Synergistic effects of diacylglycerols and fatty acids on membrane structure and protein kinase C activity.
The synergistic effects of diacylglycerol (DAG) and fatty acid (FA) in activating protein kinase C have been investigated by correlating their individual and combined effects on enzymatic activity and on membrane structure in phosphatidylcholine/phosphatidylserine (4:1) lipid mixtures using a combination of specific enzymatic assays and 31P and 2H NMR. Addition of DAGs and unsaturated FAs to the bilayers synergistically increased the tendency of the lipids to form nonbilayer phases with a concomitant increase in PKC activity until a maximum was achieved. Further increases in the DAG/FA concentration led to the formation of the nonbilayer lipid phases under the conditions of the PKC activity assays and correlated with decreased activity. The nonbilayer lipid phases still supported PKC activity, although with less than 50% efficiency as compared with the bilayer lipids. Long-chain saturated FA increased DAG-induced PKC activity by causing a lateral phase separation of gel (Lbeta) and liquid-crystalline (Lalpha) domains. Due to the preferential partitioning of DAGs into liquid-crystalline domains, the local DAG concentration increased in these domains, leading to an increase in PKC activity. Because a wide range of lipophilic compounds is capable of altering curvature stress, and therefore the tendency for nonbilayer phase formation in cellular membranes, these compounds would be expected to modulate PKC activity and the activities of a number of other membrane-associated enzymes that are sensitive to biophysical properties of lipid membranes.


Observation of whispering gallery modes through electron beam-induced deposition.
Surprisingly intense spectra of whispering gallery modes were observed in polymer microbeads after illumination with electrons in a scanning electron microscope and subsequent laser illumination and spectral analysis. It will be proposed that whispering gallery mode resonances became visible after local deposition of hydrocarbon material through electron beam-induced deposition. The illumination of deposited material with a near infrared laser generates a broad light spectrum, acting as a local "white light" source that couples, for favorable wavelengths, with the WGM sustained by the sphere. This facilitates a spectroscopic analysis of the WGM and provides the Q-factor and free spectral range for all investigated particles. The analysis by an integrated SEM and Raman micro-spectrometer offers a direct approach to the analysis of WGM resonators as they are, for instance, used in sensing.


Impact of intravascular enhancement, heart rate, and calcium score on diagnostic accuracy in multislice computed tomography coronary angiography.
To assess the effect of intravascular enhancement, heart rate, and calcium score on diagnostic accuracy in the detection of significant coronary artery stenosis using 16-row multislice computed tomography (MSCT). One hundred patients (88 males; 59+/-11 years) with suspected coronary artery disease who had undergone conventional coronary angiography (CA) and MSCT-CA were retrospectively enrolled for the study. Patients underwent a MSCT-CA, with the following protocol: collimation 16x0.75 mm, gantry rotation time 420 ms, feed/rotation 2.8 mm, kV 120, mAs 400-500. The protocol for contrast material administration was 100 ml of Iodixanol 320 mgI/ml at 4 ml/s and the scan delay was defined with a bolus tracking technique. In all patients vascular enhancement was measured in the aortic root, and in the left and right coronary arteries. The average vascular enhancement was used to divide the population in two groups of 50 patients each, one with lower enhancement (Low), and one with higher enhancement (High). In the two groups diagnostic accuracy (per coronary segment) for the detection of significant stenosis (= or >50% lumen reduction) was evaluated in vessels = or >2 mm in diameter using quantitative CA as the reference standard. The differences in diagnostic accuracy were compared with a Chi-square test and a p<0.05 was considered significant. Of the total 1116 segments (= or >2 mm lumen diameter), 173 presented significant stenosis. The sensitivity and specificity for the assessment of significant stenosis were 89.4% and 93.3% vs 94.3% and 97.4% in the presence of increasing intravascular enhancement, 92.8% and 96.7% vs 91.1% and 93.9% in the presence of increasing heart rate, and 89.7% and 97.6% vs 93.3% and 92,8% in the presence of an increasing calcium score. Increasing intravascular enhancement significantly improves diagnostic accuracy in MSCT-CA. A higher heart rate lowers the specificity in the detection of significant obstructing lesions of the coronary artery. An increasing calcium score determines a lower specificity and a higher sensitivity.


Comparison of Two Formulations of Topical Timolol for the Treatment of Infantile Hemangiomas.
This report compares the efficacy of timolol maleate 0.5% eyedrops (TM) with that of timolol maleate 0.5% ophthalmic gel-forming solution in the treatment of infantile hemangiomas (IHs). Sixty-six patients undergoing treatment with topical timolol were retrospectively reviewed; our results revealed similar therapeutic efficacies for both types of timolol formulations. Early treatment initiation (<3 mos) and superficial lesions correlated with better treatment response. TM eyedrops may be a more cost effective, equally efficacious modality of treatment for IHs.


Prognosis of ocular myasthenia in Korea: a retrospective multicenter analysis of 202 patients.
The aims of this study were to obtain data on the frequency with which Korean patients with autoimmune myasthenia gravis (MG) present solely with ocular disturbances and progress to develop generalized disease and to identify the prognostic factors associated with secondary generalization. We conducted a retrospective multicenter survey in which a total of 376 adult patients who were newly diagnosed with MG from 2000 through 2005 were reviewed for analysis. Patients with ocular MG at the time of symptom presentation (n=202, 53.7%) were divided into two subgroups according to their prognosis: the patients whose disease remained ocular throughout the follow-ups were placed in the OMG-R group, and the patients who progressed to develop generalized disease were placed in the OMG-G group. Clinical characteristics and laboratory findings were compared between the two subgroups. Secondary generalization developed in 47 (23.3%) of the 202 study subjects, mostly within the first 6 months after symptom presentation, while the disease remained ocular throughout the follow-up duration (median 11.8 months) in the remaining 155 patients (76.7%). AChR antibody, abnormal repetitive nerve stimulation tests (RNST) and thymoma were more frequently observed in the patients in the OMG-G group than in those in the OMG-R group (p<0.01 in all). In seropositive cases, the titers of AChR antibody were also significantly higher in the OMG-G group than in the OMG-R group (median, 3.8 nM vs. 6.4 nM; p<0.05). Cox proportional hazards regression analyses showed that early oral prednisolone treatment significantly reduced the risk of secondary generalization (HR, 0.24; 95% CI, 0.11-0.56), whereas abnormal AChR antibody (HR, 5.34; 95% CI, 1.60-17.8) and thymoma (HR, 2.32; 95% CI, 1.21-4.45) were predictive of the development of secondary generalization. Our findings suggest that several factors, including the AChR antibody, thymoma, early corticosteroid treatment, and possibly latent neuromuscular abnormality revealed by RNST, may have an impact on the risk of developing generalized disease in Korean patients presenting with ocular myasthenia.


Characteristics and Validation Techniques for PCA-Based Gene-Expression Signatures.
Background. Many gene-expression signatures exist for describing the biological state of profiled tumors. Principal Component Analysis (PCA) can be used to summarize a gene signature into a single score. Our hypothesis is that gene signatures can be validated when applied to new datasets, using inherent properties of PCA. Results. This validation is based on four key concepts. Coherence: elements of a gene signature should be correlated beyond chance. the general direction of the data being examined can drive most of the observed signal. Robustness: if a gene signature is designed to measure a single biological effect, then this signal should be sufficiently strong and distinct compared to other signals within the signature. Transferability: the derived PCA gene signature score should describe the same biology in the target dataset as it does in the training dataset. Conclusions. The proposed validation procedure ensures that PCA-based gene signatures perform as expected when applied to datasets other than those that the signatures were trained upon. Complex signatures, describing multiple independent biological components, are also easily identified.


Contribution of Streptococcus anginosus to infections caused by groups C and G streptococci, southern India.
Vellore, a region in southern India, has a high incidence of severe human infections with Beta-hemolytic group C and G streptococci (GCGS). To determine the causative species in these infections, we conducted 16S rRNA gene sequencing: Streptococcus dysgalactiae subsp. equisimilis (81%) and S. anginosus (19%) were the causative organisms in the 2-year study period (2006-2007). We used PCR to detect the virulence-related emm gene; results showed that it was restricted to S. dysgalactieae subsp. equisimilis isolates of 99.2% tested positive. Due to a novel marker, S. anginosus and S. constellatus can be quickly and accurately distinguished from other members of the genus. The notable contribution of the anginosus group to human infections suggests that this group of obligate pathogens deserves more attention in healthcare and research.


A retrospective review of congenital pseudarthrosis of the tibia.
Thirty-three children with congenital pseudarthrosis of the tibia seen from 1970 to 1997 at the Shriners Hospitals for Children in Lexington, KY were retrospectively reviewed. Twelve children were excluded due to follow-up of less than 2 years. Data was collected on age, sex, side and associated neurofibromatosis from the medical records of the remaining 21 children. Lesions were classified as to status at birth. The number of surgical attempts for union was recorded. Presence of bony union, deformity, and limb length discrepancy was noted. The mean age at last follow-up was 13 years. Union was reported in 10 children (48%). There was no union after more than 3 surgical attempts. The 11 children without union had an average of 4 surgical attempts (range 2-6). Amputation was performed in 7 of the 11 children without union. No predictor for nonunion was identified. Amputation was frequently needed.


Effectiveness of a modified Mother-Infant Transaction Program on outcomes for preterm infants from 3 to 24 months of age.
Mothers of hospitalised preterm infants were randomised into an intervention or control condition. Intervention mothers received a modified Mother-Infant Transaction Program over seven sessions prior to infant discharge and two sessions over the next 3 months. Infant temperament, mother-infant interaction and parenting stress were assessed at 3 and 6 months and infant development was measured by parental report at 24 months. Intervention compared with control dyads showed enhanced mother-infant interactions, infants were temperamentally more "approaching" and "easier", had fewer regulatory problems (colic, sleep, excessive crying), and had more developed communication skills, while mothers were less stressed by their infant at 3 months. These early gains in the development of preterm infants and in the relationship with and adjustment of their mothers, may explain the process by which intervention infants in the original study showed increasing cognitive advantages to 9 years of age [Rauh, V. A., Nurcombe, B., Achenbach, T., & Howell, C. (1990). The mother-infant transaction program. Clinical Perinatology, 17, 31-45].


Sulbactam/ampicillin, a new beta-lactamase inhibitor/beta-lactam antibiotic combination.
Sulbactam/ampicillin is a combination of a beta-lactamase inhibitor with minimal intrinsic antibacterial activity (sulbactam sodium), and an aminopenicillin (ampicillin sodium). The addition of sulbactam to ampicillin has no effect on the chemical stability of ampicillin in aqueous solution, and the administration guidelines of the combination are the same as for ampicillin alone. Sulbactam acts primarily by irreversible inactivation of beta-lactamases from most beta-lactamase-producing organisms. The pharmacokinetics of sulbactam are similar to those of ampicillin with an elimination half-life of about one hour in most patients. One difference is that serum and tissue concentrations of sulbactam are usually twice those of ampicillin, at equivalent doses. The sulbactam/ampicillin combination has been approved for the treatment of adults with intraabdominal, skin and skin structure, and gynecological infections due to beta-lactamase-producing bacteria such as Staphylococcus aureus, Escherichia coli, and species of Klebsiella and Bacteroides. Clinical studies to date have also shown the combination to be effective for the treatment of meningitis, pneumonia, gonorrhea, epiglottis, urinary tract infections, cervical adenitis, and as prophylaxis for abdominal and gynecological surgeries. Many of these studies, however, have included small numbers of patients and/or had design flaws. Adverse effects have been minor with most being attributed to the ampicillin component. Sulbactam/ampicillin compares favorably with other antibiotic regimens in terms of acquisition costs and ease of administration.


Model for the growth of electrodeposited ferromagnetic aggregates under an in-plane magnetic field.
The quasi-two-dimensional deposition of ferromagnetic materials by electrochemical process under the influence of a magnetic field applied in the plane of the growth leads to a surprising symmetry breaking in the dendritic structures found. The reasons for these features are still not completely understood. The original dense circular envelope becomes rectangular, as well as the sparse figures have their shapes elongated. This paper reports the results of a diffusion-limited aggregation (DLA) -like simulation. The model proposed here, a modification of the original DLA model, can deal with ferromagnetic particles under the influence of an electric field and the dipolar interactions between particles, submitted to an applied magnetic field in the plane of growth of such structures. The results were produced varying the applied magnetic field and the magnetic moment of the particles and show that the balance between these interactions is an important mechanisms that can be responsible for the changes in shape of the aggregates observed in the experiments.


Stability of dobutamine hydrochloride and verapamil hydrochloride in 0.9% sodium chloride and 5% dextrose injections.
The stability of dobutamine hydrochloride (250 micrograms/ml) and verapamil hydrochloride (160 micrograms/ml) alone and in combination in 0.9% sodium chloride injection or 5% dextrose injection was studied. Solutions were stored both in plastic i.v. bags and in amber-colored glass bottles at 24 degrees C and 5 degrees C for up to seven days. Before storage and at various times during storage, solutions were assayed at least in triplicate by high-performance liquid chromatography, pH was recorded, and visual appearance was noted. All solutions tested under all conditions retained at least 90% potency for seven days. In plastic i.v. bags, dobutamine either alone or in combination with verapamil in both diluents turned a light-pink color in 24 hours at 24 degrees C. The intensity of the pink color increased with time in 0.9% sodium chloride injection; in 5% dextrose injection, solutions, became clear in 48 hours. The pH of solutions prepared in plastic i.v. bags in 5% dextrose injection decreased from 4.0 to 3.1 during the seven-day period at 24 degrees C; results for solutions in amber bottles were similar. At 5 degrees C, the pH and clarity of all solutions in bags and bottles remained stable for seven days. At the concentrations tested, dobutamine hydrochloride combined with verapamil hydrochloride is stable in 0.9% sodium chloride injection and 5% dextrose injection for 48 hours at 24 degrees C and for seven days at 5 degrees C.


Self-assembled block copolymer thin films as water filtration membranes.
Nanoporous membranes containing monodisperse pores of 24 nm diameter are fabricated using poly(styrene-b-lactide) block copolymers to template the pore structure. A 4 mum thin film of the block copolymer is cast onto a microporous membrane that provides mechanical reinforcement; by casting the copolymer film from the appropriate solvents and controlling the solvent evaporation rate, greater than 100 cm(2) of a thin film with polylactide cylinders oriented perpendicular to the thin dimension is produced. Exposing the composite membrane to a dilute aqueous base selectively etches the polylactide block, producing the porous structure. The ability of these pores to reject dissolved poly(ethylene oxide) molecules of varying molecular weight matches existing theories for transport through small pores.


[Development of human resources and the Plan of Action].
This article (whose first part was published in the previous issue of Educación Médica y Salud) concludes an exhaustive review of manpower development in the Americas. This part considers the specific measures in this field enunciated in the Plan of Action; these measures pertain to four main areas: planning and programming of human resources, training in priority areas, utilization of human resources, and educational technology. The author discusses the present and future possibilities and obstacles of each of these activities and the steps to be taken to bring needs into line with real situations. It is of paramount importance that the national health authorities clearly spell out their policies for the development of human resources in the health field within the framework of general development policies. Another point to be insisted upon is the multiprofessional and multidisciplinary training of the health team and the importance of the education-service-supervision function, which usually results in permanent and continuing education, which in turn optimizes the utilization of personnel. However, none of this will be possible without an appropriate education technology with which to innovate, analyze and refine the entire education process and so meet the needs of both society and the health services.


Treatment of hydrofluoric acid burns.
Hydrofluoric acid injuries have a potential for both systemic as well as severe local tissue destruction. In this article the different treatment modalities will be presented. Hydrofluoric acid is frequently found in the semiconductor industry, in rust removers and façade cleansers. The negligence or carelessness of workers and ignorance of the risks of hydrofluoric acid promote the incidence of these severe burns. To prevent these burns, adequate information for the workers is necessary. Splash goggles and neoprene gloves as well as laboratory coats should be worn at all times to prevent eye and skin contact. In cases of exposure, therapy should be accurate and immediate.


Family Characteristics and Structure as Determinants of Sexual Abuse Among Female Secondary School Students in Nigeria: A Brief Report.
Child sexual abuse is associated with factors that enhance the vulnerability of the child, raising physical and mental health complications in adulthood. Three hundred and fifty students participated in this cross-sectional study. Important determinants of sexual abuse were parents not living together, not living with parents, family type, and current parents' marital status (p < 0.05). Respondents living with both parents were two times less likely to experience sexual abuse (OR = 0.5, CI: 0.3, 0.9) than respondents living with their guardians. Respondents whose parents were living together were about two times less likely to experience sexual abuse (OR = 0.6, CI: 0.3-0.9) than respondents whose parents were not living together. Respondents whose parents were either divorced or separated were about six times more likely to experience sexual abuse (OR = 5.6, CI: 1.1-27.2) than respondents with widowed parents. The study showed that parental togetherness protected against child vulnerability and risk of being sexually abused.


Type 2 diabetes is associated with a worse functional outcome of ischemic stroke.
To assess whether ischemic stroke severity and outcome is more adverse in patients with type 2 diabetes mellitus (T2DM). Consecutive patients hospitalized for acute ischemic stroke between September 2010 and June 2013 were studied prospectively (n = 482; 40.2% males, age 78.8 ± 6.7 years). T2DM was defined as self-reported T2DM or antidiabetic treatment. Stroke severity was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score at admission. The outcome was assessed with the modified Rankin scale (mRS) score at discharge and with in-hospital mortality. Adverse outcome was defined as mRS score at discharge ≥ 2 or in-hospital death. The length of hospitalization was also recorded. T2DM was present in 32.2% of the study population. Patients with T2DM had a larger waist circumference, higher serum triglyceride and glucose levels and lower serum high-density lipoprotein cholesterol levels as well as higher prevalence of hypertension, coronary heart disease and congestive heart failure than patients without T2DM. On the other hand, diabetic patients had lower low-density lipoprotein cholesterol levels and reported smaller consumption of alcohol than non-diabetic patients. At admission, the NIHSS score did not differ between patients with and without T2DM (8.7 ± 8.8 and 8.6 ± 9.2, respectively; P = NS). At discharge, the mRS score also did not differ between the two groups (2.7 ± 2.1 and 2.7 ± 2.2 in patients with and without T2DM, respectively; P = NS). Rates of adverse outcome were also similar in patients with and without T2DM (62.3% and 58.5%, respectively; P = NS). However, when we adjusted for the differences between patients with T2DM and those without T2DM in cardiovascular risk factors, T2DM was independently associated with adverse outcome [relative risk (RR) = 2.39; 95%CI: 1.21-4.72, P = 0.012]. In-hospital mortality rates did not differ between patients with T2DM and those without T2DM (9.0% and 9.8%, respectively; P = NS). In multivariate analysis adjusting for the difference in cardiovascular risk factors between the two groups, T2DM was again not associated with in-hospital death. T2DM does not appear to affect ischemic stroke severity but is independently associated with a worse functional outcome at discharge.


Ecologically benign polymers: the case of maleic polyelectrolytes.
The paper discusses a series of results that evidence the favorable effect of maleic polyelectrolytes in different fields in which a protective action of the environment is attained: (i) the exploitation of geothermal water, which is a cleaner source of energy; (ii) the improvement or preservation of the structure of agricultural soils; (iii) the substitution of phosphates in detergents; and (iv) the reduction of chromium load of effluents from tanning plants.


[Gamma-aminobutyric acid--metabolism and its disorders].
Gamma-aminobutyric acid is a major inhibitory neurotransmitter in the central nervous system. GABA metabolism is dependent on the activity of three enzymes: glutamic acid decarboxylase, GABA-transaminase and succinic semialdehyde dehydrogenase. Decreased activity of these enzymes may cause many neurological syndromes, such as stiff-person syndrome, chronic fatigue syndrome, anxiety disorders and seizures. This article is a review of most important problems related to an impairment of GABA metabolism.


Antibiotic resistance in Enterococcus faecium clinical isolates.
The worldwide ratio of Enterococcus faecalis-Enterococcus faecium infections is currently changing in favor of E. faecium. Intrinsic and acquired antimicrobial resistance traits of this latter species can explain this evolution as well as the diffusion of hospital-adapted strains belonging to the clonal complex CC17. Like other enterococci, E. faecium is naturally resistant to cephalosporins and aminoglycosides (at low level). Because of its high genome plasticity, it can also acquire numerous other resistances. It is noteworthy that most modern isolates of E. faecium are highly resistant to ampicillin while a non-negligible proportion of them (depending on geographical locations) are resistant to glycopeptides (especially in the USA). Even if resistance to newer antimicrobial agents (linezolid, daptomycin, tigecycline) is still uncommon, some clinical isolates with reduced susceptibility or resistance have already been reported and better understanding of resistance mechanisms is needed for prediction and prevention of their dissemination.


Altered Function and Expression of ABC Transporters at the Blood-Brain Barrier and Increased Brain Distribution of Phenobarbital in Acute Liver Failure Mice.
This study investigated alterations in the function and expression of P-glycoprotein (P-GP), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) at the blood-brain barrier (BBB) of acute liver failure (ALF) mice and its clinical significance. ALF mice were developed using intraperitoneal injection of thioacetamide. P-GP, BCRP, and MRP2 functions were determined by measuring the ratios of brain-to-plasma concentration of rhodamine 123, prazosin, and dinitrophenyl-S-glutathione, respectively. The mRNA and proteins expression levels of P-GP, BCRP, and MRP2 were evaluated with quantitative real-time PCR and western blot, respectively. MDCK-MDR1 and HCMEC/D3 cells were used to document the effects of the abnormally altered components in serum of ALF mice on the function and expression of P-GP. The clinical significance of alteration in P-GP function and expression was investigated by determining the distribution of the P-GP substrate phenobarbital (60 mg/kg, intravenous administration) in the brain and loss of righting reflex (LORR) induced by the drug (100 mg/kg). The results showed that ALF significantly downregulated the function and expression of both P-GP and BCRP, but increased the function and expression of MRP2 in the brain of mice. Cell study showed that increased chenodeoxycholic acid may be a reason behind the downregulated P-GP function and expression. Compared with control mice, ALF mice showed a significantly higher brain concentration of phenobarbital and higher brain-to-plasma concentration ratios. In accordance, ALF mice showed a significantly larger duration of LORR and shorter latency time of LORR by phenobarbital, inferring the enhanced pharmacological effect of phenobarbital on the central nervous system (CNS). In conclusion, the function and expression of P-GP and BCRP decreased, while the function and expression of MRP2 increased in the brain of ALF mice. The attenuated function and expression of P-GP at the BBB might enhance phenobarbital distribution in the brain and increase phenobarbital efficacy on the CNS of ALF mice.


[The significance of spontaneous variability in ventricular extrasystole in the evaluation of the effectiveness of therapy of ventricular extrasystole].
In a mixed population of 104 ambulatory patients the authors assessed, based on 24-hour Holter monitoring, the spontaneous variability of ventricular extrasystoles within one-, two-, three-, four-, six-, eight- and twelve-hour intervals. As significant they evaluated a decline of the frequency of ventricular extrasystoles by more than 90% during the subsequent period of time. The magnitude of variability is influenced substantially more by the frequency of extrasystoles than by the period of monitoring. This fact is not generally accepted so far, although it was already described in 1978. It is probable that this fact participates in a significant way in the difference of values of spontaneous variability reported by different departments.


Physiologic and pharmacologic alterations of rat leukocyte chemotaxis (Cx) in vivo.
The method of adoptively transferring 51Cr-labeled rat leukocytes iv to isologous recipients was used to quantitate the extravascular accumulation of specific cell types at the site of inflammation induced by local injection of various phlogistic agents. Experiments were designed to determine whether cellular accumulation could be modified at the level of the chemotactic factor, by serum components, or by alteration of the responding cell itself. The results indicated a selective attraction of mononuclear cells to the local injection site of BCG and of neutrophils to the injection site of aggregated but not monometric gamma-globulin. Thus, leukocytic accumulation was found to be dependent upon the local generation of specific reactants that were particular to the agent employed. Leukocytic accumulation could also be modified by serum factors. Cellular accumulation was inhibited when leukocytes were exposed to serum that contained phagocytosable particles or after phagocytosis in vitro prior to adoptive transfer. Chemotaxis of lymphocytes could be induced by their preincubation with sera from adjuvant arthritic animals. These observations were confirmed by in vitro studies and by the finding that 6 days after adjuvant injection , lymphocytes but not mononuclear cells accumulated at the noninjected extremity. In the final series of experiments, it was shown that BCG immunization was capable of inducing a unique population of peritoneal mononuclear cells that after adoptive transfer had an enhanced capacity to remain in the circulation, which, in turn, resulted in a functional increase in their accumulation at an inflammatory reaction site. In conclusion, these studies indicated that the chemotactic activity of adoptively transferred cells can be modified by changes in the chemotactic stimuli, can be enhanced or depressed by serum factors, and is a function of the physiologic capability of the cell population employed.


Alternative polyadenylation results in a truncated daf-4 BMP receptor that antagonizes DAF-7-mediated development in Caenorhabditis elegans.
The DAF-4 receptor kinase, which promotes larval development, is encoded by a 2.9 kb mRNA transcribed from the only type II TGF-beta/BMP receptor gene in Caenorhabditis elegans. Here we report that alternative polyadenylation in intron 5 of daf-4 results in a 2.0 kb mRNA that encodes an open reading frame including only the N-terminal secretion signal and ligand-binding domains, and not the transmembrane or kinase domains, of DAF-4. Northern blots and real-time RT-PCR amplifications using RNA samples from developmentally staged animals show that expression levels of both the 2.9 kb and 2.0 kb transcripts are relatively constant, and their abundances similar, except for the transition between non-dauer and dauer stages. In dauer larvae, the steady-state level of the 2.0 kb mRNA increases more than 10-fold and exceeds the 2.9 kb transcript, coincident with an absence of signaling from DAF-4. Transgenic expression of a recombinant daf-4 transgene that encodes only the 2.0 kb mRNA enhances the Daf-c phenotype of a daf-4 hypomorph, whereas the same transgene with a nonsense mutation does not. These data suggest that a polypeptide encoded by the 2.0 kb transcript can function as an antagonist of full-length DAF-4 signaling. Alternative processing of type II receptor transcripts to generate an antagonist is a novel mechanism for negative regulation of a TGF-beta signaling pathway.


Use of the Multiple Errands Test-Simplified Version in the assessment of suboptimal effort.
Most measures of suboptimal effort focus on short-term learning; fewer studies have considered non-memory feigned cognitive impairment. This study investigated the utility of the Multiple Errands Test - Simplified Version (MET-SV) in the detection of feigned executive functioning impairment. Performance of simulating malingerers (N = 47) was compared to acquired brain injury (N = 46) and neurologically healthy control groups (N = 50). Although simulating malingerers were successful at feigning a realistic level of impairment compared to the brain injury group, there were significant differences regarding pattern of performance. A logistic regression model successfully classified 84% of simulating malingerers and 74.5% of brain injured individuals. Receiver Operating Characteristic (ROC) analysis supported the discriminatory power of the model. The current study is unique in yielding some understanding of the real-life observation of suspected malingerers compared to individuals with genuine cognitive difficulties. Results suggest the MET-SV can contribute to the clinical assessment of individuals suspected of suboptimal effort in the domain of executive functioning. Further research is needed to establish whether the MET-SV can be reliably used in medico-legal settings.


Stable Longitudinal Performance of Adult Cochlear Implant Users for More Than 10 Years.
To analyze the long-term performance of cochlear implant patients. Retrospective longitudinal study. Tertiary referral center with a large cochlear implant program. Speech perception scores in quiet and in background noise in the short-term (1.12 ± 0.15 yr) and long-term (12.61 ± 2.34 yr) after implantation. Fifty-eight implanted ears from 55 patients with a mean age of 51.80 ± 1.757 years at the time of implantation were included. Speech perception scores were stable in the long-term for up to 20 years postimplantation. When alteration of speech perception over time was investigated in relation to the age at implantation, there was a deterioration of the scores in quiet in older patients (>60 years old at the time of surgery). In addition the speech comprehension in noise was negatively correlated with the age at the time of the test. The speech perception abilities of cochlear implant users are stable in the long-term and at the most may be affected by the age of the patients, as it is known from acoustic hearing.


Transplanted adult spinal cord-derived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury.
We examined the effect of spinal cord-derived neural stem/progenitor cells (NSPCs) after delayed transplantation into the injured adult rat spinal cord with or without earlier transplantation of bone marrow-derived mesenchymal stromal cells (BMSCs). Either BMSCs or culture medium were transplanted immediately after clip compression injury (27 g force), and then, 9 days after injury, NSPCs or culture medium were transplanted. Cell survival and differentiation, functional recovery, retrograde axonal tracing, and immunoelectron microscopy were assessed. A significant improvement in functional recovery based on three different measures was seen only in the group receiving NSPCs without BMSCs, and the improved recovery was evident within 1 week of transplantation. In this group, NSPCs differentiated mainly into oligodendrocytes and astrocytes, there was ensheathing of axons at the injury site by transplanted NSPCs, an increase in host oligodendrocytes, and a trend toward an increase in retrogradely labeled supraspinal nuclei. Transplantation of the BMSC scaffold resulted in a trend toward improved survival of the NSPCs, but there was no increase in function. Thus, transplantation of adult rat NSPCs produced significant early functional improvement after spinal cord injury, suggesting an early neuroprotective action associated with oligodendrocyte survival and axonal ensheathment by transplanted NSPCs.


Glycosidase-induced fusion of isoprenoid gentiobiosyl lipid membranes at acidic pH.
A difficulty in explaining the mechanism whereby archaeal lipid membrane vesicles (archaeosomes) deliver entrapped protein antigens to the MHC class I cytosolic pathway from phagolysosomes of antigen-presenting cells has been the observation that they tend not to fuse. Here, we determine that archaeosomes, composed of archaeal isoprenoid mixtures of glyco and phospholipids, can be highly fusogenic when exposed to the pH and enzymes found in late phagolysosomes. Fusions were strictly dependent on acidic pH and the presence of alpha- or beta-glucosidase. Resonance energy transfer (RET) assays demonstrated that fusion conditions induced lipid mixing of archaeosome lipids with self-unlabeled archaeosomes. Because PC/PG/cholesterol liposomes by themselves did not fuse, it was possible to unequivocally show a fusion of rhodamine-labeled liposomes with archaeosomes by fluorescence microscopy and to demonstrate lipid mixing between labeled liposomes and archaeosomes by the RET assay. Radiotracer and (1)H NMR studies revealed that glycolipids in fused archaeosomes were not degraded significantly by glucosidase treatment during fusion. Rather, the glucosidases dramatically induced small archaeosomes to rapidly and visually aggregate at pH 4.8, but not 6.8, thus bringing membranes together appropriately as a first step in the fusion process. (1)H NMR was used to demonstrate that conditions causing aggregation correlated with binding of glucosidase to the archaeosomes. Binding at acidic pH occurred by the electrostatic interaction of positively charged glucosidase with the anionic phospholipids, although the interaction also occurred with the gentiobiosyl lipids. The data indicate a mechanism of membrane-membrane fusion for archaeal glycolipid membranes induced by glycosidase and illustrate the importance for inclusion of glycolipids in compositions of vesicles designed to deliver protein antigens to the cytosol for MHC class I presentation.


Impact of breeding region and season on the content of some trace elements and heavy metals in the hair of cows.
The aim of the research was to determine the effect of the season and the breeding region on the content of selected minerals (Zn, Cu, Mn, Fe, Pb, Cd) in the hair of dairy cows. The research material covered 114 Holstein-Friesian breed cows from three breeding centres in Poland, hereafterreferred to as A, B and C. Breeding centre A is located in Opolskie province, breeding centre B in Podlaskie province and breeding centre C in Kujawsko-Pomorskie province. The cows were kept in freestanding cowsheds with den boxes. Animal nutrition involved the use of the TMR system, considering division into nutrition groups. Hair was sampled in summer and in the period of winter and spring from the side of the body, directly behind the coastal arch. The Zn, Cu, Mn, Fe analysis was performed with atomic absorption spectrometry. The Pb and Cd content was assayed with the use of the electrothermal atomic absorption spectrometry. The results demonstrated the effect of season and breeding region on the level of the minerals and heavy metals assayed in the hair of cows being in the period of drying-off. The hair sampled in winter from cows from C demonstrated a higher concentration of most elements except for Fe than in material derived in summer. Hair sampled in winter from cows from the B centre showed higher Zn, Cu and Pb concentrations as compared with summer. Higher Cu, Mn, Fe and Pb concentrations were determined in hair sampled during winter from cows from A than in the material obtained in summer. The Cd content in the cow hair did not exceed the admissible norm, however, normal levels were exceeded for Pb in hair sampled in winter from cows from breeding centre C.


Delayed afterdepolarisations and triggered activity in canine Purkinje fibres treated with neuraminidase.
We investigated the electrophysiological alterations induced by the removal of sialic acid from the sarcolemma in canine Purkinje fibres. About 70% of total sialic acid content of Purkinje fibres was removed by 120 min of exposure to neuraminidase (1 U X ml-1). The treatment with neuraminidase did not change any of the action potential characteristics at normal Ca2+ concentration (2.7 mmol X litre-1). However, action potential duration and maximum upstroke velocity of phase zero of the action potential were reduced to a greater degree in neuraminidase-treated Purkinje fibres than in non-treated controls at high Ca2+ concentration (8.1 mmol X litre-1). At high Ca2+ concentration, delayed afterdepolarisations were induced in five out of nine neuraminidase-treated Purkinje fibres and triggered activity was observed in two, when driven in trains of 20 stimuli of different cycle length (1000 to 180 ms). No discernible delayed afterdepolarisations were observed in nine non-treated control Purkinje fibres. In addition, the amplitude of delayed afterdepolarisations induced by ouabain (0.2 mumol X litre-1) in neuraminidase-treated Purkinje fibres was larger than non-treated controls. These findings suggest that sialic acid residues of glycocalyx function as a kind of barrier to Ca2+ influx.


The influence of aerobic fitness on cerebral white matter integrity and cognitive function in older adults: results of a one-year exercise intervention.
Cerebral white matter (WM) degeneration occurs with increasing age and is associated with declining cognitive function. Research has shown that cardiorespiratory fitness and exercise are effective as protective, even restorative, agents against cognitive and neurobiological impairments in older adults. In this study, we investigated whether the beneficial impact of aerobic fitness would extend to WM integrity in the context of a one-year exercise intervention. Further, we examined the pattern of diffusivity changes to better understand the underlying biological mechanisms. Finally, we assessed whether training-induced changes in WM integrity would be associated with improvements in cognitive performance independent of aerobic fitness gains. Results showed that aerobic fitness training did not affect group-level change in WM integrity, executive function, or short-term memory, but that greater aerobic fitness derived from the walking program was associated with greater change in WM integrity in the frontal and temporal lobes, and greater improvement in short-term memory. Increases in WM integrity, however, were not associated with short-term memory improvement, independent of fitness improvements. Therefore, while not all findings are consistent with previous research, we provide novel evidence for correlated change in training-induced aerobic fitness, WM integrity, and cognition among healthy older adults.


Inosiplex therapy in subacute sclerosing panencephalitis. A multicentre, non-randomised study in 98 patients.
Inosiplex was administered to 98 patients with subacute sclerosing panencephalitis (SSPE) in the United States and Canada for variable periods of time up to 9.5 years. Survival data from these 98 patients were compared by life-table analysis with survival in three SSPE control groups drawn from SSPE patients contracting the disease in Israel, Lebanon, or the United States at about the same time as the inosiplex-treated patients but treated differently or not at all. In the inosiplex-treated patients the actuarial probability of survival at 2, 4, 6, and 8 years from onset of SSPE was 78%, 69%, 65%, and 61%, compared with 38%, 20%, 14%, and 8% in a composite control group (p less than 0.01 for all four comparisons). Statistical adjustments for time-to-treatment bias did not affect this result: a modified logrank procedure demonstrated that the risk of dying in the treatment group was 43% of that in the controls. Inosiplex seems to be able to prolong life in patients with SSPE.


Multiple Methods of Dentin Translucency for Age Estimation.
Age estimation is an essential part of forensic odontology and many methods are available with variable accuracy. However, the research is going on to find the simple and most reliable method. By measuring the length and area of root dentin translucency in extracted tooth specimens manually and digitally, and comparing them, this study aims to find the most reliable technique of age assessment. One-hundred and twenty-five single-rooted extracted human permanent teeth were selected for the study. In both unsectioned and sectioned teeth, the total length of root dentin translucency was manually measured using a digital vernier caliper. Then, in a ground-sectioned tooth specimen, the total length and area of root dentin translucency were measured digitally using a scanner scale and computer software. Both the methods were compared. In both manual and digital approaches, the length and area of root dentin translucency grew with age, from younger to older age groups. On comparing the measurements, the correlation coefficient was somewhat higher for digital area measurements than other measurements (r = 0.985). The digital technique outperforms the traditional way for calculating age, and furthermore, measuring the area in the digital method for age estimation has shown to be more accurate.


Anti-inflammatory effects of praseodymium, gadolinium and ytterbium chlorides.
Anti-inflammatory effects of chloride salts of praseodymium, gadolinium and ytterbium were investigated, using various experimental inflammatory models in rats. The lanthanide salts administered by oral route showed no significant effect, but when injected intraperitoneally they significantly inhibited the carrageenin-induced oedema, proportional to their doses ranging from 15 to 75 mg/kg. They also reduced nystatin-induced oedema and vascular permeability response to histamine and serotonin. Pronounced inhibitory effect of lanthanide salts at the dose of 50 mg/kg, i.p., was observed in histamine- and serotonin-induced changes in vascular permeability. Repeated administration of lanthanide salts in the dose of 20 mg/kg for 13 d significantly inhibited arthritis development. The same dose of these salts for a 6-d period similarly reduced granuloma formation. However, praseodymium, gadolinium and ytterbium chlorides showed no significant difference among themselves and their anti-inflammatory effects were smaller than those from phenylbutazone.


An intent-to-treat method for enhancing analysis of clinical trials with rescue medication: a mixed-model approach.
An intent-to-treat (IT) analysis includes all observed data, even those obtained after the primary treatment assignment is changed or rescue treatment is substituted. The so-called "pragmatic" approach accounts for this type of treatment change or rescue treatment. The advantage of the pragmatic approach to IT analysis is that the timing and duration of the rescue treatment can be included in the analysis with mixed-effect modeling, which estimates the difference between the randomized treatment arms while adjusting for the use (timing and duration) of the subsequent treatment. We illustrate the inclusion of information on rescue treatment timing and duration in the analysis of a two-arm randomized clinical trial comparing antidepressant medications in an elderly depressed population. In this study, the randomized treatments are found to be similar. This enhanced analysis, where information about rescue treatment is implicitly added in the model, corroborates our previous two-piece spline analysis, where information about rescue treatment was not included. In addition, a significant drug by rescue interaction indicates a differential effect of the timing of rescue treatment between the two treatments. This analytic approach illustrates the importance of collecting and incorporating data after rescue, including the timing of rescue.


[Postoperative regression of desmoplastic infantile astrocytoma].
Desmoplastic infantile astrocytoma/ganglioglioma (DIA/DIG) is a rare tumor that is usually located superficially with a large cystic component. Gross total removal results in long-term survival in the majority of cases. In rare cases, postoperative regression of the residual tumor has been reported. We report another case of postoperative regression of DIA. A 3-month-old boy presented with increasing head circumference and developmental delay. A CT scan showed a large cystic tumor in his left parieto-occipital lobe. He underwent partial removal. The histopathological examination revealed an astrocytic tumor with marked desmoplasia. In the central portion of the tumor, anaplastic features, such as necrosis, mitosis, and high nucleus-cytoplasmic ratio, were noticed. Diagnosis was DIA. Six months later when he was admitted for the second-stage surgery, MRI showed regression of the tumor. The operation was therefore postponed and MRI at 12 months after surgery revealed further regression. This is the fifth case of postoperative or spontaneous regression of DIA/DIG.


Quantitative Palynology Informing Conservation Ecology in the Bohemian/Bavarian Forests of Central Europe.
In 1927, the first pollen diagram was published from the Bohemian/Bavarian Forest region of Central Europe, providing one of the first qualitative views of the long-term vegetation development in the region. Since then significant methodological advances in quantitative approaches such as pollen influx and pollen-based vegetation models (e.g., Landscape Reconstruction Algorithm, LRA) have contributed to enhance our understanding of temporal and spatial ecology. These types of quantitative reconstructions are fundamental for conservation and restoration ecology because they provide long-term perspectives on ecosystem functioning. In the Bohemian/Bavarian Forests, forest managers have a goal to restore the original forest composition at mid-elevation forests, yet they rely on natural potential vegetation maps that do not take into account long-term vegetation dynamics. Here we reconstruct the Holocene history of forest composition and discuss the implications the LRA has for regional forest management and conservation. Two newly analyzed pollen records from Prášilské jezero and Rachelsee were compared to 10 regional peat bogs/mires and two other regional lakes to reconstruct total land-cover abundance at both the regional- and local-scales. The results demonstrate that spruce has been the dominant canopy cover across the region for the past 9,000 years at both high- (>900 m) and mid-elevations (>700-900 m). At the regional-scale inferred from lake records, spruce has comprised an average of ~50% of the total forest canopy; whereas at the more local-scale at mid-elevations, spruce formed ~59%. Beech established ~6,000 cal. years BP while fir established later around 5,500 cal. years BP. Beech and fir growing at mid-elevations reached a maximum land-cover abundance of 24% and 13% roughly 1,000 years ago. Over the past 500 years spruce has comprised ~47% land-cover, while beech and fir comprised ~8% and <5% at mid-elevations. This approach argues for the "natural" development of spruce and fir locally in zones where the paleoecology indicates the persistence of these species for millennia. Contrasting local and regional reconstructions of forest canopy cover points to a patchwork mosaic with local variability in the dominant taxa. Incorporation of paleoecological data in dialogues about biodiversity and ecosystem management is an approach that has wider utility.


The complexity of evaluating and increasing adherence in inflammatory bowel disease.
Inflammatory bowel diseases (IBDs), due to their chronic and progressive nature, require lifelong treatment to relief and/or prevent inflammation and symptoms, obtaining mucosal healing at best. Therefore, adherence to treatment is an essential topic to address when treating patients with IBD. Nonetheless, adherence remains a common and complex issue in IBD care. Patient characteristics such as young age, male sex and employment has previously been verified as possible predictors of non-adherence. Additionally, evaluating adherence in itself is a challenge since both accurate and easy-to-use screening tools as well as golden standards are lacking.


Hospitalisation rates and characteristics for adult and childhood immunoglobulin A vasculitis in Western Australia.
Immunoglobulin A vasculitis (IgAV) is a systemic small-vessel vasculitis of unknown aetiology. Although commonest in children, onset in adulthood is not unusual. As Australian data are lacking, we investigated longitudinal hospitalisation rates and characteristics for both adult and paediatric IgAV patients in Western Australia (WA). Data were extracted from a state-wide register for all first hospital contacts in WA between 1980 and 2015 for patients with a primary diagnosis of IgAV. Paediatric cases were defined as those <20 years and compared with adult cases for admission rates per 100 000, demographics, complications, length of stay (LOS) and readmission rates. The study cohort included 476 children (median age 5 years; interquartile range (IQR) 3-7) and 144 adults (median age 50 years; IQR 36-77). Childhood admission rates declined from 3.85 to 0.31 over time (P < 0.001) but age at admission and LOS remained unchanged. For adults, admission rates declined from 0.40 to 0.17 (P = 0.02) while age at admission (43 vs 63 years, P = 0.01) and LOS (5 vs 9 days, P = 0.02) increased. More adults had renal (11.8 vs 1.3%, P < 0.01), intestinal (3.5 vs 0.8%, P = 0.04) and infectious (14.6% vs 5.3%, P < 0.01) complications. Readmission was more frequent in childhood cases (23.1% vs 7.6%, P < 0.05) occurring mostly within 30 days of discharge. Hospitalisation rates for adults with IgAV now nearly equal those in children as adult IgAV leads to more complications. The sharp decline in childhood IgAV admissions suggests that confidence to manage children with IgAV outside the hospital setting has increased.


Extensive alterations of the whole-blood transcriptome are associated with body mass index: results of an mRNA profiling study involving two large population-based cohorts.
Obesity, defined as pathologically increased body mass index (BMI), is strongly related to an increased risk for numerous common cardiovascular and metabolic diseases. It is particularly associated with insulin resistance, hyperglycemia, and systemic oxidative stress and represents the most important risk factor for type 2 diabetes (T2D). However, the pathophysiological mechanisms underlying these associations are still not completely understood. Therefore, in order to identify potentially disease-relevant BMI-associated gene expression signatures, a transcriptome-wide association study (TWAS) on BMI was performed. Whole-blood mRNA levels determined by array-based transcriptional profiling were correlated with BMI in two large independent population-based cohort studies (KORA F4 and SHIP-TREND) comprising a total of 1977 individuals. Extensive alterations of the whole-blood transcriptome were associated with BMI: More than 3500 transcripts exhibited significant positive or negative BMI-correlation. Three major whole-blood gene expression signatures associated with increased BMI were identified. The three signatures suggested: i) a ratio shift from mature erythrocytes towards reticulocytes, ii) decreased expression of several genes essentially involved in the transmission and amplification of the insulin signal, and iii) reduced expression of several key genes involved in the defence against reactive oxygen species (ROS). Whereas the first signature confirms published results, the other two provide possible mechanistic explanations for well-known epidemiological findings under conditions of increased BMI, namely attenuated insulin signaling and increased oxidative stress. The putatively causative BMI-dependent down-regulation of the expression of numerous genes on the mRNA level represents a novel finding. BMI-associated negative transcriptional regulation of insulin signaling and oxidative stress management provide new insights into the pathogenesis of metabolic syndrome and T2D.


Beta-catenin is critical for dendritic morphogenesis.
Regulated growth and arborization of dendritic processes are critical to the formation of functional neuronal networks. Here we identify beta-catenin as a critical mediator of dendritic morphogenesis. We found that increasing the intracellular levels of beta-catenin and other members of the cadherin/catenin complex, namely N-cadherin and alphaN-catenin, enhances dendritic arborization in rat hippocampal neurons, an effect that does not require Wnt/beta-catenin-dependent transcription. Conversely, proteins that sequester beta-catenin decreased dendritic branch tip number and total dendritic branch length. Enhancement of dendritic growth elicited by depolarization requires beta-catenin and increased Wnt release. These results identify Wnt/beta-catenin signaling as an important mediator of dendritic development and suggest that the intracellular level of the cadherin/catenin complex is a limiting factor during critical stages of dendritic morphogenesis.


Evaluation of nested polymerase chain reaction for rapid diagnosis of clinically suspected tuberculous pleurisy.
Early diagnosis of tuberculosis is important in its control. The conventional techniques like smear microscopy and culture suffer from low sensitivity for diagnosis of extra-pulmonary tuberculosis like Pleural Tuberculosis (PTB) due to paucibacillary nature of the fluid. Polymerase Chain Reaction (PCR) is presently seen as a promising alternative to conventional techniques. In this study we have evaluated IS6110 sequence based nested PCR (nPCR) for the detection of Mycobacterium tuberculosis (MTB) DNA directly from clinical samples. The results of PCR were compared with the results of conventional methods like smear, culture and Adenosine Deaminase (ADA) activity. A total of 50 pleural fluid samples from the patients with history suggestive of tuberculosis were taken. All the samples were processed for Ziehl-Neelsan (ZN) staining for Acid Fast Bacilli (AFB), culture ADA activity and PCR with primers targeting 123bp fragment of IS6110 of MTB complex. A significant difference was seen in the sensitivities of conventional methods and PCR (p<0.05). Out of these 50 samples 3 were positive by smear, culture was positive in 5 samples, 21 samples showed high ADA activity and 29 were positive by PCR with overall 100% sensitivity of PCR using culture on LJ media as gold standard. The combined analysis of nPCR, ADA activity and other lab investigations can be very useful in the rapid diagnosis in cases of PTB.


Correlation between severity of clinical signs and transcranial magnetic motor evoked potentials in dogs with intervertebral disc herniation.
Transcranial magnetic motor evoked potentials (TMMEPs) can assess the functional integrity of the spinal cord descending motor pathways. In intervertebral disc herniation (IVDH), these pathways are compromised to varying degrees reflected by the severity of neurological deficits. The hypotheses of this study were as follows: (1) TMMEPs differ in dogs with IVDH and healthy control dogs; (2) TMMEPs reflect different severities of neurological signs; and (3) TMMEPs can document functional motor improvement and therefore monitor recovery of function. TMMEPs were recorded in 50 dogs with thoracolumbar IVDH. Clinical signs ranged from spinal hyperesthesia to non-ambulatory paraparesis in 19 dogs and paraplegia with/without deep pain sensation in 31 dogs. In these 31 paraplegic dogs, transcranial magnetic stimulation (TMS) was repeated during follow-up examinations. Ten healthy Beagle dogs served as controls. There was a significant increase in onset latency and decrease in peak-to-peak amplitude in the pelvic limb TMMEPs of dogs with spinal hyperesthesia to severe paraparesis compared to control dogs. Waveforms in dogs with IVDH were predominantly polyphasic in contrast to the biphasic waveforms of the control dogs. TMMEPs could not be generated in the pelvic limbs of paraplegic dogs. However, TMMEPs with markedly increased onset latencies and decreased peak-to-peak amplitudes reappeared in the pelvic limbs of dogs that were paraplegic before surgery and showed functional motor improvement during follow-up. The severity of neurological deficits was reflected by TMMEP findings, which could be used to document functional motor recovery in IVDH. TMS could therefore be used as an ancillary test to monitor response to therapy in dogs during rehabilitation.


Evidence-based assessment of pregnancy outcome after sumatriptan exposure.
Assessment of best available evidence for tolerability of sumatriptan after inadvertent exposure during pregnancy. Migraine's demography suggests that inadvertent exposure to acute therapies is likely during the earliest undiagnosed stages of pregnancy. The tolerability of such therapies under these conditions is not amenable to clinical trial for ethical reasons. In the United States, sumatriptan is currently labeled pregnancy category C (ie, not recommended for use during pregnancy unless the potential benefit justifies the potential risk to the fetus). Three types of adverse events were studied: spontaneous abortion, fetal abnormality, and obstetric complications. Traditional evidence-based criteria were used to assess a search-protocol product of four clinical studies and two case reports. The single positive finding ("preterm delivery" without low birth weight) was in the smallest study; this study was retrospective and the finding was externally inconsistent with the other three larger studies, all of which were prospective. No study followed children for more than 4 years, which is the period needed to identify the maximum number of congenital anomalies. Rigorous teratological technique was generally not employed. Post hoc power calculations were used to provide parameters of the hazard detectable by these studies in aggregate. Pregnancy categories B and C both seem feasible for sumatriptan. Within the limits of the examined studies, there is no evidence for any specific effect of sumatriptan on pregnancy outcome. Patients inadvertently exposed to sumatriptan during an early stage of pregnancy should be reassured by these data.


[Development of full-quantified fingerprint for quality control of traditional Chinese medicines].
Full-quantified fingerprint technique combines the fingerprint technique and multiple-target determination technique. The development of full-quantified fingerprint technique includes the preparation of full-quantified fraction, the quality control in preparation process with fingerprint technique and determination of products. In this paper, the full-quantified fractions of Salvia miltiorrhiza Bge. were prepared by water extraction, deposition with the ethanol, membrane filter, separation on macroporous resin and separation with preparative high performance liquid chromatography (HPLC). Fingerprint technique was used to test the reproducibility of preparation. Three ingredients, protocatechualdehyde, rosmarinic acid, salvianolic acid B were determined and the sum of their contents was more than 50%. The pharmaceutical active compounds were taken as the preparation target. The impurities were removed effectively by multiple preparations, and the specification of full-quantified fraction was improved greatly.


Drug Consumption Rooms: Welfare State and Diversity in Social Acceptance in Denmark and in France.
Drug consumption rooms (DCRs) have the potential to have a positive impact on the opioid overdose crisis. DCRs could also potentially change the political environment for public health because they can affect the distribution of responsibility for harm reduction between the individual and society by collectivizing responsibility for harm reduction through welfare regimes. The methodology is based on 2 case studies-1 in Copenhagen, Denmark, and 1 in Paris, France-about residents, people who inject drugs (PWID), and politicians' experiences of DCRs involving semidirective interviews. Denmark has a long history of harm-reduction policy, and the implementation of DCRs in Copenhagen has happened through close collaboration between local authorities and the local community. France is far more centralized and paternalistic in terms of the distribution of authority and decision-making in welfare and drug policy. Difficulties in cohabitation between local residents and PWID happened in both countries and can sometimes make public authorities hesitate to implement DCRs because of the NIMBY ("not in my backyard") phenomenon. However, the Danish and French case studies show that DCRs have the potential to become an instrument for civic cohabitation as well as to contribute to the destigmatization and health of PWID. (Am J Public Health. 2022;112(S2):S159-S165. https://doi.org/10.2105/AJPH.2022.306808).


Myth or truth: investigation of the jumping ability of Tunga penetrans (Siphonaptera: Tungidae).
Female sand fleas (Tunga penetrans Linnaeus, 1758, Siphonaptera: Tungidae) cause a severe parasitic skin disease known as tungiasis. T. penetrans is a small flea, measuring less than 1 mm in length. The females of this species burrow into the skin of human and animal hosts and mostly affect the feet. This has led to the anecdotal assumption that T. penetrans, unlike its relatives in the Siphonaptera family, would have a limited jumping ability potentially not reaching higher body parts. However, there is no data supporting this. This study evaluated the jumping capabilities of T. penetrans for height and distance using sticky tapes. The vertical jump of the female T. penetrans ranged from 4.5 to 100 mm with a mean of 40 mm whereas the vertical jump of the male T. penetrans ranged from 1.2 to 138 mm with a mean of 46 mm. The horizontal jump of the female T. penetrans ranged from 18 to 138 mm with a mean of 64 mm and that of the male ranged from 9 to 251 mm with a mean of 80 mm. Based on the literature, fleas of various species have been described as jumping vertically 50-100 times their size and horizontally 5-100 times their size. In this respect, sand fleas appear to have equal expert jumping abilities to their relatives. Their aggregation on people's feet is not likely a result of their poor jumping ability but might be an adaptation to the host's behavior which would require further investigations.


Poly(glycerol methacrylate)-based degradable nanoparticles for delivery of small interfering RNA.
Nucleic acids therapeutic efficiency is generally limited by their low stability and intracellular bioavailability, and by the toxicity of the carriers used to deliver them to the target sites. Aminated poly(glycerol methacrylate) polymers are biodegradable and pH-sensitive polymers that have been used previously to deliver antisense oligonucleotide and show high transfection efficiency. The purpose of this study is to compare the efficiency and toxicity of aminated linear poly(glycerol methacrylate) (ALT) biodegradable polymer to the most commonly used cationic degradable (i.e. chitosan) and non-degradable (i.e. polyethylenimine (PEI)) polymers for delivery of short interfering RNA (siRNA). ALT, PEI and chitosan polymers were able to form nanosized particles with siRNA. Size, size-distribution and zeta-potential were measured over a wide range of nitrogen-to-phosphate (N/P) ratios, and the stability of the formed nanoparticles in saline and upon freeze-drying was also assessed. No significant cytotoxicity at the range of the tested concentrations of ALT and chitosan nanoparticles was observed, whereas the non-degradable PEI showed significant toxicity in huh-7 hepatocyte-derived carcinoma cell line. The safety profiles of the degradable polymers (ALT and chitosan) over non-degradable PEI were demonstrated in vitro and in vivo. In addition, ALT nanoparticles were able to deliver siRNA in vivo with significantly higher efficiency than chitosan nanoparticles. The results in the present study give evidence of the great implications of ALT nanoparticles in biomedical applications due to their biocompatibility, low cytotoxicity, high stability and simple preparation method.


[Basic Strategy for Pain Control in Rehabilitation].
Rehabilitation medicine regards pain as one disorder of whole human character and handles pain through multilateral approaches. When only the pain is treated it will not be relieved easily. Chronic pain can be more effectively handled if pain is considered as one obstacle of the whole human character and handled using many skills of rehabilitation medicine. We should apply physiotherapy including functional treatment, physical treatment and exercise from early stages of acute pain and approach chronic pain. This could improve the effectiveness of treatment for many kinds of acute pain and chronic pain disorders.


Cardiovascular effects of neuropeptide Y.
Neuropeptide Y (NPY) is present in the brain, the adrenal medulla, and peripheral sympathetic nerves. This peptide is released together with catecholamines during sympathoadrenal activation. It possesses direct vasoconstrictor properties that are not dependent on simultaneous adrenergic activation. Moreover, it potentiates the vascular effect of several stimulatory substances and may contribute to the modulation of blood pressure responsiveness under a number of circumstances. NPY may also be indirectly involved in the control of blood pressure through regulating the release of hormones with well-established actions on the cardiovascular system.


AAU-Specific RNA Cleavage Mediated by MazF Toxin Endoribonuclease Conserved in Nitrosomonas europaea.
Nitrosomonas europaea carries numerous toxin-antitoxin systems. However, despite the abundant representation in its chromosome, studies have not surveyed the underlying molecular functions in detail, and their biological roles remain enigmatic. In the present study, we found that a chromosomally-encoded MazF family member, predicted at the locus NE1181, is a functional toxin endoribonuclease, and constitutes a toxin-antitoxin system, together with its cognate antitoxin, MazE. Massive parallel sequencing provided strong evidence that this toxin endoribonuclease exhibits RNA cleavage activity, primarily against the AAU triplet. This sequence-specificity was supported by the results of fluorometric assays. Our results indicate that N. europaea alters the translation profile and regulates its growth using the MazF family of endoribonuclease under certain stressful conditions.


Increased beta 2-adrenoceptors in the superior cervical ganglia of genetically hypertensive rats.
[125I]Iodocyanopindolol binding sites were characterized by autoradiography in the superior cervical ganglia of Wistar-Kyoto (WKY) rats. A high concentration of (-)-[125I]iodocyanopindolol binding sites, characterized as beta-adrenoceptors by (-)-propranolol displacement, was distributed throughout the ganglia and in the postganglionic (internal carotid) nerve. ICI 118,551, a beta 2-selective antagonist, displaced more than 85% of the binding sites, whereas CGP 20712A, a beta 1-selective antagonist, displaced less than 10% of the binding sites, indicating that the beta-adrenoceptors were primarily of the beta 2-subtype. Emulsion autoradiography demonstrated that at least part of the binding sites were associated with principal ganglion cells. Unilateral deafferentation did not modify the number of binding sites in the superior cervical ganglia of WKY or spontaneously hypertensive rat (SHR). These results suggest that at least part of these receptors may correspond to prejunctional beta 2-adrenoceptors originated in principal ganglion cells. The concentration of beta 2-receptors was increased in the superior cervical ganglia of young and adult SHR when compared to age-matched WKY rats (49% and 39%, respectively). There were no differences in beta 2-adrenoceptor number in the stellate ganglia of young and adult WKY and SHR. These results suggest that beta 2-adrenoceptor stimulation may be selectively enhanced in some peripheral sympathetic ganglia in SHR and this could play a role in the development and maintenance of the increased sympathetic activity in this strain.


A simple and effective protocol for fast isolation of human Tenon's fibroblasts from a single trabeculectomy biopsy - a comparison of cell behaviour in different culture media.
Human Tenon's fibroblasts (HTFs) play a crucial role in wound healing. They cause postoperative scarring of the filtering bleb and are thus responsible for trabeculectomy failure. This study aimed to find an effective and fast protocol for HTF isolation from trabeculectomy biopsies. The protocol was compared with the commonly recommended HTF isolation procedure, which uses Dulbecco's modified Eagle's medium (DMEM). We used Eagle's minimum essential medium (EMEM) enriched with fibroblast growth factor (FGF), which selectively promoted the proliferation of HTF cells. A secondary goal was to compare HTF morphology, metabolism and growth during parallel cultivation of the isolated cells in FGF-enriched EMEM and DMEM. Standard procedures for HTF isolation from tissue biopsies require a 20- to 30-day culture of the explants to obtain the first monolayer. Our protocol yielded the first monolayer after approx. 15 days. More importantly, the majority of the cells were fibroblasts with only individual epithelium-derived cells present. Using FGF-enriched EMEM allowed 1.3 × 106 vimentin-positive fibroblasts to be obtained from a single biopsy within approx. 25 days. Using DMEM resulted in isolation failure and required exchange to FGF-enriched medium to recover the fibroblast culture. HTFs maintained in FGF-enriched EMEM also showed faster proliferation and a different type I collagen production ability compared to HTFs cultured in DMEM. Thus, FGF-enriched EMEM is recommended for fast propagation of HTFs unless the aim of the study is to assess the effect of a tested agent on proliferation ability or type I collagen production. Our fast protocol for HTF isolation allows easy setup of cell banks by researchers under laboratory conditions and could be very useful during testing of novel ophthalmologic anti-fibrotic agents in vitro. Molecular analysis of HTFs isolated from patients with known treatment histories may provide valuable information on the effects of some medications taken before glaucoma surgery on the subsequent wound-healing process and potential for trabeculectomy failure.


AQP4-knockout aggravation of isoprenaline-induced myocardial injury is mediated by p66Shc and endoplasmic reticulum stress.
Aquaporin 4 (AQP4) is a type of water channel protein that maintains the water balance of cardiomyocytes. However, the physiological role of AQP4 in cardiovascular disease is poorly understood. We wanted to explore whether p66Shc and endoplasmic reticulum stress participates in AQP4 knockout (KO)-mediated cardiac injury. There were two types of mice: AQP4 knockout and wild-type mice. Each type was randomly divided into three groups: Control group, isoprenaline stimulation group (ISO, 1 mg/kg, s.c., 5 days), and apocynin treatment group (APO, 100 mg/kg, p.o., 3 days). H9c2 rat cardiomyocytes were cultured for RNA interference of AQP4. Results showed increased left ventricular weight index and more severe myocardial inflammation were induced in AQP4 knockout mice relative to wild-type mice, accompanied by significantly increased levels of the oxidative stress biomarkers MDA and NOX4. In addition, the expressions of p66Shc, ER stress markers PERK, GRP78 and CHOP and proinflammatory factors such as ETA , IL6 and TNFα were upregulated in the myocardium of AQP4 knockout mice or AQP4 siRNA treated cardiomyocytes, whereas CASQ2 was downregulated. ISO stimulation aggravated these abnormalities, which were significantly attenuated by apocynin. This study showed that AQP4 knockout mice were susceptible to cardiac injury induced by ISO. The mechanism was closely connected with p66Shc and proinflammatory factors. Endoplasmic reticulum stress was also involved in the pathological process.


Budget impact analysis of temocillin insurance coverage for urinary tract infections caused by ESBL-producing pathogens in Iran.
One of the most prevalent infections with a significant disease burden is urinary tract infections (UTIs), which occurs in approximately 50% of women at least once in their lifetime. Antimicrobial resistance to pathogens causing UTIs is expanding worldwide and has been associated with increased use of broad-spectrum antibiotics, including carbapenems, leading to significant costs for insurance and healthcare systems. The emergence of resistance to carbapenems has led to an increasing need for and interest in carbapenem-sparing strategies, including the use of narrow-spectrum antibiotics, such as temocillin. Temocillin has a strong bactericidal effect, along with high tolerability and a good safety profile. It is also stable toward most extended-spectrum beta-lactamases (ESBL). The purpose of our study was to design a budget impact analysis (BIA) model and estimate the budget impact of temocillin insurance coverage for the treatment of UTIs caused by ESBL-producing bacteria from the perspective of the payer. The BIA model with insurance payer perspective was used to estimate the impact of temocillin insurance coverage on the treatment of UTIs caused by ESBL-producing bacteria over a 1-year time horizon in Iran. Direct medicine costs, hospitalization and paraclinical costs, and side effect costs were considered in this model. To assess the impact of uncertainty on the model inputs, 1-way sensitivity analyses were performed. The model demonstrates that inclusion of temocillin in insurance coverage, decreasing treatment costs from $36 million to $34 million, will result in overall savings of > $1.9 million and lead to > $9 million savings in insurance costs for antimicrobial resistance. The inclusion of temocillin in the insurance coverage in Iran for patients developing UTIs caused by ESBL-producing bacteria would be cost-saving for insurance and decrease the risk associated with emerging antimicrobial resistance.


Familial Wilms tumor.
Wilms tumor (WT), an embryonic tumor arising from undifferentiated renal mesenchyme, has been a productive model for understanding the role of genes in both tumorigenesis and normal organogenesis. Approximately 2% of WT patients have a family history of WT, and even sporadic WT is thought to have a strong genetic component to its etiology. Familial WT cases generally have an earlier age of onset and an increased frequency of bilateral disease, although there is variability among WT families, with some families displaying later than average ages at diagnosis. One WT gene, WT1 at 11p13, has been cloned, but only a minority of tumors carry detectable mutations at that locus, and it can be excluded as the predisposition gene in most WT families. Two familial WT genes have been localized, FWT1 at 17q12-q21 and FWT2 at 19q13.4; lack of linkage in some WT families to either of these loci implies the existence of at least one additional familial WT gene. Originally modeled as the inheritance of a mutation in a tumor suppressor gene, molecular analysis of familial tumors not linked to 11p13 have provided data suggesting that this model may be overly simplistic and/or not applicable to all WT families. Identification of the FWT1 and FWT2 genes will help clarify this and will also likely aid in our understanding in general of the roles of the various WT genes and their genetic interactions in the development of WT.


A novel wireless wearable fluorescence image-guided surgery system.
Segmentectomy using indocyanine green (ICG) has become a primary treatment option to achieve a complete resection and preserve lung function in early-stage lung cancer. However, owing to a lack of appropriate intraoperative imaging systems, it is a huge challenge for surgeons to identify the intersegmental plane during the operation, leading to poor prognosis. Thus, we developed a novel wireless wearable fluorescence image-guided surgery system (LIGHTEN) for fast and accurate identification of intersegmental planes in human patients. The system consists of a handle, light source, Google glass and laptop. Application software is written to capture clear real-time images and Google glass is adopted to display with augmented reality. Twelve in vivo studies of pulmonary segmentectomy in swine by intravenous injection of ICG were conducted to test the performance of the system. A distinct black-and-white transition zone image was observed and displayed simultaneously on the Google glass in all swine. The results demonstrated that surgeons using LIGHTEN can effortlessly and quickly discern intersegmental planes during the operation. Our system has enormous potential in helping surgeons to precisely identify intersegmental planes with mobility and high-sensitivity.


Household crowding is associated with higher allostatic load among the Inuit.
Household crowding is an important problem in some aboriginal communities that is reaching particularly high levels among the circumpolar Inuit. Living in overcrowded conditions may endanger health via stress pathophysiology. This study examines whether higher household crowding is associated with stress-related physiological dysregulations among the Inuit. Cross-sectional data on 822 Inuit adults were taken from the 2004 Qanuippitaa? How are we? Nunavik Inuit Health Survey. Chronic stress was measured using the concept of allostatic load (AL) representing the multisystemic biological 'wear and tear' of chronic stress. A summary index of AL was constructed using 14 physiological indicators compiled into a traditional count-based index and a binary variable that contrasted people at risk on at least seven physiological indicators. Household crowding was measured using indicators of household size (total number of people and number of children per house) and overcrowding defined as more than one person per room. Data were analysed using weighted Generalised Estimating Equations controlling for participants' age, sex, income, diet and involvement in traditional activities. Higher household crowding was significantly associated with elevated AL levels and with greater odds of being at risk on at least seven physiological indicators, especially among women and independently of individuals' characteristics. This study demonstrates that household crowding is a source of chronic stress among the Inuit of Nunavik. Differential housing conditions are shown to be a marker of health inequalities among this population. Housing conditions are a critical public health issue in many aboriginal communities that must be investigated further to inform healthy and sustainable housing strategies.


Hindlimb suspension increases insulin binding and glucose metabolism.
After 28 days of hindlimb-suspension, insulin binding, 2-deoxy-D-glucose (2-DG) uptake, and glucose metabolism (glycolysis and glycogenesis) were determined at various insulin concentrations (0.2-30 nM) in soleus muscle of young (18-day-old) and adult (150-day-old) rats. Compared with age-matched controls the young (YS) and adult suspended (AS) rats had lower soleus and body weights and insulin levels (P less than 0.05). Per milligram of protein, insulin binding, 2-DG uptake, and the rate of glycolysis were increased by approximately 200%, and the rate of glycogenesis was increased approximately 100% in the YS group (P less than 0.05). Except for a reduction in glycogenesis (P less than 0.05) all other parameters also increased in the AS rats (P less than 0.05). On the basis of the whole muscle the rate of glucose metabolism (glycogenesis + glycolysis) was reduced in the YS rats (P less than 0.05), but in the AS rats glucose metabolism was similar to the controls. Thus the increased glucose metabolism (i.e., per milligram of protein) in the YS and AS groups may represent a compensatory response by atrophied muscle to attempt to sustain glucose removal from the circulation. Because greater insulin binding occurred in YS muscle [35% slow-twitch (ST)] than in the control group (70% ST), and greater insulin binding occurred in the AS (81% ST) than in the control group (90% ST), higher insulin binding capacities are not always related to a high proportion of ST muscle fibers. In conclusion, after hindlimb suspension, marked increments in insulin binding and glucose metabolism occur in the soleus muscle.


Computergraphics in a full-service department: a three-year experience.
A three-year experience in computergraphics has proven to be cost-effective in a full-service, totally self-supporting biocommunications department. Workload has continued to increase in art and photography, and the departmental staff has increased by 1.5 full-time equivalents. A satellite computergraphics production unit with a staff of three illustrators has emerged as a viable service of the department.


Homeopathic Formulations of Syzygium jambolanum Alleviate Glycation-Mediated Structural and Functional Modifications of Albumin: Evaluation through Multi-Spectroscopic and Microscopic Approaches.
The growing interest in identifying the mode of action of traditional medicines has strengthened its research. Syzygium jambolanum (Syzyg) is commonly prescribed in homeopathy and is a rich source of phytochemicals. The present study aims to shed light on the anti-glycation molecular mechanism of Syzyg mother tincture (MT), 30c, and 200c on glycated human serum albumin (HSA) by multi-spectroscopic and microscopic approaches. The phytochemicals and antioxidant potential of the Syzyg formulations were estimated by the high-performance liquid chromatography and spectroscopic technique, respectively. Glycation was initiated by incubating HSA with methylglyoxal, three Syzyg formulations, and the known inhibitor aminoguanidine in separate tubes at 37°C for 48 hours. The formation of glycation adducts was assessed by spectrofluorometer and affinity chromatography. The structural modifications were analyzed through circular dichroism, Fourier transform infrared spectroscopy, turbidity, 8-anilinonapthalene-1-sulfonic acid fluorescence, and nuclear magnetic resonance. Further, the formation of the aggregates was examined by thioflavin T, native-polyacrylamide gel electrophoresis, and transmission electron microscopy. Additionally, the functional modifications of glycated HSA were determined by esterase-like activity and antioxidant capacity. The binding analysis of Syzyg formulations with glycated HSA was evaluated by surface plasmon resonance (SPR). Syzyg formulations MT, 30c, and 200c contained gallic acid and ellagic acid as major phytochemicals, with concentrations of 16.02, 0.86, and 0.52 µg/mL, and 227.35, 1.35, and 0.84 µg/mL, respectively. Additionally, all three formulations had remarkable radical scavenging ability and could significantly inhibit glycation compared with aminoguanidine. Further, Syzyg formulations inhibited albumin's structural and functional modifications. SPR data showed that Syzyg formulations bind to glycated HSA with an equilibrium dissociation constant of 1.10 nM. Syzyg formulations inhibited the glycation process while maintaining the structural and functional integrity of HSA.


Ethical implications in screening for ethics violations.
The process of admittance to membership in a psychological organization is an opportune time to take into consideration any questionable behavior in the professional background of a prospective member. Membership application forms of the American Psychological Association (APA) and 58 affiliated organizations are reviewed to determine the kinds of questions that are asked about ethical misconduct. The nature of the inquiry differs considerably from one association to another, with a preponderance of organizations avoiding any direct questions about professional ethics. Discussion is focused on how these different screening strategies impact on the applicant and the organization. There is a demonstrated need for appropriately formulated queries. A case is made for resolving current inconsistencies among associations by adhering to a unified procedure in the ethical screening of psychologist applicants.


Investigation of spatiotemporal output beam profile instabilities from differentially pumped capillaries.
Differentially pumped capillaries, i.e., capillaries operated in a pressure gradient environment, are widely used for nonlinear pulse compression. In this work, we show that strong pressure gradients and high gas throughputs can cause spatiotemporal instabilities of the output beam profile. The instabilities occur with a sudden onset as the flow evolves from laminar to turbulent. Based on the experimental and numerical results, we derive guidelines to predict the onset of those instabilities and discuss possible applications in the context of nonlinear flow dynamics.


Diagnosis of perioperative myocardial infarction after heart valve surgery with new cut-off point of high-sensitivity troponin T and new electrocardiogram or echocardiogram changes.
Criteria for diagnosing myocardial infarction (MI) after heart valve surgery are not collected in the Third Universal Definition of MI. We aimed to define cut-offs for high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase-MB (CK-MB) for the diagnosis of perioperative MI after heart valve surgery according to perioperative MI determined by new alterations in electrocardiogram (ECG) and/or transthoracic echocardiogram (TTE). Secondary endpoints were incidence of perioperative MI, postoperative complications, 30-day mortality, and 2-year survival. Heart valve surgery was performed in 805 patients (June 2012-January 2016). hs-cTnT and CK-MB were measured at intensive care unit (ICU) admission and 8, 16, 24, 48, and 72 hours after surgery. Blind to outcomes, we analyzed ECGs and TTEs before and after surgery. Patients were divided into 2 groups: with ECG and/or TTE criteria after surgery (following the consensus statement) and without these changes. We conducted receiver operating characteristic analyses for hs-cTnT and CK-MB in the group with ECG and/or TTE criteria. ECG and/or TTE criteria were observed in 88 patients. Receiver operating characteristic analyses in this group showed hs-cTnT levels of 732.3 pg/mL at ICU admission; 1008 pg/mL at 8 hours, 1057 pg/mL at 16 hours, and 958.3 pg/mL at 24 hours after surgery (P < .001) and CK-MB levels of 26.78 mg/dL at ICU admission, 54.88 mg/dL at 8 hours, 38.98 mg/dL at 16 hours, and 18.4 mg/dL at 24 hours after surgery (P < .001). Cut-offs for hs-cTnT and CK-MB to diagnose perioperative MI after heart valve surgery are well above upper reference limit. These findings update the Third Universal Definition providing cut-offs to diagnose perioperative MI after heart valve surgery.


Spatiotemporal patterns of ontogenetic expression of parvalbumin in the superior colliculi of rats and rabbits.
We have examined the development of parvalbumin immunoreactivity in the superior colliculi (SC) of the perinatal and mature rats and rabbits. In mature animals, parvalbumin-expressing cells (PECs) and neuropil in the retinorecipient layers were distributed in a continuous single band extending throughout the entire extent of the colliculus, whereas those in the intermediate layers formed distinct, radially oriented patches. Parvalbumin was expressed for the first time on postconceptional day 34 (PCD 34, postnatal day 12) and PCD 42 (postnatal day 11) in the SC of rat and rabbit, respectively. During ensuing development, both the thickness of the parvalbumin-expressing band in the retinorecipient layers and the numbers of PECs in this band gradually increased, reaching adultlike values by PCD 44 and PCD 50 in the rat and rabbit, respectively. In the rat, monocular eye enucleations on PCD 23 resulted in approximately 55% reduction in the number of PECs in the retinorecipient layers of the contralateral colliculi examined on PCD 44 or PCD 50. Unilateral ablations of the entire visual cortex on PCD 23 (before the first corticotectal fibers from visual cortices reach the SC) or on PCD 28 (when about half of the corticotectal fibers have reached colliculus) resulted in, respectively, approximately 55% and approximately 25% relative reduction in the number of PECs in the retinorecipient layers of the ipsilateral colliculi examined on PCD 44 or PCD 50. We conclude that the ontogenetic expression of parvalbumin in most of PECs in the retinorecipient collicular layers is induced by the activity of the contralateral retinotectal and/or the activity of the ipsilateral corticotectal afferents.


Role of glycosphingolipid conformational change in membrane pore forming activity of cobra cardiotoxin.
The major cardiotoxin from Taiwan cobra (CTX A3) is a pore forming beta-sheet polypeptide that requires sulfatide (sulfogalactosylceramide, SGC) on the plasma membrane of cardiomyocytes for CTX-induced membrane leakage and cell internalization. Herein, we demonstrate by fluorescence spectroscopic studies that sulfatides induce CTX A3 oligomerization in sulfatide containing phosphatidylcholine (PC) vesicles to form transient pores with pore size and lifetime in the range of about 30 A and 10(-2) s, respectively. These values are consistent with the CTX A3-induced conductance and mean lifetime determined previously by using patch-clamp electrophysiological experiments on the plasma membrane of H9C2 cells. We also derived the peripheral binding structural model of CTX A3-sulfatide complex in sulfatide containing PC micelles by NMR and molecular docking method and compared with other CTX A3-sulfatide complex structure determined previously by X-ray in membrane-like environment. The NMR results indicate that sulfatide head group conformation changes from a bent shovel (-sc/ap) to an extended (sc/ap) conformation upon initial binding of CTX A3. An additional global reorientation of sulfatide molecule is also needed for CTX A3 dimer formation as inferred by the difference between the X-ray and NMR complex structure. Since the overall folding of CTX A3 molecules remained the same, sulfatide in phospholipid bilayer is proposed to play an active role by involving its local and global conformational changes to promote both the oligomerization and reorientation of CTX A3 molecule for its transient pore formation and cell internalization.


PrEP Awareness and Attitudes in a National Survey of Primary Care Clinicians in the United States, 2009-2015.
As trials were assessing the safety and efficacy of daily oral antiretroviral preexposure prophylaxis (PrEP) for the prevention of HIV infection, there was a clear need to understand the evolution of knowledge of, and attitudes toward, PrEP among primary care clinicians. Physicians and nurse practitioners were surveyed in 2009 (n = 1500), 2010 (n = 1504), 2012 (n = 1503), 2013 (n = 1507), 2014 (n = 1508) and 2015 (n = 1501) to assess their awareness of PrEP, willingness to prescribe PrEP, and whether they support use of public funds to pay for PrEP. Pharmacists (n = 251) were surveyed about PrEP in 2012 only. Descriptive statistics were computed for physician demographics and PrEP-related questions. Prevalence ratios for willingness to prescribe PrEP were computed using Poisson regression analysis. Awareness of PrEP was low among clinicians (2009: 24%, 2010: 29%) but increased after trials reported effectiveness (2012: 49%, 2013: 51%, 2014: 61%, 2015: 66%). Following a description of PrEP with an estimated effectiveness of 75%, across 6 of the study years 91% of clinicians indicated a willingness to prescribe PrEP to at least one group at high risk of HIV acquisition. A smaller majority of clinicians indicated support for public funding of PrEP in 2009: 59%, 2010: 53%, and 2013: 63%. In surveys conducted before and after the release of PrEP trial results, primary care clinicians were largely unaware of PrEP. They indicated high levels of willingness to prescribe it for patients at high risk of HIV acquisition and expressed interest in education about how to deliver this new clinical HIV prevention method. It will be important to continue monitoring clinician knowledge, attitudes, and practices as the use of PrEP increases in the US.


Comparison between procalcitonin, brain natriuretic peptide, and uric acid in children with cardiomyopathy and controls.
This study was performed to determine the level of procalcitonin, Brain Natriuretic Peptide (BNP), and uric acid in children with cardiomyopathy in comparison with controls and the association with echocardiographic findings. The levels of BNP, procalcitonin, and serum uric acid were measured and the amounts of biomarkers compared with echocardiographic findings. In this study mean age of participants was the same (p=0.321). The majority of echocardiographic indices in left and right heart have different means in case and controls (p<0.05). Means of BNP, procalcitonin, and uric acid were 213.814 ± 309.601, 9.326 ± 3.881, and 6.846 ± 1.814 for case group and 2.76 ± 1.013, 1.851 ± 1.466, and 3.317 ± 0.924 for control (p<0.001), respectively. In the patients group there was relationship of Ross classification with BNP (χ (2) = 15.845, p<0.05) and with age (χ (2) = 8.946, p<0.05). For uric acid and procalcitonin no significant relationships were observed. Procalcitonin, uric acid, and BNP had significant relationship with many echocardiographic findings in participants. For patients, procalcitonin did not show correlation. The severity of illness based on the Ross classification showed significant correlation with BNP level and age in patients.


Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials.
This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD) and no abuse participants. We focused particularly on an early wave (C1/P1), the N2pc, and the P3b. Our main result indicated an early effect (55-165 ms) of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD) suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology.