[Lipoprotein (a): a genetic risk factor with atherogenic and thrombogenic properties].
Lipoprotein (a) is a relatively new independent risk factor of early atherosclerosis with atherogenic and thrombogenic properties. From the structural aspect it resembles LDL-lipoprotein and differs from the latter by the presence of another glycoprotein-apolipoprotein (a). Due to the great similarity of apolipoprotein (a) and plasminogen, lipoprotein (a) is bound to plasminogen receptors on the fibrin surface (fibrinogen) and thus prevents the cumulation and activation of local fibrinolysis. Its levels are under strict genetic control and are very little influenced by external factors and available hypolipidaemic treatment. There is a great interindividual variability of lipoprotein(a) concentrations which is due above all to the structural variability of apolipoprotein (a). At present at least 34 isoforms of apolipoprotein(a) were described which differ as to the size of the molecule. This great structural variability has an impact not only on the function and pathogenicity of lipoprotein (a) but also on methods of its assessment. High lipoprotein(a) concentrations are found in subjects with early clinical manifestations of atherosclerosis, in nephrotic syndrome, in chronic renal insufficiency, in haemodialyzed patients and other diseases. They rise in women after the menopause and are favourably influenced by hormonal substitution therapy. There is a number of immunochemical methods used for its estimation which are very well reproducible within the same laboratory. The high interlaboratory coefficients of variation indicate, however, that unification of lipoprotein(a) analyses is urgent.


Phase I trial of intoplicine (RP 60475) administered as a 72 h infusion every 3 weeks in patients with solid tumors.
Intoplicine (RP 60475) was selected for a phase I evaluation because it inhibits topoisomerase I and II, and has exhibited antitumor activity against a variety of preclinical solid tumor models. Intoplicine is a 7H-benzo[e]pyrido[4,3-b]indole that inhibits DNA nicking and closing reactions by stabilizing the cleavable complex, a transient intermediate in the religation reaction involving topoisomerase I and II and DNA. Twenty-eight patients with refractory advanced malignancies who met standard phase I eligibility criteria were enrolled in a dose-escalation study of intoplicine, ranging from 7 to 420 mg/m2/day administered as a continuous 72 h i.v. infusion. Fifty-three courses were administered and evaluated. Myelosuppression (four patients, grade 3; two patients, grade 4) and hepatic toxicity (one patient, grade 3) were dose limiting at 336 mg/m2/day. No objective antitumor responses were observed. The pharmacokinetic parameters of intoplicine were investigated in 11 patients at dose levels of 112 (n=1), 224 (n=3), 336 (n=6) and 420 (n=1) mg/m2/day. Both the area under the plasma concentration versus time curves and the maximum plasma concentrations increased linearly within the dose range studied. Intoplicine content measured in whole blood exceeded that found in plasma by 3- to 7-fold, indicating that red blood cells may serve as a drug reservoir. Preclinical cytotoxic concentrations were not achieved at the dose levels studied.


[Chilled and frozen semen: the animal experience].
The aim of this paper is to describe technologies that are currently being used in animal reproduction and those that will be used in the near future. The significant changes (news methods of conservation of chilled and frozen semen) operated these last ten years in connection with the development of animal insemination are all detailed. All these techniques are experiencing rapid improvements in terms of success rate.


Effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity.
3,4-Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a popular recreational drug used worldwide. This study aimed to determine the effects of this compound on the expression of nerve terminal serotonergic markers in rats. Experiment 1 investigated MDMA-induced changes in levels of the serotonin transporter (SERT) and the vesicular monoamine transporter 2 (VMAT-2) in the hippocampus, a region with sparse dopaminergic innervation, after lesioning noradrenergic input with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). Adult male Sprague-Dawley rats were administered 100 mg/kg DSP-4 or saline 1 week prior to either an MDMA (10 mg/kg x 4) or saline binge. Two weeks following the binge treatment, the DSP-4/MDMA group unexpectedly showed little change in hippocampal VMAT-2 protein expression compared with DSP-4/Saline controls, despite large reductions in SERT levels in all regions examined in the MDMA-treated animals. Furthermore, animals treated with binge MDMA (Experiment 2) showed a striking decrease in SERT gene expression (and a lesser effect on VMAT-2) measured by quantitative RT-PCR in pooled dorsal and median raphe tissue punches, when compared with saline-treated controls. These results demonstrate that MDMA causes substantial regulatory changes in the expression of serotonergic markers, thus questioning the need to invoke distal axotomy as an explanation of MDMA-related serotonergic deficits.


Protease-activated receptor-2 involvement in hypotension in normal and endotoxemic rats in vivo.
The protease-activated receptor-2 (PAR-2) is expressed by vascular endothelial cells and upregulated by lipopolysaccharide (LPS) in vitro. PAR-2 is activated by a tethered ligand created after proteolytic cleavage by trypsin or experimentally by a synthetic agonist peptide (PAR-2AP) corresponding to the new amino terminus of the tethered ligand. Intravenous administration of PAR-2AP (0.1, 0.3, and 1 mg/kg) to rats caused a dose-dependent hypotension. A scrambled peptide was without effect. A specific trypsin inhibitor, biotin-SGKR-chloromethylketone, inhibited trypsin-induced hypotension but not that stimulated by PAR-2AP. In animals treated with LPS 20 hours earlier, we found an increased sensitivity to trypsin and PAR-2AP in the hypotensive response. In particular, PAR-2AP caused hypotension at a low concentration of 30 ng/kg. Moreover, PAR-2 was immunolocalized to endothelial and smooth muscle cells in aorta and jugular vein in LPS-treated rats, and increased levels of PAR-2 mRNA were shown by reverse transcription-polymerase chain reaction analysis. Our findings suggest that PAR-2 is important in the regulation of blood pressure in vivo. A functional upregulation of PAR-2 by LPS was demonstrated by the activity of concentrations of PAR-2AP that were inactive in normal animals. We conclude that PAR-2 may play an important role in the hypotension associated with endotoxic shock and may represent a new therapeutic target.


Epilepsy surgery in childhood.
Epilepsy surgery in childhood can now be more readily considered as a result of enhanced presurgical investigative techniques and safer neurosurgical practice. As in adults, surgery available may be resective (focal resection or hemispherectomy) or functional. The most common procedures are temporal lobectomy and hemispherectomy, with malformative lesions and developmental tumours the next common pathology. The timing of surgery requires careful consideration, and the definition of drug resistance given specific thought in the young child. Presurgical evaluation should be noninvasive where possible, and should include optimised MRI, including 3D data set and video EEG telemetry to document seizures. Detection of temporal lobe abnormalities in temporal lobe epilepsy with MR may be enhanced using quantitative and semiquantitative techniques. Ictal and interictal SPECT may be useful in providing information about the seizure onset zone, if reviewed in conjunction with MR data and video-EEG. Interictal PET is more likely to demonstrate abnormalities relating to structural defects, but may be particularly useful in infants where incomplete myelination may restrict structural information provided by MRI. Neuropsychology testing plays a major role by the determination of verbal and nonverbal function in older children, and in the determination of cerebral dominance. Functional MRI for determination of language or motor cortex may enhance such evaluation, although it is limited to older unsedated children at present. Although the aims of the presurgical evaluation remain similar to adult practice, the range of children presenting is wide, and the aims and likely outcome of surgery require careful evaluation with the family. This aside, the benefits of seizure elimination or reduction in drug-resistant focal epilepsy prior to adolescence, as well as in certain early catastrophic epilepsies of childhood, remain self apparent.


Anterior cingulate cortex abnormalities associated with a first psychotic episode in bipolar disorder.
The anterior cingulate cortex is frequently implicated in the pathophysiology of bipolar disorder, but magnetic resonance imaging (MRI) studies have reported variable findings owing to a reliance on patient samples with chronic illness and to limited appreciation of the region's heterogeneity. To characterise anterior cingulate cortex abnormalities in patients with bipolar disorder experiencing their first episode of psychosis while accounting for regional anatomical variability. Grey matter volume, surface area and cortical thickness were measured in six anterior cingulate cortex subregions per hemisphere using MRI scans acquired from 26 patients with bipolar I disorder experiencing first-episode psychosis and 26 healthy controls matched for age, gender and regional morphological variability. Relative to controls, male patients displayed increased thickness in the right subcallosal limbic anterior cingulate cortex. No significant differences were identified in females for grey matter volume or surface area measures. The findings were not attributable to medication effects. These data suggest that first-episode psychosis in bipolar disorder is associated with a gender-specific, right-lateralised thickness increase in anterior cingulate cortex subregions known to play a role in regulating physiological stress responses.


Effect of the π-conjugation length on the properties and photovoltaic performance of A-π-D-π-A type oligothiophenes with a 4,8-bis(thienyl)benzo[1,2-b:4,5-b']dithiophene core.
Benzo[1,2-b:4,5-b']dithiophene (BDT) is an excellent building block for constructing π-conjugated molecules for the use in organic solar cells. In this paper, four 4,8-bis(5-alkyl-2-thienyl)benzo[1,2-b:4,5-b']dithiophene (TBDT)-containing A-π-D-π-A-type small molecules (COOP-nHT-TBDT, n = 1, 2, 3, 4), having 2-cyano-3-octyloxy-3-oxo-1-propenyl (COOP) as terminal group and regioregular oligo(3-hexylthiophene) (nHT) as the π-conjugated bridge unit were synthesized. The optical and electrochemical properties of these compounds were systematically investigated. All these four compounds displayed broad absorption bands over 350-600 nm. The optical band gap becomes narrower (from 1.94 to 1.82 eV) and the HOMO energy levels increased (from -5.68 to -5.34 eV) with the increase of the length of the π-conjugated bridge. Organic solar cells using the synthesized compounds as the electron donor and PC61BM as the electron acceptor were fabricated and tested. Results showed that compounds with longer oligothiophene π-bridges have better power conversion efficiency and higher device stability. The device based on the quaterthiophene-bridged compound 4 gave a highest power conversion efficiency of 5.62% with a VOC of 0.93 V, JSC of 9.60 mA·cm-2, and a FF of 0.63.


The Stereotactic Intracerebral Hemorrhage Underwater Blood Aspiration (SCUBA) technique for minimally invasive endoscopic intracerebral hemorrhage evacuation.
Endoscopic intracerebral hemorrhage (ICH) evacuation techniques have gained interest as a potential therapeutic option. However, the instrumentation and techniques employed are still being refined to optimize hemostasis and evacuation efficiency. We describe the application of a specific endoscopic technique in the treatment of ICH called the Stereotactic Intracerebral Hemorrhage Underwater Blood Aspiration (SCUBA) technique. It differs from previously described minimally invasive ICH interventions in that it combines two separate neuroendoscopic strategies in two phases, the first under dry-field conditions and the second using a wet-field strategy. All patients who underwent endoscopic ICH evacuation with the SCUBA technique from December 2015 to September 2017 were included. The SCUBA technique was performed in 47 patients. The average evacuation percentage was 88.2% (SD 20.8). Active bleeding identified to derive from a specific source was observed in 23 (48.9%) cases. Active bleeding was addressed with irrigation alone in five cases (10.6%) and required electrocautery in 18 cases (38.3%). Intraoperative bleeding occurred in 3 patients (6.4%) and postoperative bleeding occurred in a single case (2.1%). The SCUBA technique provides surgeons with a defined strategy for true endoscopic hematoma evacuation. In particular, the fluid-filled cavity in SCUBA Phase 2 has the potential to provide several advantages over the traditional air-filled strategy, including clear identification and cauterization of bleeding vessels and visualization of residual clot burden. Further investigation is necessary to compare this technique to others that are currently used.


Cardiac awareness and autonomic cardiac reactivity during emotional picture viewing and mental stress.
This study investigated the relationship between autonomic cardiovascular reactivity and cardiac awareness during the following conditions: baseline, emotional picture viewing, mental stress, and heartbeat tracking. Cardiac parameters were examined by using power spectrum analysis of heart rate variability and impedance cardiography. According to their performance in a heartbeat tracking task, 38 participants were classified as good (n=19) or poor (n=19) heartbeat perceivers. Neither group differed during baseline and heartbeat tracking, but good compared to poor heartbeat perceivers demonstrated greater sympathetic reactivity during mental stress and more vagal reactivity and subjective arousal during emotional picture viewing. The results suggest that cardiac awareness is related to greater responsivity of the autonomic nervous system during situations evoking autonomic reactivity.


Homoeologous recombination in allopolyploids: the polyploid ratchet.
Polyploidization and recombination are two important processes driving evolution through the building and reshaping of genomes. Allopolyploids arise from hybridization and chromosome doubling among distinct, yet related species. Polyploids may display novel variation relative to their progenitors, and the sources of this variation lie not only in the acquisition of extra gene dosages, but also in the genomic changes that occur after divergent genomes unite. Genomic changes (deletions, duplications, and translocations) have been detected in both recently formed natural polyploids and resynthesized polyploids. In resynthesized Brassica napus allopolyploids, there is evidence that many genetic changes are the consequence of homoeologous recombination. Homoeologous recombination can generate novel gene combinations and phenotypes, but may also destabilize the karyotype and lead to aberrant meiotic behavior and reduced fertility. Thus, natural selection plays a role in the establishment and maintenance of fertile natural allopolyploids that have stabilized chromosome inheritance and a few advantageous chromosomal rearrangements. We discuss the evidence for genome rearrangements that result from homoeologous recombination in resynthesized B. napus and how these observations may inform phenomena such as chromosome replacement, aneuploidy, non-reciprocal translocations and gene conversion seen in other polyploids.


Fostering critical thinking skills in students with learning disabilities: an instructional program.
An instructional unit was developed to enhance the critical thinking skills of middle school and high school students with learning disabilities by teaching them the principles of scientific reasoning. Student-teacher dialogues were used to engage the students in an active process of critical inquiry. Students analyzed everyday information presented in brief magazine articles and advertisements by applying the principles of the scientific method. The students made statistically significant improvements in their ability to (a) identify the principal claim made in an article or advertisement, (b) graph the relevant data, and (c) evaluate the claims made in the article and explain their support or rejection of the claims based on data. After the instructional unit, the overall performance of the special education students exceeded that of a control group composed of regular education students who had not received instruction in critical thinking.


Surfactant nebulization does not alter airflow obstruction and bronchial responsiveness to histamine in asthmatic children.
To test the hypothesis that surfactant nebulization improves pulmonary function and reduces bronchial responsiveness to histamine, we studied 12 children with asthma. We measured before and after inhalation of 100 mg nebulized natural-derived bovine surfactant (Alveofact (registered)) and after nebulization of 0.9% NaCl the change in peak expiratory flow, vital VC, FEV1, and forced expiratory flows at 50 and 75% of the flow-volume curve. In addition, we performed a histamine inhalation challenge. We did not find any significant changes in these parameters after nebulization of surfactant. These findings indicate that the inhalation of nebulized surfactant does not alter airflow obstruction and does not alter bronchial responsiveness to histamine in asthmatic children with airflow obstruction.


Comparison of interface stresses and strains for onlay and inlay unicompartmental tibial components.
There are several types of designs used for unicompartmental tibial components. The all-plastic inlay component is recessed and it preserves bone around the outer edge of the tibia. For an onlay component, the entire condyle is resected, and the plastic bearing is usually metal-backed, although all-plastic components are also available. The purpose of this study was to investigate the hypothesis that while 6-mm inlay components require less bone removal, the peak stresses and strains at the surface of the bone will be much greater when compared with 8-mm metal-backed onlay components, and that all-plastic onlays will be only a slight advantage over inlays. Tibial models were generated using computed tomography (CT) scans, while typical inlay and onlay components were modeled. Finite element analyses of bones and components were completed by assigning material properties based on the CT scans and applying loads. Results indicated that plastic inlays generated 6 times more peak stress at the tibial surface when compared with metal-backed onlays. Moreover, models using inlay components produced strain values exceeding onlay components by a factor of 13.5 due to areas of softer bone at the interface. Off-center loading toward the anterior or posterior of the components produced similar results. The stresses and strains for the 8-mm all-plastic onlay were reduced compared with the inlay but still much higher than for the metal-backed onlay. These findings indicated that metal-backed onlays may be a better option when considering load distribution on the tibial surface.


The cysteine-rich protein family of highly related LIM domain proteins.
Here we describe a family of closely related LIM domain proteins in avian cells. The LIM motif defines a zinc-binding domain that is found in a variety of transcriptional regulators, proto-oncogene products, and proteins associated with sites of cell-substratum contact. One type of LIM-domain protein, called the cysteine-rich protein (CRP), is characterized by the presence of two LIM domains linked to short glycine-rich repeats and a potential nuclear localization signal. We have identified and characterized two evolutionarily conserved members of the CRP family, CRP1 and CRP2, in chicken and quail. Expression of the genes encoding both CRP1 and CRP2 is differentially regulated in normal versus transformed cells, raising the possibility that members of the CRP family may function in control of cell growth and differentiation.


[Bioavailability of cyproterone acetate after oral and intramuscular application in men (author's transl)].
Cyproterone acetate was administered orally and intramuscularly to 5 male patients. The level of the active substance in plasma was monitored at intervals during the period of application using radioimmunoassay specific for cyproterone acetate. The areas under the drug level curves were similar after oral and intramuscular application of cyproterone acetate when taking into consideration the different doses used. Accordingly, cyproterone acetate is not dependent upon a "first-pass" effect. The bioavailability of the active substance was complete following oral application.


Erbium energy bridging upconversion mechanism studies on BAKL:Er3+/Yb3+ glass-ceramics and simultaneous enhancement of color purity of the green luminescence.
Borate oxyfluoride glasses are transparent in the infrared, ultraviolet and visible regions and represent an ideal host matrix for optically active dopants. Due to their lower phonon energies compared to a silicate glass matrix, non-radiative transitions are suppressed and high luminescence efficiency is expected. This work reports on a complete upconversion (UC) luminescence study of the optically active B2O3-Al2O3-KF-LiO (BAKL) glass-ceramics incorporated with Er3+/Yb3+ ions. The triclinic BAKL:Er3+/Yb3+ glass-ceramic (GC) phosphor was synthesized using the conventional melt-quenching technique and the subsequent heat treatment of the precursor glass. The successful synthesis of BAKL:Er3+/Yb3+ GCs was confirmed by X-ray diffraction, Fourier transform infra-red and differential thermal analysis measurements. The glasses were crystallized under controlled conditions, and the influence of phase composition (glass-to-crystalline phase ratio) on the wavelength and UC luminescence was thoroughly studied under 980 nm excitation. Interesting color tuning properties (white to intense green emission) of the sample were observed with laser pump power increment. The color tuning properties were explained using a new strategy i.e. the energy bridging mechanism between Er3+ ion clusters through an intermediate Yb3+ level. Moreover, their high color purity is well retained by varying the NIR excitation pump power densities and photometric characterization indicated the suitability in light emitting diodes and Er3+ doped fiber amplifier applications.


Prevalence of Alcohol Use and Associated Factors among Dilla University Students, Dilla Town, Southern Ethiopia: A Cross-Sectional Study.
Globally, alcohol is one of the most prevalent forms of substance use that is particularly high among young age groups. Despite the adverse health and social challenges associated with alcohol use, it is one of the most common risky behaviours among university students. This study aimed to assess the prevalence of alcohol use and associated factors among Dilla University students in Southern Ethiopia. An institution-based cross-sectional study was conducted at Dilla University among undergraduate regular students from January to February 2018. A systematic random sampling technique was used to get a total sample of 803 students each year from the department of the university. The collected data were coded, entered into Epi Info version 7.1, and analyzed with SPSS version 20. A total of 803 participants were successfully interviewed with a response rate of 91.7%. Alcohol use prevalence was 41.8% (n = 336) among participants. Being in fourth year (AOR = 2.66, 95% CI: 1.64, 4.31), having friends who use the substance (AOR = 1.53, 95% CI: 1.09, 2.1), being a khat user (AOR = 1.48, 95% CI: 1.05, 2.09), and being a cigarette smoker (AOR = 1.76, 95% CI: 1.09, 2.84) were found to be significantly associated with alcohol use. The current study revealed that fourth-year students, having friends who use the substance, being khat user, and being cigarette smoker had higher odds of alcohol use among the students. So the findings suggest that effective campus-based counselling and peer education should be implemented for early prevention, detection, and alleviation of alcohol use among students in the university.


Pleomorphic Adenoma of the Deep Lobe of the Parotid Gland Presenting With Dysphagia: A Case Report.
Dysphagia is a common clinical manifestation with a wide range of underlying medical conditions. Here, we present a case of a 52-year-old man with dysphagia, found to have a pleomorphic adenoma in the right parotid gland causing significant pharyngeal wall distortion. The patient underwent a successful total parotidectomy with facial nerve preservation using a transparotid-transcervical approach. A histological examination confirmed the diagnosis. While the patient experienced temporary facial weakness post-surgery, he had a successful recovery with no further issues during the 2-year follow-up. This case highlights the importance of considering parotid gland tumors as a potential cause of dysphagia when a mass is present in the oropharynx. Additionally, it demonstrates the feasibility of using a transparotid-transcervical approach for total parotidectomy with facial nerve preservation.


Occult Mediastinal Yolk Sac Tumor Producing α-Fetoprotein Detected by 18F-FDG PET/CT.
Malignant mediastinal yolk sac tumor (YST), especially adult onset, is rare. Herein, we report a case of occult mediastinal YST with α-fetoprotein production revealed by F-FDG PET/CT in a young adult, in which the intense tracer uptake was demonstrated in the anterior mediastinum. This case indicates F-FDG PET/CT may be a useful tool for detecting the occult primaries of YST.


A putative bactoprenol glycosyltransferase, CsbB, in Bacillus subtilis activates SigM in the absence of co-transcribed YfhO.
Bacteria are equipped with complex cell surface structures, such as cell walls. How they maintain cell surface integrity through cell wall metabolism during growth and adaptation to unfavorable environmental conditions is still elusive. In the Gram-positive soil bacterium Bacillus subtilis, one extracytoplasmic function (ECF) sigma factor, SigM, is believed to play a primary role in cell surface integrity. Here, we find that expression of CsbB, which is known to be involved in the extracellular stress response, causes constitutive activation of SigM when YfhO, a membrane protein with unknown function, is lost. CsbB has similarity with the well-characterized bactoprenol glucosyltransferase GtrB found in Gram-negative bacteria. Substitution of a single amino acid residue at the putative catalytic site of CsbB abolishes this constitutive activation, and expression of Escherichia coli GtrB in B. subtilis causes similar effects as expression of CsbB, suggesting that SigM is activated by the glycosyltransferase activity of CsbB. A comparison with the Gtr system in Gram-negative bacteria suggests that accumulation of glycosylated bactoprenol catalyzed by CsbB reduces the bactoprenol pool in the absence of YfhO. Reduction of bactoprenol synthesis causes similar effects as expression of CsbB. We propose that it is the shortage of available bactoprenol within a cell that induces SigM activity.


The relationship between fatigue and psychiatric disorders: evidence for the concept of neurasthenia.
Fatigue and psychiatric disorders frequently occur comorbidly and share similar phenomenological features. There has been debate as to whether chronic fatigue, or neurasthenia, should be considered an independent syndrome distinct from psychiatric disorders. We aimed to establish whether persistent fatigue can occur independently from psychiatric disorders and to test the hypothesis that fatigue without comorbid psychiatric symptoms has unique premorbid risk factors. We also aimed to investigate the psychological outcome of any individuals with fatigue. The MRC National Survey of Health and Development was used to prospectively follow 5362 participants from birth. A sample of nonfatigued individuals without psychiatric disorder was selected at age 36 and followed until age 43 years (n=2714). At age 43, the presence of new onset fatigue and/or psychiatric disorder was assessed. Information on a number of potential premorbid risk factors was collected between ages 0 and 36 years. Individuals with fatigue but no comorbid psychiatric disorder were then followed up at age 53 years. At age 43 years, 201 (7.4%) participants reported significant levels of new onset fatigue in the absence of comorbid psychiatric disorder. Despite the absence of case level psychiatric disorder, these individuals did report increased levels of some psychological symptoms. Excessive childhood energy (adjusted OR 2.63, 95% CI 1.55-4.48, P<.001) and being overweight at age 36 (adjusted OR 1.62, 95% CI 1.05-2.49, P=.03) were specific risk factors for fatigue without psychiatric disorder but not fatigue with comorbid psychiatric illness. Neuroticism was a risk factor for fatigue both with and without comorbid psychiatric disorder. Negative life events and a family history of psychiatric illness were only risk factors for fatigue when it occurred comorbidly with psychiatric illness. A significant proportion of the adult population will suffer from fatigue without comorbid psychiatric disorder. While fatigue and psychiatric disorders share some risk factors, excessive energy in childhood and being overweight as an adult appear to be specific risk factors for fatigue. Our results confirm the significant overlap between fatigue and psychiatric disorders, while also providing evidence for neurasthenia as a separate diagnosis.


Carotid angioplasty and stenting: will periprocedural transcranial Doppler monitoring be important?
To explore the value of transcranial Doppler (TCD) ultrasonography in the periprocedural monitoring of patients undergoing angioplasty procedures for stenosis of the internal carotid artery. Thirty-two patients were included in the study between April 1991 and September 1995 (6 females, 26 males; average age 66 years). All patients were interrogated before and after angioplasty by a standard TCD examination protocol. Intraprocedurally, TCD was used continuously to monitor cerebral blood flow and supply evidence of embolic particulates. Nineteen patients were treated by percutaneous transluminal angioplasty (PTA) alone; the other 13 underwent primary stent (PS) implantation. High-intensity transient signals indicative of emboli appeared to be more frequent in the PTA group than in the PS cohort. Preoperative TCD identified 3 (9%) high-risk patients with incompetent collateral pathways through the circle of Willis. Intraoperatively, TCD detected two postdilation carotid occlusions, a sylvian embolism, and one case of arterial spasm. The preprocedural TCD in a patient with contralateral carotid occlusion showed good collateral circulation, providing reassurance during conversion to endarterectomy when an undeployed stent obstructed blood flow. Postoperatively, TCD confirmed restored intracerebral circulation and identified one hyperperfusion syndrome. TCD is a simple, relatively inexpensive examination that can preprocedurally identify carotid stenosis patients at high risk for intraoperative cerebral ischemia in whom PTA might be preferable to surgery. During the procedure, TCD can document the benefits of endovascular treatment and offer early detection of ischemic complications.


Young people's attitudes towards wife-beating: Analysis of the Ghana demographic and health survey 2014.
Intimate Partner Violence is a global public health problem. Attitude towards wife-beating is a major determinant of both intimate partner violence perpetration and victimization. However, little is known about the attitudes of Ghanaian young people towards wife-beating. The objectives of this study were to assess young people's attitudes towards wife-beating, and identify salient factors influencing young people's acceptance of wife-beating. Data used in this study were obtained from the 2014 Ghana Demographic and Health Survey. The survey was nationally representative and provides estimates for population and health indicators across the former ten regions of Ghana, including rural and urban areas. Data were analyzed with Stata/SE version 16. We found that 32% of young women and 19% of young men accepted wife-beating. Among young women, acceptance of wife-beating was significantly influenced by younger age, wealth index, low educational status, religion, the region of residence, ethnicity, frequency of reading newspaper and frequency of listening to radio (p < 0.05). Among young men, acceptance of wife-beating was significantly influenced by wealth index, the region of residence and frequency of reading newspaper (p < 0.05). This study demonstrates that a substantial proportion of young people in Ghana accept wife-beating. Young women were more likely to accept wife-beating compared to young men. Acceptance of wife-beating was influenced by socio-demographic and behavioral factors. Efforts to end violence against women and girls in Ghana should focus on promoting girl education, economic empowerment of women and public education on laws that prohibit Intimate Partner Violence.


Expression of p56lck in B-cell neoplasias.
The protooncogene p56lck is considered to participate in malignant transformation of lymphoid cells. In order to evaluate the role of this tyrosine kinase in B cell neoplasias, we investigated the expression of p56lck by Western blot analysis. In 12/16 Burkitt's lymphoma derived cell lines, 3/3 lymphoblastoid cell lines, 1/6 Hodgkin's disease derived cell lines, and 10/10 freshly isolated chronic lymphocytic leukemia cells constitutive expression of the protein was detected. Protein tyrosine kinase assays detected a catalytic active form of p56lck in all p56lck expressing samples. Stimulation experiments of the different cell lines and primary tumour cells by the phorbol ester TPA and the B-cell specific stimulation with SAC/anti-IgM respectively indicated a change of the expression level in comparison with the unstimulated cells and, a higher molecular weight species of the protein tyrosine kinase p56lck was observed. This was probably due to hyperphosphorylation of p56lck. No correlation between an infection with the Epstein-Barr virus and the expression of p56lck was found in the cell lines used and in primary tumour cells. Inhibition of p56lck activity by the specific inhibitor 4-amino-6-hydroxyflavone revealed a decrease of proliferation of the T-cell line Jurkat, but not of the Burkitt's lymphoma cell lines. In the analysed cell lines we found a reduction of the kinase activity of p56lck of approximately 70%. These results suggest that lck may contribute to the maintenance of the transformation of the analysed B cell neoplasias but that lck does not support a model for an initial event in B cell transformation.


Selecting Infrared Absorption Lines-with Innocuous Neighbors.
Whether two neighboring infrared absorption lines, both in the square-root region of the curve of growth, are nearly free of mutual intrusion or so overlapped as to nearly coincide over a broad range of experimental conditions and line parameters is formulated. We also are able to estimate the unsullied equivalent width of the collision-broadened line pair at these limits. This should greatly extend the number of isolated infrared vibration-rotation band members that may be measured and tested for the validity of assigned line parameters and tested for the assumed Lorentz shape. The experimentally reported strong water lines at nu0 = 1429.96 cm(-1), 1447.98 cm(-1), and 1464.93 cm(-1) in the 6.3-micro band are confirmed to be independent of their strong neighbors.


Terbium-based coordination polymer nanoparticles for detection of ciprofloxacin in tablets and biological fluids.
The metal-organic coordination polymers with tunable structures and properties have been rapidly emerging as very important functional materials. In this work, we prepared terbium (Tb(3+))-based coordination polymer nanoparticles (CPNPs) by employing adenine (Ad) as bridging ligands. The CPNPs was further used as a receptor reagent for ciprofloxacin (CF) detection in aqueous solution. Addition of CF induces a typical emission of Tb(3+) due to the formation of Ad/Tb-CF complex and the sensitization of CF. The fluorescent intensity of Tb(3+) was enhanced linearly with increasing the CF concentration from 60 nM to 14 μM. The detection limit for CF in aqueous solution is 60 nM. The Ad/Tb CPNPs was successfully applied to detect CF in tablet and urine samples and showed a satisfactory result. Compared with other methods, the proposed method is advantageous because that it provides a very simple strategy for CF detection, which does not require complicated sample pretreatment processes or special reaction media. The proposed strategy could be contributed to expand the potential applications of lanthanide coordination polymers in biological and environmental fields.


Sensitive temperature gradiometer for use at low temperatures.
A device capable of very sensitive temperature gradient measurements in the presence of relatively large ambient temperature fluctuations is described. The device uses a pair of ''matched'' superconducting thin films in a bridge arrangement, with a SQUID magnetometer probe as the null detector.


Probiotics-host communication: Modulation of signaling pathways in the intestine.
The intestinal microbiota includes a diverse group of functional microorganisms, including candidate probiotics or viable microorganisms that benefit the host. Beneficial effects of probiotics include enhancing intestinal epithelial cell function, protecting against physiologic stress, modulating cytokine secretion profiles, influencing T lymphocyte populations, and enhancing antibody secretion. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases, but the mechanisms responsible for these effects remain to be fully elucidated. Accumulating evidence demonstrates that probiotics communicate with the host by modulating key signaling pathways, such as NFκB and MAPK, to either enhance or suppress activation and influence downstream pathways. Beneficial microbes can profoundly alter the physiology of the gastrointestinal tract, and understanding these mechanisms may result in new diagnostic and therapeutic strategies.


Thymic Polypeptide Fraction Biomodulina T Decreases Exhausted and Terminally Differentiated EMRA T Cells in Advanced Lung Cancer Patients Treated With Platinum-Based Chemotherapy.
Lung cancer is the second cause of cancer related deaths worldwide. Chemotherapy and immunotherapy represent the current standard of care for advanced NSCLC. Platinum-based chemotherapy expands late-differentiated T cell populations. Therefore, immune restoration after chemotherapy to adjuvate the immunotherapeutic potential could be crucial. The aim of this study was to evaluate the effect of Biomodulina T (BT), a thymic polypeptide fraction, on peripheral lymphocytes subpopulations in the context of cancer disease. Additionally, whether these effects might induce a better response to CIMAvax-EGF, an epidermal growth factor (EGF) depleting immunotherapy. Eighteen advanced NSCLC patients were evaluated after being treated with platinum-based chemotherapy. We found that the frequency of terminally differentiated effector T cells re-expressing CD45RA (EMRA) CD4+ (p=0.0031) and CD8+ (p=0.0372) T cells decreased with the administration of BT, whereas CD4+ naive T cells increase in more than 70% of the patients. Remarkably, CD4+ and CD8+ T lymphocytes expressing programmed cell death receptor-1 (PD1) significantly decreased after BT administration (p=0.0005 and p<0.0001, respectively). We also found an enhancement of the anti-EGF antibody response with a large percentage of patients treated with CIMAvax-EGF reaching the good antibody response condition after four vaccine doses. Moreover, the median overall survival of patients treated with CIMAvax-EGF was 16.09 months. In conclusion, our results suggest that the immunorestoration generated by the administration of BT after first-line chemotherapy may induce a better immune response to CIMAvax-EGF that could translate into the clinical benefit of patients diagnosed with advanced NSCLC.


Experimental and mechanistic insights into copper(ii)-dioxygen catalyzed oxidative N-dealkylation of N-(2-pyridylmethyl)phenylamine and its derivatives.
A di-(2-pyridylmethyl)phenylamine ((PyCH2)2NPh) supported Cu(ii)/O2 catalytic system was explored with the synthesis of pyridylmethyl-based compounds of carboxylate (PyCOOH), amide (PyC(O)NHPh), and imine (PyCH[double bond, length as m-dash]NPh) from the oxidative N-dealkylation of N-(2-pyridylmethyl)phenylamine (PyCH2NHPh) and its derivatives, by means of controlling the addition of a base and/or water to the reaction system under a dioxygen atmosphere at room temperature. Experimental studies showed that the imine and amide species could be precursors in succession in the way to the final oxidation state of carboxylates. A cyclic catalytic mechanism was proposed including the base triggered C-H bond activation of the 2-pyridylmethyl group (PyCH2-) and the intermolecular Cu-OOH α-hydrogen atom abstraction from the coordinated imine substrate (PyCH[double bond, length as m-dash]NPh).


Increased activity of hypothalamic corticotropin-releasing hormone neurons in multiple sclerosis.
Clinical observations and animal studies suggest that the hypothalamo-pituitary-adrenal (HPA) axis plays a role in the susceptibility to and the recovery from multiple sclerosis (MS). Since the HPA-axis is under the control of corticotropin-releasing hormone (CRH) neurons of the hypothalamus, we determined 2 parameters for activation of the CRH neurons in the hypothalamic paraventricular nucleus (PVN) in MS patients. Since the HPA-axis is more activated in MS, we expected an increased activity of CRH neurons. We also expected to see an age-related increase in CRH activity, because of the possible role of the HPA-axis in the age-related decrease in susceptibility to MS. The number of CRH cell profiles and the proportion of CRH neurons co-expressing vasopressin were used as parameters for activity. CRH cell population became more activated both in control and MS patients, from 40 years of age onwards, when the prevalence of MS starts to decrease in the population. The CRH neurons showed a significantly higher level of activation in MS patients than in controls, as appeared from the 3-fold increase in CRH cell number and the 4.5-fold increase in cells co-expressing CRH and vasopressin (AVP).


Photolyases and Cryptochromes in UV-resistant Bacteria from High-altitude Andean Lakes.
"High-altitude Andean Lakes" (HAAL) are pristine environments harboring poly-extremophilic microbes that show combined adaptations to physical and chemical stress such as large daily ambient thermal amplitude, extreme solar radiation levels, intense dryness, alkalinity, high concentrations of arsenic (up to 200 ppm) and dissolved salts. In this work, we compared the UV resistance profiles, pigment content and photoreactivation abilities of three UV-resistant bacteria isolated from distinct niches from HAALs, that is Acinetobacter sp. Ver3 (water, Lake Verde; 4400 m), Exiguobacterium sp. S17 (stromatolite, Lake Socompa, 3570 m) and Nesterenkonia sp. Act20 (soil, Lake Socompa, 3570 m). UV resistance ability of HAAL's strains indicate a clear adaptation to high radiation exposure encountered in their original habitat, which can be explained by genetic and physiological mechanisms named as the UV-resistome. Thus, the UV-resistome depends on the expression of a diverse set of genes devoted to evading or repairing the damage it provoked direct or indirectly. As pigment extraction and photoreactive assays indicate the presence of photoactive molecules, we characterized more in detail proteins with homology to photolyases/cryptochromes members (CPF). Phylogenetic analyses, sequence comparison and 3D modeling with bona fide CPF members were used to prove the presence of functional domains and key residues in the novel proteins.


Accounting for Genetic Differences Among Unknown Parents in Bubalus bubalis: A Case Study From the Italian Mediterranean Buffalo.
The use of genetic evaluations in the Water Buffalo by means of a Best Linear Unbiased Prediction (BLUP) animal model has been increased over the last two-decades across several countries. However, natural mating is still a common reproductive strategy that can increase the proportion of missing pedigree information. The inclusion of genetic groups in variance component (VC) and breeding value (EBV) estimation is a possible solution. The aim of this study was to evaluate two different genetic grouping strategies and their effects on VC and EBV for composite (n = 5) and linear (n = 10) type traits in the Italian Mediterranean Buffalo (IMB) population. Type traits data from 7,714 buffalo cows plus a pedigree file including 18,831 individuals were provided by the Italian National Association of Buffalo Breeders. VCs and EBVs were estimated for each trait fitting a single-trait animal model and using the official DNA-verified pedigree. Successively, EBVs were re-estimated using modified pedigrees with two different proportion of missing genealogies (30 or 60% of buffalo with records), and two different grouping strategies, year of birth (Y30/Y60) or genetic clustering (GC30, GC60). The different set of VCs, estimated EBVs and their standard errors were compared with the results obtained using the original pedigree. Results were also compared in terms of efficiency of selection. Differences among VCs varied according to the trait and the scenario considered. The largest effect was observed for two traits, udder teat and body depth in the GC60 genetic cluster, whose heritability decreased by -0.07 and increased by +0.04, respectively. Considering buffalo cows with record, the average correlation across traits between official EBVs and EBVs from different scenarios was 0.91, 0.88, 0.84, and 0.79 for Y30, CG30, Y60, and CG60, respectively. In bulls the correlations between EBVs ranged from 0.90 for fore udder attachment and udder depth to 0.96 for stature and body length in the GC30 scenario and from 0.75 for udder depth to 0.90 for stature in the GC60 scenario. When a variable proportion of missing pedigree is present using the appropriate strategy to define genetic groups and including them in VC and EBV is a worth-while and low-demanding solution.


Cell electrospinning: an in vitro and in vivo study.
Cell electrospinning and aerodynamically assisted bio-threading are novel bioplatforms for directly forming large quantities of cell-laden scaffolds for creating living sheets and vessels in three-dimensions. The functional biological architectures generated will be useful in both the laboratory and the clinic.


Functional connectivity between brain regions involved in learning words of a new language.
Previous studies have identified several brain regions that appear to be involved in the acquisition of novel word forms. Standard word-by-word presentation is often used although exposure to a new language normally occurs in a natural, real world situation. In the current experiment we investigated naturalistic language exposure and applied a model-free analysis for hemodynamic-response data. Functional connectivity, temporal correlations between hemodynamic activity of different areas, was assessed during rest before and after presentation of a movie of a weather report in Mandarin Chinese to Dutch participants. We hypothesized that learning of novel words might be associated with stronger functional connectivity of regions that are involved in phonological processing. Participants were divided into two groups, learners and non-learners, based on the scores on a post hoc word recognition task. The learners were able to recognize Chinese target words from the weather report, while the non-learners were not. In the first resting state period, before presentation of the movie, stronger functional connectivity was observed for the learners compared to the non-learners between the left supplementary motor area and the left precentral gyrus as well as the left insula and the left rolandic operculum, regions that are important for phonological rehearsal. After exposure to the weather report, functional connectivity between the left and right supramarginal gyrus was stronger for learners than for non-learners. This is consistent with a role of the left supramarginal gyrus in the storage of phonological forms. These results suggest both pre-existing and learning-induced differences between the two groups.


Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells.
Previously, we demonstrated that CK30PEG10k-compacted DNA nanoparticles (NPs) efficiently target photoreceptor cells and improve visual function in a retinitis pigmentosa model. Here, we test the ability of these NPs in driving transgene expression in the retinal pigment epithelium (RPE), using an RPE-specific reporter vector (VMD2-eGFP). NPs, uncompacted plasmid, or saline were subretinally delivered to adult BALB/c mice. NP-based expression was specific to RPE cells and caused no deleterious effects on retinal structure and function. eGFP expression levels in NP-injected eyes peaked at post-injection day 2 (PI-2), stabilized at levels ~3-fold higher than in naked DNA-injected eyes, and remained elevated at the latest time-point examined (PI-30). Unlike naked DNA, which only transfected cells at the site of injection, NPs were able to transfect cells throughout the RPE. Subretinal injections of rhodamine labeled NPs and naked DNA showed comparable initial uptake into RPE cells. However, at PI-7 and -30 days significantly more fluorescence was detected inside the RPE of NP-injected eyes compared to naked DNA, suggesting NPs are stable inside the cell which could possibly lead to higher and sustained expression. Overall, our results demonstrate that NPs can efficiently deliver genes to the RPE and hold great potential for the treatment of RPE-associated diseases.


16-[3-Methoxy-4-(2-piperidin-1-ylethoxy)benzylidene]-17-oxoandrost-5-en-3beta-yl acetate monohydrate.
The title compound, C(36)H(49)NO(5).H(2)O, has the outer two six-membered rings of the steroid nucleus in chair conformations. The central ring B of the steroid nucleus is in an 8beta,9alpha-half-chair conformation, while ring D of the steroid adopts a slightly distorted 13beta,14alpha-half-chair conformation. The piperidine ring is in a chair conformation. The methoxybenzylidene moiety has an E configuration with respect to the carbonyl group at position 17. Intermolecular O-H.O and O-H.N hydrogen bonds link the steroid and water molecules into chains which run parallel to the b axis.


Conducting Community Health Needs Assessments in rural communities: lessons learned.
The Affordable Care Act of 2010 requires all nonprofit hospitals in the United States to conduct a Community Health Needs Assessment (CHNA) at least every 3 years. With this law in its infancy, the best practice to conduct an assessment that complies with the law is unknown. Research designs vary across states and agencies, and little is known about the reliability or representativeness of results. The rural community group model (RCGM) is a newly developed model designed for conducting assessments in rural communities. Key components of the model are disseminating surveys, conducting key informant interviews, facilitating focus groups, and integrating secondary data of county-level health behaviors and outcomes. It has been used to conduct CHNAs on more than half the critical access hospitals in North Dakota (58%). Given this large sample size, which used the same methodology, this article provides an evaluation of the model focusing on lessons learned and challenges encountered in the conduct of CHNAs. Particular strategies for assessment planners are warding off group think, monitoring against bias creep in data collection, and integrating multiple data sources to inform decision making. The model is recommended for replication in rural settings to provide meaningful feedback that allows a hospital to match long-term planning with community needs.


Genomic heterogeneity and structural variation in soybean near isogenic lines.
Near isogenic lines (NILs) are a critical genetic resource for the soybean research community. The ability to identify and characterize the genes driving the phenotypic differences between NILs is limited by the degree to which differential genetic introgressions can be resolved. Furthermore, the genetic heterogeneity extant among NIL sub-lines is an unaddressed research topic that might have implications for how genomic and phenotypic data from NILs are utilized. In this study, a recently developed high-resolution comparative genomic hybridization (CGH) platform was used to investigate the structure and diversity of genetic introgressions in two classical soybean NIL populations, respectively varying in protein content and iron deficiency chlorosis (IDC) susceptibility. There were three objectives: assess the capacity for CGH to resolve genomic introgressions, identify introgressions that are heterogeneous among NIL sub-lines, and associate heterogeneous introgressions with susceptibility to IDC. Using the CGH approach, introgression boundaries were refined and previously unknown introgressions were revealed. Furthermore, heterogeneous introgressions were identified within seven sub-lines of the IDC NIL "IsoClark." This included three distinct introgression haplotypes linked to the major iron susceptible locus on chromosome 03. A phenotypic assessment of the seven sub-lines did not reveal any differences in IDC susceptibility, indicating that the genetic heterogeneity among the lines does not have a significant impact on the primary NIL phenotype.


The Importance of the Human Mass Balance Study in Regulatory Submissions.
The human mass balance study is a key study in the Clinical Pharmacology package of new drug applications. This study, along with the mass balance studies in toxicology species, provides essential information on the exposure of the parent compound and metabolites. Despite current regulatory guidance and previous publications, a lack of this study, or deficiencies in the study, are still seen in regulatory submissions today. This restricts the assessment of the benefit/risk in all populations and on the potential for drug-drug interactions leading to unnecessary precautions in the label. A review of new drug applications identifies a number of examples of inadequate characterization of circulating drug-related components or of elimination pathways, with questions raised during the regulatory review. In light of this, new insight is given on what is required from the mass balance study and on how to ensure sufficient information is captured.


[Use of liposomes for vaccines design].
Reviews reports on the creation of liposomal vaccines published during recent 25 years. Describes methods of antigen and immunomodulator incorporation in liposomes and their immunogenic properties. Presents data on development of influenza vaccines and prospects for their utilization as universal carriers of viral and bacterial antigens.


Improving the diagnostic accuracy of MR in the detection of infraspinatus tendon injuries.
Our goal was to determine the accuracy of MRI in the diagnosis of infraspinatus tendon injury and more specifically to determine if the antero-posterior extent of a rotator cuff tear is predictive of infraspinatus tearing. The MR images of 41 shoulders with surgically proven supraspinatus tears at surgery were retrospectively reviewed. The following were assessed for each of the 41 studies: the number of oblique coronal images on which a tendon defect could be seen, the angle subtended by the tear on axial images (the rotator cuff "axial angle"), and the extent of signal abnormality on sagittal images. The rotator cuff axial angle was 75.6 degrees in patients with infraspinatus tendon tears (ITTs) versus 40 degrees in those without ITTs, and this difference was significant (p < 0.001, t = 3.06). The mean number of oblique coronal images (obtained with a 4 mm slice and 1 mm gap) showing signal abnormality was 5.4 in the ITT group versus 2.9 in those without ITTs, and this difference was also significant (p < 0.001, t = 4.45). The mean sagittal extent of the tendon abnormality was 24.6 mm in the ITT group and 11.6 mm in those without ITTs, but the difference was not significant (p > 0.05, t = 1.1364). The axial angle and the number of oblique coronal images in which signal abnormality was present were significantly related to a higher incidence of infraspinatus tears.


Update of long-term trends analysis of ambient 8-hour ozone and precursor monitoring data in the South Central U.S.; encouraging news.
In the South Central U.S., lower tropospheric ozone pollution continues to be a challenging problem. This paper provides an update on long-term trends analyses of the ambient ozone and precursor monitoring data collected over the past 25 years (1986-2010) in four South Central U.S. cities, following up on a previous published review of 20 year trends (M.E. Sather and K. Cavender, J. Environ. Monit., 2007, 9, 143-150). The results of these analyses should be useful to air quality scientists, managers, planners, and modelers in assessing the effectiveness of nitrogen oxides (NO(x)) and volatile organic compounds (VOC) pollution controls for ambient ozone concentration reduction programs. Large amounts of quantitative information for each South Central U.S. city are concisely synthesized into one graphic per city. Results reported in this paper show significant long-term decreases in ambient ozone and precursor concentrations in all four South Central U.S. cities, especially over the recent five-year period 2006-2010.


Novel progestogenic activity of environmental endocrine disruptors in the upregulation of calbindin-D9k in an immature mouse model.
Endocrine disruption is a major global health concern in the industrialized world. The induction of uterine calbindin-D9k (CaBP-9k), which belongs to a large family of intracellular calcium binding proteins, was used to assess the exposure of endocrine disruptors (EDs) in an immature mouse model. Sex steroid hormones have been demonstrated to regulate uterine CaBP-9k expression in the uterus of rats and mice. In particular, the mouse CaBP-9k gene was predominantly regulated by progesterone (P4), whereas rat CaBP-9k was mainly induced by 17-beta-estradiol (E2) in the uterus. In the present study, immature (14-day-old) female mice were injected with 4-tert-octylphenol (OP), nonylphenol (NP), bisphenol A (BPA), E2, or P4 to determine their effects on uterine CaBP-9k mRNA and protein expression. In addition, to specify estrogenic or progestogenic activity of EDs in the regulation of CaBP-9k, the mice were co-treated with ICI 182,780, an estrogen receptor (ER) antagonist, or RU486, a progesterone receptor (PR) antagonist,. Treatments with OP, NP, or BPA resulted in an increase in CaBP-9k mRNA and protein in the uterus of immature mice in a dose-dependent and time-dependent manner. The EDs-induced expression of CaBP-9k mRNA and protein was reversed or abolished by pretreatment with RU486 or ICI 182,780, suggesting that these synthetic chemicals may have both progestogenic and estrogenic properties by acting through PR or ER in the induction of uterine CaBP-9k mRNA and protein in this model. These results describe a novel in vivo model for detection of both estrogenic and progestogenic activities of EDs in the induction of CaBP-9k mRNA and protein in the uterus of immature mice.


Leber congenital amaurosis: first genotyped Hungarian patients and report of 2 novel mutations in the CRB1 and CEP290 genes.
To introduce the first Hungarian patients with genetically defined Leber congenital amaurosis (LCA) and to report 2 novel mutations. Seven otherwise healthy patients (4-29 years, 5 male and 2 female) who had an onset of severe visual impairment before age 2 years were investigated. The diagnosis was established in all individuals by medical history, funduscopy, and full-field electroretinogram (ERG). Ocular examination included visual acuity testing, digital fundus photography, and in 6 patients retinal imaging with optical coherence tomography (OCT). Arrayed primer extension microarray screening was performed in all probands. In 2 patients, further Sanger sequencing and targeted next-generation sequencing revealed the second disease allele. A cone-rod type LCA was revealed in 4 patients and a rod-cone type disease in 3 patients. Five patients presented with maculopathy. Optical coherence tomography (OCT) imaging showed diffuse retinal thickening in 3 probands with severe macular atrophy in one. Full-field ERGs were undetectable or residual in all patients. Genetic screening revealed AIPL1, CRB1, and CEP290 gene-related pathology in 6 patients; in 1 proband, no mutation was found. Three homozygous and 3 compound heterozygous mutations were identified. Two novel variants were detected: c.2536G>T (p.G846X) in the CRB1 gene and c.4929delA (p.Lys1643fsX2) in the CEP290 gene. Genetic subtypes identified are among the most common ones in LCA; the phenotypes are consistent with those reported previously. Both novel mutations are predicted to result in a premature translation termination. The phenotype related to the novel CRB1 mutation results in severe atrophic maculopathy.


Hepatic expression of ErbB3 is repressed by insulin in a pathway sensitive to PI-3 kinase inhibitors.
ErbB3 is an epidermal growth factor receptor-related type I tyrosine kinase receptor capable, in conjunction with ErbB2 or epidermal growth factor receptor, of transmitting proliferative and differentiative signals in a variety of cell types. We previously showed that ErbB3 messenger RNA and protein increase in cultured hepatocytes during the first 12 h in culture, as does the binding of heregulin beta1, a ligand for ErbB3. Insulin inhibits the increase in heregulin beta1 binding, as well as the increase in ErbB3 messenger RNA and protein. Two models of insulin deficiency in vivo (diabetes and fasting) demonstrated elevated levels of hepatic ErbB3 protein, strengthening the relevance of our observations in vitro. Using chemical activators or antagonists, we sought to identify the signaling pathways that link insulin to ErbB3 expression. The PI-3 kinase inhibitors, wortmannin and LY294002, completely blocked the inhibition of ErbB3 protein expression by insulin, suggesting a role for PI-3 kinase in the regulation of this growth factor receptor. Rapamycin, an inhibitor of p70 S6 kinase, an enzyme downstream of PI-3 kinase, failed to block the effect of insulin on ErbB3 expression. These results suggest a complex regulatory paradign for ErbB3 that includes PI-3 kinase and may be linked, via insulin, to the metabolic status of the animal.


Immunocytochemical localization of synaptophysin (protein p38) and synapsin I in nerve terminals of rat neurohypophysis.
Synaptophysin and synapsin I, the synaptic vesicle-associated proteins, were demonstrated immunocytochemically in nerve terminals of the neurohypophysis of rats. Although both are associated with microvesicles 50-60 nm in diameter, they are not localized on or around the large neurosecretory granules nor the clear vacuoles, 100-200 nm in diameter. These findings strongly suggest that the microvesicles in the nerve terminal of the neurohypophysis are, for the most part, not the structures involved in the retrieval of the limiting membranes of the released neurosecretory granules, but rather typical synaptic vesicles. The clear vacuoles, which are negative for synaptophysin and synapsin I, are considered to be related to the retrieval of the limiting membranes of the released neurosecretory granules.


Future orientation, impulsivity, and problem behaviors: a longitudinal moderation model.
In the current study, based on a sample of 1,873 adolescents between 11.4 and 20.9 years of age from the first 3 waves of the National Longitudinal Study of Adolescent Health, we investigated the longitudinal effects of future orientation on levels of and developmental changes in problem behaviors, while controlling for the effects by impulsivity; we also tested the moderating effects by future orientation on the impulsivity-problem behaviors link over time. Additionally, we examined future orientation operationalized by items measuring education, marriage, and life domains. Findings based on growth curve analyses provided evidence of longitudinal effects by education and life future orientation on both levels of and developmental changes in problem behaviors; the effect of marriage future orientation was not significant for either test. In addition, only life future orientation moderated the effect by impulsivity on levels of problem behaviors over time. More specifically, impulsivity had a weaker effect on levels of problem behaviors over time for adolescents who reported higher levels of life future orientation.


Detection of mineral density on the surface of mouse parietal bones: backscattered electron imaging of low accelerating voltage scanning electron microscopy.
Backscattered electron (BSE) imaging of scanning electron microscopy (SEM) was applied to a study on the mineral density of the bone surface. The neonatal and adult mouse parietal bones freed of the periosteum and covering cells were examined in a field emission scanning electron microscope equipped with a high sensitivity BSE detector at 1-30 kV accelerating voltages. The mineral density of the bone surface was observable in BSE images at 5 kV accelerating voltage while only the topographic structures of the surface were obtained under an accelerating voltage less than 5 kV. As the accelerating voltages increased from 5 kV, the bright areas were extended, probably due to the imaging of the calcified bone matrix under the uncalcified osteoid. The bone surface is usually divided into smooth and rough areas according to its irregularities. BSE images at 5 kV clearly showed that the smooth areas were further divided into dark and bright areas which apparently corresponded to the uncalcified osteoid and calcified bone matrix, respectively. Bright granules, about 1.0-3.0 microns in diameter, were sometimes observed at the border between the osteoid and calcified bone matrix; these granular calcified areas were regarded as the calcifying front forming the calcified bone matrix from the osteoid. The present study demonstrated that the distribution of the osteoid on the mouse parietal bone surface changes depending on age: the osteoid occupied a large area in the parietal bone surface in neonatal mice, but was small in adult mice. Thus, low accelerating voltage SEM using BSE provides new information on the distribution of the osteoid and the bone matrix calcification under both normal and pathological conditions.


Experimental and computational thermochemistry of 1,4-benzodioxan and its 6-R derivatives.
The derivatives of 1,4-benzodioxan are found widely spread in nature and have great biomedical importance. The present work reports an experimental and computational study on the thermochemistry of 1,4-benzodioxan and several of its 6-R derivatives in the gaseous phase, at T = 298.15 K. Our current results were obtained from measurements of combustion energies, at T = 298.15 K, using a static bomb calorimeter. The standard molar enthalpies of vaporization/sublimation were measured by Calvet microcalorimetry and corrected to T = 298.15 K. Additionally, estimates were performed of the enthalpies of formation of all the studied compounds in the gas phase, using DFT and other more accurate correlated calculations, together with appropriate isodesmic or homodesmic reactions. There is a reasonable agreement between computational and experimental results.


Para-bromophenacyl bromide inhibits endothelium-dependent arterial relaxation and cyclic GMP accumulation by effects produced exclusively in the smooth muscle.
The alkylating agent para-bromophenacyl bromide (PBPB) has been reported to block endothelium-dependent relaxation of arteries, presumably by inhibiting phospholipase in the endothelium. We have investigated the site of action of PBPB-induced inhibition of melittin (MEL)- and bradykinin (BK)-stimulated endothelium-dependent relaxation and vascular smooth muscle (VSM) cyclic GMP (cGMP) accumulation. Studies were performed using short-term co-cultures of bovine pulmonary artery endothelial cells (EC) grown on microcarrier beads and rat aortic VSM. The culture system allowed separate pretreatment of ECs and VSM cells with PBPB (3 X 10(-5) M) before placement of the two cell types in co-culture. Because PBPB is an alkylating agent, it was felt that any blockade would endure after washout. Intracellular (VSM) concentrations of cGMP rose in response to MEL or BK stimulation only when EC were present, and were not decreased when only the EC had been pretreated with PBPB. cGMP accumulation induced by MEL or BK was significantly (P less than .01) inhibited in co-cultures where either the VSM alone or VSM and EC combined were pretreated with PBPB. The PBPB pretreatment adequately blocked EC phospholipase activity as measured by attenuation of the release of [3H]arachidonate from prelabeled EC by MEL. In parallel studies, when endothelium-derived relaxing factor was transferred by superfusion of EC to denuded rabbit aortic rings contracted with phenylephrine and pretreated with PBPB, the relaxation response induced by MEL or BK was inhibited. Similarly, when endothelium-derived relaxing factor was transferred to wells of cultured VSM pretreated with PBPB, cGMP accumulation was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)


Contributing factors associated with impulsivity-related falls in hospitalized, older adults.
Impulsivity-related falls (IRFs) sustained by hospitalized, older adults can lead to critical adverse events. The purpose of this study was to determine whether 7 common fall risk factors contributed to the occurrence of IRF in hospitalized, older adults. This study found that 31% of falls were classified as IRF. Logistic regression indicated that inattention and mobility were contributors to IRF. Early identification of these 2 risk factors could improve identification of potential IRFs and reduce fall rates.


Modulation of benzo[a]pyrene induced immunotoxicity in mice actively immunized with a B[a]P-diphtheria toxoid conjugate.
Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also toxic for mammalian immune cells. To develop a prophylactic immune strategy against detrimental effects of B[a]P, we have immunized mice with a B[a]P-diphtheria toxoid conjugate vaccine. We showed that high levels of antibodies against B[a]P and its metabolites modulate the redistribution of these PAHs in the blood. After immunization, increased levels of B[a]P and its metabolites were recovered in the blood. B[a]P significantly suppressed the proliferative response of both T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice also the immunotoxic effect of B[a]P on IFN-gamma, IL-12, TNF-alpha production and the reduced B cell activation was restored. Finally, our results showed that specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. Thus, we demonstrate that vaccination with a B[a]P conjugate vaccine based on a carrier protein used in licensed human vaccines reduces immunotoxicity and possibly other detrimental effects associated with B[a]P.


Idiopathic hypereosinophilic syndrome: A rare diagnosis in children.
Idiopathic hypereosinophilic syndrome (IHES) is one of numerous hypereosinophilic syndromes. The incidence of IHES among children is unknown, but it is considered a rare disease. We report a pediatric case of IHES and the challenges to finding an effective treatment. The patient described here was responsive to prednisolone and thalidomide.


Comprehensibility of material safety data sheets.
The Hazard Communications Standard, commonly known as the Worker Right to Know law, requires that a chemical information sheet, known as a material safety data sheet (MSDS), be produced for all hazardous chemicals. This study examines the comprehensibility of a sample of MSDSs to a group of about 100 unionized workers in manufacturing industries located in the state of Maryland. Workers were given several MSDSs and performed the equivalent of an open-book test answering questions regarding health and safety information that was provided on the MSDS. On average, the information on the MSDSs was found to be about one-third incomprehensible. This result raises concerns regarding policies and practices for hazard communication. There is a clear indication that MSDSs need to be improved if workers must rely on them for health and safety information.


Prevalence of cataract complications in patients with pseudoexfoliation syndrome in Northwestern Spain.
To assess the relationship between pseudoexfoliation syndrome and incidence of complications and related clinical factors in patients undergoing cataract surgery. We conducted a retrospective cohort study of 503 of 551 patients who underwent phacoemulsification surgery over 2 years in a health care district in Northwest Spain. In total, 120 of 681 eyes undergoing the procedure had pseudoexfoliation syndrome. Data on the surgical procedure and associated complications were extracted from the medical record. Complications included any combination of posterior capsular rupture, vitreous loss, zonular dialysis, and nuclear or lens luxation. We found a significant association between pseudoexfoliation syndrome and zonular dialysis (odds ratio [OR], 6.89; 95% CI, 2.27-20.93), intraoperative miosis (OR, 2.15; 95% CI, 1.10-4.22), and lens luxation >1.5 mm (OR, 9.49; 95% CI, 0.85-105.54). However, when adjusting for the overall risk of complications in pseudoexfoliation syndrome patients in consideration of myopia, use of anticoagulants or α-agonists, previous mydriasis, and anterior chamber length, the OR decreased to 1.02 (95% CI, 0.47-2.21) and was therefore not significant. Zonular dialysis and intraoperative miosis were intraoperative complications in cataract surgery patients with pseudoexfoliation syndrome when compared to controls.


Granulocyte function in coronary artery disease.
Granulocytes defend the body against invading microbes by producing a complex armamentarium of toxic substances, such as proteolytic enzymes, oxygen radicals and arachidonic acid metabolites. Under certain circumstances, however, such compounds may be released in the absence of phagocytosable particles, resulting in injury to normal cell and connective tissue degradation. Recent experimental studies have emphasized the potential role of granulocytes in the pathogenesis of myocardial ischemia. Clinical investigations have also shown alterations in neutrophil function in stable and unstable clinical manifestations of ischemic heart disease. "Priming" of granulocytes in stable forms of coronary disease may predispose to the subsequent development of acute coronary events, whereas activation of neutrophils may lead to alterations in vascular permeability and coronary flow regulation, leading to further myocardial and endothelial injury in acute myocardial infarction, unstable angina and coronary angioplasty.


Effects of Irrational Use of Antibiotics on Intestinal Health of Children with Extraintestinal Infectious Diseases.
The effects of different antibiotic treatment regimens on intestinal function and flora distribution in children with extraintestinal infectious diseases are explored. A total of 150 cases of extraintestinal infectious diseases admitted to our hospital from January 2021 to January 2022 and 50 healthy subjects during the same period were selected for the study. These 150 children were randomly divided into cephalosporin group, piperacillin group, and combined group and were successively treated with ceftazidime, piperacillin, and two drug combination regimens. The efficacy of the drug, intestinal microflora, intestinal mucosal barrier function, and incidence of antibiotic-associated diarrhea (AAD) were compared among the different groups. The experimental results showed that ceftazidime combined with piperacillin can effectively improve the intestinal health of children with extraintestinal infectious diseases but destroy the microecological environment of intestinal flora, affect the intestinal mucosal barrier function, and increase the risk of AAD.


Role of IFN-gamma in Th1 differentiation: IFN-gamma regulates IL-18R alpha expression by preventing the negative effects of IL-4 and by inducing/maintaining IL-12 receptor beta 2 expression.
Two key events occur during the differentiation of IFN-gamma-secreting Th1 cells: up-regulation of IL-12Rbeta2 and IL-12-driven up-regulation of IL-18Ralpha. We previously demonstrated that IL-12-driven up-regulation of IL-18Ralpha expression is severely impaired in IFN-gamma(-/-) mice. However, it was unclear from these studies how IFN-gamma influenced IL-18Ralpha since IFN-gamma alone had no direct effect on IL-18Ralpha expression. In the absence of IL-4, IL-12-dependent up-regulation of IL-18Ralpha/IL-12Rbeta2 was independent of IFN-gamma. However, in the presence of IL-4, IFN-gamma functions to limit the negative effects of IL-4 on both IL-18Ralpha and IL-12Rbeta2. Neutralization of IL-4 restored IL-12-driven up-regulation of IL-18Ralpha/IL-12Rbeta2 in an IFN-gamma-independent fashion. In the absence of both IL-12 and IL-4, IFN-gamma up-regulates IL-12beta2 expression and primes IFN-gamma-producing Th1 cells. When T cells were primed in the presence of IL-4, no correlation was found between the levels of expression of the IL-18Ralpha or the IL-12Rbeta2 and the capacity of these cells to produce IFN-gamma, suggesting that IL-4 may also negatively affect IL-12-mediated signal transduction and thus Th1 differentiation. These data clarify the role of IFN-gamma in regulation of IL-18Ralpha/IL-12Rbeta2 during both IL-12-dependent and IL-12-independent Th1 differentiation.


Reliability of clinical assessment in diagnosing cauda equina syndrome.
Cauda equina syndrome (CES) is a neurological syndrome presenting with non-specific symptoms and signs that often leads to diagnostic confusion and delay. Acute onset CES is a surgical emergency. The common aetiology is a prolapsed lumbar disc. If the diagnosis is missed, it can have devastating consequences for the patient and a high financial cost to healthcare providers. The objective of this study was to evaluate the efficacy of clinical assessment in clinching the diagnosis. Eighty patients who underwent urgent clinical assessment and magnetic resonance imaging (MRI) for suspected CES over a 1-year period (from January 1st 2008 to 31 December 2008) were included in the study. Fifteen of these patients had a CES and underwent urgent lumbar discectomy and decompression. Medical notes and MRI scans of all these patients were reviewed. The presenting symptoms and signs were analysed against a positive MRI scan. Chi-square test with Yates correction was used to test association of each clinical symptom and sign for a positive MRI. In this study, only 18.8% of assessed patients had a CES producing compression seen on the MRI. Presence of saddle sensory deficit was the only clinical feature with a statistically significant association with MRI positive CES (p = 0.03). This series shows that saddle sensory deficit has a higher predictive value than other clinical features in diagnosing a CES. However, as there is no symptom or sign which has an absolute predictive value in establishing the diagnosis of CES, any patient in whom a reasonable suspicion of CES arises must undergo urgent MRI to exclude this diagnosis.


A model for multiparametric mri tissue characterization in experimental cerebral ischemia with histological validation in rat: part 1.
After stroke, brain tissue undergoes time-dependent heterogeneous histopathological change. These tissue alterations have MRI characteristics that allow segmentation of ischemic from nonischemic tissue. Moreover, MRI segmentation generates different zones within the lesion that may reflect heterogeneity of tissue damage. A vector tissue signature model is presented that uses multiparametric MRI for segmentation and characterization of tissue. An objective (unsupervised) computer segmentation algorithm was incorporated into this model with the use of a modified version of the Iterative Self-Organizing Data Analysis Technique (ISODATA). The ability of the model to characterize ischemic tissue after permanent middle cerebral ischemia occlusion in the rat was tested. Multiparametric ISODATA measurements of the ischemic tissue were compared with quantitative histological characterization of the tissue from 4 hours to 1 week after stroke. The ISODATA segmentation of tissue identified a gradation of cerebral tissue damage at all time points after stroke. The histological scoring of ischemic tissue from 4 hours to 1 week after stroke on all the animals was significantly correlated with ISODATA segmentation (r=0.78, P<0.001; n=20) when a multiparametric (T2-, T1-, diffusion-weighted imaging) data set was used, less correlated (r=0.70, P<0.01; n=20) when a T2- and T1-weighted data set was used, and not correlated (r=-0.12, P>0.47; n=20) when only a diffusion-weighted imaging data set was used. Our data indicate that an integrated set of MRI parameters can distinguish and stage ischemic tissue damage in an objective manner.


Facial epicrania fugax: A prospective series of eight new cases.
Introduction Epicrania fugax (EF) is a primary headache whose main feature is the dynamic character of the pain. EF pain typically moves across different dermatomes in a linear or zigzag trajectory. Recently, a facial variant of EF has been described, with the pain starting in the lower face and radiating upwards. Aim We report eight patients with an EF-type of pain of facial location and either upward or downward radiation. Methods For each patient, we recorded relevant demographic and clinical data. Magnetic resonance imaging (MRI) with fast imaging employing steady state acquisition (FIESTA) was obtained in all cases for the assessment of neurovascular compression of the trigeminal nerve. Results There were seven women and one man, and the mean age was 76.1 years (standard deviation, 11.3). Six patients had a paroxysmal pain starting at the lower face and moving upwards, while two patients had downward radiation. The pain always followed a fixed linear trajectory across different dermatomes. All cases had triggers, and pain intensity was consistently severe. Half of the patients had accompanying autonomic features. Neurovascular compression with imprinting over the trigeminal root on the symptomatic side was identified in three patients. All cases responded to antiepileptic drugs, and three had spontaneous remissions. Conclusions This series reinforces the facial variant of EF and extends the phenotype with cases of downward radiation. It also contributes to enriching the differential diagnosis of facial pain. Neurovascular compression of the trigeminal nerve may be found in some cases, although a possible pathogenic link needs further research.


Expression of myb-related genes in the moss, Physcomitrella patens.
Three cDNA clones encoding proteins containing a myb-related DNA binding domain have been isolated from a cDNA library prepared from protonemal tissue of the moss, Physcomitrella patens. The three cDNA clones between them encode two different classes of myb-like proteins, termed Pp1 and Pp2, that, outside of the myb domain, show no regions of significant homology. Acidic domains, capable of forming alpha-helical structures, are present in the carboxy-termini of the derived amino acid sequences from Pp1 and Pp2cDNAs suggesting that, like other myb genes, these proteins probably function as transcriptional activators. In contrast to other plants, where extensive myb-related gene families are present in the genome, a relatively small family is present in P. patens. Analyses of transcript levels during development of P. patens showed that maximum levels of transcription of the two genes occurred in young wild-type protonemal tissue that correlated with the time of maximum mitotic index. A decline in the expression of both genes occurs with increasing age of the wild-type tissue. Aberrant levels of expression of the two genes were observed in developmental mutants of P. patens which, as well as carrying specific morphological mutations, have greatly retarded protonemal growth rates. Transformation of wild-type P. patens with antisense constructs derived from Pp1 and Pp2 cDNA clones led to a dramatically reduced frequency of transformants when the expression of the reporter gene within the constructs was selected. Taken together, the data strongly suggest that expression of Pp1 and Pp2 is essential for cell growth during normal gametophytic development of P. patens.


Carbon monoxide-releasing molecules (CO-RMs) modulate respiration in isolated mitochondria.
Emerging evidence reveals that heme oxygenase-1 (HO-1) and its product carbon monoxide (CO) can exert diverse biological and cytoprotective effects. Our group has recently identified a new class of compounds (CO-releasing molecules or CO-RMs) that can carry and deliver CO to biological systems and can be used to examine the physiological properties of CO. Here, we evaluated the influence of endogenously-generated CO (via HO-1 induction by hemin) and CO liberated from exogenously supplied CO-RMs on mitochondrial function. Renal mitochondria were isolated either from rats with increased HO-1 or from untreated animals, the latter being exposed to different concentrations of CO-RMs (10-100 microM). We found that mitochondrial oxygen uptake was significantly reduced in kidneys after HO-1 induction and, in a similar fashion, CO-RMs inhibited mitochondrial function in a concentration-dependent manner. Specifically, a marked depression of state 3 was observed resulting in a significant decrease in respiratory control index (RCI) values. When mitochondria were incubated with the inactive forms of CO-RMs, which are devoid of CO, the respiratory parameters remained unchanged. In summary, the results indicate that HO-1 induction and enhanced CO decrease renal oxygen consumption and alter mitochondrial function suggesting that CO could be a physiological regulator of mitochondrial oxidative phosphorylation.


Circular and linear plasmids of Lyme disease spirochetes have extensive homology: characterization of a repeated DNA element.
We have cloned three copies of a repeated DNA segment from Borrelia burgdorferi sensu stricto strain B31, present on both circular and linear plasmids of this and other B. burgdorferi sensu lato strains. The DNA sequences are characterized by a highly homologous segment containing two open reading frames (ORFs), ORF-A and ORF-B. Five additional ORFs can be found on the slightly less homologous flanking sequences: ORF-G on the opposite strand upstream of ORF-A, and ORF-C, ORF-D, ORF-E, and ORF-F downstream of ORF-B. The 4.6-kb-long element containing ORF-A through ORF-E is flanked by approximately 180-bp-long imperfect inverted repeats (IRs). The putative gene product of ORF-C displays homology to proteins involved in plasmid maintenance in a number of gram-positive and gram-negative bacteria. ORF-E features several short, highly homologous direct repeats. ORF-A, ORF-B, and ORF-D are homologous to three ORFs on a recently described 8.3-kb circular plasmid of Borrelia afzelii Ip21 that are flanked by similar IRs (J. J. Dunn, S. R. Buchstein, L.-L. Butler, S. Fisenne, D. S. Polin, B. N. Lade, and B. J. Luft, J. Bacteriol. 176:2706-2717,1994). ORF-C and ORF-E, however, are missing from this region on the Ip21 plasmid. Furthermore, the repeated DNA element as defined by the IRs is present in opposite orientations relative to the flanking sequences on the B31 and Ip21 plasmids.


Case Report: Combination of Pressure Guidewire and Optical Coherence Tomography-Guided Drug-Coated Balloon Revascularization for Renal Artery Fibromuscular Dysplasia.
Fibromuscular dysplasia (FMD) is the second common cause of renovascular hypertension. With the advent of endovascular therapy, angiography has become a diagnostic gold standard for FMD. Optical coherence tomography (OCT) by reflecting in vivo histology may improve diagnostic and classification accuracy. Renal fractional flow reserve (rFFR), measured by pressure guidewire, may distinguish the patients who may benefit from revascularization by identifying physiologically significant stenoses. However, the role of usage of both OCT and rFFR is not well-studied. We herein report a 17-year-old male with renovascular hypertension due to FMD. Angioplasty of drug-coated balloon (DCB) guided by OCT and FFR favorably achieved blood pressure (BP) control. In conclusion, the utility of both OCT and FFR may be useful for the appropriate selection of patients with renal FMD.


[The effect of amino acids on neurotransmitter metabolites in the cerebrospinal fluid].
Metabolites of neurotransmitters of dopamine, homomovanillic acid (HVA), and of serotonin, 5-hydroxyindole acetic acid (5-HIAA), were assessed in cerebrospinal fluid by the method of high pressure liquid chromatography with electrochemical detection. The HVA concentration in cerebrospinal fluid rose markedly in a two-month-old infant with intracranial hypertension caused by a communicating hyporesorptive hydrocephalus following administration of tyrosine, the precursor of dopamine. The 5-HIAA concentration in cerebrospinal fluid rose significantly in a 20-month-old boy with epilepsy and arrested psychomotor development after administration of 5-hydroxytryptophan, the precursor of dopamine. Biochemical normalization of concentrations of neurotransmiteed metabolites did not lead to changes in the clinical condition of the children.


A simple chromatographic route for the isolation of meso diaminopimelic acid.
Meso diaminopimelic acid is an important noncoded amino acid found in Gram-negative bacterial peptidoglycan. In spite of its importance, this stereoisomer is not available commercially. A simple, economical procedure was developed for the isolation of pure meso diaminopimelic acid via an high-performance liquid chromatography separation. In our new approach, the underivatized three isomers of diaminopimelic acid were separated on a crown ether-based chiral stationary phase. For the structure identification, (1)H NMR spectroscopy was applied.


Individual differences in quality-of-life treatment response.
Individual differences in treatment responses to health-related quality-of-life interventions arise ubiquitously and prominently in clinical trials. These differences do not reflect error, but instead represent patterns of response that vary reliably across patients. Individual differences complement and qualify the information conveyed by average health-related quality-of-life effects for treatment arms. If clinicians and patients are to use health-related quality-of-life findings from clinical trials to make treatment decisions, they must have information about the extent and nature of such individual variation. The relatively small effect sizes of health-related quality-of-life outcomes in clinical trials offer a weak basis for generalizing results to new persons, and patients routinely anticipate likely treatment benefits for themselves that exceed these small effects. A focus on individual differences in treatment response can promote more realistic appreciation of expected benefit and uncertainty. A pharmacogenetic example shows how individual differences in drug metabolism can directly affect health-related quality-of-life treatment outcomes such as pain and physical functioning. The authors suggest how graphical displays can summarize individual responses and provide a context for interpreting the size and generality of the average treatment. Mixed-effects modeling subsumes average treatment differences and individual differences in a unified statistical analysis. Analysis of health-related quality-of-life data from an advanced colorectal cancer trial illustrates this approach. Objective statistical criteria indicate that, for this example, individual differences dominate the treatment difference. The authors suggest that presentation of the spectrum of individual responses and associated prediction intervals can convey clinically meaningful information regarding the impact of a treatment on health-related quality of life.


Stereological and morphological analysis of the effects of aging on spermatogenesis in rat testis 1.
To quantify, through stereological and morphometric analysis, spermatogenesis in rats undergoing the natural aging process. Seventy-two male Wistar rats were divided into 6 equal groups according to age at the time of killing: 3, 6, 9, 12, 18, and 24 months. All the rats were subjected orchiectomy and collection of testicular parenchymal fragments for histological and morphometric analysis. The numerical density of spermatids was calculated using a stereological study, and morphometric analysis was conducted to measure the height of the germinal epithelium and the area of the seminiferous tubules. We found that the 18 and 24 months groups showed a significant reduction in the number of round spermatids. However, the height of the germinal epithelium was not significantly different between the groups. The area of seminiferous tubules was also significantly reduced in the elderly rats compared to that in the young ones. Aging of rats showed a significant reduction in the number of round spermatids and the area of the seminiferous tubules, more pronounced in the rats at 18 and 24 months of life.


Development of mucosal protection against the heat-stable enterotoxin (ST) of Escherichia coli by oral immunization with a genetic fusion delivered by a bacterial vector.
An LT-B-ST (LT-B/ST) fusion peptide was constructed by genetically joining the 5' terminus of a synthetic gene coding for the heat-stable enterotoxin (ST) of Escherichia coli to the 3' terminus of the gene coding for the binding subunit of the heat-labile enterotoxin (LT-B) of E. coli. An eight-amino-acid, proline-containing linker was included between the LT-B and ST moieties. An aroA mutant of Salmonella dublin transformed with a plasmid carrying this genetic construct was shown to express a fusion peptide with antigenic determinants of both LT-B and ST. Mice were immunized orally with this strain or with a control strain expressing just LT-B from the same plasmid. Sera and mucosal secretions were obtained and analyzed for the presence of serum immunoglobulin G and mucosal immunoglobulin A that were able to recognize LT-B and ST by enzyme-linked immunosorbent assay (ELISA) and, more importantly, were able to neutralize native ST in the suckling mouse assay. Sera and mucosal secretions from animals immunized with the strain expressing the LT-B/ST fusion exhibited detectable ELISA reactivity against LT-B but not against native ST. However, even in the absence of detectable ELISA reactivity, both sera and mucosal secretions from these animals were able to neutralize the biological activity of native ST in the suckling mouse assay. These findings are important because they demonstrate the development of mucosal protection against ST by oral immunization with a genetic fusion delivered by a bacterial vector.


Rapid and dynamic intracellular patterning of cell-internalized magnetic fluorescent nanoparticles.
Conjugated magnetic nanoparticles have recently demonstrated potential in activating unique and specific activity within cells. Leveraging microfabrication, we have developed a technique of localizing nanoparticles to specific, subcellular locations by a micropatterned ferromagnetic substrate. Controlled patterns of nanoparticles were assembled and dynamically controlled with submicrometer precision within live cells. We anticipate that the technique will be useful as a compact, simple method of generating localizable, subcellular chemical and mechanical signals, compatible with standard microscopy.


Design of a rangefinder for military purposes.
Design considerations for military pulse rangefinders are discussed. The practical aspects of modularity, cooling, optical design, and solid state receiver performance are reviewed. A measure of overal system performance is developed and compared for several military rangefinders.