Comparative Analyses of Physicochemical Properties of Artisanal Refined Gasoline and Regular Automotive Gasoline.
Physicochemical properties of artisanal refined gasoline (ARG) and regular automotive gasoline (RAG) sampled from the Eastern Obolo Creek and Mkpat Enin, Akwa Ibom State, Nigeria were investigated. This was to compare the physicochemical properties of the two gasoline samples with each other and their compliance with American Society for Testing and Materials (ASTM) standards. The finding revealed an antiknock index of RAG (91.15%) and ARG (83.05%), atmospheric distillation of RAG (185°C) and ARG (184°C), Reid vapor pressure of RAG (0.53 kg/cm3) and ARG (0.36 kg/cm3), gravity of RAG (0.771) and ARG (0.683), sulfur content of RAG (0.014%/wt) and ARG (0.02%/wt), while Flash point for RAG were Pensky Martens -25°C, Abel-Pensky -33°C and ARG Pensky Martens -27°C, Abel-Pensky -35.36°C, respectively. The research octane number, motor octane number, Reid vapor pressure, sulfur content, and specific gravity of RAG were (ASTM) compliant while only the final boiling point and sulfur content of ARG were within ASTM range. Based on the findings, the LRG might have been poorly refined or adulterated and could constitute problems in automotive engines if used. However, this crude technology can be upgraded and the gasoline quality improved through alkylation, isomerization, and cyclization. Artisanal refiners should be trained to become proficient with the intent of becoming incorporated into the upstream petroleum sector.


Life stress, maternal optimism, and adolescent competence in single mother, African American families.
Although research demonstrates many negative family outcomes associated with single-parent households, little is known about processes that lead to positive outcomes for these families. Using 3 waves of longitudinal data, we examined how maternal dispositional optimism and life stressors are associated with parenting and child outcomes in 394 single mother African American families. Confirming prior research, we found that mothers' childhood adversities, current economic pressure, and internalizing problems were associated with lower levels of maternal warmth and child management and with lower child school competence. Extending previous studies, we found that maternal optimism was a positive resource, predicting lower levels of maternal internalizing symptoms and higher levels of effective child management and moderating the impact of economic stress on maternal internalizing problems. These findings highlight the need for further investigation of processes and resources that promote positive outcomes for African American mother-headed families and single mother families in general.


Cost-Effectiveness of Oral Anticoagulants for Ischemic Stroke Prophylaxis Among Nonvalvular Atrial Fibrillation Patients.
The objective of the study is to compare the cost-effectiveness of oral anticoagulants among atrial fibrillation patients at an increased stroke risk. A Markov model was constructed to project the lifetime costs and quality-adjusted survival (QALYs) of oral anticoagulants using a private payer's perspective. The distribution of stroke risk (CHADS2 score: congestive heart failure, hypertension, advanced age, diabetes mellitus, stroke) and age of the modeled population was derived from a cohort of commercially insured patients with new-onset atrial fibrillation. Probabilities of treatment specific events were derived from published clinical trials. Event and downstream costs were determined from the cost of illness studies. Drug costs were obtained from 2015 National Average Drug Acquisition Cost data. In the base case analysis, warfarin was the least costly ($46 241; 95% CI, 44 499-47 874) and apixaban had the highest QALYs (9.38; 95% CI, 9.24-9.48 QALYs). Apixaban was found to be a cost-effective strategy over warfarin (incremental cost-effectiveness ratio=$25 816) and dominated other anticoagulants. Probabilistic sensitivity analysis showed that apixaban had at least a 61% chance of being the most cost-effective strategy at willingness to pay value of $100 000 per QALY. Among patients with CHADS2 ≥3, dabigatran was the dominant strategy. The model was sensitive to efficacy estimates of apixaban, dabigatran, and edoxaban and the cost of these drugs. All the newer oral anticoagulants compared were more effective than adjusted dosed warfarin. Our model showed that apixaban was the most effective anticoagulant in a general atrial fibrillation population and has an incremental cost-effectiveness ratio <$50 000/QALY. For those with higher stroke risk (CHADS2≥3), dabigatran was the most cost-effective treatment option.


Isolation of Streptococcus suis from 2 lambs with a history of lameness.
Streptococcus suis was isolated postmortem from 2 lambs with a history of lameness. Identity of S. suis was confirmed by species-specific polymerase chain reaction (PCR) and by 16S rRNA gene sequencing. One isolate was untypable by serotyping and non-encapsulated, while the other isolate was serotype 33. The lambs had come from the same farm, and there was no evidence of contact between the lambs and pigs. Although the natural niche for S. suis is considered to be the pig, a wide range of host species may be affected by this pathogen.


Glass Transition Temperature of PLGA Particles and the Influence on Drug Delivery Applications.
Over recent decades, poly(lactic-co-glycolic acid) (PLGA) based nano- and micro- drug delivery vehicles have been rapidly developed since PLGA was approved by the Food and Drug Administration (FDA). Common factors that influence PLGA particle properties have been extensively studied by researchers, such as particle size, polydispersity index (PDI), surface morphology, zeta potential, and drug loading efficiency. These properties have all been found to be key factors for determining the drug release kinetics of the drug delivery particles. For drug delivery applications the drug release behavior is a critical property, and PLGA drug delivery systems are still plagued with the issue of burst release when a large portion of the drug is suddenly released from the particle rather than the controlled release the particles are designed for. Other properties of the particles can play a role in the drug release behavior, such as the glass transition temperature (Tg). The Tg, however, is an underreported property of current PLGA based drug delivery systems. This review summarizes the basic knowledge of the glass transition temperature in PLGA particles, the factors that influence the Tg, the effect of Tg on drug release behavior, and presents the recent awareness of the influence of Tg on drug delivery applications.


Alpha-melanocyte-stimulating hormone (MSH) inhibits insulin secretion in HIT-T 15 cells.
alpha-Melanocyte-stimulating hormone (MSH) antagonizes the binding of interleukin-1 beta (IL-1) to its type I receptors on T cells. IL-1 modulates insulin secretion in the insulin-secreting tumor cell line, HIT-T 15 cells. In the present studies, we examined a hypothesis that alpha-MSH may modulate insulin secretion in HIT-T 15 cells. The addition of alpha-MSH over the concentrations of 10(-10) M inhibited insulin secretion for 4 h. In addition, the carboxyl-terminal tripeptide of alpha-MSH [alpha-MSH(11-13)], which is supposed to be an important sequence of alpha-MSH on its antipyretic effects, significantly inhibited insulin secretion at the concentration of 10(-9) M. In contrast, acetyl-[Nle4,D-Phe7] alpha-MSH(4-10)-amide (10(-11) to 10(-9) M) failed to inhibit insulin secretion. The maximal effect of alpha-MSH on insulin secretion was obtained at the concentration of 10(-9) M. The addition of alpha-MSH from 10(-11) to 10(-9) M significantly inhibited 7.5 mM glucose-stimulated insulin secretion at each period of 0-5, 5-15, and 15-30 min. Radioreceptor assay suggested that HIT-T 15 cells possess the specific binding sites for 125I-labeled alpha-MSH. The present studies indicated that alpha-MSH inhibits insulin secretion through the specific binding site in HIT-T 15 cells.


Evaluation of a dental society-based ABCD program in Washington state.
The authors present a two-year evaluation of a dental society-managed dental care program in Washington state. A variation of the Access to Baby and Child Dentistry, or ABDC, program, the Mom & Me program was initiated to increase access to dental care for Medicaid-enrolled children younger than age 6 years in Yakima County. This evaluation includes enrollment and visit data, first- and second-year cost data and results of a survey conducted with dental society members. The number of dentists treating Medicaid-enrolled children on a regular basis more than doubled, from 15 to 38 general dentists. In the first two years of the program, 4,705 children were enrolled and approximately 51 percent visited a dentist. The responses of dentists surveyed were positive, and the authors suggest that a dental society-managed program under the ABCD program -umbrella is a unique strategy for improving access to dental care for Medicaid clients. ABCD programs provide an avenue for dentists to treat children who otherwise would not receive care.


Intracranial pressure: cerebrospinal fluid dynamics and pressure-volume relations.
Continuous measurement of the intracranial pressure (ICP) is routine in todays evaluation of various intracranial diseases and increased ICP is a common therapeutical problem in neurosurgical patients. Still, very little is known about the patho-physiological and biomechanic events that lead to increased ICP. ICP is governed by 1) the resistance to absorption of cerebrospinal fluid (Rout), 2) the production rate of CSF (If) (taken together Rout and If are referred to as the "CSF dynamics"), and 3) the pressure in the Sagittal Sinus (Pss) in accordance with the equation: ICP = If X Rout + Pss. When an intracranial mass grows the cranio-spinal volume buffering capacity is exhausted and the ICP subsequently rises. This event has been imitated in experiments and is described by the classical exponential pressure-volume curve. In a semilogarithmic coordinate system the curve will be linear and if one exchanges the abscissa and ordinate (x = log ICP, y = volume) the slope is the pressure-volume index (PVI). In normal adults PVI = 25 ml and defines the volume that theoretically will increase the ICP tenfold when injected into the CSF space. The main goal of the present study was to analyse the ICP in accordance with the above mentioned principles by measurements of Rout and the PVI. Furthermore, to evaluate the PVI method (synonymous with the "bolus injection" method) described by Marmarou and coworkers. By this method a bolus of a few milliliters of fluid is injected into the ventricles via an intraventricular cannula. PVI is computed based on the immidate ICP rise. The following slowlier ICP decrement defines the Rout. Another goal was to analyse whether measurements of the ICP pulse amplitude, which cancels the need of manipulations of the CSF space, could replace PVI measurements. Finally, to evaluate whether or not CT of the brain depicts pressure-volume relations and Rout in adult patients with hydrocephalus. The study comprised 63 patients with subarachnoid haemorrhage, cranio-cerebral injury or so-called normal-pressure hydrocephalus. The following variables were measured: 1) ICP, 2) pulseamplitude, 3) PVI and 4) Rout. The latter was measured by means of the PVI method and in some instances for reasons of comparison with the constant rate infusion technique and "controlled withdrawal". The main conclusions of the studies were: 1) For estimates of PVI the bolus injection technique was applicable. For Rout measurements the method was only safe at relatively low ICP levels.(ABSTRACT TRUNCATED AT 400 WORDS)


A European Database of Fusarium graminearum and F. culmorum Trichothecene Genotypes.
Fusarium species, particularly Fusarium graminearum and F. culmorum, are the main cause of trichothecene type B contamination in cereals. Data on the distribution of Fusarium trichothecene genotypes in cereals in Europe are scattered in time and space. Furthermore, a common core set of related variables (sampling method, host cultivar, previous crop, etc.) that would allow more effective analysis of factors influencing the spatial and temporal population distribution, is lacking. Consequently, based on the available data, it is difficult to identify factors influencing chemotype distribution and spread at the European level. Here we describe the results of a collaborative integrated work which aims (1) to characterize the trichothecene genotypes of strains from three Fusarium species, collected over the period 2000-2013 and (2) to enhance the standardization of epidemiological data collection. Information on host plant, country of origin, sampling location, year of sampling and previous crop of 1147 F. graminearum, 479 F. culmorum, and 3 F. cortaderiae strains obtained from 17 European countries was compiled and a map of trichothecene type B genotype distribution was plotted for each species. All information on the strains was collected in a freely accessible and updatable database (www.catalogueeu.luxmcc.lu), which will serve as a starting point for epidemiological analysis of potential spatial and temporal trichothecene genotype shifts in Europe. The analysis of the currently available European dataset showed that in F. graminearum, the predominant genotype was 15-acetyldeoxynivalenol (15-ADON) (82.9%), followed by 3-acetyldeoxynivalenol (3-ADON) (13.6%), and nivalenol (NIV) (3.5%). In F. culmorum, the prevalent genotype was 3-ADON (59.9%), while the NIV genotype accounted for the remaining 40.1%. Both, geographical and temporal patterns of trichothecene genotypes distribution were identified.


Invasive Haemophilus influenzae type B disease.
Invasive bacterial disease due to Haemophilus influenzae is a cause of sudden death in children. It must be considered by medical examiners when a child dies with a fulminant course and nonspecific symptoms. Three fatal cases are presented in children 7 weeks to 15 months of age. Two had meningitis and petechiae or purpura. All three had bilateral adrenal hemorrhage and a rapidly fatal course. The potential for rapid and accurate diagnosis of H. influenzae infection is widely available due to latex agglutination technique against bacterial capsular wall antigens. Diagnosis is critical because of its public-health implications. Up to 50% of cases may be acquired in day-care settings. Chemoprophylaxis is recommended for household and day care contacts. With the recent introduction of Haemophilus b conjugate vaccines for routine administration to infants beginning at 2 months of age, a change in the epidemiology of the disease is anticipated.


An approach to the stereoselective synthesis of Sp-dinucleoside phosphorothioates using phosphotriester chemistry.
An approach to the stereoselective synthesis of Sp- dinucleoside phosphorothioates has been investigated which utilizes phosphotriester chemistry. The stereoselectivity of internucleotide bond formation between N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3'-O-(S2-cyano-e thyl) phosphorothioate (3) and 3'-O-acetylthymidine has been studied using either mesitylenesulphonyl-5-(pyridin-2-yl)tetrazole (MSPy) or 1-mesitylenesulphonyl-3-nitro-1,2,4-triazole (MSNT) as the activating agent. The removal of the cyanoethyl group from the protected dinucleoside phosphorothioate has been studied, and conditions are reported which provide rapid deprotection without concomittant desulphurisation.


Bone-implant interface strength and osseointegration: Biodegradable magnesium alloy versus standard titanium control.
Previous research on the feasibility of using biodegradable magnesium alloys for bone implant applications mainly focused on biocompatibility and corrosion resistance. However, successful clinical employment of endosseous implants is largely dependent on biological fixation and anchorage in host bone to withstand functional loading. In the present study, we therefore aimed to investigate whether bone-implant interface strength and osseointegration of a novel biodegradable magnesium alloy (Mg-Y-Nd-HRE, based on WE43) is comparable to that of a titanium control (Ti-6Al-7Nb) currently in clinical use. Biomechanical push-out testing, microfocus computed tomography and scanning electron microscopy were performed in 72 Sprague-Dawley rats 4, 12 and 24 weeks after implantation to address this question. Additionally, blood smears were obtained from each rat at sacrifice to detect potential systemic inflammatory reactions. Push-out testing revealed highly significantly greater maximum push-out force, ultimate shear strength and energy absorption to failure in magnesium alloy rods than in titanium controls after each implantation period. Microfocus computed tomography showed significantly higher bone-implant contact and bone volume per tissue volume in magnesium alloy implants as well. Direct bone-implant contact was verified by histological examination. In addition, no systemic inflammatory reactions were observed in any of the animals. We conclude that the tested biodegradable implant is superior to the titanium control with respect to both bone-implant interface strength and osseointegration. These results suggest that the investigated biodegradable magnesium alloy not only achieves enhanced bone response but also excellent interfacial strength and thus fulfils two critical requirements for bone implant applications.


Orthophosphate Interactions with Destabilized PbO2 Scales.
This research presents two case studies in which a change in the disinfectant from free chlorine to chloramine caused an increase in lead corrosion. In both systems, the predominantly tetravalent lead (PbO2) scales destabilized as a result of disinfectant change. Orthophosphate corrosion control was used in both systems, and the effect of this treatment chemical on the destabilized PbO2 scales was examined. The absence of chemical reactivity between PbO2 and phosphorus is well known, and this research confirms that phosphorus does not interact with the legacy PbO2 scales. Instead, phosphorus and calcium were found to permeate through the destabilized PbO2 material and react with divalent lead [Pb(II)] at the surface of a basal litharge (PbO) layer. This reaction precipitated a crystalline lead phosphate in both systems, which could not be specifically identified by any known powder diffraction files. Further analysis suggested that the compound formed was not the typically modeled hydroxypyromorphite but rather a calcium-substituted hydroxypyromorphite. During scale formation, calcium is frequently bound to the Pb(II) phosphate crystal lattice structure, causing measurable crystal lattice distortion in powder X-ray diffraction patterns. The results of this study illustrate the longevity of legacy scales and how disequilibrium compounds persist long after treatment changes have been made.


Coherence analysis of invasive blood pressure and its noninvasive indicators for improvement of cuffless measurement accuracy.
Cuffless technology for blood pressure (BP) measurement offers great potential for unobtrusive monitoring of hypertension. However, the accuracy is still a challenging issue probably owning to the inadequacy of existing noninvasive BP indicators in tracking BP changes, i.e., either the poor trackability of the indicators or the lack of relationship to map the indicators to BP. To figure out the covariation of BP-related noninvasive indicators and BP, we propose to analyze the coherence of intra-arterial systolic BP (SBP) and a selected group of noninvasive indicators, including the mostly used pulse transit time (PTT), photoplethysmogram intensity ratio (PIR) and RR interval (RRI) of electrocardiogram (ECG), in both time domain, with singular spectrum analysis (SSA), and frequency domain, with cross-spectral analysis. Through SSA the SBP and the indicators are decomposed into fast oscillations superimposed on a slow time-varying component. It is found that the fast variation components oscillate at similar frequencies for the SBP and the indicators, while that their slow variation components are out of phase synchronization. Cross-spectra between SBP and the indicators further illustrate stronger coherence correlation at high frequencies (HF, 0.15-0.40 Hz) (PTT: 0.54±0.30, PIR: 0.73±0.25, RRI: 0.63±0.25) than at low frequencies (LF, 0.04-0.15 Hz) (PTT: 0.24±0.19, PIR: 0.37±0.23, RRI: 0.33±0.23). The results suggest that the widely used indicators are poor to track the LF component of BP. Our study reveals the importance of exploring LF-related BP indicators as well as new models to integrate LF and HF information for improvement of cuffless BP measurement accuracy.


Pharmacokinetic and pharmacodynamic considerations of antimicrobial drug therapy in cancer patients with kidney dysfunction.
Patients with cancer have a high inherent risk of infectious complications. In addition, the incidence of acute and chronic kidney dysfunction rises in this population. Anti-infective drugs often require dosing modifications based on an estimate of kidney function, usually the glomerular filtration rate (GFR). However, there is still no preferential GFR formula to be used, and in acute kidney injury there is always a considerable time delay between true kidney function and estimated GFR. In most cases, the anti-infective therapy should start with an immediate and high loading dose. Pharmacokinetic as well as pharmacodynamic principles must be applied for further dose adjustment. Anti-infective drugs with time-dependent action should be given with the target of high trough concentrations (e.g., beta lactam antibiotics, penems, vancomycin, antiviral drugs). Anti-infective drugs with concentration-dependent action should be given with the target of high peak concentrations (e.g., aminoglycosides, daptomycin, colistin, quinolones). Our group created a pharmacokinetic database, called NEPharm, hat serves as a reference to obtain reliable dosing regimens of anti-infective drugs in kidney dysfunction as well as renal replacement therapy. To avoid the risk of either too low or too infrequent peak concentrations, we prefer the eliminated fraction rule for dose adjustment calculations.


Elongation factor NusG interacts with termination factor rho to regulate termination and antitermination of transcription.
NusG is a transcriptional elongation factor in Escherichia coli that aids transcriptional antitermination by the phage lambda N protein. By using NusG affinity chromatography, we found that NusG binds directly and selectively to termination factor rho. NusG was shown previously to be needed for termination by rho in vivo, and we show here that NusG increases the efficiency of termination by rho at promoter-proximal sites in vitro. The rho026 mutation makes termination by rho less dependent on NusG. It also makes antitermination by N at rho-dependent terminators and the binding of rho to NusG temperature sensitive. Therefore, the interaction of NusG with rho is important both for rho-dependent termination and for antitermination by N at rho-dependent terminators.


Relative sensitivity of photosynthetic assimilation and translocation of carbon to water stress.
The relationship between photosynthesis and translocation rate changes as affected by water stress intensity and stage of plant development was evaluated in cotton and sorghum, representing a C(3) and a C(4) photosynthetic type, respectively. Photosynthetic rates were reduced as midday leaf water potentials declined from -14 to -27 bars in both species. Sorghum maintained higher photosynthesis and translocation rates compared to cotton at comparable leaf water potentials; however, the rate of change per bar decline in water potential was greater in sorghum than in cotton. Photosynthetic rates were reduced with increasing water stress prior to any significant change in translocation rates suggesting that photosynthesis is the more sensitive of the two processes. Severe water stress, corresponding to leaf water potentials of -27 bars, did not completely inhibit either photosynthesis or translocation.


Gastrointestinal stromal tumor complicated by Streptococcus milleri bacteremia and liver abscess.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Often discovered incidentally, GISTs can present with nonspecific abdominal symptoms or more overt symptoms of bleeding, obstruction, or perforation. Despite a myriad of clinical presentations, bacteremia associated with a GIST has not been described. In this report, we present an unusual clinical case that illustrates how GISTs can become infected, and demonstrate the importance of Streptococcus milleri bacteremia as an indicator of possible underlying gastrointestinal neoplasm.


Interfacial catalysis in and initial reaction mechanism of Al2O3 films fabricated by atomic layer deposition using non-hydrolytic sol-gel chemistry.
Atomic layer deposition (ALD) is a powerful nanofabrication technique that can precisely control the composition, structure, and thickness of thin films at the atomic scale, and is widely used in the fields of electronic displays, microelectronics, catalysis, coatings, and energy storage and conversion. ALD of metal oxide thin films can be completed using metal alkoxides as the oxygen source, which is similar to the non-hydrolytic sol-gel (NHSG) technique. Density functional theory calculations show that metal alkoxides, such as Al(OiPr)3 and Al(OEt)3, can directly form M-O bonds through strong chemisorption on the surface. Meanwhile, alkyl groups can be eliminated through the formation of alkyl halides and alkenes, which can be catalyzed by interfacial interactions between alkyl groups and the surface. Such noncovalent catalysis resulting from interfacial interaction can be termed as interfacial catalysis. This can be characterized by the difference between the interfacial interaction energies of the transition state and the corresponding intermediate based on natural bond analysis. We expect that such interfacial catalysis can be used in precursor designs, improvement of ALD of oxides and as a new characterization method for other interfacial catalysis and noncovalent catalysis processes.


Walking facilitates positive affect (even when expecting the opposite).
Across 3 experiments, we rely on theoretical advancements that connect movement, embodiment, and reward-seeking behavior to test the proposal that walking incidental to routine activity (heretofore referred to as "incidental ambulation")-not specifically "exercise"-is a robust facilitator of positive affect. Experiment 1 reveals that ambulation facilitates positive affect even when participants are blind to the purpose of this activity. Experiment 2 further demonstrates the robustness of this effect of incidental ambulation by documenting its operation under conditions of low interest, as well as its power to override expectations of mood worsening. Experiment 3 replicates the main finding while eliminating the possibility that posture, ambient events, or experimenter bias account for the results. Taken together, the experiments demonstrate that incidental ambulation systematically promotes positive affect regardless of the focus on such movement, and that it can override the effects of other emotionally relevant events such as boredom and dread. The findings hold key implications for understanding the role of movement in shaping affect as well as for clarifying the embodied nature of emotion. (PsycINFO Database Record


A comparison of prostatic development in xenografts of human fetal prostate and human female fetal proximal urethra grown in dihydrotestosterone-treated hosts.
The goal of this paper is to explore the ability of the human female urogenital sinus immediately below the bladder (proximal urethra) to undergo prostatic development in response to dihydrotestosterone (DHT). To establish this idea, xenografts of human fetal female proximal urethra were grown in castrated nude mouse hosts receiving a subcutaneous DHT pellet. To verify the prostatic nature of the resultant glands, DHT-treated human fetal female urethral xenografts were compared with human fetal prostatic xenografts (derived from male specimens) grown in untreated and DHT-treated castrated mouse hosts and human fetal female proximal urethral xenografts grown in untreated castrated hosts. The resultant glands observed in DHT-treated human fetal female proximal urethral xenografts expressed 3 prostate-specific markers, NKX3.1, prostate specific antigen and prostatic acid phosphatase as well as the androgen receptor. Glands induced by DHT exhibited a protein expression profile of additional immunohistochemical markers (seven keratins, RUNX1, ESR2, TP63 and FOXA1) consistent with the unique spatial pattern of these proteins in prostatic ducts. Xenografts of human fetal female proximal urethra grown in DHT-treated hosts also expressed one of the salient features of prostatic development, namely androgen responsiveness. The experimental induction of prostatic differentiation from human fetal female proximal urethra makes possible future in-depth analysis of the molecular pathways directly involved in initiation of human prostatic development and subsequent epithelial differentiation, and more important whether the molecular pathways involved in human prostatic development are similar/identical versus different from that in murine prostatic development.


A method for deriving normal ranges from laboratory specimens applied to uric acid in males.
Plasma specimens from male blood donors gave a normal range for uric acid concentration of 3.3 to 7.5 mg/100 ml. Specimens from male outpatients, which were received in the laboratory for the analysis of urea but not of uric acid and proved to have normal concentrations of urea, showed a positively skewed distribution of values for uric acid from which a ;normal range' of 3.2 to 7.6 mg/100 ml was derived. We suggest that specimens from outpatients selected in the way described here may prove to be a convenient source of data for determining the normal range of other substances.


[Effects of fluvastatin on plasma lipid abnormalities in hemodialysis patients with chronic renal failure].
Fluvastatin, an HMG-CoA reductase inhibitor, was administered at a dosage of 20 mg/day for 24 weeks to 11 hemodialysis patients with a high plasma total cholesterol (TC) level (> or = 220 mg/dl). Serum lipids, apolipoprotein, and malondialdehyde (MDA) levels were measured every 12 weeks. After 24 weeks of fluvastatin administration, the TC level had decreased by 10.5% (238 +/- 15 mg/dl-->203 +/- 25 mg/dl), the low density lipoprotein cholesterol (LDL-C) level had decreased by 16.2% (142 +/- 32 mg/dl-->119 +/- 26 mg/dl), and the HDL-C level had increased by 23.4% (47 +/- 15 mg/dl-->58 +/- 19 mg/dl). These changes were statistically significant and resulted in a reduction of the atherogenic index (AI: TC-HDL-C/HDL-C). The triglyceride (TG) level did not change significantly. The apolipoprotein A1 level increased by 9.1% (121 +/- 22 mg/dl-->132 +/- 20 mg/dl) and the apolipoprotein B level decreased by 20.2% (114 +/- 25 mg/dl-->91 +/- 20 mg/dl). The MDA level also decreased significantly (1.16 +/- 0.92 nmol/ml-->0.58 +/- 0.38 nmol/ml). No particular side effects were observed during the 24 weeks of fluvastatin administration. In conclusion, fluvastatin may play an important role in preventing significant oxidative stress and was shown to be safe and effective in reducing the TC, LDL-C, MDA and AI levels in dialysis patients with hypercholesterolemia. The possibility that this improvement in the plasma lipid profile of dialysis patients may decrease atherogenic complications requires further investigation, including long-term clinical observations.


Malaria in foreign visitors to Britain.
Malaria cases reported in Britain are increasing. Foreign visitors ill with malaria while visiting Britain form an important category. This paper reviews notifications to the Malaria Reference Laboratory (M.R.L.) of cases of malaria in foreign visitors in 1985. There were 427 cases reported in this group which is nearly 20% of the total number reported. It was found that the foreign visitors had a higher proportion of Plasmodium falciparum and that a third of the cases were aged 20-29 years. Sixty per cent of the cases were born in Nigeria or India and 7.5% claim to have become ill on the day they arrived in Britain. The behaviour of the malaria and the individual with malaria were also studied.


Glucocorticoid deficiency increases phospholipase A2 activity in rats.
An important mechanism for the antiinflammatory effect of pharmacological doses of glucocorticoids is the inhibition of arachidonic acid release from phospholipids by phospholipase A2 (PLA2). As a corollary, one might predict that low endogenous concentrations of glucocorticoids favor inflammatory disease states. Indeed, clinical and experimental observations revealed an association between glucocorticoid deficiency and disease states caused by immunological and/or inflammatory mechanisms. The purpose of the present investigation was to study the regulation of PLA2 mRNA, protein, and enzyme activity in adrenalectomized (ADX) rats where glucocorticoid concentrations were below physiological levels. The mRNA of group I and II PLA2 were measured by PCR. Group II PLA2 mRNA was increased by 126 +/- 9% in lung tissue of ADX rats, whereas group I PLA2 was increased only by 27 +/- 1.5%. The increase in group II mRNA in ADX rats was reflected by a corresponding increase of group II PLA2 protein (70-100%) in lung, spleen, liver, and kidney. This increase was reversed by the administration of exogenous corticosterone. After ADX, the percentage increase in total PLA2 activity was higher than that of mRNA or PLA2 protein, suggesting that the activity of the enzyme was modulated by inhibitors or activators. The concentration of lipocortin-I, an inhibitor of PLA2 enzyme was strongly correlated with the activity of PLA2 in the tissues (lung, spleen, liver, and kidney). In all these tissues, the concentrations of lipocortin-I declined after ADX. Thus upregulation of PLA2 enzyme and downregulation of lipocortin-I might account for the enhanced inflammatory response in hypoglucocorticoid states.


Cutis marmorata telangiectatica congenita with skin ulcerations in a new born.
Cutis marmorata telangiectatica congenita (CMTC) is a rare congenital disorder with persistent cutis marmorata, telengiectasia, and phlebectesia, which may be associated with cutaneaus atrophy and ulceration of the involved skin. We herewith report a full-term newborn female baby with CMTC at birth with ulceration over the extensor aspects of both the knee joints and right elbow joint. CMTC is a benign vascular anomaly representing dilatation of capillaries and veins of dermis and is apparent at birth. The baby had a reticulated bluish purple skin changes all over the body including the face and limb. Although it resembled physiological cutis marmorata, it was strikingly pronounced and definitely was unvarying and permanent. A variety of vascular malformation has been described along with this disorder. Etiology is not very clear and may be multifactorial, teratogens and genes are also been suggested. Prognoses in uncomplicated cases are good.


A non-canonical E-box within the MyoD core enhancer is necessary for circadian expression in skeletal muscle.
The myogenic differentiation 1 (MyoD) gene is a master regulator of myogenesis. We previously reported that the expression of MyoD mRNA oscillates over 24 h in skeletal muscle and that the circadian clock transcription factors, BMAL1 (brain and muscle ARNT-like 1) and CLOCK (circadian locomotor output cycles kaput), were bound to the core enhancer (CE) of the MyoD gene in vivo. In this study, we provide in vivo and in vitro evidence that the CE is necessary for circadian expression of MyoD in adult muscle. Gel shift assays identified a conserved non-canonical E-box within the CE that is bound by CLOCK and BMAL1. Functional analysis revealed that this E-box was required for full activation by BMAL1/CLOCK and for in vitro circadian oscillation. Expression profiling of muscle of CE(loxP/loxP) mice found approximately 1300 genes mis-expressed relative to wild-type. Based on the informatics results, we analyzed the respiratory function of mitochondria isolated from wild-type and CE(loxP/loxP) mice. These assays determined that State 5 respiration was significantly reduced in CE(loxP/loxP) muscle. The results of this work identify a novel element in the MyoD enhancer that confers circadian regulation to MyoD in skeletal muscle and suggest that loss of circadian regulation leads to changes in myogenic expression and downstream mitochondrial function.


Influence of Intramuscular Application of Autologous Conditioned Plasma on Systemic Circulating IGF-1.
Platelet-rich plasma (PRP) to increase levels of platelets and growth factors has been used for the treatment of sports injuries suggesting to improve healing and regeneration. This method offers some potential especially for elite athletes. However, the insulin like growth factor-1 (IGF-1) is prohibited by the World Anti Doping Agency and, in addition, there may be a possible link between increased levels of IGF-1 and cancer risk. Aim of the study was to evaluate a systemic increase of IGF-1 after local intramuscular administration of PRP in young healthy moderately trained male subjects. Blood samples were drawn and PRP preparation was performed by means of centrifugation. Enriched plasma was injected into the gluteus muscle. Venous blood was collected and serum prepared before as well as after 0.5, 3 and 24 hours after PRP administration. IGF-1 analysis was performed applying an ELISA test kit. No significant systemic increase of mean IGF-1 was found after the PRP injection. Only one subject showed an increase after 24 h, but all IGF-1 values were found within reference limits. We conclude that a single intramuscular application of PRP does not significantly increase systemic IGF-1 levels. Therefore, a single application of PRP is safe with respect to systemic IGF-1 response and cancer risk and this should be allowed for treatment of muscle injuries in elite athletes. Key pointsThere is no increase of systemic IGF-1 levels after a single local intramuscular administration of PRP.Professional athletes and non-athletes alike can benefit from such a treatment option for muscle injuries and related sports injuries without an increased risk of cancer.More studies are warranted to provide definitive evidence to guide surgeon's decision making regarding the appropriate use for PRP products.


Aortoenteric fistula as a late complication of thrombolysis and bare metal stenting for perioperative occlusion of aortofemoral bypass.
We previously described the case of a 47-year-old man who experienced perioperative graft occlusion after infrarenal aortic endarterectomy and aortobifemoral expanded polytetrafluoroethylene bypass graft for occlusive disease. The patient was treated with local graft thrombolysis and stenting of an intimal flap at the level of the endarterectomized aorta next to the aortic anastomosis. An urgent laparotomy performed 6 years later showed aortic wall perforation by the stent with a large aortoenteric fistula. Surgical treatment included removal of the stent and the aortobifemoral graft, bowel repair, and extra-anatomic lower-limb revascularization by axillofemoral and cross-femoral bypass grafting. The patient was discharged 12 days later with no early complications. Although local thrombolysis and stenting may be a technically feasible technique instead of reoperation in early aortofemoral graft thrombosis, long-term results of this procedure may be affected by perigraft hematoma due to perioperative thrombolysis, increased risk of infection due to the prolonged intragraft cannulation, and risk of stent-related aortic injury, especially if an endarterectomy has been performed. All these issues may increase the risk of late aortoenteric fistula. More experience with hybrid, open/endovascular procedures, and more contemporary stent-based devices is needed to assess the efficacy and safety of this alternative treatment.


New PET imaging agent for the serotonin transporter: [(18)F]ACF (2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine).
A new F-18-labeled phenylthiophenyl derivative specific for imaging of serotonin transporters (SERT) in the brain by positron emission tomography (PET) is described. Fluorinated phenylthiophenyl derivative, ACF, 2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine, was prepared by first coupling 2,5-dichloro-4-nitroaniline with 2-mercapto-N,N-dimethylbenzamide. The amino group of the coupled adduct was converted to a fluoro group through a Schiemann reaction. Subsequently, a one pot reduction of both nitro and amide groups by BH(3)-tetrahydrofuran yielded the nonradioactive ACF (yield 25%). In vitro binding assays using cell membrane homogenates of LLC cells expressing SERT, dopamine transporters (DAT), or norepinephrine transporters (NET) showed excellent binding affinity and selectivity for SERT (K(i) = 0.05, 3020, and 650 nM for SERT, DAT, and NET, respectively). For preparation of the [(18)F]ACF, the NH(2) group of the initially coupled adduct was converted to the trimethylammonium salt, which was replaced by [(18)F]fluoride in the presence of Kryptofix 222 and potassium carbonate. The final product, [(18)F]ACF, was obtained after a borane and stannous chloride reduction reaction. The combined two step reaction gave a radiochemical yield of 10-15% (EOB) and a radiochemical purity of >99%. Synthesis of the novel PET tracer, [(18)F]ACF, as a probe for binding to SERT in the brain was successfully achieved. The new tracer [(18)F]ACF showed excellent brain penetration and selective localization after an iv injection in rats (brain uptake at 2, 30, 60, 120, and 240 min was 3.27, 1.28, 0.69, 0.21, and 0.06% dose/organ, respectively). The hypothalamus/cerebellum ratio at 60 min post iv injection was 3.55. This specific localization in the hypothalamus was blocked by pretreatment of (+)McN5652. This novel ligand is a potential PET tracer for in vivo evaluation of SERT in the brain.


Implementing an interprofessional user-centered design approach to develop a bedside leg exercise device.
Early mobilization is important to improve critically ill patients' outcomes, but barriers to its implementation are common. A suitable in-bed device to exercise patients' legs might facilitate early mobilization. The aim of this study was to develop an in-bed leg press that would facilitate early mobilization and enhance strength training of patients in acute care settings. A user-centered design approach was applied to develop the device. The process was assessed by different instruments: the system usability scale (SUS) questionnaire, the Kano model questionnaire and interviews with end-users. Through several iterations of a user-centered design process, the prototype of an in-bed leg press was developed and tested. The assessment, based on SUS, Kano and interviews, indicates high usability and demonstrates the advantages of a user-centered design process. An interprofessional user-centered design approach was successfully implemented to develop a medical device. The early involvement of end-users resulted in a design that already shows a high degree of production readiness. The resulting device fulfilled all core requirements from a therapeutic point of view and included key features related to its practical use.


Effects of aerobic exercise on cognitive and psychosocial functioning in patients with mild hypertension.
The effects of 16 weeks of physical exercise training on the psychological functioning of 90 patients with mild hypertension were examined. At baseline and after 16 weeks of training, patients completed a psychometric test battery that included objective measures of neuropsychological performance and standardized self-report measures of psychosocial functioning. Patients were randomly assigned to one of three groups: aerobic exercise, strength training and flexibility exercise, or a waiting list control group. After training, there were no group differences on any of the psychological measures, even though patients who engaged in exercise perceived themselves as functioning better in a number of psychological domains.


Ca' Granda, Hortus simplicium: Restoring an Ancient Medicinal Garden of XV-XIX Century in Milan (Italy).
This work is based on the study of 150 majolica vases dated back to the mid XVII century that once preserved medicinal remedies prepared in the ancient Pharmacy annexed to the Ospedale Maggiore Ca' Granda in Milan (Lombardy, Italy). The Hortus simplicium was created in 1641 as a source of plant-based ingredients for those remedies. The main objective of the present work is to lay the knowledge base for the restoration of the ancient Garden for educational and informative purposes. Therefore, the following complementary phases were carried out: (i) the analysis of the inscriptions on the jars, along with the survey on historical medical texts, allowing for the positive identification of the plant ingredients of the remedies and their ancient use as medicines; (ii) the bibliographic research in modern pharmacological literature in order to validate or refute the historical uses; (iii) the realization of the checklist of plants potentially present in cultivation at the ancient Garden, concurrently with the comparison with the results of a previous in situ archaeobotanical study concerning pollen grains. For the species selection, considerations were made also regarding drug amounts in the remedies and pedoclimatic conditions of the study area. Out of the 150 vases, 108 contained plant-based remedies, corresponding to 148 taxa. The remedies mainly treated gastrointestinal and respiratory disorders. At least one of the medicinal uses was validated in scientific literature for 112 out of the 148 examined species. Finally, a checklist of 40 taxa, presumably hosted in the Hortus simplicium, was assembled.


Molecular basis of HLA-C recognition by p58 natural killer cell inhibitory receptors.
NK cells express several inhibitory receptors that recognize class I MHC molecules expressed on target cells. The NK cell inhibitory receptors (KIRs) provide a key regulatory function for NK cells via specific interaction with MHC/peptide complexes, but the molecular details for recognition of class I MHC molecules by KIRs still remain unclear. Here we report cDNA cloning and expression of p58 KIRs and a p50 killer cell activatory receptor (KAR) from a Korean blood donor and demonstrate direct binding between recombinant soluble p58 KIRs and recombinant soluble HLA-C molecules. We identified three p58/p50 killer cell receptors (KAR-K1, KIR-K6, and KIR-K7), which are homologous to p50 cl-39, p58 47.11, and p58 cl-6, respectively. Native gel shift assay revealed that p58 KIR-K6 and KIR-K7 bind both HLA-Cw3 and HLA-Cw6 molecules, but p50 KAR-K1 binds neither of the HLA-C molecules. However, binding of HLA-C molecule by p58 KIR is affected by the antigenic peptide bound on the MHC molecule, suggesting that the p58 KIR binding to the HLA-C molecule may be dependent on the peptide. In addition, the binding interaction requires the presence of both p58 Ig domains, suggesting that the binding mode of HLA-C and p58 KIR may have some similarity to that of the neonatal Fc receptor and the Fc fragment of Ab and may be distinct from that of TCR and MHC.


DosS Is required for the complete virulence of mycobacterium tuberculosis in mice with classical granulomatous lesions.
Mycobacterium tuberculosis (Mtb) must counter hypoxia within granulomas to persist. DosR, in concert with sensor kinases DosS and DosT, regulates the response to hypoxia. Yet Mtb lacking functional DosR colonize the lungs of C57Bl/6 mice, presumably owing to the lack of organized lesions with sufficient hypoxia in that model. We compared the phenotype of the Δ-dosR, Δ-dosS, and Δ-dosT mutants to Mtb using C3HeB/FeJ mice, an alternate mouse model where lesions develop hypoxia. C3HeB/FeJ mice were infected via aerosol. The progression of infection was analyzed by tissue bacterial burden and histopathology. A measure of the comparative global immune responses was also analyzed. Although Δ-dosR and Δ-dosT grew comparably to wild-type Mtb, Δ-dosS exhibited a significant defect in bacterial burden and pathology in vivo, accompanied by ablated proinflammatory response. Δ-dosS retained the ability to induce DosR. The Δ-dosS mutant was also attenuated in murine macrophages ex vivo, with evidence of reduced expression of the proinflammatory signature. Our results show that DosS, but not DosR and DosT, is required by Mtb to survive in C3HeB/FeJ mice. The attenuation of Δ-dosS is not due to its inability to induce the DosR regulon, nor is it a result of the accumulation of hypoxia. That the in vivo growth restriction of Δ-dosS could be mimicked ex vivo suggested sensitivity to macrophage oxidative burst. Anoxic caseous centers within tuberculosis lesions eventually progress to cavities. Our results provide greater insight into the molecular mechanisms of Mtb persistence within host lungs.


Accuracy of the deterministic travel time retrieval from cross-correlations of non-diffuse ambient noise.
Measurements of long-range cross-correlations of ambient noise underlie acoustic noise interferometry, a promising technique for passive remote sensing of the environment. Previously established simple, exact relations between deterministic Green's functions and the cross-correlation function of perfectly diffuse noise do not necessarily hold for noise fields in the ocean and atmosphere. Here, the method of a stationary phase is applied to study the information content of the cross-correlation function of non-diffuse noise and to quantify the accuracy of passive measurements of the acoustic travel times.


Quantification of the presigmoid transpetrosal keyhole approach to petroclival region.
Despite the presigmoid transpetrosal approach has been used by different researchers in various ways, the surgical injury rate remains high. Applying a minimally invasive keyhole idea, we devised a presigmoid transpetrosal keyhole approach (PTKA), classified and quantitatively assessed their approach to the petroclival area on a cadaver model by using a neuronavigation system. The presigmoid transpetrosal keyhole approach was divided into four increasingly morbidity-producing steps: retrolabyrinthine, partial labyrinthectomy with petrous apicectomy, translabyrinthine and transcochlear keyhole approaches. Six latex-injected cadaveric heads (twelve sides) underwent dissection in which a neuronavigation system was used. An area of exposure 10 cm superficial to a central target (working area) was calculated. The area of clival exposure with each subsequent dissection was also calculated. The retrolabyrinthine keyhole approach (RLK) spares hearing and facial function in theory but provides for only a small window of upper clival exposure. The view afforded by partial labyrinthectomy with petrous apicectomy keyhole approach (PLPAK) provides for up to four times this exposure. The translabyrinthine keyhole approach (TLK) and transcochlear keyhole approach (TCK), although producing more morbidity, add little in terms of a larger petroclival window. However, with each step, the surgical freedom for manipulation of instruments increases. The presigmoid transpetrosal keyhole approach to the petroclival area is feasible and useful. The RLK has relatively limited utility. For lesions without bone invasion, the PLPAK provides a much more versatile exposure with an excellent chance of hearing and facial nerve preservation. The TLK provides for greater versatility in treating lesions but clival exposure is not greatly enhanced. The TCK adds little in terms of intradural exposure but should be reserved for cases in which access to the petrous carotid artery is necessary.


Ancestral diet transgenerationally influences offspring in a parent-of-origin and sex-specific manner.
Parent-of-origin effects, whereby specific phenotypes are differentially inherited paternally or maternally, provide useful clues to better understand transgenerational effect transmission. Ancestral diet influences offspring phenotypes, including body composition and fitness. However, the specific role that mothers and fathers play in the transmission of altered phenotypes to male and female offspring remains unclear. We investigated the influence of the parent-of-origin's diet on adult progeny phenotypes and reproductive output for three generations in fruit flies ( Drosophila melanogaster). Males and females reared on a control diet were exposed to the control diet or one of two altered (no- or high-) sugar treatment diets for a single generation. Flies from one of the two altered diet treatments were then mated to control flies in a full-factorial design to produce F1 offspring and kept on control media for each following generation. We found parent-of-origin (triglyceride) and non-parent-of-origin (sugar) body composition effects, which were transgenerational and sex-specific. Additionally, we observed a negative correlation between intergenerational maternal reproductive output and triglyceride levels, suggesting that ancestral diet may affect fitness. This work demonstrates that ancestral diet can transmit altered phenotypes in a parent-of-origin and sex-specific manner and highlights that mechanisms regulating such transmission have been greatly overlooked. This article is part of the theme issue 'The role of plasticity in phenotypic adaptation to rapid environmental change'.


[Almitrine bismesylate and ventilation-perfusion ratios].
Almitrine bismesilate (Vectarion) is characterised by its specific activity on carotid and aortic chemoreceptors. A simultaneous study of the ventilatory and blood gas changes in the anaesthetised dog has shown a dissociation between these two effects. At a dose of 10 to 30 micrograms/kg IV Almitrine bismesilate induces a significant rise in the PaO2 whereas no change in the ventilatory output is observed. A significant transitory rise in the pulmonary arterial pressure also appears at these doses. The juxta position of these results suggests that a feeble doses Almitrine bismesilate improves the blood gases of the arterial blood by a re-distribution of the pulmonary blood flow. Clinical pharmacological studies carried out in bronchitic patients have shown an improvement in the distribution of ventilation perfusion ratios VA/Q by Almitrine bismesilate. These experiments were carried out in animals in order to determine whether the drug had a preferential action on one or other side of the VA/Q ratio. Whereas in an animal with intact lungs, Almitrine bismesilate potentiates hypoxia induced vaso-constriction, in animals whose lungs are ventilated in a heterozygous fashion in such a way as to reproduce zones with a shunt effect, the potentiation of hypoxic vasoconstriction was not again found. At low doses in the hypoxic rat Almitrine bismesilate increases alveolar ventilation (VH) by a significant rise in tidal volume and inspiratory output (VT/TI) without increasing external ventilation. Overall the rise of PaO2 induced by Almitrine bismesilate at low doses may be accompanied by a similar effect on the pulmonary circulation noted in the anaesthetised dog. In the hypoxic rat, it is changes in the alveolar ventilation that are observed.(ABSTRACT TRUNCATED AT 250 WORDS)


[The role of repeated transurethral resection in the treatment of bladder tumor]
Complete removal of the tumour or deep invasion can be proven by repeated transurethral resection of bladder wall at the previous tumour site. Six weeks after transurethral resection of bladder tumour (TURB), in all but TaG1 cases repeated resection were performed for the evaluation of radicality in 62 patients, 43 males and 19 females, suffering bladder cancer, from October 1998. In the case of positive histology another resection was performed for security reason. In the case of 38 superficial (Tis, Ta, T1) cancers, repeated resection revealed negative, identical or different T stage compared with previous histology in 28, 5 and 5 cases, respectively. In 7 cases repeated resection was applied as second intervention after the incomplete resection of large tumour mass. Indication of repeated resection was insufficient depth of resection and carcinoma in situ in 13 and 4 cases, respectively. Based on our data, we conclude that repeated resection should be performed when tumour-free status is not justified and biopsy according to Bressel was not taken.


Chemical Insights into the Antioxidant Mechanisms of Alkylseleno and Alkyltelluro Phenols: Periodic Relatives Behaving Differently.
The possible antioxidant reaction mechanisms of recently synthesized and tested alkylseleno (telluro) phenols have been explored using density functional theory by considering two solvents physiologically relevant, water and pentylethanoate (PE). In addition, the possible pathway for the antioxidant regeneration with ascorbic acid has been investigated. Results show that selenium and tellurium systems follow different chemical behaviors. In particular, the alkylseleno phenol (ebselenol) antioxidant activity is justified through a sequential proton loss-electron-transfer mechanism in water media, whereas in PE the hydrogen-atom transfer process is favored. In the case of the tellurium derivative, the oxygen-transfer mechanism represents the preferential one. Furthermore, electronic properties have been analyzed to rationalize the different reactivity of the selenium- and tellurium-containing systems. To confirm the results, smaller but similar systems were also investigated. The calculated data support the different mechanism (Se vs. Te) proposals.


Psychometric properties of a culture-adapted Spanish version of AIDA (Assessment of Identity Development in Adolescence) in Mexico.
The construct "identity" was discussed to be integrated as an important criterion for diagnosing personality disorders in DSM-5. According to Kernberg, identity diffusion is one of the relevant underlying structures in terms of personality organization for developing psychopathology, especially borderline personality disorder. Therefore, it would be important to differentiate healthy from pathological development already in adolescence. With the questionnaire termed AIDA (Assessment of Identity Development in Adolescence), a reliable and valid self-rating inventory was introduced by Goth, Foelsch, Schlueter-Mueller, & Schmeck (2012) to assess pathology-related identity development in healthy and disturbed adolescents. To test the usefulness of the questionnaire in Mexico, we contributed to the development of a culture-specific Spanish translation of AIDA and tested the reliability and aspects of validity of the questionnaire in a juvenile Mexican sample. An adapted Spanish translation of AIDA was developed by an expert panel from Chile, Mexico, and Spain in cooperation with the original authors, focusing on content equivalence and comprehensibility by considering specific idioms, life circumstances, and culture-specific aspects. The psychometric properties of the Spanish version were first tested in Mexico. Participants were 265 students from a state school (N = 110) and private school (N = 155), aged between 12 and 19 years (mean 14.15 years). Of these, 44.9% were boys and 55.1% were girls. Item characteristics were analyzed by several parameters, scale reliability by Cronbach's Alpha, and systematic effects of gender, age, and socioeconomics by an analysis of variance (ANOVA). We evaluated aspects of criterion validity in a juvenile justice system sample (N = 41) of adolescent boys in conflict with the law who displayed various types of behavioral problems by comparing the AIDA scores of a subgroup with signs for borderline pathology (N = 14) with the scores obtained in the student sample using T-tests. The psychometric properties of the Spanish version of AIDA proved satisfactory in the Mexican sample for items as well as scales. The reliability coefficients were α = .94 for the total scale "Identity Diffusion", α = .85 and .92 for the two primary scales "Discontinuity" and "Incoherence", and between α = .70 and .83 for the subscales. However, some items of the item pool in the Spanish version of AIDA did not meet all criteria for test equivalence and should thus be reformulated, taking the Mexican culture into account. Significant effects for gender and age were found. In line with our theory, the AIDA scores in the domains "Discontinuity" (high effect size) and "Incoherence" (medium effect size) were markedly higher in the delinquent boys than in the student group. The Spanish version of AIDA can be used in Mexico with satisfying psychometric properties, with only minor adaptions required. Our study contributes to the intercultural applicability of the AIDA instrument using the construct "identity integration vs. diffusion" as it was defined in the AIDA model for diagnostic purposes. Cultural differences, even those present in the various Spanish-speaking countries, should be modeled carefully.


Feasibility of Segmental Colectomy Followed by Endoscopic Surveillance as a Treatment Strategy for Colorectal Cancer Patients with Lynch Syndrome.
Initial surgical procedures for colorectal cancer (CRC) patients with Lynch syndrome remain controversial. This study assessed the validity of segmental colectomy (SGC) followed by endoscopic surveillance as a treatment strategy for CRC patients with Lynch syndrome. Among consecutive patients who underwent surgery for primary CRC between April 1985 and December 2014, 49 patients were observed to have germline mutations in a mismatch repair gene, and 38 patients who underwent SGC followed by periodic endoscopic surveillance at our institution were evaluated for metachronous CRC, need for secondary surgery, and the details of endoscopic surveillance. Of the 38 patients who underwent SGC followed by periodic endoscopic surveillance at our institution, 6 (15.8%) patients showed metachronous CRC, 3 (7.9%) patients underwent endoscopic resection, and the other 3 patients (7.9%) underwent secondary surgery. The dispersion of the endoscopic surveillance interval was significantly greater in patients with metachronous CRC (364 ± 332.9 days) than in those without metachronous CRC (370 ± 129.7 days; p < 0.001). SGC followed by annual endoscopic surveillance was feasible as a treatment strategy for CRC patients with Lynch syndrome, because the incidence of metachronous CRC and the need for secondary surgery were low. Annual and periodic endoscopic surveillance might be essential for early detection of metachronous CRC and prevention of secondary surgery because of metachronous CRC in CRC patients with Lynch syndrome after SGC.


Unraveling the origins of catalyst degradation in non-heme iron-based alkane oxidation.
A series of potentially tetradentate and pentadentate ligands modelled on BPMEN has been prepared and their iron(II) bis(triflate) complexes have been isolated and characterised by spectroscopic and crystallographic techniques (BPMEN = N,N'-bis(pyridylmethyl)ethylenediamine). Changes to the BPMEN ligand have invariably led to complexes with different coordination modes or geometries and with inferior catalytic efficiencies for the oxidation of cyclohexane with H2O2. The reaction of an iron(II) complex containing a pentadentate BPMEN-type ligand with O2 has resulted in ligand degradation via oxidative N-dealkylation and the isolation of a bis(hydroxo)-bridged dinuclear iron(III) complex with a picolinate-type ligand.


Effects of volitional walking control on postexercise changes in motor cortical excitability.
To explore the effects of qualitative or quantitative changes in walking on motor cortical excitability, a transcranial magnetic stimulation procedure was used to examine the alterations of motor-evoked potential (MEP) amplitude following walking. Eight healthy participants completed a series of two walking tasks on a treadmill at 2 km/h. The ratio of the left stance duration to the right stance duration was 1 : 2 in the asymmetrical walking task and 1 : 1 in the symmetrical walking task. In each task, walking for 10 min followed by MEP measurement for ∼4 min was repeated three times. MEP measurements were also performed before a walking task as a baseline and continued every 10 min for a further 30 min after the completion of the walking task. During slight voluntary contraction of the left tibialis anterior muscle, MEP measurements were conducted four times. Although a significant MEP depression was found after the asymmetrical walking task with increasing amount of walking, no significant decrease in MEP below baseline was observed after the symmetrical walking task throughout all measurement sessions. This MEP depression was the prominent response to the asymmetrical walking task compared with the symmetrical walking task. These findings indicate that the intentional control of walking pattern has both temporal and task-specific influences on excitability changes in the cerebral cortex, and suggest that motor cortical excitability may be altered by controlling the amount of central commands to the legs even during gait exercise.


Stabilizing brokerage.
A variety of social and economic arrangements exist to facilitate the exchange of goods, services, and information over gaps in social structure. Each of these arrangements bears some relationship to the idea of brokerage, but this brokerage is rarely like the pure and formal economic intermediation seen in some modern markets. Indeed, for reasons illuminated by existing sociological and economic models, brokerage is a fragile relationship. In this paper, we review the causes of instability in brokerage and identify three social mechanisms that can stabilize fragile brokerage relationships: social isolation, broker capture, and organizational grafting. Each of these mechanisms rests on the emergence or existence of supporting institutions. We suggest that organizational grafting may be the most stable and effective resolution to the tensions inherent in brokerage, but it is also the most institutionally demanding.


Structure and ion exchange properties of a new cobalt borate with a tunnel structure "templated" by Na+.
The new anhydrous borate Na2Co2B12O21 has been synthesized by flux methods and studied by single-crystal X-ray diffraction (space group I2/a with a = 17.1447(15) A, b = 4.5530(5) A, c = 19.4408(15) A, beta = 103.212(5) degrees , V = 1477.4(2) A3, Z = 4). Refinement of its structure reveals it is the first metaborate exhibiting a tunnel network, with internal dimensions of 4.5 x 8.8 A2. Further single-crystal diffraction studies show that the Na+ ions within the tunnels are exchangeable with Li+ along with the absorption of water molecules to form Li2(H2O)2Co2B12O21, making this compound a unique non-siliceous zeotype.


Detection of Wuchereria bancrofti specific antigens in the serum of endemic residents.
A sandwich enzyme-linked immunosorbent assay (s-ELISA) is developed for detecting circulatory antigens in individuals infected with Wuchereria bancrofti in an endemic area using antibody (Ig) against excretory-secretory-metabolic antigens of the microfilariae raised in rabbit (anti-mf-ESM) and labelled with alkaline phosphatase (ESM-Ig-conjugate). An optical density reading of a sample greater than 0.075 (after subtracting the background) was taken as positive in the s-ELISA. When homologous (WbmfESM) and heterologous (sonicated antigens of human and model intestinal helminths-Ascaris lumbricoides. Trichuris muris, Necator americanus and Strongyloides ratti) antigens were spiked at 2.5, 5, and 7.5 microgram/well, rabbit ESM-Ig-conjugate reacted specifically with the samples containing homologous antigens. Amongst 21 sera in five different categories of non-endemic group, only four (two in helminth-ve and two in mixed intestinal helminthic group) were found to be positive. Out of 19 sera from endemic residents, three of 7 endemic normals (ENS), all microfilaraemics (mf+) (n = 7) and 4 out of 5 elephantoid patient sera were positive. This preliminary data show that rabbit mfESM-Ig-conjugate is efficient in detecting sera samples containing antigenic components of microfilariae. This assay was found to be discriminatory in detecting individuals carrying current infection. This test requires further validation with larger number of samples and it may prove of value for detecting lymphatic filarial infection.


The β subunit of soluble guanylyl cyclase GUCY1B3 exerts cardioprotective effects against ischemic injury via the PKCε/Akt pathway.
The soluble form of guanylyl cyclase (sGC) is the main receptor for the signaling agent nitric oxide (NO), which regulates cardiomyocyte contractile function and attenuates cardiomyocyte hypertrophy. sGC catalyzes the formation of cyclic guanosine monophosphate (cGMP), a regulator of vascular tone, and cardiac NO-sGC-cGMP signaling modulates cardiac stress responses, including ischemia and reperfusion (IR) injury. Here, we investigated the role of GUCY1B3 (the β subunit of sGC) in cardiomyocyte IR injury and myocardial infarction (MI) in vitro and in vivo. GUCY1B3 was upregulated in neonatal rat ventricular myocytes in response to IR injury, and GUCY1B3 overexpression restored IR-induced cell death and apoptosis. Treatment with specific inhibitors of PKCδ, PKCε, and Akt suggested that the protective effects of GUCY1B3 were mediated by PKCε/Akt signaling. In a mouse model of coronary artery ligation-induced MI, GUCY1B3 silencing aggravated MI-induced cardiac dysfunction and increased infarct size and exacerbated cardiomyocyte apoptosis in association with the inactivation of PKCε and Akt. Our results suggest that GUCY1B3 exerts cardioprotective effects through the modulation of the PKCε/Akt activity and identify a potential mechanism involved in NO-sGC-cGMP signaling in the heart.


Could I-FABP Be an Early Marker of Celiac Disease in Children with Type 1 Diabetes? Retrospective Study from the Tertiary Reference Centre.
Patients with type 1 diabetes (T1D) are at higher risk of celiac disease (CD). Recently, intestinal fatty acid binding protein (I-FABP) has been shown to be a serological biomarker of impaired intestinal barrier in CD. Thus, the aim of this study was to verify whether I-FABP could be an early marker of CD in pediatric T1D patients. I-FABP was measured in sera of patients with T1D (n = 156), active CD (n = 38), T1D with active CD (T1D-CD, n= 51), and age-matched healthy children (n = 55). Additionally, I-FABP was determined in T1D patients with negative CD serology at least one year before CD diagnosis (T1D-CD-1, n = 22), in CD patients on a gluten-free diet (CD-GFD, n = 36), and T1D-CD patients on GFD (T1D-CD-GFD, n = 39). Sera were tested using immunoenzymatic assay. Significantly increased levels of I-FABP were found in the T1D, active CD, and T1D-CD groups (1153 ± 665, 1104 ± 916, and 1208 ± 878, respectively) in comparison to healthy with controls (485 ± 416, p < 0.05). GFD induced a significant decrease in I-FABP levels in CD and T1D-CD groups (510 ± 492 and 548 ± 439, respectively). Interestingly, in T1D-CD-1 and T1D, I-FABP levels were comparable (833 ± 369 vs. 1153 ± 665), and significantly increased in relation to healthy controls and T1D-CD values on GFD. The results indicate that the epithelial barrier is disrupted in T1D patients independently of CD development; therefore, I-FABP cannot serve as an early marker of CD in T1D patients. Although GFD can improve epithelial recovery, the question remains as to whether GFD could exert beneficial effects on the intestinal barrier in early stages of T1D.


Gene mapping and cross-resistance in cyclodiene insecticide-resistant Drosophila melanogaster (Mg.).
Resistance to the cyclodiene insecticide dieldrin maps to a single gene (Rdl) on the left arm of chromosome III in Drosophila melanogaster (Meigen). The gene was further mapped by the use of chromosomal deficiencies to a single letter sub-region, 66F, on the polytene chromosome. The cross-resistance spectrum of a backcrossed strain lacking elevated mixed function oxidase activity, a common resistance mechanism, was examined. Levels of resistance similar to those found in other insects were found to dieldrin, aldrin, endrin, lindane, and picrotoxinin. Strong similarity of this single major gene with that found in other cyclodiene resistant insects is suggested by its cross-resistance spectrum and chromosomal location, via homology with other Diptera. The significance of major genes in insecticide resistance is discussed.


[Acute intoxication with fenspiride].
According to the best of our knowledge this is the first publication in medical literature about the acute intoxication with fenspiride. The two cases of a young female patients, intoxicated with Eurespal, were described. The orthostatic hypotonia with the blood pressure about 105-115/70 mm Hg in the horizontal position and 70-80/40 mm Hg in the sitting position was dominating. The heart rate was 100-110/min. when lying and 130-140/min. when sitting. The main symptoms were probably caused by inhibition of alpha1 adrenergic receptors. Main clinical manifestations make us reconsider the opinion about safety of fenspiride especially after acute intoxication.


Time for reflection.
The Department of Health (DH) announced in May that £650,000 will be spent to help 40 NHS trusts implement Schwartz Center Rounds, a scheme developed in the United States to improve compassion in health care.


The unequal distribution of parathyroid neoplasms in male patients.
There is a known lesser incidence of primary hyperparathyroidism and parathyroid neoplasms in male patients. Any difference in the anatomic distribution between males and females has not been documented. Review of our institutional experience with 125 pathologically confirmed parathyroid adenomas (119) or carcinomas (six) from 2000 through 2012 was conducted. The anatomic location was identified from operative records and the distributions between males and females were compared. Ninety-two females with parathyroid neoplasms had equal anatomic distributions between left and right sides and no significant difference between superior and inferior locations (P = 0.381). In marked contrast, tumors in 33 male patients had a significant predilection for the right side (67%, P = 0.016) and inferior position (85%, P = 0.033) and most notably the right inferior position (64%, P = 0.026). For the group as a whole, inferior adenomas were significantly more common (70%, P = 0.044). All patients had postoperative normalization of serum calcium levels. Late biochemical recurrence was noted in two patients. This is the first operatively confirmed delineation of the anatomic distributions of parathyroid neoplasms in separate sexes. Based on the unexpected findings of this study, we recommend the right inferior cervical region be explored first in males with suspected parathyroid tumors of indeterminate location.


Attitudes toward reproduction in a nonpatient population.
A basic question to be answered in an attempt to understand human reproductive behavior as it manifests itself in clinical practice is, why do people want to have children? A psychometric instrument for the assessment of reproductive attitudes was developed. A total of 746 men and women at 20, 30, and 40 years of age, who were randomly selected from a nonpatient population, answered. Data were analyzed by factor analysis. Reproductive profiles were constructed. The two most important factors in both sexes were "children as existential satisfaction" and "children as lack of freedom," indicating a basic conflict. The third most important factor in both sexes was "the importance of one's own parents as examples in parenthood," supporting earlier findings that reproductive conflicts are transmitted from one generation to another. Reproductive profiles were uniform in the different age groups. The element of ambivalence may be a clue to a deeper understanding of human reproductive behavior.


[Hallux valgus mild and moderate; treatment by minimally invasive surgery and its follow-up to 2 years].
The hallux valgus is a very frequent and complex orthopedic pathology. It involves the bone and soft tissue structures of the first toe. There are multiple techniques described for the alignment of the first toe. All technics aim to restore the normal angulation of the toe while using a stable osteotomy through a painless surgical procedure. The minimal invasive techniques have been growing in acceptance since the year 2000, as a viable surgical alternative to treat this pathology. We included patients with a diagnostic of mild or moderate hallux valgus on whom a minimal invasive procedure was performed to correct the deformity of the first toe. We performed a distal Reverdin/Isham osteotomy on the first metatarsal and an akin osteotomy in the proximal phalanx, a lateral capsular release and a abductor tenotomy. These patients were followed for 24 months after their surgery. Our patients had an adequate correction angular correction, for a distal osteotomy. They had a good pain control, with an adequate mobility in the postoperative period. The patients presented an adequate personal satisfaction, 87% of them had good results. We found an important and statistically significant improvement in the Kitaoka scale. The minimal invasive technics for the correction of mild or moderated hallux valgus are a good alternative. Our patients are satisfied with the functional, and cosmetic results.


Men, masculinity and the new coronavirus: sharing gender issues in the first phase of the pandemic.
This article presents reflections on masculinity and the social construction of gender - based on the global phenomenon of the new coronavirus pandemic - produced by researchers who are part of the national research team on comprehensive health care policy for men in Brazil. From a gender-based standpoint, the article contends that it is necessary to note that cis heteronormative male socialization is guided by three core issues: 1) the submission to practices of care of self and others; 2) the rejection of preventive health practices, due to a distorted matrix of risk perception (and a certain sense of "invulnerability"); 3) the domestic dynamics marked by postures of command, order, and honor. These dimensions of everyday life were profoundly upset in this first phase of the epidemic, in which confinement became the most recommended alternative. These issues are configured as recurring (though not recent) repertoires that glorify the central model of a male order that needs to become an object of reflection, insofar as they endanger the health of men and women and, more broadly, of the status quo of the accepted tenets of domestic and social order.


Prepubertal Fischer 344 rats display stronger morphine-induced taste avoidance than prepubertal Lewis rats.
The present report asked if the previously reported differences in morphine-induced conditioned taste avoidance between adult F344 and LEW rats (F344 > LEW) are also evident in prepubescence (early adolescence). To assess this possibility, adult (Experiment 1) and prepubertal (Experiment 2) F344 and LEW rats were assessed for their ability to acquire morphine-induced taste avoidance (0, 3.2, 10, or 18 mg/kg) in a modified taste avoidance procedure. In each experiment, rats of both strains were given repeated pairings of saccharin and morphine followed by a final two-bottle avoidance test. Adult and prepubertal F344 subjects displayed a more rapid acquisition of the avoidance response as well as stronger suppression of consumption than their LEW counterparts. These data suggest the strains differ in their sensitivity to the aversive effects of morphine and that this differential sensitivity is evident early in development and is developmentally stable. The basis for these strain differences in morphine-induced avoidance was discussed.


On the Problem of Small Objects.
We discuss how to assess computationally the aesthetic value of "small" objects, namely those that have short digital descriptions. Such small objects still matter: they include headlines, poems, song lyrics, short musical scripts and other culturally crucial items. Yet, small objects are a confounding case for our recent work adapting ideas from algorithmic information theory (AIT) to the domain of computational creativity, as they cannot be either logically deep or sophisticated following the traditional definitions of AIT. We show how restricting the class of models under analysis can make it the case that we can still separate high-quality small objects from ordinary ones, and discuss the strengths and limitations of our adaptation.


The mechanism-based inactivation of human cytochrome P450 2B6 by phencyclidine.
Phencyclidine (PCP) was analyzed for its ability to inactivate human cytochrome p450 (p450) 2B6. PCP inactivated the 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of p450 2B6 in a concentration-, time-, and NADPH-dependent manner and exhibited pseudo-first order kinetics. The K(I) was 10 microM, k(inact) was 0.01 min(-1), which corresponds to a t(1/2) of 31 min. The partition ratio was approximately 45. Spectral analysis of the heme moiety demonstrated that the heme was not modified during inactivation. Extensive dialysis of the PCP-inactivated p450 2B6 did not cause a return in catalytic activity demonstrating PCP inactivation was irreversible. Including 7-ethoxycoumarin, an alternate substrate, protected 2B6 from inactivation by PCP indicating competition of the two substrates for the active site. Exogenous nucleophiles such as glutathione (GSH) and cyanide could not protect p450 2B6 from PCP inactivation demonstrating that the reactive intermediate remained within the p450 active site. High performance liquid chromatography analysis of p450 2B6 inactivated in the presence of (3)H-labeled PCP showed that PCP binding was specific for the p450 and not to other proteins in the reaction mixture. The stoichiometry of binding of PCP to p450 2B6 was demonstrated using (3)H-labeled PCP. In the absence of GSH, the stoichiometry was 5.5:1 (PCP/p450). In the presence of GSH, the stoichiometry was 1:1. This stoichiometry was further supported using electrospray ionization-liquid chromatography-mass spectrometry to analyze PCP-inactivated p450 2B1, 2B4, and 2B6.


[Some new tendencies in diagnosis and complex treatment of vulvar cancer--our and foreign experience].
The aim of this research work was to summarize our and foreign experience in the field of diagnosis, complex treatment and prognostic factors connected with vulvar cancer. We evaluated our and foreign experience for 10 years period (2000-2010) and evaluated 625 patients diagnosed and treated for vulvar cancer. We assessed the complex treatment, prognostic factors and some new tendencies towards more conservative surgical treatment of vulvar cancer. The all 5 years survival rate was 70%; 10 years survival rate was 50%. The level of recurrence was 30% (187 p.), local recurrences were 50% (93 p.), the groin recurrences were 7% (13 p.). The biggest recurrence rate was in local recurrences of the vulva. Older age and metastases in lymph nodes were independent bad prognostic factors. The stages of the lymph nodes, LVSI and the stage were connected with survival and disease free survival. The different kinds of treatment were analyzed- surgery, chemo and radiotherapy. We analyzed the tendencies towards more conservative surgical treatment connected with vulvar cancer. We tried to summarize our and foreign experience in the complex treatment of vulvar cancer for 10 years period. Our main idea was to show some new tendencies in the latest 10 years towards relatively more conservative treatment of this neoplasia.


[Endoscopic placement of self-expandable metallic stents (Wallstent) for malignant biliary stenosis, with special reference to preventive endoscopic nasal bile drainage against acute obstruction after stenting].
From December 1993 to December 1994, we inserted 14 biliary endoprostheses (Wallstent) endoscopically in 12 consecutive patients (5 men and 7 women; 55-91 years [mean 69.8 years] of age) with malignant biliary stenosis. Successful placement of Wallstent was achieved in all 12 patients. Procedure related death was encountered in one patient (8.3%) who was complicated with emphysematous cholecystitis, combined with a slipping migration of the stent. In 11 of the 12 patients, serum bilirubin levels reduced to less than 2.0 mg/dl. Acute obstruction, which was defined as the obstruction of the stent within 24 hours after the stent placement, occurred in 2 patients (16.7%). Endoscopic nasal bile drainage (ENBD) following stent placement was performed in 4 patients and acute obstruction was not developed in these cases. After endoprosthesis 8 patients were discharged with 6-47 hospital days and the average hospitalized period excluding a case with cerebral infarction was 12.7 days. Excluding one procedure related death, 6 patients died of primary malignancy 39-189 days (average 90.7 days) after endoprosthesis and in 2 cases recurrence of jaundice was observed. The other 4 patients have been alive for 60-174 days (average 102.5 days) without jaundice. The survival rate of the all patients was 64% for 3 months and 32% for 6 months, respectively. In conclusion, we suggested that the endoscopic Wallstent placement would contribute to the improvement of the quality of life for patients with malignant biliary stenosis. However, acute obstruction may be developed in some cases. For the purpose of managing acute obstruction, we recommend ENBD for a few days following the placement of a Wallstent.


Detection of colistin resistance among multidrug-resistant Klebsiella pneumoniae and Escherichia coli clinical isolates in Turkey.
In this study investigation of plasmid-mediated mcr 1-5 resistance genes was performed among multidrug-resistant (MDR) colistin sensitive and resistant Klebsiella pneumoniae and Escherichia coli strains isolated in our laboratory. We aimed to evaluate automated system (Vitek-2), broth microdilution (BMD) reference method and chromogenic media performance. Totally 94 MDR K. pneumoniae and six E. coli isolates were included in the study. CHROMID® Colistin R agar (COLR) (bioMerieux, France) was used to determine the colistin resistance by chromogenic method. Standard PCR amplification was performed using specific primers to screen the plasmid-mediated mcr 1-5 genes. Sixty-one isolates were resistant to colistin and 39 were susceptible with reference BMD. The essential and categorical agreement of Vitek-2 was determined as 100 and 99%. The sensitivity of COLR medium was 100%, the specificity was 97.5%. In our study mcr-1 was detected in eight isolates, while other mcr genes were not detected. Due to the high sensitivity and specificity of the COLR medium, it can be used in routine diagnostics for the detection of colistin resistance. In our study we detected 8% prevalence of mcr-1 among MDR strains however, two mcr-1 positive isolates were found sensitive to colistin by BMD.


Establishment of hybridomas secreting monoclonal antibodies to placental alkaline phosphatase and development of an enzyme immunoassay for its determination.
We established seven hybridomas secreting murine IgG monoclonal antibodies (MoAbs) to placental alkaline phosphatase (PLAP). The seven hybridomas were designated (1) 7C6, (2) 6G10, (3) 5B9, (4) 6D5, (5) 6B5, (6) 11G6 and (7) 3E10, respectively. The characteristics of these hybridomas were evaluated by radioimmunoassay (RIA) with 125I-PLAP. Their reactivity with the intestinal alkaline phosphatase, one of the alkaline phosphatase isozymes, was (1) 0.04, (2) 0.2, (3) 1.4, (4) 1.8, (5) 0, (6) 4.0 and (7) 6.2(%), respectively. None of them showed signs of cross-reactivity with the liver-type alkaline phosphatase, also one of the alkaline phosphatase isozymes, within a PLAP concentration of 2,000 IU/l. The subtype of 5B9 was IgG1, and that of the others was IgG2a. We then used 7C6, to develop a sensitive, specific and convenient enzyme immunoassay (EIA) for the determination of PLAP, and assayed sera from patients with various gynecologic diseases. The incidence of increased PLAP was 6.4% in patients with benign diseases, 21.5% in cervical cancer, 36.4% in endometrial carcinoma, and 39.5% in malignant ovarian tumors. The specificity for malignant diseases seemed to be higher than that of CA125. Among endometrial carcinomas, well-differentiated adenocarcinoma had the highest incidence of an increased concentration. Among malignant ovarian tumors, serous cystadenocarcinoma, endometrioid carcinoma, dysgerminoma and Krukenberg's tumor showed a higher incidence than the other types.


Rationale and design of the OPTIMAL-REPERFUSION trial: A prospective randomized multi-center clinical trial comparing different fibrinolysis-transfer percutaneous coronary intervention strategies in acute ST-segment elevation myocardial infarction.
Primary percutaneous coronary intervention (PPCI), the preferred reperfusion strategy for all acute ST-segment elevation myocardial infarction (STEMI) patients, is not universally available in clinical practice. Pharmacoinvasive strategy has been proposed as a therapeutic option in patients with STEMI when timely PPCI is not feasible. However, pharmacoinvasive strategy has potential delay between clinical patency and complete myocardial perfusion. The optimal reperfusion strategy for STEMI patients with anticipated PPCI delay according to current practice is uncertain. OPTIMAL-REPERFUSION is an investigator-initiated, prospective, multicenter, randomized, open-label, superiority trial with blinded evaluation of outcomes. A total of 632 STEMI patients presenting within 6 hours after symptom onset and with an expected time of first medical contact to percutaneous coronary intervention (PCI) ≥120 minute will be randomized to a reduced-dose facilitated PCI strategy (reduced-dose fibrinolysis combined with simultaneous transfer for immediate invasive therapy with a time interval between fibrinolysis to PCI < 3 hours) or to standard pharmacoinvasive treatment. The primary endpoint is the composite of death, reinfarction, refractory ischemia, congestive heart failure, or cardiogenic shock at 30-days. Enrollment of the first patient is planned in March 2021. The recruitment is anticipated to last for 12 to 18 months and to complete in September 2023 with 1 year follow-up. The OPTIMAL-REPERFUSION trial will help determine whether reduced-dose facilitated PCI strategy improves clinical outcomes in patients with STEMI and anticipated PPCI delay. This study is registered with the ClinicalTrials.gov (NCT04752345).


Complete subtyping of the HLA-A locus by sequence-specific amplification followed by direct sequencing or single-strand conformation polymorphism analysis.
A variety of reasons related to the HLA class I system has complicated the application of molecular approaches to HLA class I typing. Here we present a PCR-based HLA-A typing strategy considering the sequence variations of the two most polymorphic exons which allows complete subtyping of the HLA-A locus. The method is based on a sequence-specific amplification identifying the serologically defined HLA-A specificities. The PCR products generated by these group-specific primers bear the sequence information necessary for a postamplification specificity step. The primer pairs are located within one exon, either exon 2 or exon 3, which avoids amplification of polymorphic intron sequences allowing subsequent single-strand conformation polymorphism analysis and facilitating direct sequencing. Using this method we investigated 48 cell lines and 153 clinical samples. 23 PCR reactions are performed per individual for the assignment of the serological specificities A1-A80. The reproducibility was 100% in all cell lines and 85 clinical samples typed on two separate occasions. With the exception of 13 out of 231 possible serological combinations all homozygous and heterozygous combinations of A1-A80 can be distinguished by specific amplification patterns. Comparing the PCR based typing results with those of serology in 12% a discrepancy was found. Solid-phase sequencing or SSCP analysis of the group-specific PCR fragments allowed complete subtyping of the HLA-A locus. This strategy can identify all 48 HLA-A alleles based on the sequence variations of the 2nd and 3rd exon. 1128 homozygous and heterozygous allele combinations are possible for the HLA-A locus. Only 4 out of these 1128 allele combinations remained unresolved.


The effect of a structured behavioral intervention on poorly controlled diabetes: a randomized controlled trial.
Although maintaining nearly normal glycemia delays onset and slows progression of diabetes complications, many patients with diabetes and their physicians struggle to achieve glycemic targets. The best methods to support patients as they follow diabetes prescriptions and recommendations are unclear. To test the efficacy of a behavioral diabetes intervention in improving glycemia in long-duration, poorly controlled diabetes, we randomized 222 adults with diabetes (49% type 1) (mean [SD] age, 53 [12] years; mean [SD] disease duration 18 [12] years; mean [SD] hemoglobin A(1c) [HbA(1c)] concentration, 9.0% [1.1%]) to attend (1) a 5-session manual-based, educator-led structured group intervention with cognitive behavioral strategies (structured behavioral arm); (2) an educator-led attention control group education program (group attention control); or (3) unlimited individual nurse and dietitian education sessions for 6 months (individual control). Outcomes were baseline and 3-, 6-, and 12-month postintervention HbA(1c) levels (primary) and frequency of diabetes self-care, 3-day pedometer readings, 24-hour diet recalls, average number of glucose checks, physical fitness, depression, coping style, self-efficacy, and quality of life (secondary). Linear mixed modeling found that all groups showed improved HbA(1c) levels (P < .001). However, the structured behavioral arm showed greater improvements than the group and individual control arms (3-month HbA(1c) concentration changes: -0.8% vs -0.4% and -0.4%, respectively (P = .04 for group × time interaction). Furthermore, participants with type 2 disease showed greater improvement than those with type 1 (P = .04 for type of diabetes × time interaction). Quality of life, glucose monitoring, and frequency of diabetes self-care did not differ by intervention over time. A structured, cognitive behavioral program is more effective than 2 control interventions in improving glycemia in adults with long-duration diabetes. Educators can successfully use modified psychological and behavioral strategies. clinicaltrials.gov Identifier: NCT000142922.


Nasal carriage rate and antibiotic susceptibility pattern of Neisseria meningitidis in healthy Ethiopian children and adolescents: A cross-sectional study.
Community nasal meningococcal carriage rates are high across Africa. Meningococcal infections are major causes of morbidity and mortality in the continent; especially among children and adolescents. This study aimed to determine the prevalence of nasal carriage and antibiotic susceptibilities of meningococcal isolates from healthy Ethiopian children and adolescents. A cross-sectional study was conducted in one of the sub-cities of Addis Ababa, Ethiopia. Nasal swabs were collected and processed for identification, serogrouping and testing susceptibilities for three antibiotics using standard microbiological techniques. Data on epidemiologic risk factors were collected using a structured questionnaire and the magnitude of their association with carriage was assessed using bivariate and multivariate analysis. A total of 240 samples were collected (115 from males and 125 from females). The mean age of study participants was 11.1 years. The prevalence of nasal carriage for Neisseria meningitidis was 20.4% (49/240). Carriage was significantly higher among children living under crowded conditions (OR 1.268; 95% CI: 1.186-1.355; p = 0.006). The predominant serogroups were W135-20/49 isolates (40.8%) and C-12/49 isolates (24.5%) and 83.7% of meningococci were sensitive for Ciprofloxacin. In contrast, isolates showed high resistance to Ceftriaxone (69.4%) while only 4.2% were sensitive for Penicillin. Multi-drug resistance was documented for 14.3% of the isolates. Meningococcal carriage rate was found to be high with higher rates associated with children and adolescents living in crowded living conditions. Predominant isolates were of serogroup W135 and C and the isolates showed marked susceptibility to Ciprofloxacin and resistance to Ceftriaxone and Penicillin.


[Behavior of various spirometry parameters during bronchial provocation tests with D. pteronyssinus in patients with asthma, sensitized to housedust mites].
Changes in particular spirometry parameters during specific bronchial provocation test (BPT) with an allergen in asthmatics sensitized to house dust mites were evaluated. Studies were carried out on 130 patients. Specific BPT with D. pteronyssinus was performed according to the Ryan's method using a jet De Villbiss 646 nebuliser powered by compressed air and connected to the French Rosenthal dosimeter. The spirometry was measured using Pneumoscreen II (Jaeger - Germany). The provocation was terminated when a value of FEV1 fell at least 20% from baseline and then the spirometry parameters were measured hourly for a period 8 hours. Early and late asthmatic responses were founded. Results were expressed as a percentage of the maximum decrease from the baseline in particular parameters. To the statistical calculations only positive sBPT results founded in 96 patients were selected. The mean values of the decreases during of the EAR were as follow: FEV1 = 30.6 +/- 9.9%, FVC = 18.9 +/- 9.9%, FEV/FVC = 14.6 +/- 9.2%, FEV25-27 = 41.5 +/- 15.7%, PEF = 30.8 +/- 15.7%. The correlation coefficients were between FEV1 and FVC -0.57, FEV1 and FEV1/FVC -0.56, FEV1 and FEF25.75 -0.65, FEV1 and PEF -0.6. The results were statistically significant. Decreases in FEV1 and PEF were very similar each other. The greatest changes were observed in FEF25.75. The curves of the FEV1 and PEF averages observed during LAR were quite close to each other and almost parallel. The usefulness of the both parameters seems to be equal.