptive ε constraint methods, and further improves the optimization performance of the algorithm by initializing the population with a good point set, reverse differential evolution, and optimal individual t-distribution perturbation strategy. Based on this, an improved Pelican algorithm coupled with adaptive ε constraint method is proposed (ε-IPOA). The performance of the algorithm was tested through 24 constraint testing functions to find the optimal ability and solve constraint optimization problems. The results showed that the algorithm has strong optimization ability and stable performance. In this paper, we select Sanmenxia and Xiaolangdi reservoirs as the research objects, establish the maximum peak-cutting model of terrace reservoirs, apply the ε-IPOA algorithm to solve the model, and compare it with the ε-POA (Pelican algorithm coupled with adaptive ε constraint method) and ε-DE (Differential Evolution Algorithm) algorithms, the results indicate that ε. The peak flow rate of the Huayuankou control point solved by the IPOA algorithm is 12,319 m3/s, which is much lower than the safe overflow flow rate of 22,000 m3/s at the Huayuankou control point, with a peak shaving rate of 44%, and other algorithms do not find effective solutions meeting the constraint conditions. This paper provides a new idea for solving the problem of flood control optimal operation of cascade reservoirs.


The history of schistosomiasis japonica in Taiwan.
Studies of schistosomiasis japonica in Taiwan indicate that the Formosan strain of Schistosoma japonicum is zoophilic in nature. After the discovery of the adult worm of S. japonicum in 1914, a considerable number of epidemiologic studies and experimental infection studies were conducted. This paper is a review of the history of schistosomiasis japonica in Taiwan from before World War II to 2003.


Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV.
Persons with HIV (PWH) have both more frequent depression and higher levels of plasma inflammatory biomarkers compared to persons without HIV (PWoH). Inflammation and depressive symptoms are linked, including in PWH; however, it is unclear whether these associations differ by HIV serostatus and biological sex. Six plasma inflammatory biomarkers were assessed using samples from PWH and PWoH who participated in six NIH-funded studies through the UCSD HIV Neurobehavioral Research Program (HNRP) from 2011 to 2019. Factor analysis was performed to identify intercorrelated groups of biomarkers. Factors and their components were then examined for relationships with Beck Depression Inventory-II (BDI-II) and modifying effects of sex or HIV serostatus using multivariable linear regression, adjusting for demographics, substance use diagnoses, and relevant co-morbidities. Participants included 150 PWH (age = 48.3 ± 13.1 yr; 88% biologically male) and 138 PWoH (age = 46.3 ± 15.9; 56% male). Two inflammatory factors were identified: Factor 1 loaded on interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer; Factor 2 loaded on interleukin-8, chemokine C-C ligand 2 (CCL2), and chemokine C-X-C ligand 10 (CXCL10). Sex modified the effect of Factor 1 on BDI-II, with a more positive association for men than women (p = 0.04). No significant association between Factor 2 and BDI-II was found. Of the biomarkers in Factor 1, only IL-6 was significantly associated with BDI-II and was modified by sex (p = 0.003). In sex-stratified analysis, a positive association was found for men (β = 5.42; 95% confidence interval = [1.32, 9.52]) but not women (β = -3.88; 95% C.I. = [-11.02, 3.26]). No HIV-related interactions were detected. We identified a depression-associated inflammatory factor present in both PWH and PWoH, consistent with prior studies of PWH only. The association was driven by a correlation between IL-6 and depression exclusively in men, suggesting that the depression-inflammation link differs by sex. Future studies of depression etiology or treatment, including those on persons with HIV, should consider the impact of biological sex in both design and analysis.


Granulomatous biliary tract obstruction due to sarcoidosis. Report of a case and review of the literature.
A 29-year-old woman with sarcoidosis developed obstructive jaundice due to granulomatous involvement of the common hepatic duct and surrounding lymph nodes. After temporary decompression by T-tube, obstruction was alleviated by corticosteroid therapy.


Head trauma and Cochlear implant displacement - A systematic review.
Cochlear implant (CI) migration due to head trauma is a rare complication, and there is limited data summarizing this topic. This review seeks to provide a more comprehensive understanding of risk factors, clinical presentations, diagnosis, and intervention strategies for traumatic CI displacement. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocol was followed using the PubMed and MED-LINE databases from 2000 to 2021, with manual cross-checks of reference lists of identified articles for additional relevant studies. The keywords used for database searches included "cochlear implant", "migration", "displacement", "extrusion" and "head trauma". All full-text articles available in English were screened, including single case presentations. Abstracts, commentaries, and publications deemed outside the scope of our study aims were excluded from review. After the removal of duplicate articles, a total of 152 articles were screened. After applying inclusion and exclusion criteria, 11 articles were included in the review. Due to heterogeneity of the available literature, a qualitative synthesis was employed to integrate results by identifying common themes among the relevant studies. The incidence of traumatic CI migration is extremely low and can be due to receiver-stimulator displacement, magnet displacement, or electrode extrusion. Migration occurred anywhere from 3 months to 26 years after implantation, suggesting that risk of migration from head trauma does not depend solely on time from implantation. There are several methods for repairing migrated CI, but there is limited data comparing operative techniques, specifically in the prevention of traumatic CI migration.


Non-hypoxic stabilization of HIF-Iα during coordinated interaction between Akt and angiopoietin-1 enhances endothelial commitment of bone marrow stem cells.
We previously reported that mesenchymal stem cells (MSC) co-expressing Akt and angiopoietin-1 (Ang-1) preserved infarcted heart function via angiomyogenesis. The present study determined the mechanism of co-overexpression of Akt and Ang-1 in promoting endothelial commitment of MSC. The cells were transduced with vectors encoding for Akt ((Akt)MSC), Ang-1 ((Ang-1)MSC), and both Akt and Ang-1 ((AA)MSC) using Empty vector transduced MSC ((Emp)MSC) as control. Molecular studies indicated a coordinated interaction between Akt and Ang-1 in (AA)MSC and led to non-hypoxic stabilization of hypoxia inducible factor-1α (HIF-Iα) which accentuated under 4-h anoxia. We also observed HIF-Iα dependent induction of hemeoxygenase-1, endothelial specific markers and VEGF in (AA)MSC. Vascular commitment of (AA)MSC was confirmed by immunostaining, Western blotting and flow cytometry for endothelial specific early and late markers including Flt1, Flk1, Tie2, VCAM-1, and von Willebrand Factor-VIII (vWF-VIII) in HIF-Iα dependent fashion besides exhibiting higher emigrational activity and angiogenesis in vitro. (AA)MSC transplanted into rat model of myocardial infarction showed higher Flk1 and Flt1 positivity and also promoted intrinsic Flk1(+) and Flt1(+) cell mobilization into the infarcted heart. Given the ease of availability of MSC and simplicity of approach to co-overexpress Ang-1 and Akt to enhance their endothelial commitment, the strategy will be significant for cellular angiogenesis to treat ischemic heart.


Synthesis of 9-membered masked enediyne analogues possessing DNA intercalator and sugar moieties.
Syntheses of hybrid DNA cleaving molecules which have the 9-membered enediyne structure of kedarcidin with the DNA intercalator of NCS and/or the sugar moieties were accomplished. Introduction of the sugar moieties to the masked enediyne was achieved via S-alkylation of a bromoacetate derivative with a sugar-containing thiol without the need for protection of the sugar moiety.


Effect of flunarizine on the attenuation of baroreflex by transient cerebral ischemia.
Baroreflex sensitivity assessed by phenylephrine-induced reflex bradycardia was markedly decreased by 5- an 10-min global cerebral ischemia in anesthetized dogs. Flunarizine, 0.1 and 1 mg/kg i.v., administered 5 min prior to 5-min ischemia, completely inhibited the decrease in baroreflex sensitivity while such a protective effect of the latter dose was incomplete against 10-min ischemia. In contrast, papaverine, 0.5 mg/kg per min i.v., infused for 5 min prior to 5-min ischemia, failed to protect the decrease in baroreflex sensitivity. Flunarizine may possess a certain direct cerebroprotective effect in addition to its cerebrocirculatory effect.


Medicinal plants utilized in the management of epilepsy in Ethiopia: ethnobotany, pharmacology and phytochemistry.
Epilepsy is a common central nervous system (CNS) disorder that affects 50 million people worldwide. Patients with status epilepticus (SE) suffer from devastating comorbidities and a high incidence of mortalities. Antiepileptic drugs (AEDs) are the mainstream treatment options for the symptomatic relief of epilepsy. The incidence of refractory epilepsy and the dose-dependent neurotoxicity of AEDs such as fatigue, cognitive impairment, dizziness, attention-deficit behavior, and other side effects are the major bottlenecks in epilepsy treatment. In low- and middle-income countries (LMICs), epilepsy patients failed to adhere to the AEDs regimens and consider other options such as complementary and alternative medicines (CAMs) to relieve pain due to status epilepticus (SE). Plant-based CAMs are widely employed for the treatment of epilepsy across the globe including Ethiopia. The current review documented around 96 plant species (PS) that are often used for the treatment of epilepsy in Ethiopia. It also described the in vivo anticonvulsant activities and toxicity profiles of the antiepileptic medicinal plants (MPs). Moreover, the phytochemical constituents of MPs with profound anticonvulsant effects were also assessed. The result reiterated that a lot has to be done to show the association between herbal-based epilepsy treatment and in vivo pharmacological activities of MPs regarding their mechanism of action (MOA), toxicity profiles, and bioactive constituents so that they can advance into the clinics and serve as a treatment option for epilepsy.


Fellowship of the Spring: An initiative to document and protect the world's oases.
An 'oasis' signifies a refugium of safety, recovery, relaxation, fertility, and productivity in an inhospitable desert, a sweet spot in a barren landscape where life-giving water spills forth from the Earth. Remarkable mythological congruencies exist across dryland cultures worldwide where oases or 'arid-land springs' occur. In many places they also provide specialised habitats for an extraordinary array of endemic organisms. To inform their management, and maintain their integrity, it is essential to understand the hydrogeology of aquifers and springs. Gravity-fed vs artesian aquifers; actively recharged vs fossil aquifers, and sources of geothermal activity are important concepts presented here. There consequences for oases of sustainable and unsustainable groundwater extraction, and other examples of effective conservation management. Oases are archetypes for human consciousness, habitats that deserve protection and conservation, and a lingua franca for multicultural values and scientific exchange. We represent an international Fellowship of the Spring seeking to encompass and facilitate the stewardship of oases and aquifers through improved knowledge, outreach, and governance.


Mathematical models of the population biology of Ostertagia ostertagi and Teladorsagia circumcincta, and the economic evaluation of disease control strategies.
The construction and use of mathematical models of the population biology of Ostertagia ostertagi and Teladorsagia circumcincta is discussed. Simulated field trials implemented by deterministic mathematical models currently share with actual field trials the disadvantage that they convey no information concerning the risk associated with the net return demonstrated by the trial. This has important implications when it is necessary to rank disease control strategies in order of usefulness.


New versatile restraining device for use with rats in pharmacokinetic or pharmacological studies involving chronically implanted cannulae or electrodes.
A new design for a rat restraining device is described. Features of the device include facilities to allow the accommodation of rats of a very wide weight range and to maximize its convenience in use in a variety of procedures including the collection of blood, feces, and urine. The restrainer is designed to minimize stress in the rat in the course of pharmacokinetic or pharmacological studies. The device is particularly useful for studies involving chronically cannulated animals.


A brief intervention to improve college success and equity.
A large-scale experiment focused on social belonging shows impacts on first-year full-time completion.


Treatment of rebound and chronic pulmonary hypertension with oral sildenafil in an infant with congenital diaphragmatic hernia.
We describe a case of chronic pulmonary hypertension in a 7-wk-old infant with congenital diaphragmatic hernia and an oral teratoma. Our patient was dependent on low-dose inhaled nitric oxide and was still very unstable with systemic right ventricular pressures leading to frequent oxygen desaturations. We administered sildenafil therapy to stabilize the infant with discontinuation of inhaled nitric oxide. We describe successful discontinuation of the inhaled therapy as well as a period of stabilization and improvement with continued sildenafil administration. Case report. Intensive care nursery in tertiary academic center. A 7-wk-old infant with congenital diaphragmatic hernia who was mechanically ventilated from birth. Oral sildenafil 0.3 mg/kg/dose every 12 hrs. Right ventricular pressure (from tricuspid valve regurgitant flow) to systemic systolic arterial pressure was measured by echocardiogram. Right ventricular to systemic pressure ratio was marginally improved with the initiation of sildenafil therapy. Inhaled nitric oxide was successfully discontinued, and the patient clinically stabilized temporarily, but he ultimately succumbed to his pulmonary hypertension. Sildenafil may be a useful therapy for chronic pulmonary hypertension in congenital diaphragmatic hernia, but further studies of safety and efficacy need to be performed.


Perceptions of Home Dialysis Training and Experience Among US Nephrology Fellows.
Prior research suggests a lack of confidence among graduating US nephrology trainees in implementing both peritoneal dialysis (PD) and home hemodialysis (HHD). Gaps in fellowship training may represent an obstacle to achieving the Advancing American Kidney Health Initiative's goal of increasing the use of home dialysis. We sought to identify the strengths of and limitations in home dialysis training. A cross-sectional study surveying nephrology trainees regarding their confidence with home dialysis management and perceptions of home dialysis educational resources provided by their training program. A paper survey was distributed to 110 nephrology trainees with at least 1 year of nephrology fellowship training who attended any 1 of 3 home dialysis conferences. Data were summarized as percentages. χ2, Fisher exact, and Kruskal-Wallis rank sum tests were used for statistical analysis. Self-perception of readiness to manage PD and HHD patients. 76 of 110 (66%) attendees completed the survey. Most respondents were moderately confident regarding principles of PD. However, only 3% had initiated patients on "urgent-start PD" and 11% observed a PD catheter insertion. The level of confidence for HHD was low. Most trainees attended a home dialysis continuity clinic with mentorship from faculty. A small number of participants and the inability to verify respondent-provided data for the number of PD and HHD patients seen and clinics attended. Potential lack of generalizability owing to inclusion of only trainees who attended a home dialysis conference. Nephrology trainees perceive low and moderate levels of preparedness for managing HHD and PD, respectively. Educational innovation and optimization of resources at both the institutional and national levels may improve confidence and promote public policy goals regarding home dialysis therapies.


Adaptation measures under the impacts of climate and land-use/land-cover changes using HSPF model simulation: Application to Gongola river basin, Nigeria.
Recently, there is an upsurge in flood emergencies in Nigeria, in which their frequencies and impacts are expected to exacerbate in the future due to land-use/land cover (LULC) and climate change stressors. The separate and combined forces of these stressors on the Gongola river basin is feebly understood and the probable future impacts are not clear. Accordingly, this study uses a process-based watershed modelling approach - the Hydrological Simulation Program FORTRAN (HSPF) (i) to understand the basin's current and future hydrological fluxes and (ii) to quantify the effectiveness of five management options as adaptation measures for the impacts of the stressors. The ensemble means of the three models derived from the Coupled Model Intercomparison Project Phase 5 (CMIP5) are employed for generating future climate scenarios, considering three distinct radiative forcing peculiar to the study area. Also, the historical and future LULC (developed from the hybrid of Cellular Automata and Markov Chain model) are used to produce the LULC scenarios for the basin. The effective calibration, uncertainty and sensitivity analyses are used for optimising the parameters of the model and the validated result implies a plausible model with efficiency of up to 75 %. Consequently, the results of individual impacts of the stressors yield amplification of the peak flows, with more profound impacts from climate stressor than the LULC. Therefore, the climate impact may trigger a marked peak discharge that is 48 % higher as compared to the historical peak flows which are equivalent to 10,000-year flood event. Whilst the combine impacts may further amplify this value by 27 % depending on the scenario. The proposed management interventions such as planned reforestation and reservoir at Dindima should attenuate the disastrous peak discharges by almost 36 %. Furthermore, the land management option should promote the carbon-sequestering project of the Paris agreement ratified by Nigeria. While the reservoir would serve secondary functions of energy production; employment opportunities, aside other social aspects. These measures are therefore expected to mitigate feasibly the negative impacts anticipated from the stressors and the approach can be employed in other river basins in Africa confronted with similar challenges.


Predicting the risk of cobalt deprivation in grazing livestock from soil composition data.
The objective was to derive predictive equations for acetic acid-extractable cobalt (A-ECo) in soils so that extensive national databases for total (T) Co in soils and stream sediments could be converted to 'plant available' concentrations for the purpose of predicting risk of Co deficiency in grazing livestock. Data on the chemical and physical properties of 103 soils from 15 different parent materials and 54 soil series in England and Wales were used. Ranges for the mean values for parent materials were: TCo, 5.0-20.4 and A-ECo, 0.20-1.30 mg kg-1; percentage (P) A-ECo, 3.4-13.5; soil manganese (Mn) 268-1174 mg kgDM-1; pH, 3.7-8.0. There were significant effects of parent material on all parameters with Chalks, Old and New Red Sandstones particularly low in A-ECo. Multiple linear regression yielded the following equation for predicting A-ECo, which accounted for 56% of the variance with 12 outliers, including the lowest pH values, omitted: [figure: see text] REML was used on the complete, unbalanced, log-transformed data set to fit a Generalised Mixed Model with parent material as random effect and soil Mn and pH as fixed effects; the effect of parent material was no longer significant. It was concluded that A-ECo can be satisfactorily predicted for most soils in England and Wales from TCo, TMn and soil pH.


Video-assisted thoracic surgery for left lung cancer in a patient with a right aortic arch.
We report a rare case of left lung cancer in a patient with a right aortic arch. A 65-year-old woman was diagnosed to have an adenocarcinoma in the left upper lobe (S3) in addition to a right aortic arch (type II), with the left subclavian artery originating from the descending aorta. Left upper lobectomy and lymph node dissection was performed by video-assisted thoracic surgery (VATS). For the mediastinal dissection, the upper mediastinal lymph nodes were easily resected after verifying the location of the arterial ligament and the recurrent laryngeal nerve (RLN). This is the first report of using VATS to remove a lung cancer from a patient with a right aortic arch.


Histomorphometric analysis of nuclear and cellular volumetric alterations in oral lichen planus, lichenoid lesions and normal oral mucosa using image analysis software.
Lichen planus is a chronic inflammatory mucocutaneous disease that clinically and histologically resembles lichenoid lesions, although the latter has a different etiology. Though criteria have been suggested for differentiating oral lichen planus from lichenoid lesions, confusion still prevails. To study the cellular and nuclear volumetric features in the epithelium of normal mucosa, lichen planus, and lichenoid lesions to determine variations if any. A retrospective study was done on 25 histologically diagnosed cases each of oral lichen planus, oral lichenoid lesions, and normal oral mucosa. Cellular and nuclear morphometric measurements were assessed on hematoxylin and eosin sections using image analysis software. Analysis of variance test (ANOVA) and Tukey's post-hoc test. The basal cells of oral lichen planus showed a significant increase in the mean nuclear and cellular areas, and in nuclear volume; there was a significant decrease in the nuclear-cytoplasmic ratio as compared to normal mucosa. The suprabasal cells showed a significant increase in nuclear and cellular areas, nuclear diameter, and nuclear and cellular volumes as compared to normal mucosa. The basal cells of oral lichenoid lesions showed significant difference in the mean cellular area and the mean nuclear-cytoplasmic ratio as compared to normal mucosa, whereas the suprabasal cells differed significantly from normal mucosa in the mean nuclear area and the nuclear and cellular volumes. Morphometry can differentiate lesions of oral lichen planus and oral lichenoid lesions from normal oral mucosa. Thus, morphometry may serve to discriminate between normal and premalignant lichen planus and lichenoid lesions. These lesions might have a high risk for malignant transformation and may behave in a similar manner with respect to malignant transformation.


Value in acute care surgery, part 2: Defining and measuring quality outcomes.
The prior article in this series delved into measuring cost in acute care surgery, and this subsequent work explains in detail how quality is measured. Specifically, objective quality is based on outcome measures, both from administrative and clinical registry databases from a multitude of sources. Risk stratification is key in comparing similar populations across diseases and procedures. Importantly, a move toward focusing on subjective outcomes like patient-reported outcomes measures and financial well-being are vital to evolving surgical quality measures for the 21st century.


Clinical evaluation of a multi-parameter customized respiratory TaqMan(®) array card compared to conventional methods in immunocompromised patients.
Respiratory viral infections can cause significant morbidity and mortality in immunocompromised patients. Conventional tests routinely available at most institutions are limited by the number of detectable pathogens, by a poor sensitivity and/or a long turnaround time. To compare the performance of routine conventional testing with direct fluorescent antibody assays and viral culture to a customized TaqMan® array card (TAC) real-time PCR method, targeting 24 viruses, 8 bacteria and 2 fungi simultaneously. We collected 143 respiratory samples from 120 symptomatic immunocompromised patients. Samples for which conventional and TAC results were discordant underwent further verification testing. The TAC assay identified viral pathogens in more samples than did conventional testing (77/143 versus 27/143; McNemar P<0.0001), even when TAC results for viruses that could not be detected by conventional testing were excluded from analysis (59/143 versus 26/143; P<0.0001). In addition, the TAC assay identified 18 samples with non-viral pathogens. Verification testing confirmed positive TAC results for 50 out of 55 samples for which conventional testing was negative. Two out of three samples with a positive conventional test but negative TAC result were confirmed positive. A viral and a total pathogen co-infection rate of 5.6% and 11.8% were found, respectively. The customized TAC assay resulted in a significantly increased identification of respiratory viruses. This study provides a practical real-life assessment of the performance of the TAC assay in a population for whom rapid and accurate diagnosis of viral and atypical pathogens is crucial for appropriate clinical management.


Child-Adult Relationship Enhancement (CARE): An evidence-informed program for children with a history of trauma and other behavioral challenges.
Child maltreatment impacts approximately two million children each year, with physical abuse and neglect the most common form of maltreatment. These children are at risk for mental and physical health concerns and the ability to form positive social relationships is also adversely affected. Child Adult Relationship Enhancement (CARE) is a set of skills designed to improve interactions of any adult and child or adolescent. Based on parent training programs, including the strong evidence-based treatment, Parent-Child Interaction Therapy (PCIT), CARE was initially developed to fill an important gap in mental health services for children of any age who are considered at-risk for maltreatment or other problems. CARE subsequently has been extended for use by adults who interact with children and youth outside of existing mental health therapeutic services as well as to compliment other services the child or adolescent may be receiving. Developed through discussions with Parent-Child Interaction Therapy (PCIT) therapists and requests for a training similar to PCIT for the non-mental health professional, CARE is not therapy, but is comprised of a set of skills that can support other services provided to families. Since 2006, over 2000 caregivers, mental health, child welfare, educators, and other professionals have received CARE training with a focus on children who are exposed to trauma and maltreatment. This article presents implementation successes and challenges of a trauma-informed training designed to help adults connect and enhance their relationships with children considered at-risk.


Body Politics in the COVID-19 Era from a Feminist Lens.
The premises of the feminist economist tradition from the Global South center their analysis in the wellbeing of people and the planet, under the human rights framework, gender equality and environmental integrity, as cross-cutting principles. The pandemic brought to the surface what the feminist movement has been saying all along, namely that the wellbeing of persons, and the planet they live in, depends on a complex web of elements beyond a limited notion of bodily health. The current capitalistic system has always kindled a tension between life and profits, a game that has undermined human rights of all persons by prioritizing the circulation of merchandises, goods and capitals. That struggle is more acutely felt now with the confinement measures imposed all around the world, and the ensuing impossibility for millions of people in precarious circumstances of respecting the lockdown measures. Women are even more carrying the burden of subsidizing entire economies. The feminist movement is now looking at solutions of solidarity at the crossroad between and within social movements, public policy, local and community resistance, while refusing to go back to a world where women may have to subsidize even more entire economies under recession.


MetaBlasts: tracing protein tyrosine phosphatase gene family roots from Man to Drosophila melanogaster and Caenorhabditis elegans genomes.
At increasing speed, sequencing data are being made public from both complex and simple life forms. Although biomedical interests tend to focus on mammalian genes, only simple organisms allow rapid genetic manipulation and functional analysis. A prerequisite for the meaningful extrapolation of gene functional studies from invertebrates to man is that the orthologs under study are unambiguously linked. However, identifying orthologs is not trivial, especially where large gene families are involved. We present here an automated sequence analysis procedure that allows a rapid visualization of most likely ortholog pairs. We illustrate the utility of this approach for the human gene family of protein tyrosine phosphatases (PTPs) as compared with the full set of Caenorhabditis elegans and Drosophila melanogaster conceptual ORFs. The approach is based on a reciprocal series of BLAST searches, which are automatically stored and represented in an HTML-formatted table. We have used this 'MetaBlast' approach to compile lists of human PTPs and their worm and fly orthologs. Many of these PTP orthologs had not been previously identified as such.


Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases.
Mitochondria are the organelles that generate energy for the cells and act as biosynthetic and bioenergetic factories, vital for normal cell functioning and human health. Mitochondrial bioenergetics is considered an important measure to assess the pathogenesis of various diseases. Dysfunctional mitochondria affect or cause several conditions involving the most energy-intensive organs, including the brain, muscles, heart, and liver. This dysfunction may be attributed to an alteration in mitochondrial enzymes, increased oxidative stress, impairment of electron transport chain and oxidative phosphorylation, or mutations in mitochondrial DNA that leads to the pathophysiology of various pathological conditions, including neurological and metabolic disorders. The drugs or compounds targeting mitochondria are considered more effective and safer for treating these diseases. In this review, we make an effort to concise the available literature on mitochondrial bioenergetics in various conditions and the therapeutic potential of various drugs/compounds targeting mitochondrial bioenergetics in metabolic and neurodegenerative diseases.


The primary interpretation workstation: information beyond image data.
With the advent of picture archival and communication systems (PACS), the importance of design surrounding primary review workstations has become apparent. To help acceptance of filmless medical imaging, workstations must be developed that serve the needs of both radiologists and referring clinicians. This report will discuss integral requirements of workstation design, including information creation, medical management, medical knowledge, and enabling technologies.


A fast method to measure the degree of oxidation of dialdehyde celluloses using multivariate calibration and infrared spectroscopy.
The properties of dialdehyde celluloses, which are usually generated by periodate oxidation, are highly dependent on the aldehyde content, i.e. the degree of oxidation (DO). Thus far, the established methods for determining the DO in dialdehyde celluloses lack simplicity or sufficient speed. More than 60 dialdehyde cellulose samples with varying aldehyde content were analysed by near-infrared and Fourier-transform infrared spectroscopy. This was found to be a reliable method for quickly predicting the DO if combined with partial least squares regression (PLSR). The proposed PLSR models can predict the DO with a high determination coefficient (R2) of 99% when applied to a single pulp type and 94% when applied to multiple types. This new approach quickly and reliably determines the DO of dialdehyde celluloses. It can be easily implemented in everyday research to save money, time and resources, especially because the raw datasets and measured DO values are provided.


Serological examination for HIV-I antibodies in Nicaragua, Columbia and El Salvador.
22 of 182 sera samples from Nicaragua, 6 of 111 samples from Columbia, and 25 of 388 samples from El Salvador were positive in the ELISA test. 37 of the 53 positive sera samples were positive again in a further ELISA test, and 1 of them was positive in the IFT and Western Blot test.


Placement of Short Implants: A Viable Alternative?
The placement of short implants, which measure less than 10 mm in length, requires the practitioner to have a thorough comprehension of implant dentistry to achieve acceptable results. Innovation of the rough-surface implant and the progression of the implant-abutment interface from an external hex to an internal connection have considerably influenced the longevity of short implants. Dentists are better equipped to serve their patients because the utilization of short implants may preclude the need for advanced surgical bone-grafting procedures.


New frontiers in animal research of psychiatric illness.
Alterations in neurodevelopment are thought to modify risk of numerous psychiatric disorders, including schizophrenia, autism, ADHD, mood and anxiety disorders, and substance abuse. However, little is known about the cellular and molecular changes that guide these neurodevelopmental changes and how they contribute to mental illness. In this review, we suggest that elucidating this process in humans requires the use of model organisms. Furthermore, we advocate that such translational work should focus on the role that genes and/or environmental factors play in the development of circuits that regulate specific physiological and behavioral outcomes in adulthood. This emphasis on circuit development, as a fundamental unit for understanding behavior, is distinct from current approaches of modeling psychiatric illnesses in animals in two important ways. First, it proposes to replace the diagnostic and statistical manual of mental disorders (DSM) diagnostic system with measurable endophenotypes as the basis for modeling human psychopathology in animals. We argue that a major difficulty in establishing valid animal models lies in their reliance on the DSM/International Classification of Diseases conceptual framework, and suggest that the Research Domain Criteria project, recently proposed by the NIMH, provides a more suitable system to model human psychopathology in animals. Second, this proposal emphasizes the developmental origin of many (though clearly not all) psychiatric illnesses, an issue that is often glossed over in current animal models of mental illness. We suggest that animal models are essential to elucidate the mechanisms by which neurodevelopmental changes program complex behavior in adulthood. A better understanding of this issue, in animals, is the key for defining human psychopathology, and the development of earlier and more effective interventions for mental illness.


In vivo pharmacokinetics of calreticulin S-domain, an inhibitor of the classical complement pathway.
Inhibition of the complement system is potentially therapeutic in diseases where uncontrolled or overshooting complement activation plays a significant role in the pathogenesis of the disorder. Calreticulin (CRT) is a multifunctional protein whose cell-surface form (ectocalreticulin) is reported to be a C1q receptor. A 124-residue domain within CRT, the S-domain, binds to C1q, prevents the formation of C1 and so inhibits activation of the classical pathway. To assess the usefulness of CRT S-domain as a complement inhibitor, recombinant S-domain was expressed, radiolabeled, and the fate of the radiolabeled peptide followed in vivo. In rats, CRT-S-domain shows a half-life of 1.21 +/- 0.34 and 40.5 +/- 2.7 min in the distribution and elimination phases from plasma, respectively. The peptide remains largely intact, and is cleared from the circulation by the kidneys, where it accumulates in the proximal convoluted tubules, but is not excreted. Much smaller amounts of the peptide accumulate in other tissues, and essentially none crosses the blood-brain barrier.


Phenol Oxidation by a Nickel(III)-Fluoride Complex: Exploring the Influence of the Proton Accepting Ligand in PCET Oxidation.
In order to gain insight into the influence of the H+ -accepting terminal ligand in high-valent oxidant mediated proton coupled electron transfer (PCET) reactions, the reactivity of a high valent nickel-fluoride complex [NiIII (F)(L)] (2, L=N,N'-(2,6-dimethylphenyl)-2,6-pyridinecarboxamidate) with substituted phenols was explored. Analysis of kinetic data from these reactions (Evans-Polanyi, Hammett, and Marcus plots, and KIE measurements) and the formed products show that 2 reacted with electron rich phenols through a hydrogen atom transfer (HAT, or concerted PCET) mechanism and with electron poor phenols through a stepwise proton transfer/electron transfer (PT/ET) reaction mechanism. The analogous complexes [NiIII (Z)(L)] (Z=Cl, OCO2 H, O2 CCH3 , ONO2 ) reacted with all phenols through a HAT mechanism. We explore the reason for a change in mechanism with the highly basic fluoride ligand in 2. Complex 2 was also found to react one to two orders of magnitude faster than the corresponding analogous [NiIII (Z)(L)] complexes. This was ascribed to a high bond dissociation free energy value associated with H-F (135 kcal mol-1 ), which is postulated to be the product formed from PCET oxidation by 2 and is believed to be the driving force for the reaction. Our findings show that high-valent metal-fluoride complexes represent a class of highly reactive PCET oxidants.


Subclinical dermal involvement is detectable by high frequency ultrasound even in patients with limited cutaneous systemic sclerosis.
The aim of the study was to detect by skin high-frequency ultrasound (US) possible subclinical skin involvement in patients affected by limited cutaneous systemic sclerosis (lcSSc), in those skin areas apparently not affected by the disease on the basis of a normal modified Rodnan skin score (mRSS). Differences in dermal thickness (DT) in comparison with healthy subjects were investigated. Fifty patients with lcSSc (age 62 ± 13 years (mean ± SD), disease duration 5 ± 5 years) and 50 sex-matched and age-matched healthy subjects (age 62 ± 11 years) were enrolled. DT was evaluated by both mRSS and US at the usual 17 skin areas (zygoma, fingers, dorsum of the hands, forearms, upper arms, chest, abdomen, thighs, lower legs and feet). Non-parametric tests were used for the statistical analysis. Subclinical dermal involvement was detected by US even in the skin areas in patients with lcSSc, who had a normal local mRSS. In addition, statistically significantly higher mean DT was found in almost all skin areas, when compared to healthy subjects (p < 0.0001 for all areas). In particular, DT was significantly greater in patients with lcSSc than in healthy subjects in four out of six skin areas with a normal mRSS (score = 0) (upper arm, chest and abdomen), despite the clinical classification of lcSSc. This study strongly suggests that subclinical dermal involvement may be detectable by US even in skin areas with a normal mRSS in patients classified as having lcSSc. This should be taken into account during SSc subset classification in clinical studies/trials.


Effect of pH on bile salt injury to mouse gastric mucosa. A light- and electron-microscopic study.
Bile salts break the gastric mucosal barrier. To explain this, the suggestion has been made that bile salts may disrupt surface epithelial cell membranes or break the tight junctions between cells, but appropriate ultrastructural studies are lacking. We therefore instilled control and bile salt-containing solutions into the stomachs of fasted mice at pH, 1, 3, 5, AND 7. Taurocholate (pKa equals 1.8) caused mucosal injury only at pH 1, whereas glycochenodeoxycholate (pKa equals 4.2) injured the mucosa at pH 1 and 3. By electron microscopy, areas of mild mucosal injury were characterized by clumping of nuclear chromatin and loss of cytoplasmic density within surface mucous cells. The apical cell membranes and tight junctions remained intact. In areas of severe damage surface cells were ruptured but tight junctions still appeared unbroken. These studies indicate that acid pH markedly augments the damaging effects of bile salts on mouse gastric mucosa. Moreover, as an initial step in the mechanism of bile salt-induced gastric injury, the nonionized moiety of a given bile salt which exists below its pKa may be important in altering the gastric surface epithelial cell in a way which allows the ingress of bile salt and/or hydrogen ion to cause intracellular damage.


Delayed brachial artery dilation response and increased resting blood flow velocity in young children with mild sleep-disordered breathing.
This study aimed to evaluate whether the vascular dysfunction perceived in adults with sleep-disordered breathing (SDB) was also evident in children with snoring referred for evaluation of clinically suspected SDB. This study compared flow-mediated dilatation (FMD), measured at the brachial artery, at rest and during hyperaemic stress between children who snore [n = 23; mean standard deviation (SD) age = 7.51 (1.3) years] and healthy, non-snoring children [n = 11; age = 8.0 (1.3) years]. Children with suspected obstructive sleep apnoea (OSA) and healthy non-snoring controls underwent overnight polysomnography (PSG). Using standard techniques, non-invasive FMD and brachial arterial blood flow velocity during rest and hyperaemia were subsequently measured by ultrasound imaging Resting and hyperaemic velocity time integral (area under the curve of mean systolic velocity × ejection time), maximal dilation response (highest percentage difference from baseline diameter) and the time taken to reach maximal dilation were calculated. Children awaiting adenotonsillectomy compared to healthy non-snoring control children had higher velocity time integrals at rest (14 ± 3 m vs. 20 ± 8 m, p < 0.01) and during hyperaemic stress (56 ± 6m vs. 63 ± 13m, p < 0.01) despite having only mild SDB on polysomnographic assessment. Lower nadir oxygen saturation values during non-rapid eye movement sleep were negatively associated with higher resting (r = -0.58, p <0.001) and hyperaemic (r = -0.36, p < 0.05) velocity time integrals. Maximal FMD dilatation response was not significantly different between snoring and non-snoring groups, but the estimated time to reach maximal dilation was significantly delayed in children who snored (60.7 ± 28.4 vs. 39.2 ± 13.2 s, p < 0.05). Children with mild SDB showed increased blood flow velocity at rest and during hyperaemic stress suggesting altered cardiovascular and haemodynamic function. The delay in time to maximal vessel dilatation in children who snored also suggests possible reduced vascular compliance in response to hyperaemic sheer stress. Mild SDB appears to alter the peripheral vascular response in young children. The long-term vascular implications of these changes in the growing child are unknown and warrant further investigation.


In vitro vertical misfit evaluation of cast frameworks for cement-retained implant-supported partial prostheses.
To evaluate the influence of the alloy type and the associated investing and casting techniques, on the marginal adaptation of bridge structures luted onto prefabricated implant abutments. Thirty frameworks for three-unit posterior-lower bridges were waxed and cast (10 of cobalt-chromium, 10 of titanium and 10 of palladium-gold). Each structure was cemented onto two prefabricated implant abutments with a special clamp designed to maintain constant seating pressure. The vertical discrepancy around the abutments' margins was assessed by scanning electron microscopy (SEM). One-way ANOVA for independent samples and Scheffe's test were applied to analyze the effect of the alloy type and its recommended investing and casting system on vertical misfit. Student's t-test for independent samples was used to compare misfit values concerning the abutment design (premolar and molar). The significance level was set at alpha=0.05. Cobalt-chromium samples recorded the greatest vertical discrepancies, revealing significant differences with respect to both titanium and palladium-gold structures (p<0.0001). Vertical gaps of the palladium-gold and the titanium casts were not significantly different (p=0.292). Neither statistically significant differences were found between the anterior and posterior abutments' vertical misfit independently from the alloy type and nor within each group of alloys tested (p>0.05). The vertical fit of the frameworks cast for implant-cemented bridges was influenced by the alloy type and the investing and casting methods. The marginal discrepancy of the three tested alloys could be considered clinically acceptable. A polished technique in the management of titanium could optimize the accuracy of this cast frameworks.


Prenatal and post-natal cost of small for gestational age infants: a national study.
Small for gestational age (SGA) infants are at increased risk for preterm birth morbidities as well as a range of adverse perinatal outcomes that result in part from associated premature birth. We sought to evaluate the costs of SGA versus appropriate for gestational age (AGA) infants in France from pregnancy through the first year of life and separate the contributions of prematurity from the contribution of foetal growth on costs. This is a cross-sectional population-based study using national hospital discharge data from French public and private hospitals. SGA infants were defined as newborns with a birth weight below the 10th percentile of French intrauterine growth curves adjusted for foetal sex. AGA infants were defined as newborns with a birth weight between the 25th and the 75th. All births were selected between January 1st, 2011 and December 31st, 2011. Costs were calculated from the hospital perspective for both mothers and children using their diagnostic related group and the French national cost study. Hospital outcomes were extracted from the database and compared by gestational age and mode of delivery. Of 777,720 total births in 2011, 84,688 SGA births (10.9%) and 395,760 AGA births (50.8%) were identified. After adjustment for gestational age, the cost for an SGA infant was €2,783 higher than for an AGA infant. The total maternal and infant hospital cost of SGA in France was estimated at 23% the total cost for deliveries. The high cost is explained by higher complication rates, more frequent hospital readmissions and longer lengths of stay. Being small for gestational age is an independent contributor to 1-year hospital costs for both mothers and infants.


Incidence and Predictors of Pre-Eclampsia Among Pregnant Women Attending Antenatal Care at Debre Markos Referral Hospital, North West Ethiopia: Prospective Cohort Study.
Pre-eclampsia is a pregnancy-induced hypertension that occurs after 20 weeks of gestation. It is the leading cause of maternal and perinatal morbidity and mortality globally, but it is higher in developing countries. In Ethiopia, conducting research on the incidence and predictors of pre-eclampsia is crucial due to the paucity of information. A prospective cohort study was undertaken using 242 pregnant women between November 1, 2018 and March 30, 2019 at Debre Markos Referral Hospital. All eligible women who fulfilled the inclusion criteria were included in this study. Data were entered into the epic-data Version 4.2 and analyzed using the STATA Version 14.0 software. The Cox-proportional hazard regression model was fitted and Cox-Snell residual test was used to assess the goodness of fit. Pre-eclampsia free survival time was estimated using the Kaplan-Meier survival curve. Both bivariable and multivariable Cox-proportional hazard regression models were fitted to identify predictors of pre-eclampsia. The overall incidence rate of pre-eclampsia was 3.35 per 100 person-years. Having a pre-existing history of diabetes mellitus [AHR=2.7 (95% CI=1.43-8.81)], having a history of multiple pregnancy [AHR=3.4 (95% CI=2.8-6.9)] and being ≥35 years old age [AHR=2.5 (95% CI=1.42-3.54)] were the significant predictors of pre-eclampsia. The incidence of pre-eclampsia was high in this study. Having (pre-existing diabetes and multiple pregnancy) and being ≥35 years old age were the significant predictors of pre-eclampsia. Inspiring pregnant women's health-seeking behavior should provide a chance to diagnose pre-eclampsia early to prevent the medical complication of pre-eclampsia.


Multivariate discriminant analysis distinguishes metal- from non metal-related biomarker responses in the clam Chamaelea gallina.
Molecular biomarkers are among the most sensitive and earliest responses to pollutants. However, lack of detailed knowledge on variability of responses and their possible seasonal variation limit their use. In addition, the seasonality of biological processes modulates the response of organisms to pollutant stressors. Using multivariate statistics, we have studied the influence of environmental and biological factors on the response of a battery of molecular biomarkers in the clam Chamaelea gallina collected along the South-Spanish littoral. Multivariate discriminant analysis clearly distinguished biomarker response between clean and polluted areas, using heavy metals as indicator of pollution. Such differences disappeared when the dataset was normalised for metal content, thus indicating that pollution was the main significant cause of the changes observed between clean and polluted sites. In conclusion, this work shows that, when applying a complete biomarker panel, multivariate statistical tools can be used to discern pollutant- from non pollutant-related responses.


Treatment of cervical chlamydial infection with amoxicillin/clavulanate potassium.
To determine if amoxicillin/clavulanate potassium is effective in the treatment of Chlamydia trachomatis endocervicitis. Thirty-two patients with culture-proven endocervical infection were treated with amoxicillin/clavulanate potassium, 500 mg orally 3 times a day for 10 days. Post-treatment endocervical specimens were obtained at 2, 4, and 6 weeks for culture of C. trachomatis. Male partners were treated with doxycycline, 100 mg orally twice daily for 10 days. The couples were provided condoms and asked to use them throughout the duration of the study. All patients treated with amoxicillin/clavulanate potassium were cured of signs of cervicitis. All were found to be free of C. trachomatis at their follow-up visits. Amoxicillin/clavulanate potassium is effective in eradicating C. trachomatis.


Adipose-derived stem cell-secreted exosomes enhance angiogenesis by promoting macrophage M2 polarization in type 2 diabetic mice with limb ischemia via the JAK/STAT6 pathway.
Diabetic lower limb ischemia is an intractable disease that leads to amputation and even death. Recently, adipose-derived stem cell-secreted exosomes (ADSC-Exo) have been reported as a potential therapeutic approach, but its specific mechanism of action is unknown. Studies have found that exosomes derived from stem cells can reduce inflammation and promote tissue repair. Macrophages play an important role in the development and repair of inflammation in lower limb ischemic tissue, but the specific regulation of ADSC-Exo in macrophages has rarely been reported. The present study aimed to verify whether ADSC-Exo could promote angiogenesis by regulating macrophages to reduce the level of inflammation in diabetic ischemic lower limbs. In this study, adipose-derived stem cells (ADSCs) were obtained and identified, and ADSC-Exos were isolated using ultracentrifugation and characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blotting analysis. The uptake of ADSC-Exos by macrophages was observed using immunofluorescence, and macrophage polarization induced by ADSC-Exos was identified by flow cytometry, immunofluorescence and ELISA. The effects of ADSC-Exos on the proliferation, apoptosis, migration and adhesion of macrophages were evaluated using CCK-8 assay, flow cytometry, Transwell assay, scratch and adhesion experiments, and ELISA assay. The polarization-related JAK/STAT6 signaling pathway was explored by using western blotting. A lower limb ischemic model of type 2 diabetic mice was established and ADSC-Exos was intramuscularly injected into the mice. The blood flow in the lower limbs was assessed using a laser Doppler flowmeter, while the level of angiogenesis was determined using immunohistochemistry and immunofluorescence. The results of this study prove that ADSC-Exos induced M2-phenotype polarization of macrophages via the JAK/STAT6 signaling pathway can promote the proliferation, migration and adhesion of M2 macrophages, inhibit the apoptosis of macrophages, and promote the angiogenesis and revascularization of ischemic lower limbs in type 2 diabetic mice. Thus, this study provides a theoretical and experimental basis for the clinical treatment of diabetic lower limb ischemic disease.


Acute glomerulonephritis and exposure to organic solvents in father and daughter.
A man and his daughter had acute glomerulonephritis, the daughter eight years after the father. Both were exposed to vapours of organic solvents shortly before the onset of nephritis.


The new immunosuppressant PLNPK prolongs allograft survival in mice.
The pentapeptide PLNPK (Pro-Leu-Asn-Pro-Lys) is extracted from the spleen. Preliminary studies have shown that PLNPK could inhibit T lymphocyte transformation and antibody production. In the present study, we detected the inhibitory effect of PLNPK on one-way mixed leukocyte reaction (MLR) in vitro and observed the effect of PLNPK on the duration of allograft survival in mouse models of skin or cardiac transplantation. Pathological damage and T cell infiltration of the grafts were also detected. Results showed that PLNPK could significantly inhibit T lymphocyte proliferation, with an optimized inhibition of 40%. Also PLNPK could significantly prolong the mean survival time of skin allograft and cardiac allograft, producing survival rates of 42% and 38.7%, respectively. PLNPK at a dose of 200 μg/kg/d or 100 μg/kg/d could significantly suppress ConA-induced T cell proliferation and T cell IL-2 secretion in transplant recipient mice, compared to the saline group (P<0.05). This information suggests that PLNPK can effectively antagonize transplant rejection, possibly by reducing IL-2 secretion by T cells and inhibiting T cell proliferation and activation.


[A psycho-educational program for family caregivers of people with Alzheimer's disease entering an institution].
The caregiver of a loved one suffering from a chronic pathology (Alzheimer's disease, Parkinson's disease, stroke, etc.) can be in psychological distress at all stages of the disease, including when the loved one enters an institution. We have designed and implemented a psycho-educational program for family caregivers of institutionalized patients. A preliminary study showed that this program was feasible, gave satisfaction to the caregivers and improved their understanding of the functioning of the institution, their communication with the professionals of the institution and their relationship with their relative in the institution. The program allowed caregivers to find their place within the institution by redefining their role.


Effectiveness of BCG vaccination in England and Wales in 1983.
The effectiveness of BCG vaccination, at about age 13 years, in the prevention of tuberculosis at ages 15-24 years in England and Wales in 1983, has been determined by the same method as in two previous surveys in 1973 and 1978. In 1983, the tuberculosis notification rate among those vaccinated in the schools' scheme was 3.30 per 100,000, compared with an estimated rate of 13.20 per 100,000 among those who were tuberculin negative and not vaccinated in the scheme. The protective effectiveness of BCG vaccination at ages 15-24 years in England and Wales in 1983 is thus estimated as 75%; the estimated efficacy in the white ethnic group is closely similar, namely 76%. The estimated efficacy of BCG at ages 15-19 and 20-24 years in the three surveys, both in the white ethnic group and in the entire cohort, has been compared with that found in the Medical Research Council's controlled trial of tuberculosis vaccines which began in 1950. There is no evidence of any decrease in the protective efficacy of BCG vaccination between the four cohorts of young adults, which span a total period of 29 years. However, there were steep decreases between the cohorts in the annual notification rates for the white ethnic group; these decreases occurred in the BCG vaccinated and in the tuberculin negative unvaccinated groups, as well as among those found tuberculin positive (and not vaccinated) in the schools' scheme. It is concluded that the level of protective efficacy of BCG vaccination at ages 15-24 years is high, and has remained unchanged since the start of the BCG in schools' scheme. However, as the tuberculosis notification rate in young adults has decreased steeply throughout this period, and is continuing to decrease, the benefits to be expected from the BCG in schools' scheme will decrease equally rapidly.


Self-Assembling Peptide Hydrogels for 3D Microarrays.
Recent advances in biosensing analytical platforms have brought relevant outcomes for novel diagnostic and therapy-oriented applications. In this context, hydrogels have emerged as appealing matrices to locally confine biomolecules onto sensing surfaces under solution mimetic conditions, preserving their structural integrity and function. Here, we describe the application of a self-assembling peptide hydrogel as a suitable matrix for 3D microarray bioassays. The hydrogel is printable and self-adhesive and allows for fast analyte diffusion. As a showcase example, we describe its application in a diagnostic immunoassay for the detection of arbovirus infection.


Lipid and fatty acid composition of brush border membrane of rat intestine during starvation.
Alterations in the lipid and fatty acid composition of brush border membrane (BBM) of small intestine were studied in well-fed, starved, and refed rats. The ratios of cholesterol/phospholipid (mol/mol), sphingomyelin/phosphatidylcholine (mol/mol), protein/lipid (w/w), and free fatty acids (w/w) decreased whereas the total phospholipid (w/w) ratio and the double-bond index increased in BBM of the intestine of the starved rat compared to that of the well-fed rat. Analyses of fatty acids showed higher percentage of stearic and arachidonic acids whereas oleic and linoleic acids decreased under starvation. The acyl chain of starved rat BBM was less ordered compared with that of well-fed rat BBM. On refeeding, these changes were restored to well-fed levels. The change in membrane state under starvation is associated with alterations in the lipid and fatty acid composition of BBM and may be responsible for functional changes that occur under nutritional stress.


Significance of HIF-1α and CD105 in establishing oral squamous cell carcinoma associated with oral submucous fibrosis a distinct clinicopathological entity.
Oral squamous cell carcinoma associated with oral submucous fibrosis (OSCC with OSMF) is clinicopathologically a distinct entity. However, scientific proof in view of assessment of biomarkers of hypoxia and neoangiogenesis to differentiate them are lacking. The expression of hypoxia-inducible factor 1-α (HIF-1α) and CD105 in OSCC with and without OSMF possibly will be explicated along these lines. This study aims to evaluate the molecular basis of hypoxia and neoangiogenesis in terms of immunohistochemical expression of HIF-1α and CD105 in OSCC with and without OSMF cases. A retrospective cohort. The study comprise of 203 histopathologically diagnosed surgically operated cases of OSCC retrieved from the departmental archives. The OSCC cases were subgrouped into two, OSCC with OSMF (Group I) and OSCC without OSMF (Group II). The evaluation of hypoxia and angiogenesis was carried out by immunohistochemical markers, HIF-1α and CD105. MVD is the parameter of angiogenesis expressed by CD105. Differences in CD105, and HIF-1α immunoreactivity between study groups were done using descriptive statistics using "Kruskal-Wallis test," "Mann-Whitney test." Statistical significance was set at P < 0.05. On comparison of MVD in Group I and II, statistically significant difference was found in MVD (8.88 ± 3.41, 16.13 ± 5.86, P = 0.0001). The HIF1-α expression was less in Group I (6.85 ± 2.62) as compare to Group II (7.22 ± 3.08) but the difference was statistically nonsignificant (P = 0.35). The OSCC with OSMF is not only clinicopathologically distinct entity of OSCC but also diverse in its molecular pathogenesis as explicited by distinct expression of HIF-1 α and CD105.


Metastatic phenotype of murine tumor cells expressing different cooperating oncogenes.
Four murine cellular tumor models expressing various combinations of oncogenes (SV40 large T and v-Ha-ras, SV40 large T and v-src, SV40 large T and neu, adenovirus EIA and v-Ha-ras) induce sarcoma when they are inoculated s.c. into the DBA/2 syngenic mice. The metastatic patterns, distribution and fate of these tumor cells transplanted by two different routes into syngenic DBA/2 mice have been studied. All the tumor cell lines except EIA-ras, induce massive overt artificial metastases principally in the lung after i.v. injection. In s.c. tumor-bearing mice, a few resting cells colonize the lung as micrometastases. When removed from this tissue context and injected s.c. these cells regain their proliferative potential and grow as local tumors which again give rise to occult pulmonary micrometastases.


The work of the Medical Research Council.
The above committee is one of Parliament's select committees that undertake enquiries of considerable depth in their particular fields. Its latest enquiry looked at the MRC in general, and also specifically at how it is handling the Biobank project. Its general findings are scathing of the MRC's performance and mismanagement of its funds, concluding that 'the anger of the research community at MRC's funding problems is not only understandable but entirely justified.' The following are the committee's conclusions and recommendations on Biobank--the collection of blood samples, lifestyle details and medical histories from 500,000 middle-aged Britons, and its general conclusions.


[Histochemical demonstration of the zinc activated tartrate resistant phosphatase (ZnTP) in the glial reaction of rat brains following stabbing injuries (author's transl)].
ZnTP shows a characteristic pattern of activity in experimentally induced cerebral tumours of rats. Our previous investigations demonstrated a high activity of this enzyme in astrocytomas and in blood vessels within the tumours. The question arose, whether the increased activity is specific for tumours of astrocytic origin or occurs in reactive astrocytic proliferations as well. The present investigation is aimed at the elucidation of this problem.


The influence of cationic lipid type on in-vitro release kinetic profiles of antisense oligonucleotide from cationic nanoemulsions.
Novel formulations of cationic nanoemulsions based on three different lipids were developed to strengthen the attraction of the polyanionic oligonucleotide (ODN) macromolecules to the cationic moieties on the oil nanodroplets. These formulations were developed to prolong the release of the ODN from the nanoemulsion under appropriate physiological dilutions as encountered in the eye following topical application. Increasing the concentration of the new cationic lipid exhibiting two cationic amine groups (AOA) in the emulsion from 0.05% to 0.4% did not alter markedly the particle size or zeta potential value of the blank cationic nanoemulsion. The extent of ODN association did not vary significantly when the initial concentration of ODN remained constant at 10 microM irrespective of the cationic lipid nature. However, the zeta potential value dropped consistently with the low concentrations of 0.05% and 0.1% of AOA in the emulsions suggesting that an electrostatic attraction occurred between the cationic lipids and the polyanionic ODN molecules at the o/w interface. Only the nanoemulsion prepared with N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium salts (DOTAP) remained physically stable over time. DOTAP cationic lipid nanoemulsion was the most efficient formulation capable of retaining the ODN despite the high dilution of 1:100 with simulated tear solution (STS). Less than 10% of the ODN was exchanged in contrast to 40-50% with the other cationic nanoemulsions. The in-vitro release kinetic behavior of ODN exchange with physiological anions present in the STS appears to be complex and difficult to characterize using mathematical fitting model equations. Further pharmacokinetic studies are needed to verify our kinetic assumptions and confirm the in-vitro ODN release profile from DOTAP cationic nanoemulsions.


Is price a barrier to eating more fruits and vegetables for low-income families?
To determine if price is a barrier to fruit and vegetable consumption for low-income families by comparing the average cost of a market basket of fruits and vegetables from the Thrifty Food Plan and the Dietary Guidelines for Americans 2005 (2005 Dietary Guidelines), investigating variations in price by neighborhood income and by type of supermarket, and estimating the influence of a 2005 Dietary Guidelines fruit and vegetable basket on the food budget of a low-income family. A market basket survey was conducted at 25 supermarkets across three time periods to allow for seasonal variation in produce prices. Stores were selected from census tracts with a variety of income levels in Sacramento, CA, and Los Angeles, CA. The average cost of a Thrifty Food Plan and 2005 Dietary Guidelines market basket for fruits and vegetables. Student t tests were used to compare the mean cost of market baskets. The 2005 Dietary Guidelines market basket cost 4% less than the Thrifty Food Plan (P<0.001), and was significantly less expensive in low-income areas at 65 dollars (P<0.05), and in bulk supermarkets at 59 dollars (P<0.05). The 2005 Dietary Guidelines market basket would require a low-income family to devote 43% to 70% of their food budget to fruits and vegetables. Public policies should examine ways to make fruits and vegetables more affordable to low-income families.


Changes in Prescribed Drugs Between Admission and the End of Life in Patients Admitted to Palliative Care Facilities.
The aim of prescribing medication in palliative end-of-life care should be symptom control. Data are lacking regarding the prescription of medication at the end of life. To investigate the prescription of medication in patients at the end of life in palliative care facilities. An observational multicenter study in 7 inpatient palliative care facilities. Participants were adults with an estimated life expectancy of less than 3 months. The study was conducted from February 1, 2012, to January 1, 2013. A total of 155 patients were enrolled. On average, patients were prescribed 6.1 drugs at the moment of admission and 4.6 drugs on the day of death. The prescription of analgesics, psycholeptics, and drugs for functional gastrointestinal disorders increased from admission until death. In general, these are drug classes prescribed for symptom control. All other drug classes decreased between admission and the day of death, including different drug classes for the treatment of comorbid disease, such as anticoagulants, beta-blocking agents, drugs used in diabetes, and lipid-modifying agents. A reduction in the total amount of medication is seen between admission and death in the palliative care facilities. Although there is an increase in prescribed symptom-specific medication and a reduction in medication prescribed for comorbid disease, there are still patients dying with medication not used for symptom control. This increases pill burden and indicates that physicians need to develop guidelines and educational programs for decreasing medication for comorbidities at the end of life.


Does age influence the blood pressure and sodium excretion responses to sodium depletion in rats?
Experiments were performed in 3- and 24-month-old male Wistar rats in order to assess the influence of age on the response by systolic blood pressure and sodium excretion to abrupt sodium restriction. In response to the sodium deprivation, urinary sodium excretion was markedly reduced in all animals; however, the cumulative sodium excretion (from days 1 to 6 of depletion) was significantly higher in aged rats (1299 +/- 243 mumol) than in young rats (757 +/- 70 mumol). After 6 days of a low-sodium diet, the systolic blood pressure was similar in both groups. Plasma renin activity was higher in young compared with aged rats (27 +/- 5 versus 14 +/- 3 ng/ml per h). These results indicate that ageing is associated with a significant disturbance in the renal but not the systemic response to an abrupt restriction in sodium intake.


Thrombospondin-1 accelerates wound healing of corneal epithelia.
To investigate a role of thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein, in corneal epithelial wound healing, we analyzed the expression of TSP-1 in the normal and wounded mouse corneal epithelia and the effect of exogenous TSP-1 on the wound healing. In immunohistochemical analyses of unwounded corneas, TSP-1 was only detectable in endothelial cells. In contrast, TSP-1 appeared on the wounded corneal surface and on the corneal stroma, at 30 min and 8-16 h, respectively, after making an abrasion on the corneal epithelium. This expression of TSP-1 disappeared after 36-48 h, when re-epithelialization was completed. The TSP-1 mRNA level in the wounded corneas increased as much as three fold compared with that in the unwounded corneas. In organ culture, exogenous TSP-1 stimulated the re-epithelialization of corneal epithelial wounds whereas anti-TSP-1 antibody significantly inhibited the re-epithelialization. These findings suggest the possibility that epithelial defects in the corneas stimulate the expression of TSP-1 in the wound area, resulting in the accelerated re-epithelialization of the cornea.


Development of an HPLC fluorescence method for determination of boldine in plasma, bile and urine of rats and identification of its major metabolites by LC-MS/MS.
Boldine belongs to the group of aporphine alkaloids isolated from Boldo tree. In contrast with numerous reports on the pharmacological effects of boldine, the data about its pharmacokinetics and biotransformation are scarce. No validated bioanalytical method of sufficient sensitivity has so far been described in the literature which could be used for quantification of boldine in various body fluids collected in pharmacokinetic studies. This work presents, for the first time, the assay for boldine in the plasma, bile and urine of rats. It includes liquid-liquid extraction/back-extraction of boldine, its chromatographic separation and sensitive fluorescence detection. Separation was carried out on a pentafluorophenyl core-shell column (Kinetex PFP, 150×3mm, 2.6μm) in gradient elution mode with solvent system consisting of an acetonitrile-ammonium formate buffer (5mM, pH=3.8). Fluorimetric detection (λEX=320nm, λEM=370nm) was used for quantitative work. Validation according to the EMEA guideline proved the assay LLOQ (0.1μmolL(-1)), linearity over a broad range of 0.1-50μmolL(-1), precision (intra- and inter-day CVs less than 4.5% and 6.1%, respectively) and accuracy (relative errors between -5.8% and 4.8%). In a pilot pharmacokinetic experiment, the concentration-time profiles were described for boldine (single i.v. bolus 50mgkg(-1)) in plasma and bile and cumulative excretion in urine was investigated. The major metabolites identified by means of LC-MS(n) were boldine-O-glucuronide, boldine-O-sulphate and disulphate, boldine-O-glucuronide-O-sulphate and N-demethyl-boldine-O-sulphate.


Concussion Baseline Retesting Is Necessary When Initial Scores Are Low.
To determine whether (1) initial baseline scores are significantly better for those who have valid (initial valid) versus invalid scores (initial invalid) on their concussion baseline testing, (2) retesting results in significantly improved baseline scores, and (3) there is a significant difference in scores between those who have valid scores on their initial attempt and those who retook baseline tests (retest valid). Prospective, repeated-measures. Two years of collegiate preparticipation concussion baseline testing. Five hundred forty-seven male and female Division I collegiate athletes (19.02 ± 1.31 years, female = 217). Participants were divided into initial valid and initial invalid. The retest group was further divided into their initial (initial invalid) and final valid attempt (retest valid). Data were analyzed to determine the relationship between the 3 groups and overall initial and final scores on 28 individual items: total symptoms score, coordination, near-point convergence, CNS Vital Signs (CNSVS), Senaptec Sensory Station, and Neurocom Sensory Organization Test (SOT). The initial valid group scored significantly better than the initial invalid group on 8 CNSVS items and 5 Senaptec items (P < 0.002). The retest valid scores were significantly better compared with the initial invalid scores on 17 items (P < 0.002). Retesting is recommended for individuals who score below acceptable ranges. This is important because athletes may experience a learning effect and are highly motivated during postinjury testing, so accurate baseline scores are imperative for athlete safety. Completion time for the coordination test may be a more informative option.


Analysis of essential histidine residues of maize branching enzymes by chemical modification and site-directed mutagenesis.
Incubation of maize branching enzyme, mBEI and mBEII, with 100 microM diethylpyrocarbonate (DEPC) rapidly inactivated the enzymes. Treatment of the DEPC-inactivated enzymes with 100500 mM hydroxylamine restored the enzyme activities. Spectroscopic data indicated that the inactivation of BE with DEPC was the result of histidine modification. The addition of the substrate amylose or amylopectin retarded the enzyme inactivation by DEPC, suggesting that the histidine residues are important for substrate binding. In maize BEII, conserved histidine residues are in catalytic regions 1 (His320) and 4 (His508). His320 and His508 were individually replaced by Ala via site-directed mutagenesis to probe their role in catalysis. Expression of these mutants in E. coli showed a significant decrease of the activity and the mutant enzymes had Km values 10 times higher than the wild type. Therefore, residues His320 and His508 do play an important role in substrate binding.


A novel web-based 24-h dietary recall tool in line with the Nova food processing classification: description and evaluation.
This paper describes the first web-based self-completed 24-h recall designed to categorise food intake according to Nova groups - Nova24h - and its agreement with a reference tool in estimating the dietary relative contribution of the four Nova food groups (% of total energy intake). Comparisons of estimates of dietary relative contributions of Nova groups obtained by Nova24h and one standard interviewer-led 24-h recall. Nationwide adult cohort study in Brazil. The subjects were 186 participants of the NutriNet Brasil Cohort Study (n 186). No statistically significant differences were observed between the Nova24h and the reference tool mean contributions of unprocessed or minimally processed foods (52·3 % v. 52·6 %), processed culinary ingredients (11·6 % v. 11·9 %), processed foods (17·1 % v. 14·7 %) and ultra-processed foods (19·0 % v. 20·9 %). Intraclass correlation coefficients between individual estimates obtained for each Nova group showed moderate to good agreement (0·54-0·78). Substantial or almost perfect agreement between the tools was seen regarding the ability to rank participants according to quintiles of contribution of each Nova group (PABAK 0·69-0·81). Nova24h is a suitable tool for estimating the dietary relative energy contribution of Nova food groups in the NutriNet Brasil cohort. New studies are necessary to verify its adequacy in other populations.


[Our experience with the treatment of Chlamydia trachomatis in acute and chronic inflammatory diseases of the female genitalia].
The effect of antibiotic treatment was studied on 41 women with inflammatory gynecological diseases at the acute and chronic stages as the patients were examined for presence of Chlamydia trachomatis in the endocervix. The high frequency of isolated Chlamydia trachomatis in these women (44.1%) with predominance at the age of 21-25 years show the important role of Chlamydia trachomatis in the etiology of the inflammatory process. Possibilities for therapeutic effect by using various antibiotic combinations are discussed.


In vitro bioaccessibility and activity of basil (Ocimum basilicum L.) phytochemicals as affected by cultivar and postharvest preservation method - Convection drying, freezing, and freeze-drying.
The effects of convection drying, freezing, and freeze-drying, on phytochemicals content, in vitro activity and bioaccessibility of sweet basil, cinnamon basil, red rubin basil, and lemon basil were investigated. For evaluation of bioaccessibility, rosmarinic acid content, phenolic content, and antioxidant potential of samples before and after gastric and intestinal steps of digestion were determined. Results showed that the content, activity and bioaccessibility of basil phytochemicals varied depending on the cultivar as well as the applied postharvest preservation. It was found that the frozen and freeze-dried plant materials were characterized by a higher phenolic level and antioxidant activity compared to the convection dried. However, in general, convection drying allows obtaining samples with higher bioaccessibility of phytochemicals compared to the low-temperature processed samples. These findings highlight the need for evaluation of basil cultivars and postharvest preservation methods regarding phytochemicals bioaccessibility, which might help in the classification in terms of pro-health quality.


Deep hydrocarbon genesis and accumulation model of strike-slip fault reservoirs in the Yuemanxi area of the Tarim Basin.
As a clean and environmentally friendly energy source, deep oil and gas has always been the focus of the oil and gas industry. The study of hydrocarbon accumulation in deep strike-slip fault zones is a challenging and important area of research in the oil and gas industry. In particular, accurately modeling oil and gas accumulation in the Yuemenxi area of the Tarim Basin presents significant difficulties due to the varying physical properties and gas composition of the Ordovician reservoirs, as well as the complex origin of oil and gas in the area. However, by calculating biomarker parameter maturity on oil samples from strike-slip faults, researchers have discovered that the light oil in the area is sourced from high maturity source rocks in the Later Caledonian, with vitrinite reflectance ranging from 0.79% to 1.11%. The complete distribution of n-alkanes and high concentration of low-carbon n-alkanes in the crude oil suggest that the fluid in the reservoir has not undergone any secondary alteration since its initial accumulation. The carbon isotope and component ratio analysis of natural gas in the Yuemanxi area indicates that the Ordovician natural gas is predominantly kerogen cracking gas. Comprehensive hydrocarbon genesis and accumulation conditions, this paper presents a differential accumulation model for the Ordovician reservoirs in the region, which were controlled by strike-slip faults and source rocks. Based on these findings, it can be inferred that there is significant potential for oil and gas exploration and development in the deeper layers of these strike-slip fault zones.